American Journal of Kidney Diseases

AJKD
American Journal of
Kidney Diseases
Editorial correspondence should be addressed to Bertram L. Kasiske, MD, Editor-in-Chief, AJKD, Hennepin
Faculty Associates, 600 HFA Building, Room D508, 914
South 8th Street, Minneapolis, MN 55404. Telephone:
(612) 347-7770
Business correspondence (subscriptions, change of
address) should be addressed to the Publisher, Elsevier,
Periodicals Department, 6277 Sea Harbor Dr, Orlando,
FL 32887-4800. E-mail: elspcs@elsevier.com
Change of address notices, including both the old and
new addresses of the subscriber, should be sent at least one
month in advance.
Customer Service: 1-800-654-2452; outside the United
States and Canada, 1-407-345-4000.
Yearly subscription rates: United States and possessions: individual, $389.00; institution, $671.00; single
issue, $61.00. All other countries: individual, $551.00;
institution, $725.00; single issue, $61.00. For all areas
outside the United States and possessions, there is no
additional charge for surface delivery. Student and resident: United States and possessions, $194.00; all other
countries, $255.00. To receive student/resident rate,
orders must be accompanied by name of affiliated institution, date of term, and the signature of program/
residency coordinator on institution letterhead. Orders
will be billed at individual rate until proof of status is
received. Single issues, both current and back, exist in
limited quantities and are offered for sale subject to
availability. Current prices are in effect for back volumes and back issues. Back issues sold in conjunction
with a subscription are on a prorated basis. Prices are
subject to change without notice. Checks should be
made payable to Elsevier and sent to American Journal of
Kidney Diseases, W.B. Saunders, Periodicals Department, PO Box 628239, Orlando, FL 32862-8239.
Copyright 2006, National Kidney Foundation. All
rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means now
or hereafter known, electronic or mechanical, including
photocopy, recording, or any information storage and
retrieval system, without permission in writing from the
publisher. Printed in the United States of America.
Permissions may be sought directly from Elseviers
Rights Department in Philadelphia, PA, USA: phone 215239-3804, fax 215-239-3805, e-mail healthpermissions@
elsevier.com. Requests may also be completed on-line
via the Elsevier homepage (www.elsevier.com/locate/
permissions).
The appearance of the code at the bottom of the first
page of an article in this journal indicates the copyright
owners consent that copies of the article may be made for
personal or internal use, or for the personal or internal use of specific clients. This consent is given on the
condition, however, that the copier pay the stated per-copy
fee through the Copyright Clearance Center, Inc (222
Rosewood Dr, Danvers, MA 01923; (978) 750-8400) for
copying beyond that permitted by Sections 107 or 108 of
the US Copyright Law. This consent does not extend to
other kinds of copying, such as copying for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. Absence of the code
indicates that the material may not be processed through
the Copyright Clearance Center, Inc. Reprints of single
articles available online may be obtained by purchasing
Pay-Per-View access for $30 per article on the journal web
site, www.ajkd.org
Reprints: To order 100 or more reprints for educational,
commercial, or promotional use, contact the Commercial
Reprints Department, Elsevier Inc., 360 Park Avenue
South, New York, NY 10010-1710. Fax: 212-462-1935;
e-mail: reprints@elsevier.com.
Advertising representative: Cunningham Associates,
180 Old Tappan Rd, Old Tappan, NJ 07675. Telephone
1-201-767-4170; fax 1-201-767-8065.
The ideas and opinions expressed in the American
Journal of Kidney Diseases do not necessarily reflect
those of the National Kidney Foundation, the Editor, or
the Publisher. Publication of an advertisement or other
product mentioned in the American Journal of Kidney
Diseases should not be construed as an endorsement of
the product or the manufacturers claims. Readers are
encouraged to contact the manufacturer with any questions about the features or limitations of the products
mentioned. The National Kidney Foundation and the
Publisher do not assume any responsibility for any
injury and/or damage to persons or property arising out
of or related to any use of the material contained in this
periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be
administered to verify the dosage, the method and duration of administration, or contraindications. It is the
responsibility of the treating physician or other health
care professional, relying on independent experience
and knowledge of the patient, to determine drug dosages and the best treatment for the patient.
The contents of the American Journal of Kidney Diseases are indexed in Index Medicus and MEDLINE, Current Contents/Clinical Medicine, Science Citation Index, EMBASE/Excerpta Medica, ISI, and CINAHL.
The American Journal of Kidney Diseases home page is
located at www.ajkd.org.
AJKD
EDITORIAL BOARD
American Journal of
Kidney Diseases
Editor-in-Chief
Bertram L. Kasiske, MD
Minneapolis, MN
Co-Editors
Robert Foley, MB
Minneapolis, MN
Suzanne Swan, MD
Minneapolis, MN
Blanche Chavers, MD
Minneapolis, MN
Mark Rosenberg, MD
Minneapolis, MN
Education Editor
Stuart Linas, MD
Denver, CO
Sharon Andreoli, MD
Indianapolis, IN
Rashad Barsoum, MD
Cairo, Egypt
Gavin Becker, MD
Melbourne, Australia
Jeffrey Berns, MD
Philadelphia, PA
Edward Cole, MD
Toronto, Canada
Bengt Fellstrom, MD
Uppsala, Sweden
Ulrich Frei, MD
Berlin, Germany
Ronald Hogg, MBChB
Dallas, TX
Pathology Editor
Agnes Fogo, MD
Nashville, TN
Associate Editors
Kunitoshi Iseki, MD
Okinawa, Japan
Michel Jadoul, MD
Brussels, Belgium
Bryce Kiberd, MD
Halifax, Canada
Kar Neng Lai, MD
Hong Kong, China
Norbert Lameire, MD
Gent, Belgium
Mark Perazella, MD
New Haven, CT
Bernardo Rodrguez-Iturbe, MD
Maracaibo, Venezuela
Gerald Schulman, MD
Nashville, TN
Yoav Segal, MD
Minneapolis, MN
Der-Cherng Tarng, MD
Taipei, Taiwan
Armando Torres, MD
Tenerife, Spain
Pablo Urena, MD
Aubervilliers, France
Stefan Vtko, MD
Prague, Czech Republic
Matthew Weir, MD
Baltimore, MD
Andrzej Wiecek, MD
Katowice, Poland
Carmine Zoccali, MD
Reggio Calabria, Italy
Statistical Reviewers
David Gilbertson, PhD
Minneapolis, MN
Jon Snyder, MS
Minneapolis, MN
Editorial Office
Minneapolis, MN
Managing Editor
Deanna Gunderson
Associate Managing Editor

Anna Gillette
Editorial Assistant
Michelle Parkin
AJKD
VOL 48, NO 1, SUPPL 1, JULY 2006
American Journal of
Kidney Diseases
CONTENTS
KDOQI Advisory Board Members ..................................................................................
S1
CLINICAL PRACTICE GUIDELINES FOR HEMODIALYSIS ADEQUACY, UPDATE

2006
Hemodialysis Adequacy 2006 Work Group Membership ...........................................
S2
Tables ...............................................................................................................................
S3
Figures .............................................................................................................................
S3
Abbreviations and Acronyms ........................................................................................
S4
Foreword ..........................................................................................................................
S6
Introduction .....................................................................................................................
S8
I. Clinical Practice Guidelines for Hemodialysis Adequacy ..................................
S12
S13
S17
S24
S28
S33
S40
S42
S45
Guideline 1. Initiation of Dialysis..............................................................................

Guideline 2. Methods for Measuring and Expressing the Hemodialysis Dose ...........
Guideline 3. Methods for Postdialysis Blood Sampling .............................................
Guideline 4. Minimally Adequate Hemodialysis .......................................................
Guideline 5. Control of Volume and Blood Pressure .................................................
Guideline 6. Preservation of Residual Kidney Function ............................................
Guideline 7. Quality Improvement Programs ...........................................................
Guideline 8. Pediatric Hemodialysis Prescription and Adequacy ..............................
II. Clinical Practice Recommendations for Hemodialysis Adequacy ....................
Clinical Practice Recommendation for Guideline 1: Initiation of Dialysis ................

Clinical Practice Recommendations for Guideline 2: Methods for Measuring and
Expressing the Hemodialysis Dose........................................................................
Clinical Practice Recommendations for Guideline 4: Minimally Adequate
Hemodialysis ........................................................................................................
Clinical Practice Recommendation 5: Dialyzer Membranes and Reuse .....................
Clinical Practice Recommendations for Guideline 6: Preservation of Residual
Kidney Function ...................................................................................................
S48
S49
S50
S53
S63
S68
III. Research Recommendations ...............................................................................
S71
Appendix. Methods for Adding Residual Clearance to Hemodialyzer Clearance ....
S75
Work Group Biographies................................................................................................
S78
References .......................................................................................................................
S80
CLINICAL PRACTICE GUIDELINES FOR PERITONEAL DIALYSIS ADEQUACY,

UPDATE 2006
Peritoneal Dialysis Adequacy 2006 Work Group Membership...................................
S91
Tables ...............................................................................................................................
S92
S93
Foreword ..........................................................................................................................
S95
Introduction .....................................................................................................................
S96
I. Clinical Practice Guidelines for Peritoneal Dialysis Adequacy .........................
S98
S99
S103
S117
S122
S125
S127
Guideline 1. Initiation of Dialysis..............................................................................

Guideline 2. Peritoneal Dialysis Solute Clearance Targets and Measurements..........
Guideline 3. Preservation of Residual Kidney Function ............................................
Guideline 4. Maintenance of Euvolemia....................................................................
Guideline 5. Quality Improvement Programs ...........................................................
Guideline 6. Pediatric Peritoneal Dialysis .................................................................
II. Clinical Practice Recommendations for Peritoneal Dialysis Adequacy ...........
Clinical Practice Recommendation for Guideline 1: Initiation of Dialysis ................

Clinical Practice Recommendations for Guideline 2: Peritoneal Dialysis
Prescription Targets and Measurements ...............................................................
Clinical Practice Recommendations 3: Recommended Laboratory Measurements
for Peritoneal Membrane Function and Ultrafiltration Volume ...........................
Clinical Practice Recommendations 4: Writing the Peritoneal Dialysis
Prescription ..........................................................................................................
Clinical Practice Recommendations for Guideline 6: Pediatric Peritoneal Dialysis .........
S130
S131
S132
S138
S143
S146
S159
S164
References .......................................................................................................................
S167
CLINICAL PRACTICE GUIDELINES FOR VASCULAR ACCESS, UPDATE 2006

Vascular Access 2006 Work Group Membership ........................................................
S176
Tables ...............................................................................................................................
S177
Figures .............................................................................................................................
S177
S178
Glossary ...........................................................................................................................
S180
Foreword ..........................................................................................................................
S183
Introduction .....................................................................................................................
S184
I. Clinical Practice Guidelines for Vascular Access...............................................

Guideline 1. Patient Preparation for Permanent Hemodialysis Access ......................
Guideline 2. Selection and Placement of Hemodialysis Access..................................
Guideline 3. Cannulation of Fistulae and Grafts and Accession of Hemodialysis
Catheters and Port Catheter Systems ....................................................................
Guideline 4. Detection of Access Dysfunction: Monitoring, Surveillance, and
Diagnostic Testing ................................................................................................
Guideline 5. Treatment of Fistula Complications .....................................................
Guideline 6. Treatment of Arteriovenous Graft Complications.................................
Guideline 7. Prevention and Treatment of Catheter and Port Complications ...........
Guideline 8. Clinical Outcome Goals ........................................................................
S187
S188
S192
II. Clinical Practice Recommendations for Vascular Access .................................

Clinical Practice Recommendations for Guideline 1: Patient Preparation for
Permanent Hemodialysis Access ...........................................................................
Clinical Practice Recommendations for Guideline 2: Selection and Placement of
Hemodialysis Access .............................................................................................
Clinical Practice Recommendations for Guideline 3: Cannulation of Fistulae and
Grafts and Accession of Dialysis Catheters and Ports ............................................
Clinical Practice Recommendations for Guideline 4: Detection of Access
Dysfunction: Monitoring, Surveillance, and Diagnostic Testing ...........................
Clinical Practice Recommendations for Guideline 5: Treatment of Fistula
Complications.......................................................................................................
Clinical Practice Recommendations for Guideline 7: Prevention and Treatment of
Catheter and Port Complications..........................................................................
Clinical Practice Recommendation 8: Vascular Access in Pediatric Patients .............
S264
S277
S286
References .......................................................................................................................
S288
S307
Appendix 1. Methods for Evaluating Evidence ............................................................
S308
Appendix 2. Medline Search Strategies ........................................................................
S317
S201
S210
S234
S243
S248
S258
S265
S267
S268
S269
S271
S272
S274
KDOQI Disclaimer
SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINES AND CLINICAL PRACTICE
RECOMMENDATIONS
These Clinical Practice Guidelines (CPGs) and Clinical Practice Recommendations (CPRs) are
based upon the best information available at the time of publication. They are designed to provide
information and assist decision-making. They are not intended to define a standard of care, and
should not be construed as one. Neither should they be interpreted as prescribing an exclusive course
of management.
Variations in practice will inevitably and appropriately occur when clinicians take into account the
needs of individual patients, available resources, and limitations unique to an institution or type of
practice. Every health-care professional making use of these CPGs and CPRs is responsible for
evaluating the appropriateness of applying them in the setting of any particular clinical situation. The
recommendations for research contained within this document are general and do not imply a
specific protocol.
SECTION II: DISCLOSURE
The National Kidney Foundation makes every effort to avoid any actual or potential conflicts of
interest that may arise as a result of an outside relationship or a personal, professional, or business
interest of a member of the Work Group.
Specifically, all members of the Work Group are required to complete, sign, and submit a
Disclosure Questionnaire showing all such relationships that might be perceived as real or potential
conflicts of interest. All affiliations are published in their entirety at the end of this publication in the
Biographical Sketch section of the Work Group members.
In citing this document, the following format should be used: National Kidney Foundation. KDOQI
Clinical Practice Guidelines and Clinical Practice Recommendations for 2006 Updates: Hemodialysis
Adequacy, Peritoneal Dialysis Adequacy and Vascular Access. Am J Kidney Dis 48:S1-S322, 2006
(suppl 1).
Support for the development of the KDOQI Clinical Practice Guidelines and Clinical Practice
Recommendations for Hemodialysis Adequacy 2006, Peritoneal Dialysis Adequacy 2006 and
Vascular Access 2006 was provided by: Amgen, Inc., Baxter Healthcare Corporation, Fresenius
USA, Inc., Genentech, Inc., and Watson Pharmaceuticals, Inc.
The National Kidney Foundation gratefully acknowledges the support of Amgen, Inc. as the
founding and principal sponsor of KDOQI.
Hemodialysis Adequacy 2006

Work Group Membership
Work Group Co-Chairs
Thomas A. Depner, MD
University of California, Davis
Sacramento, CA
John T. Daugirdas, MD
University of Illinois Medical Center
Chicago, IL
Work Group
Stuart Goldstein, MD
Baylor College of Medicine
Texas Childrens Hospital
Houston, TX
Klemens B. Meyer, MD
Tufts University School of MedicineNew England Medical Center
Boston, MA
Todd S. Ing, MD
Hines VA/Loyola University Medical Center
Wilmette, IL
Keith Norris, MD
Dean of Research
Charles R. Drew University
Lynwood, CA
Victoria Kumar, MD
University of California, Davis
Kaiser Permanente Medical Group, Los Angeles, CA
Evidence Review Team

National Kidney Foundation Center for Guideline Development and Implementation at Tufts-New England
Medical Center, Boston, MA
Ethan Balk, MD, MPH, Project Director, Hemodialysis and Peritoneal Dialysis Adequacy
Katrin Uhlig, MD, Project Director, Vascular Access
George Fares, MD, Assistant Project Director, Hemodialysis and Peritoneal Dialysis Adequacy
Ashish Mahajan, MD, MPH, Assistant Project Director, Vascular Access,
Hemodialysis and Peritoneal Dialysis Adequacy
Amy Earley, BS
Rebecca Persson, BA
Gowri Raman, MD
Christina Kwack Yuhan, MD
Priscilla Chew, MPH

Stanley Ip, MD
Mei Chung, MPH
In addition, oversight was provided by:

Joseph Lau, MD, Program Director, Evidence Based Medicine
Andrew S. Levey, MD, Center Director
Tables
Table 1.
Table 2.
Table 3.
Table 4.
Table 4A.
Table 5.
Table 6.
Table 7.
Table 8.
Table 9.
Table 10.
Table 11.
Table 12.
Table 13.
Table 14.
Table 15.
Table 16.
Table 17.
Table 18.
Table 19.
Validated GFR-Estimating Equations................................................................................ S14

Causes of Unusually Low or High Endogenous Creatinine Generation............................ S14
Causes of Unusually Low or High Kidney Tubular Creatinine Secretion ......................... S15
Methods for Calculating eKt/V ......................................................................................... S20
Preferred Measures of the Delivered Dose (in Order of Preference)................................. S23
Recommended Predialysis Blood-Drawing Procedure ..................................................... S25
Slow-Blood-Flow Method for Obtaining the Postdialysis Sample.................................... S26
Stop-Dialysate-Flow Method of Obtaining the Postdialysis Sample ................................ S26
Effect of HD Dose on Mortality ........................................................................................ S30
Fraction of Treatments With an spKt/V Greater Than 1.2 When Targeting 1.2
to 1.4 per Dialysis .............................................................................................................. S31
Effect of Residual Kidney Function on Mortality ............................................................. S41
Complications That May Prompt Initiation of Kidney Replacement Therapy .................. S49
Effect of High Flux Dialysis on Mortality, Cardiovascular Mortality and
2 Microglobulin (2M) ................................................................................................... S55
Minimum spKt/V Values Corresponding to a stdKt/V of Approximately 2.0 per Week ... S58
Effect of Dialyzer Reuse on Mortality............................................................................... S64
Efforts to Protect RKF ....................................................................................................... S69
Potential Insults to RKF .................................................................................................... S69
Effect of Pharmacologic Interventions on Loss of Residual Kidney Function.................. S70
Values for k at Different Dialysis Frequencies and BUN Targets...................................... S76
Minimum spKt/V Required to Achieve a stdKt/V of 2.0 per Week................................... S76
Figures
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Impact of Ultrafiltration on Delivered Dose of HD Measured By Using spKt/V and URR. ... S19
eKt/V as a Function of Dialysis Treatment Time. .............................................................. S21
Components of Postdialysis Urea (BUN) Rebound........................................................... S25
Stop-dialysate Method for Postdialysis Blood Sampling................................................... S27
Illustration of the Lag Phenomenon ............................................................................... S34
Effect of Residual Native Kidney Clearance (Kr).............................................................. S75
American Journal of Kidney Diseases, Vol 48, No 1, Suppl 1 (July), 2006: p S3
S3
Abbreviations and Acronyms
2M
AAMI
ACE
ADMA
AR
ARB
AV
BMI
BSA
BUN
BW
C
C0/C
CANUSA
CAPD
CAPR
Cav
CFU
CI
CKD
CMS
COX-2
CPG
CPR
CQI
CVD
DOPPS
DOQI
eKt/V
ECF
ECV
EKR
G
GFR
HbA1c
HD
HEMO Study
HMG
HR
HRQOL
IDEAL
JNC
Kce
Kd
KDOQI
KDQOL-SF
Kecn
KLS
K0A
S4
Standardized coefficient
2-microglobulin
Association for the Advancement of Medical Instrumentation
Angiotensin-converting enzyme
Asymmetric dimethylarginine
Access recirculation
Angiotensin receptor blocker
Arteriovenous
Body mass index
Body surface area
Blood urea nitrogen
Body weight
Concentration
Predialysis to postdialysis concentration ratio
Canada-USA Study
Continuous ambulatory peritoneal dialysis
Cardiopulmonary recirculation
Average concentration
Colony-forming unit
Confidence interval
Chronic kidney disease
Centers for Medicare and Medicaid Services
Cyclooxygenase-2
Clinical Practice Guideline
Clinical Practice Recommendation
Continuous quality improvement
Cardiovascular disease
Dialysis Outcomes and Practice Patterns Study
Dialysis Outcomes Quality Initiative
Urea-equilibrated Kt/V
Extracellular fluid
Extracellular volume
Equivalent renal clearance
Urea generation rate
Glomerular filtration rate
Hemoglobin A1c
Hemodialysis
Kidney Disease Clinical Studies Initiative Hemodialysis Study
3-Hydroxy-3-methylglutaryl
Hazard ratio
Health-related quality of life
Initiating Dialysis Early And Late
Joint National Committee
Continuous equivalent clearance
Dialyzer clearance
Kidney Disease Outcomes Quality Initiative
Kidney Disease and Quality of Life Short Form
Dialyzer clearance estimated by conductivity
Kidney Learning System
Dialyzer mass transfer area coefficient
American Journal of Kidney Diseases, Vol 48, No 1, Suppl 1 (July), 2006: pp S4-S5
ABBREVIATIONS AND ACRONYMS
Kr
KRT
Kt/V
Kt/Vurea
Kuf
Kurea
LVH
MDRD
NCDS
nd
nEKR
NIH
NIVM
NKF
nPCR
nPNA
NS
OR
PD
p38MAPK
QOL
rKt/V
RC
RCT
RKF
RR
SD
spKt/V
stdKt/V
SRI
t
td
TAC
TCV
TMP
UFR
URR
USRDS
V
Vurea
Residual native kidney urea clearance

Kidney replacement therapy
Clearance expressed as a fraction of urea or body water volume
Urea clearance expressed as Kt/V
Ultrafiltration coefficient
Effective (delivered) dialyzer urea clearance
Left ventricular hypertrophy
Modification of Diet in Renal Disease
National Cooperative Dialysis Study
No data reported
Equivalent renal clearance normalized to body size
National Institutes of Health
Noninvasive monitoring
National Kidney Foundation
Normalized protein catabolic rate
Normalized protein nitrogen appearance rate
Not significant
Odds ratio
Peritoneal dialysis
p38 mitogen-activated protein kinase
Quality of life
Residual Kt/V
Remote compartment
Randomized controlled trial
Residual kidney function
Relative risk
Standard deviation
Single-pool delivered Kt/V (by dialysis only, exclusive of RKF)
Standard Kt/V
Solute removal index
Treatment time
Time from beginning to end of dialysis
Time-averaged concentration
Total cell volume
Transmembrane pressure
Ultrafiltration rate
Urea reduction ratio
United States Renal Data System
Volume, usually of body urea distribution or total body water
Patients volume of urea distribution
S5
AJKD
VOL 48, NO 1, SUPPL 1, JULY 2006
American Journal of
Kidney Diseases
Foreword
he publication of the second update of the

Clinical Practice Guidelines (CPGs) and
Clinical Practice Recommendations (CPRs) for
Hemodialysis represents the second update of
these guidelines since the first guideline on this
topic was published in 1997. The first set of
guidelines established the importance of measuring the dose of dialysis in all long-term dialysis
patients and the benefits of placing an arteriovenous fistula in a timely manner to reduce the
complications that can occur from using either a
gortex graft or a permanent catheter for longterm hemodialysis access. Several of these guidelines have been selected as clinical performance
measures by regulatory agencies to drive the
process of quality improvement in long-term
dialysis patients.
A number of important randomized clinical
trials have been performed in long-term hemodialysis patients since the publication of the first
set of guidelines. The Kidney Disease Clinical
Studies Initiative Hemodialysis (HEMO) Study,
a National Institutes of Health (NIH)-sponsored
randomized clinical trial of dialysis dose and
flux, is the largest study to date performed in
long-term hemodialysis patients. Results of these
and other studies of long-term hemodialysis patients have been included in the literature review
for this updated set of guidelines. In addition,
this update includes new guidelines on the preservation of residual kidney function, the management of volume status and blood pressure, and
the importance of patient education on all dialysis modalities.
2006 by the National Kidney Foundation, Inc.
0272-6386/06/4801-0101$32.00/0
doi:10.1053/j.ajkd.2006.04/063
S6
This document has been divided into 3 major

areas. The first section consists of guideline
statements that are evidence based. The second
section is a new section that consists of opinionbased statements that we are calling clinical
practice recommendations or CPRs. These CPRs
are opinion based and are based on the expert
consensus of the Work Group members. It is the
intention of the Work Group that the guideline
statements in Section I can be considered for
clinical performance measures because of the
evidence that supports them. Conversely, because the CPRs are opinion based, and not evidence based, they should not be considered to
have sufficient evidence to support the development of clinical performance measures. The third
section consists of research recommendations
for these guidelines and CPRs. We have decided
to combine all research recommendations for the
guidelines into 1 major section and also have
ranked these recommendations into 3 categories:
critical importance, high importance, and moderate importance. Our intended effect of this change
in how the research recommendations are presented is to provide a guidepost for funding
agencies and investigators to target research efforts in areas that will provide important information to benefit patient outcomes.
This final version of the Clinical Practice
Guidelines and Recommendations for Hemodialysis has undergone extensive revision in response to comments during the public review.
Whereas considerable effort has gone into their
preparation during the past 2 years and every
attention has been paid to their detail and
scientific rigor, no set of guidelines and clinical practice recommendations, no matter how
well developed, achieves its purpose unless it
is implemented and translated into clinical
FOREWORD
practice. Implementation is an integral component of the KDOQI process and accounts for
the success of its past guidelines. The Kidney
Learning System (KLS) component of the National Kidney Foundation is developing implementation tools that will be essential to the
success of these guidelines.
In a voluntary and multidisciplinary undertaking of this magnitude, many individuals
make contributions to the final product now in
your hands. It is impossible to acknowledge
them individually here, but to each and every
one of them, we extend our sincerest appreciation. This limitation notwithstanding, a special
S7
debt of gratitude is due to the members of the

Work Group and their co-chairs, John Daugirdas of The University of Illinois at Chicago
and Tom Depner at the University of California at Davis. It is their commitment and dedication to the KDOQI process that has made this
document possible.
Adeera Levin, MD, FACP

KDOQI Chair
Michael Rocco, MD, MSCE
KDOQI Vice-Chair
Introduction
Nephrologists in the United States in general
are savvy physicians who respond quickly to
public information about care of their patients.
Even before the Kidney Disease Clinical Studies
Initiative Hemodialysis (HEMO) Study was concluded, average dialysis doses were increasing in
the United States, perhaps stimulated by the
study itself, which was widely publicized to
promote enrollment among the 72 participating
clinics.1,2 The original National Kidney Foundation (NKF)-Dialysis Outcomes Quality Initiative
(DOQI) guidelines for hemodialysis (HD) in
1997 probably also fueled the dose increase. At
the time the study was completed, the average
single-pool fractional urea clearance Kt/V
(spKt/V) in the United States was 1.52 per dialysis given 3 times per week.3 This was and continues to be significantly greater than the minimum
of 1.2 established originally in 1994 by a consortium of nephrologists.4,5 The original minimum
recommended dose was based mostly on opinions generated from observational studies and
was reiterated by the Kidney Disease Outcomes
Quality Initiative (KDOQI) in 2001.6
The HEMO Study showed that the minimum
dose established by the previous KDOQI guidelines is appropriate when dialysis is performed 3
times per week for 2.5 to 4.5 hours.1 Dialysis
providers no longer need to focus on providing
more dialysis by using bigger dialyzers and higher
flow rates, but they cannot sit back and relax
because the yearly mortality rate for patients
with chronic kidney disease (CKD) stage 5 remains unacceptably high in the United States
(20% per year in 2002, and 17% per year in the
HEMO Study). This ongoing high mortality rate
has served as an incentive for investigators seeking better alternative solutions for dialysisdependent patients and has spurred interest in
alternative therapies and modes of therapy, such
as hemofiltration, daily dialysis, sorbent therapy,
better volume control, use of ultrapure water, and
other interventions. Mortality differences among
countries are now explained partially by differences in patient selection and comorbidity, but a
2006 by the National Kidney Foundation, Inc.
0272-6386/06/4801-0102$32.00/0
doi:10.1053/j.ajkd.2006.03.055
S8
considerable gap remains, especially when statistics in the United States are compared with those
in Japan, where annual mortality rates are less
than 10%. The Dialysis Outcomes and Practice
Patterns Study (DOPPS) analyses show that these
differences are not caused by different methods
for gathering statistics.7 The HEMO Study
showed that the differences are not caused by
higher doses in Japan.1 Better survival in the
Japanese may be caused by genetic differences
that enhance survival of Asian dialysis patients,
whether treated in the United States or Japan.8,9
Some consolation can be gained from the most
recent data published by the United States Renal
Data System (USRDS) and Centers for Medicare
& Medicaid Services (CMS) that show a reduction in mortality rates during the past 2 decades.10
The HEMO Study broadened the scope of
interest and opened the eyes of the dialysis health
care industry to the issue of dialysis adequacy. It
did not settle the question of small-solute toxicity, but it served to redirect attention to other
possible causes of morbidity, mortality, and poor
quality of life (QOL). These include retention
of solutes that are poorly removed by diffusion
or convection because of their large size or
binding to serum proteins, solute sequestration,
physiological stress caused by either the dialysis
itself or the intermittent schedule of dialyses that
causes fluctuations in fluid balance and solute
concentrations, or accumulation of such non
uremia-associated toxins as drug metabolites that
are known to accumulate in dialyzed patients. In
the latter case, reducing or stopping antihypertensive drug therapy may have hidden benefits. The
caregiver can be a source of the problem, as
evidenced by past experience with aluminum
toxicity.
The enormous risk for cardiovascular disease
(CVD) in patients with CKD stage 5 compared
with patients with normal renal function suggests
a toxic phenomenon. Perhaps alternate pathways
for toxin removal are damaged in patients with
CKD, causing accumulation of toxins not normally eliminated by the kidneys. Other possible
explanations for the high risk for CVD and
cerebrovascular disease include a yet to be discovered renal effect that may protect the vascular
INTRODUCTION
endothelium. This role of kidney disease in patients with heart failure and the cardiorenal
syndrome may be related to cardiovascular risks
in patients with renal disease.11 It is worth noting
that the loss of hormones normally produced by
the kidney is a well-established cause of disability and mortality that is not responsive to dialysis. The strong association of survival with residual native kidney function in both HD and
peritoneal dialysis (PD) patients is consistent
with such an effect.
The potential for inflammation caused by contaminated dialysate or soft-tissue reactions to
calcium deposits may contribute to the observed
strong relationship among inflammatory markers, CVD, and renal disease. It is possible that
the high morbidity and mortality rates are not
related to dialysis at all. If so, more attention
should be given to comorbidity and QOL and
less attention to the adequacy of dialysis. At this
juncture in the search for answers and solutions,
both imagination and science are needed.
New issues addressed in these updated guidelines include the timeline for initiation of dialysis
therapy, which also is addressed by the PD and
Vascular Access Work Groups. Emphasis was
placed on patients destined for HD therapy, but
efforts also were made to coordinate these guidelines with the initiation guidelines generated by
the other work groups that recommended stepped
increases in the prescribed dialysis dose, early
referral, and early access placement.
Predialysis blood urea nitrogen (BUN) is easy
to measure, but the postdialysis concentration is
a moving target. Its decrease during dialysis is
sharply reversed when the treatment ceases; thus,
timing of the postdialysis blood sample is critical. The Work Group determined that markedly
slowing blood flow at the end of dialysis before
sampling the blood is the safest and simplest
technique for achieving the uniformity needed
for reliable and reproducible values of Kt/V.
The delivered Kt/V determined by single-pool
urea kinetic modeling continues to be preferred
as the most precise and accurate measure of
dialysis. Simplified formulas are acceptable
within limits, and urea reduction ratio (URR)
continues to be viable, but with pitfalls. Conductivity (ionic) clearance also is accepted, but tends
to underestimate dialyzer urea clearance. The
Work Group believed that more attention should
S9
be given to residual kidney function (RKF) in

light of recent evidence linking outcomes more
closely to RKF than to dialysis dose. Although
we do not recognize a state of overdialysis,
patient QOL is compromised by dialysis; therefore, giving unnecessary treatment should be
avoided, especially now that we recognize a
ceiling dose above which morbidity and mortality are not improved. Pitfalls and controversies
about methods for adding RKF to dialyzer clearance were reviewed, but were considered too
complex for the average dialysis clinic to manage. Implementation was simplified by setting a
cutoff urea clearance of 2 mL/min, above which
inclusion of residual native kidney urea clearance (Kr) is recommended and below which it
can be ignored. Although the cutoff value is
somewhat arbitrary, it serves to separate patients
into 2 groups: 1 group in which the trouble and
expense of measuring RKF can be avoided, and
the other group in which more attention should
be focused on RKF to potentially improve QOL.
In the latter group are patients for whom recovery of renal function may be anticipated. Patients
in the group with RKF greater than 2 mL/min
(10% to 30%) should have regular measurements of native kidney clearance to avoid underdialysis as function is lost and to avoid prolonging dialysis if function recovers. Twice-weekly
dialysis may be permissible in a few patients
within the group with RKF greater than 2 mL/
min who have stable function and do not have
excessive fluid gains. Because RKF is preserved
better in current HD patients compared with the
past, a separate guideline was established to
encourage preservation of RKF.
More frequent dialysis is becoming more common; thus, methods for measuring the dose are
required. Partially controlled studies suggest that
QOL improves, hypertension is alleviated, left
ventricular hypertrophy (LVH) regresses, and
sleep disturbances abate with daily or nocturnal
HD. The Work Group reviewed current methods
and gave practice recommendations for measuring the dose in these patients. More definitive
recommendations may come from the National
Institutes of Health (NIH) Frequent HD Network
Study that currently is enrolling patients.
The Work Group focused more intently on the
target dose and its relationship with the minimum dose which, in light of HEMO Study find-
S10
ings, remains 1.2 Kt/V units per dialysis for

patients dialyzed 3 times per week. Data from
the HEMO Study also revealed a coefficient of
variation within patients of approximately 0.1
Kt/V units; therefore, the previous target of 1.3
was considered too low. To grant 95% confidence that the dose will not decrease to less than
1.2 per dialysis, the target dose was increased to
1.4 per dialysis. This is in keeping with current
practice and is consistent with the target spKt/V
of approximately 1.4 set by the European Standards Group.12 The Work Group favored highflux membranes. The HEMO Study did not provide definitive answers, but data suggested that
dialysis vintage and flux are related and CVD
might be affected favorably by the use of highflux dialysis.1 The issue of sex also was addressed by the Work Group, which believed that
dialysis doses and targets should remain the
same in women compared with men. However,
in light of suggestive findings from the HEMO
Study and observational studies, clinicians should
be aware of a possible increased responsiveness
to dialysis in females compared with males.13
Concern was raised by the Work Group about
malnourished patients with respect to both the
initiation and adequacy of HD. Initiation is confounded by errors in calculation of glomerular
filtration rate (GFR) for patients with diminishing muscle mass, and adequacy is confounded by
the effect of malnutrition on patients water
volume (V), the denominator of the integrated
urea clearance expression (Kt/V). Estimation
equations for calculating GFR before starting
dialysis therapy are based on serum creatinine
level, but are adjusted for sex, size, race, and
other factors that tend to alter the relationship
between concentration and clearance. Most of
these factors either increase or decrease the generation of creatinine, but the patients state of
nutritionwhich is well known to affect creatinine generationis not a variable in this equation. The consequent error in malnourished patients would tend to underestimate GFR and thus
endanger the patient from the ill consequences of
the delayed initiation of dialysis therapy. In addition, if the patient is malnourished, dialysis probably is better started early.
After a patient starts dialysis therapy, loss of
weight because of malnutrition will decrease V,
increasing the Kt/V, potentially to values higher
GUIDELINES FOR HEMODIALYSIS ADEQUACY
than the desired target range. Reducing the dialysis dose (Kt/V) in such patients may lead to
potential harm from inadequate dialysis. The
Work Group addressed this problem in Clinical
Practice Recommendation (CPR) 4.6, which calls
for an increase in Kt/V when signs of malnutrition are present. The magnitude of the increase is
left to the clinician, who might take into consideration the absolute level of Kt/V and cause of
the malnutrition. If Kt/V is already much greater
than the minimum, an additional increase probably would not benefit the patient. Similarly, if
malnutrition is caused by a condition other than
uremia, increasing the dose may have no effect.
This issue will require revisiting in the future,
hopefully with more available hard data.
The importance of missed dialysis treatments
was emphasized repeatedly by the Work Group.
Although difficult to quantify in terms of a guideline, patient cooperation and compliance is a
major determinant of survival.14-16 To ensure
compliance, efforts should be made to maintain
the patients confidence in the health care system
at all levels. However, patient satisfaction in
general and patient encounters with physicians
have not shown a strong correlation with survival.17
Other aspects of dialysis adequacy were addressed, including fluid balance, blood pressure
control, and membrane biocompatibility. Reuse
has moved to the background among issues of
concern in dialysis clinics for 2 reasons: (1)
many clinics in the United States no longer reuse
dialyzers, and (2) risks associated with reuse
were examined and found to be very small.
Monitoring outcome goals within each dialysis
clinic is vitally important for quality assurance
and quality improvement, and this issue been
added as a Clinical Practice Guideline (CPG) for
HD and PD adequacy. This outcomes-monitoring guideline is not intended to guide individual
patient care, but is intended for the dialysis clinic
as a whole.
More data are available regarding adequacy in
pediatric HD patients, but the numbers thankfully remain small, so definitive evidence is
lacking. The greater metabolic rate per unit of
surface area in children has been invoked by
some to justify a higher dose. Use of V as a
denominator (see previous discussion of V) also
may endanger smaller patients. In other respects,
INTRODUCTION
for younger smaller patients, we have little evidence to support a different dosing regimen than
that delivered to adults.
Since the last issuance of the KDOQI Guidelines, the Standards Group of the European Renal Association in 2002 published adequacy
guidelines for HD measurement, dosing, and
minimum standards.12 The HD adequacy group
chose urea-equilibrated Kt/V (eKt/V), recommending the Daugirdas method69 for converting
spKt/V to eKt/V, with a target of 1.2 per dialysis
(spKt/V 1.4). The target was higher than that
previously recommended by KDOQI (spKt/V
1.3 per dialysis), but the rationale for increasing
the target was not clearly delineated. The group
recommended using the mean of creatinine and
urea clearance as a measure of RKF and discouraged twice-weekly dialysis.
In the United States, we have come a long
way, from marveling about how HD can snatch
patients from the jaws of death and keep them
alive indefinitely to coping with 0.1% of the
S11
population depending on HD for life support.

Nephrologists have learned that, although numbering more than 300,000, these patients represent a small segment of approximately 20 million people in the United States with kidney
disease who have survived tremendous risks for
CVD and other morbid diseases to develop CKD
stage 5. They often arrive in the dialysis clinic
with a legacy of diabetes, CVD, and inflammatory diseases that continue to progress. The challenge for todays health care workers and the
dialysis industry is to provide an opportunity for
these patients to live long and comfortably with
freedom to pursue their dreams, even if for only a
relatively short length of time in those at high
risk. We need to be all things for these patients,
but first and foremost, we must deliver the best
dialysis therapy we can with available technology. These new KDOQI HD CPGs, CPRs, and
Research Recommendations are designed to provide a clearer pathway and help everyone move
in that direction.
I. CLINICAL PRACTICE GUIDELINES FOR

HEMODIALYSIS ADEQUACY
GUIDELINE 1. INITIATION OF DIALYSIS

1.1 Preparation for kidney failure:
Patients who reach CKD stage 4 (estimated GFR < 30 mL/min/1.73 m2) should
receive timely education about kidney
failure and options for its treatment, including kidney transplantation, PD, HD
in the home or in-center, and conservative
treatment. Patients family members and
caregivers also should be educated about
treatment choices for kidney failure. (B)
1.2 Estimation of kidney function:
Estimation of GFR should guide decision
making regarding dialysis therapy initiation. GFR should be estimated by using a
validated estimating equation (Table 1) or
by measurement of creatinine and urea
clearances, not simply by measurement of
serum creatinine and urea nitrogen. Table
2 and Table 3 summarize special circumstances in which GFR estimates should be
interpreted with particular care. (B)
1.3 Timing of therapy:
When patients reach stage 5 CKD (estimated GFR < 15 mL/min/1.73 m2), nephrologists should evaluate the benefits, risks,
and disadvantages of beginning kidney
replacement therapy. Particular clinical
considerations and certain characteristic
complications of kidney failure may prompt
initiation of therapy before stage 5. (B)
BACKGROUND
Optimum timing of treatment for patients with
CKD prevents serious and uremic complications,
including malnutrition, fluid overload, bleeding,
serositis, depression, cognitive impairment, peripheral neuropathy, infertility, and increased susceptibility to infection. However, all forms of
kidney replacement therapy entail important
trade-offs. As GFR decreases, patients and physicians must weigh many risks and benefits. Decision making is more complex for older and more
fragile patients. Together, patients and physicians must continually reconsider whether the
anticipated physiological benefits of solute clearance and extracellular fluid (ECF) volume control now outweigh the physical risks and psychosocial toll of therapy. In some cases, social and
psychological factors may lead to earlier dialysis
therapy initiation, and in some cases, to later
initiation. The initiation of dialysis therapy remains a decision informed by clinical art, as well
as by science and the constraints of regulation
and reimbursement.
For some patients, conservative therapy, without dialysis or transplantation, is the appropriate
option.27-29 If the patient makes this choice, the
health care team should strive to maximize QOL
and length of life by using dietary and pharmacological therapy to minimize uremic symptoms
and maintain volume homeostasis. These include, but are not limited to, use of low-protein
diets, ketoanalogs of essential amino acids, loop
diuretics, and sodium polystyrene sulfonate.
Nephrologists also should be familiar with the
principles of palliative care30 and should not
neglect hospice referral for patients with advanced kidney failure.
RATIONALE
Preparation for Kidney Failure (CPG 1.1)
Timely Education in Stage 4 CKD
Timely patient education as CKD advances
can both improve outcomes and reduce cost.31
Planning for dialysis therapy allows for the initiation of dialysis therapy at the appropriate time
and with a permanent access in place at the start
of dialysis therapy. Planning for kidney failure
should begin when patients reach CKD stage 4
for several reasons. The rate of progression of
kidney disease may not be predictable. There is
substantial variability in the level of kidney function at which uremic symptoms or other indications for dialysis appear. Patients vary in their
ability to assimilate and act on information about
kidney failure. Local health care systems vary in
the delays associated with patient education and
scheduling of consultations, tests, and procedures. Results of access creation procedures vary,
and the success or failure of a procedure may not
be certain for weeks or months. Timely education will: (1) allow patients and families time to
assimilate the information and weigh treatment
options, (2) allow evaluation of recipients and
donors for preemptive kidney transplantation,
(3) allow staff time to train patients who choose
home dialysis, (4) ensure that uremic cognitive
impairment does not cloud the decision, and
(5) maximize the probability of orderly and
S13
S14
planned treatment initiation using the permanent

access.
Predialysis education to inform the patient and
support persons about the relative value of various renal replacement modalities offers a freedom of choice that must be honored. Education
and choice of modality also are vital to the timely
placement of vascular or peritoneal access, training for home dialysis, and actual timing of the
initiation of the selected first modality. A comprehensive preemptive discussion of these issues
will enable patients and their support groups to
make rational decisions and will serve to involve
patients as active participants in their personal
health care. Playing an active role in ones own
health care, although thwarting the natural defense mechanism of denial, reduces risks from
negligence and psychological depression that
have been associated with poor outcomes after
dialysis therapy is started.32
Contingency Plans
Optimal timing of vascular access creation
may depend on plans regarding transplantation
and/or PD treatment. Early attempts at native
vein arteriovenous (AV) fistula creation are particularly important in patients who are: (1) not
transplant candidates or (2) lack potential living
kidney donors and also seem unlikely to perform
PD. For patients hoping to undergo preemptive
transplantation, thus avoiding dialysis treatment,
the decision about whether to attempt AV fistula

creation at CKD stage 4 (and, if so, when in stage
4) depends on the nephrologists estimate of the
likelihood that preemptive transplantation will
be accomplished. For patients interested in performing PD, the decision about whether to attempt AV fistula creation at CKD stage 4 depends on the nephrologists estimate of the
probability that PD will be successful. The benefits of planning for kidney failure treatment are
reflected in the literature comparing the consequences of early and late referral of patients with
CKD to nephrologists.33-36
Education of Health Care Providers and Family
Members
Optimally, education in preparation for kidney
failure will include not only the patient, but also
other individuals who are likely to influence his
or her decisions. These may include family, close
friends, and primary care providers. Their understanding of such issues as the impact of interventions designed to slow progression, the absence
of symptoms despite underlying kidney disease,
transplantation eligibility, the choice between
PD and HD, and the choice and timing of vascular access may have critical consequences for the
patient.
Estimation of Kidney Function (CPG 1.2)
Use of GFR-Estimating Equations and
Clearances Rather Than Serum Creatinine to
Guide Dialysis Initiation
Variability in creatinine generation across the
population makes serum creatinine level alone
an inaccurate test for patients with kidney failure
likely to benefit from dialysis treatment. For
most patients in CKD stages 4 and 5, estimating
equations based on values of serum creatinine
and other variables approximate GFR with adequate accuracy. For most patients, measured
Table 2. Causes of Unusually Low or High Endogenous Creatinine Generation

Condition
Creatinine Generation
Vegetarian diet 22
Muscle wasting 22
Amputation 22
Spinal cord injury 23
Advanced liver disease 24,25
Muscular habitus 22
Asian race 26
Low
Low
Lo w
Low
Low
High
Lo w
INTRODUCTION
S15
Table 3. Causes of Unusually Low or High Kidney Tubular Creatinine Secretion

Drug or Condition
Kidney Tubular Creatinine Secretion
Trimethoprim 22
Cimetidine 22
Fibrates (except gemfibrozil) 22
Advanced liver disease 25
clearance does not offer a more accurate estimate

of GFR than prediction equations.37
Variation in Creatinine Generation
It is well established that creatinine generation
may be unusually low in patients with a number
of conditions and may be increased in individuals of unusually muscular habitus (Table 2). In
these situations, GFR estimated by using creatinine and urea clearances may be substantially
more accurate (compared with radionuclide GFR)
than results of creatinine-based estimating equations. In patients for whom endogenous creatinine generation is likely to be unusually low or
high, GFR should be estimated by using methods
independent of creatinine generation, such as
measurement of creatinine and urea clearances.
Variation in Tubular Creatinine Secretion
Several drugs are known to compete with
creatinine for tubular secretion, and advanced
liver disease has been associated with increased
tubular creatinine secretion (Table 3). Decreased
secretion will result in artifactually low GFR
estimates, and increased secretion will result in
overestimation of GFR by means of estimating
equations. In patients for whom tubular creatinine secretion is likely to be unusually low or
high, the consequent bias to all creatinine-based
measures should be considered in interpreting
GFR estimates.
Timing of Therapy (CPG 1.3)
Initiation of Kidney Replacement Therapy
This guideline is based on the assumption that
overall kidney function correlates with GFR.
Because the kidney has many functions, it is
possible that 1 or more functions will decrease
out of proportion to the decrease in GFR. Therefore, caregivers should be alert to signs of declining health that might be directly or indirectly
attributable to loss of kidney function and initiate
kidney replacement therapy (KRT) earlier in
Low
Low
Low
High
such patients. However, they should consider

that dialysis therapy is not innocuous and does
not replace all functions of the kidney and that
HD-related hypotension may accelerate the loss
of RKF. This may particularly be true of HD.
Individual factorssuch as dialysis accessibility, transplantation option, PD eligibility, home
dialysis eligibility, vascular access, age, declining health, fluid balance, and compliance with
diet and medicationsoften influence the decision about the timing of when to start dialysis
therapy. It may be optimal to perform kidney
transplantation or begin home dialysis before
patients reach CKD stage 5. Even when GFR is
greater than 15 mL/min/1.73 m2, patients may
have a milder version of uremia that may affect
nutrition, acid-base and bone metabolism, calcium-phosphorus balance, and potassium, sodium, and volume homeostasis. Conversely,
maintenance dialysis imposes a significant burden on the patient, family, society, and health
system. This is complicated further by the potential risks of dialysis therapy, especially those
related to dialysis access and dialysate. These
considerations necessitate conservative management until GFR decreases to less than 15 mL/min/
1.73 m2, unless there are specific indications to
initiate dialysis therapy. Thus, the recommended
timing of dialysis therapy initiation is a compromise designed to maximize patient QOL by extending the dialysis-free period while avoiding
complications that will decrease the length and
quality of dialysis-assisted life.
Theoretical considerations support initiation
of dialysis therapy at a GFR of approximately 10
mL/min/1.73 m2, and this was the recommendation of the 1997 NKF KDOQI HD Adequacy
Guideline.38-40 In 2003, mean estimated GFR at
the initiation of dialysis therapy was 9.8 mL/min/
1.73 m2. This mean value reflects lower average
values (7 to 9 mL/min/1.73 m2) for young and
middle-aged adults and higher average values
S16
(10 to 10.5 mL/min/1.73 m2) for children and

elderly patients. Average GFR at initiation has
increased in all age groups since 1995; it has
increased most in the oldest patients.41
It is difficult to make a recommendation for
initiating KRT based solely on a specific level of
GFR. Several studies concluded that there is no
statistically significant association between renal
function at the time of initiation of KRT and
subsequent mortality.42-45 However, others suggested that worse kidney function at initiation of
KRT is associated with increased mortality or
morbidity.40-46 When corrections are made for
lead-time bias, there is no clear survival advantage to starting dialysis therapy earlier in comparative outcome studies of patients initiating
dialysis therapy at higher versus lower GFRs.47,48
Furthermore, it now is clear from observational registry data from the United States, Canada, and the United Kingdom48A that patients
with comorbidities initiate dialysis therapy at
higher levels of estimated GFR.41,49,50 It is reasonable to assume that this practice is based on
experience and the speculation, hope, and/or
impression that dialysis therapy may alleviate or
attenuate symptoms attributed to the combination of the comorbidity plus CKD. Because symptoms of early uremia are fairly nonspecific, one
can expect that patients with symptoms associated with their comorbidities would initiate dialysis therapy early. Healthy and hardy patients with
less comorbidity likely will develop symptoms at
a later stage than a frailer, early-starting comparative group. Frail patients who start dialysis
therapy earlier do not live as long as hardy
patients who start dialysis later. However, this
remains merely an interpretation of observational data. A more definitive answer may emerge
from properly designed prospective trials. One
such trial expects to report in 2008. The Initiat-
ing Dialysis Early and Late (IDEAL) Study from

New Zealand and Australia is a prospective,
multicenter, randomized, controlled trial (RCT)
to compare a broad range of outcomes in patients
starting dialysis therapy with a Cockcroft-Gault
GFR of 10 to 14 versus 5 to 7 mL/min/1.73 m2.51
In 2000, the NKF KDOQI CPG on Nutrition
in CKD advocated thatin patients with CKD
and estimated GFR less than 15 mL/min/1.73 m2
who are not undergoing maintenance dialysis
if: (1) protein-energy malnutrition develops or
persists despite vigorous attempts to optimize
protein-energy intake, and (2) there is no apparent cause for it other than low nutrient intake,
initiation of KRT should be recommended.52
Furthermore, those guidelines set forth measures
for monitoring nutritional status and identifying
its deterioration. Those guidelines are consistent
with the present recommendations.
LIMITATIONS
Individuals vary tremendously in the physiological response to uremia and dialysis treatment. Patients expected to experience uremic
complications often survive much longer than
the physician anticipates, without apparent adverse consequences. Patients also vary in their
willingness and ability to adhere to a medical
regimen intended to forestall the need for dialysis treatment. Health care systems and providers
vary greatly in their capability to monitor patients with advanced kidney failure safely without dialysis treatment. At best, the decision to
initiate dialysis treatment or perform preemptive
transplantation represents a joint decision by
patient and physician, reflecting their mutual
understanding of the compromises and uncertainties. It requires clinical judgment based on clinical experience.
GUIDELINE 2. METHODS FOR MEASURING AND

EXPRESSING THE HEMODIALYSIS DOSE
Quantifying HD is the first step toward
assessment of its adequacy. Fortunately, the
intermittent rapid decrease in urea concentration during HD allows a relatively easy measurement of the dose.
2.1 The delivered dose of HD should be measured at regular intervals no less than
monthly. (A)
2.2 The frequency of treatments should be
included in the expression of dose. (A)
2.3 The dose of HD should be expressed as
(Kurea Td)/Vurea (abbreviated as Kt/V),
where Kurea is the effective (delivered)
dialyzer urea clearance in milliliters per
minute integrated over the entire dialysis,
Td is the time in minutes measured from
beginning to end of dialysis, and Vurea is
the patients volume of urea distribution
in milliliters. (B)
2.4 The preferred method for measurement
of the delivered dose is formal urea kinetic modeling. Other methods may be
used provided they give similar results
and do not significantly overestimate the
modeled dose. (A)
2.5 Methods described in Appendix can be
used to add the continuous component of
residual urea clearance to the intermittent dialysis spKt/V to compute an adjusted intermittent Kt/V. Laboratories reporting adjusted session Kt/V values
should clearly identify such measurements by a different name (eg, adjusted
Kt/V or total Kt/V). (B)
BACKGROUND
HD is a process that removes accumulated
solute from a patient who has total or near-total
loss of kidney function. The process is diffusion
of solute from the blood into a physiological salt
solution (dialysate) that is separated from the
blood by a thin semipermeable membrane, the
major component of the dialyzer. The rate of
solute diffusion is a vital part of any measurement of dialysis or its adequacy, but the rate of
diffusion across the dialyzer membrane is driven
by blood concentration and is proportional to it
(following first-order kinetics). This linear pro-
portionality for simple diffusion (and convection) allows expression of the dialysis effect as a
ratio of the diffusional removal rate (eg, mg/mL)
to blood concentration (eg, mg/mL). This ratio,
defined as clearance, is a fundamental measure
of dialysis that tends to remain constant during
intermittent treatments as both blood concentrations of small solutes and solute removal rates
decrease. Clearance can be measured instantaneously by sampling blood on both sides of the
dialyzer or, more appropriately for clinical applications, as an average measurement during the
entire duration of a single dialysis treatment by
sampling blood at the beginning and end of
treatment. This latter approach is simpler and
gives a measure of the true delivered dose of HD.
RATIONALE
Frequency of Measurements (CPG 2.1)
Numerous outcome studies have shown a
correlation between delivered dose of HD and
patient mortality and morbidity (see Table 8,
Guideline 4).14,53-58 To ensure that patients with
CKD treated with HD receive adequate treatments, delivered dose of dialysis must be measured. Clinical signs and symptoms alone are not
reliable indicators of dialysis adequacy. In studies of the relationship between delivered doses of
HD and patient outcomes, the typical frequency
of measurement was monthly.1,54-56,58 Less frequent measurements may compromise the timeliness with which deficiencies in the delivered
dose of HD are detected and hence may delay
implementation of corrective action. Monthly
measurements also are pragmatic because patients undergo blood testing on a monthly basis
in nearly all dialysis clinics. Alternatively, the
dose can be measured more frequently by using
on-line methods (see the discussion of on-line
clearance that follows).
Duration and Frequency of HD (CPG 2.2)
Becauseas currently appliedtherapeutic
HD is nearly always delivered intermittently,
expression of the dialysis dose as a clearance is
advantageous because clearance is relatively constant throughout the treatment despite a marked
decrease in blood concentrations of easily dia-
S17
S18
lyzed solutes. To account for variations in the

duration and schedule of treatments, dose expression must include factors for both duration and
frequency. This contrasts with measurements of
continuous kidney function and continuous (peritoneal) dialysis for which a simple clearance rate
suffices. To account for the variable time each
patient spends on dialysis (treatment time or t),
the clearance rate can be expressed per dialysis
instead of per unit of time. Expression of the
dose as a volume processed per dialysis instead
of volume flow (volume per unit of time) eliminates the need to measure t when calculating
the dose (see calculation of clearance next). To
account for differences in frequency, either the
number of treatments per week must be appended to the expression of dose (eg, 3 treatments per week) or the dose can be expressed as
a function of repeating intervals (eg, per week
instead of per dialysis). To compare doses among
treatments given at different frequencies, the
dose for a single treatment typically is multiplied
by the number of treatments per week. For example, a target dose of 1.3 urea volumes per
dialysis would equate to a target of 3.9 volumes
per week for patients treated 3 times per week.
Because a more frequent schedule also is more
efficient, additional adjustments are required for
frequency. The Work Group believed that doses
expressed per dialysis should include an element for the number of treatments per week
(eg, spKt/V[3] for 3 treatments per week). A
more detailed discussion of these effects can be
found under Effects of Dialysis Frequency in
CPR 4, Minimally Adequate Hemodialysis.
Value of Urea as a Marker of Dialyzer
Clearance (CPG 2.3)
While the ultimate goal of dialysis treatments is a decrease in solute levels in the
patient, measurement of isolated solute levels
can be misleading if the solute measured is not
representative of all uremic toxins. Because no
solute probably qualifies in this respect, it is
reasonable to pick as a marker an easily dialyzed solute, such as urea, for which concentrations in the patient decrease significantly during the treatment. Urea clearance determined
from a ratio of concentrations, rather than from
an absolute value, is a sensitive marker of
small-solute diffusion across the dialyzer. Be-
cause dialysis most effectively removes small

solutes, urea Kt/V is a sensitive measure of the
overall dialysis dose.
The Denominator Is the Patients Water
Volume (CPG 2.3)
Native kidney clearance traditionally is adjusted to body size and specifically to body
surface area (BSA). This adjustment normalizes
the clearance effect among larger and smaller
individuals and among species of widely differing size.59,60 However, for intermittent dialysis
of solutes that distribute in body water, it is
mathematically more convenient to use body
water volume as the denominator because by
doing so, the clearance expression is reduced
from a flow to a fractional removal rate (the rate
constant). The product of the rate constant (K/V)
and time (t) can be determined easily as a logarithmic function of the predialysis to postdialysis
concentration ratio (C0/C): Kt/V ln(C0/C).61,62
Kt/V is a measure of clearance per dialysis
factored for patient size, measured as V. Expressing clearance in this manner eliminates the need
to specifically measure the individual components of Kt/V (clearance, time, and body size).
Instead, predialysis and postdialysis solute concentrations (C0 and C) provide a measure of
average clearance per dialysis factored for the
patients size in this simplified setting with no
ultrafiltration or urea generation.
Ultrafiltration and Other Components (CPG 2.4)
However, enhancement of clearance caused
by ultrafiltration that almost always occurs simultaneously with diffusional clearance during therapeutic dialysis adds a significant component that
must be included along with the simultaneous
solute generation rate in the Kt/V calculation.
The more complex mathematical expressions
that incorporate these vital components require
computer programs to precisely calculate Kt/V
by iterating the following equation363:
METHODS FOR MEASURING AND EXPRESSING THE HEMODIALYSIS DOSE
S19
where V is postdialysis urea distribution volume, G is urea generation rate, Kr is residual

native kidney urea clearance, B is rate of
change in V during dialysis, and Kd is dialyzer
urea clearance. Despite the complexities of the
equation and the iterative computer model, the
expression of clearance simulates solute removal from only a single compartment. Finite
diffusion rates among multiple body compartments add complexities that require additional
mathematical adjustments, usually requiring numerical analysis for a solution. Fortunately, the
errors encountered when applying the simpler model
to the usual thrice-weekly dialysis schedule tend to
cancel one another, allowing accurate assessment
of dose with the single-compartment model.63,64
Simpler Methods (CPG 2.4)
The arguments discussed show that the major
determinants of Kt/V are the decrease in urea
concentration during dialysis, contraction of body
water volume during dialysis, and generation of
urea during the treatment. Use of these 3 variables in an empirical formula allows an approximation of Kt/V from a single equation, bypassing the need for formal modeling65:
Fig 1. Impact of ultrafiltration on delivered dose of

HD measured by using spKt/V and URR. The curves
are derived from formal single-pool modeling of urea
kinetics assuming a 3-hour dialysis, no RKF, and a
volume of urea distribution that is 58% of BW. Wt
refers to net ultrafiltration losses as a fraction of final
BW. Reprinted with permission.67
substitute for complex equations or formal urea

modeling to calculate dialysis dose.
URR = (C 0 C)/C 0
where R is the ratio of postdialysis BUN to

predialysis BUN, t is time on dialysis in hours,
and BW is body weight. Although this and
other similar methods give an approximation
of the true spKt/V, calculated Kt/V matches the
computer-derived modeled Kt/V fairly closely
when applied to dialysis given 3 times per
week for 2.5 to 5 hours. Disadvantages of this
equation when used alone to measure Kt/V
include no measure of the net protein catabolic
rate (PCR) that urea modeling generates and
errors when applied to short, frequent, or
prolonged dialysis. 65 However, additional
simplified equations that include the absolute
value of predialysis BUN can be used to calculate normalized PCR (nPCR), also called normalized protein nitrogen appearance rate
(nPNA).66
Because the relative decrease in urea concentration during therapeutic dialysis is the most
significant determinant of Kt/V, direct measurement of URR has been proposed as a simpler
Although URR correlates well with spKt/V in

population studies, significant variability in correlation in individual patients occurs because
URR fails to include both the contraction in
extracellular volume (ECV) and the urea generation that typically occur during routine HD.
Fig 1 shows that for a given value of Kt/V,
URR may vary considerably depending on the
fraction of weight lost during dialysis. However, when outcomes, including death, are correlated with either URR or Kt/V, no difference
in degree of correlation is detectable. The
reason for this lack of a better correlation with
Kt/V probably results from the narrow range
of doses achieved during HD and the curvilinear relationship between the 2 parameters.
When level of kidney replacement increases,
especially when treatment is given daily, URR
approaches zero. URR also is zero in continuously dialyzed patients or patients with normal
kidney function. Other disadvantages of URR
include the inability to adjust the prescription
S20
accurately when the value is off target (by

adjusting K or t), inability to add the effect of
RKF, and inability to troubleshoot by comparing prescribed with delivered dose.
Native Kidney Function (CPG 2.5)
The Canada-USA (CANUSA) Study of PD
patients suggested that native kidney function
contributed more than dialysis function to improve outcomes at each level of total creatinine
or urea clearance.68 In view of the HEMO Study
findings that prolonging HD in the current thriceweekly model does not improve outcome or
QOL1, failure to include residual clearance in
calculation of the required dose could lead to
excessive dialysis that would compromise patient QOL. The reduction in quality years may
vary from patient to patient, who consider time
spent on dialysis of variable quality. These observations strongly support the notion that native
kidney function should be included in any expression of overall kidney function (both native and
replacement). However, omission will protect
the patient from underdialysis when RKF is lost.
For further discussion and practice recommendations, see CPR 2, Methods for Measuring and
Expressing the HD Dose.
Equilibrated Kt/V (eKt/V)(CPG 2.3)
When the time is shortened and dialysis is
intensified, the treatment is less efficient because
solute disequilibrium is enhanced and more time
is available for solutes to accumulate between
treatments. Allowance for solute disequilibrium
can be made by adjusting spKt/V for the rebound

in urea concentration at the end of dialysis. The
resulting eKt/V has a time-dependent factor that
reflects the intensity of dialysis for a given delivered dose (spKt/V), as shown in Table 4. The first
formula by Daugirdas shown in Table 4, often
called the rate equation, was derived from
regression data that showed a tight fit with values
measured by using the rebounded BUN measured 30 or 60 minutes after dialysis.69 The
Tattersall equation was derived from theoretical
considerations of disequilibrium and rebound,
but the coefficient was derived from fitting to
actual data.70 The Leypoldt equation is a recent
addition, also based on empirical fitting of measured data.71
Many, including our European colleagues,12
would like to convert the dose benchmark from
spKt/V to eKt/V for HD (for PD, eKt/V and
spKt/V are identical). Concern is raised about
rapid dialysis in small patients, for whom the
difference between spKt/V and eKt/V is larger
(Fig 2). After debating this issue in depth, the
KDOQI HD Work Group unanimously decided
to disallow shortened dialysis for treatments 3
times per week, but to do this explicitly rather
than as a modification of Kt/V (see CPG 4). Use
of eKt/V as a benchmark does not prohibit ultrashort dialysis provided the clearance can be
increased, for example, by increasing blood and
dialysate flow rates or increasing dialyzer surface area. For such highly sequestered solutes as
phosphate, this would not improve removal and

1.4
1.3
Kt/V
1.2
1.1
1.0
0.9
0.8
0.0
2.0
4.0
6.0
8.0
10.0
time (hours)
Fig 2. eKt/V as a function of dialysis treatment time.
The rate equations for eKt/V (lower 3 lines) predict that
dialysis efficiency decreases as time is shortened,
creating a larger difference between eKt/V and spKt/V.
( spKt/V, Daugirdas,69 ---- Tattersall et al,70 -
Leypoldt et al71 )
the shortened dialysis time would compromise

fluid removal, as noted in CPG 5. For pediatric
and small adult patients, the size-associated mortality risk may be related in part to the shortened
dialysis time often prescribed for small patients.
Previous reports and recent evidence from the
DOPPS showing a positive correlation between
dialysis treatment time and mortality support the
concept that ultrashort dialysis (3 hours), despite an adequate spKt/V, should be avoided.72,72A
Of note, eKt/V determined by using all the formulas in Table 4 first requires measurement of
spKt/V, and if the prescribed dose requires adjustment, conversion back to spKt/V is required to
determine the change in dialyzer K that is required. Equilibrated K cannot be adjusted directly. In the absence of more evidence that
would favor the additional effort and targetrange adjustment required to substitute eKt/V for
spKt/V, the Work Group elected to stay with the
currently established standard.
On-line Clearance (CPG 2.4)
The requirement for monthly measurements
of HD adequacy is a compromise between cost
and the utility of the measurement. The dose can
be assessed more frequently by measuring conductivity (or ionic) clearance across the dialyzer
membrane. This method does not require consumables or blood sampling and can be used with
each dialysis treatment to predict the delivered
Kt/V in real time before the treatment is fin-
S21
ished.73-76 The method is based on the assumption that changes in dialysate conductivity are
caused by transmembrane movement of small
electrolytes, mostly sodium, that behave like
urea. A step up in dialysate sodium concentration
followed by a step down while measuring conductivity changes in the effluent dialysate tends to
eliminate the effect of cardiopulmonary recirculation (CAPR) and provides a sodium clearance
that is similar to or only slightly less than the
simultaneously measured cross-dialyzer urea
clearance.76 When applied in this fashion, conductivity clearance can be used safely as a substitute for the blood-side urea method for measuring dialysis dose.
To avoid errors from changes in clearance
during dialysis, multiple ionic clearance measurements must be performed throughout the treatment. To calculate Kt/V, time on dialysis and V
must be determined accurately. The latter is a
potential problem if anthropometric formulas are
used to estimate V because these formulas are
estimates that often differ significantly from the
true value. Discrepancies between anthropometric estimates of BSA and apparent need for
dialysis have similarly confounded interpretations of creatinine clearance and GFR during
CKD stages 1 to 4. Conversely, errors in modeled V do not translate directly to errors in
dialysis dose because they are caused most often
by errors in estimated K. The dose, which is
based on the ratio K/V, which, in turn, is derived
mostly from the log ratio of predialysis to postdialysis BUN (see previous discussion), is more
accurate and patient specific. In addition, anthropometric formulas for V recently were shown to
overestimate V in HD patients on average by
approximately 15%.77 However, this systematic
overestimation of V tends to protect the patient
from underdialysis.
Instead of estimating V, one approach uses
modeled V, measured monthly from urea kinetic
modeling, as the denominator.76 If conductivity
clearance is measured during the modeled dialysis, it can be used in place of the predicted
clearance, eliminating the necessity to record
blood flow, dialysate flow, and dialyzer urea
mass transfer-area coefficient (K0A) to calculate
K and V. This approach reduces the variance
associated with anthropometric V, as discussed;
preserves the value of V as a patient-specific
S22
measure of body composition; and allows calculation of the patients G and nPCR.
Another suggested approach uses BSA instead
of V as the denominator (see previous discussion
of the denominator and V).78 This measure of
dialysis dose is appealing because it tends to
equate dialyzer function with native kidney function by using the same denominator, which is
closer than V to the universal scaling factor
discussed. However, it sacrifices the individual
specificity of V and G, relying instead on population averages to calculate BSA from body height
and weight.
Although these approaches to measuring the
dialysis dose are intriguing and increasingly popular, the HD Work Group believed that compelling evidence for an improvement that would
justify changing the current methods for measuring dialysis is lacking. Measurement of the integrated clearance as Kt/V from a simple ratio of
predialysis to postdialysis BUN is possible only
in patients dialyzed intermittently for whom BUN
values fluctuate greatly. These fluctuations provide an opportunity to measure adequacy, V, and
nPCR that is unparalleled in other therapeutic
settings. The suggested newer methods using
on-line clearance and/or a different denominator
beg for research that could, in the future, provide
evidence for superior performance as a measure
of dialysis adequacy (see HD Research Recommendations).
Summary of Methods
Table 4A lists the expressions of dose and
methods currently used in clinical practice to
measure the delivered dose of dialysis. Preference continues to be given (similar to the previous KDOQI recommendations) to delivered Kt/
Vurea as the best outcome correlate and to the
method of single-pool urea kinetic modeling
because of its simplicity, accuracy, and targeting
of small-solute clearance, the principal therapeutic effect of HD. While eKt/V theoretically is
more indicative of the true dialysis effect, its
major advantage is seen during short treatments;
it cannot be adjusted directly and it requires
measurement of spKt/V for estimation from the
regression-based formulas shown in Table 4.
Because CPR 4 now limits shortened dialysis
and for lack of standards, as well as evidence,
that eKt/V correlates better with outcome, the
KDOQI Work Group, in contrast to the European

Standards Group,12 did not strongly recommend
this expression of dose.
LIMITATIONS
To accurately measure Kt/V from the decrease
in BUN levels during dialysis, the decrease must
be significant, ie, the 2 concentrations (C0 and C)
must be significantly different from one another
(ratio 1.5). This means that the dialysis
schedule must be truly intermittent to avoid
excessive mathematical variance. As the frequency and duration increase, measurement of
Kt/V becomes less precise.
Measurement of HD dose and adequacy can
be anticipated by both the dialysis staff and the
patient. Even if unannounced in advance, modeled or measured dialysis may differ from the
typical dialysis because staff are alerted by the
predialysis BUN sampling. This issue was addressed by a study that found a higher average
blood volume processed during the measured
dialysis.79 In 20% of their patients, the difference
was clinically relevant. Quality assurance programs should take this into account by examining elements of the dialysis prescription, including blood volume processed, time on dialysis,
and average flow rates during the nonmeasured
treatments.
The ideal denominator for dialysis dosage
among patients of varying size is the generation
rate of uremic toxins because in a steady state of
regular dialysis treatments, levels of toxins in the
patient are likely to be directly proportional to
their generation rates (and inversely proportional
to clearance). Therefore, the increase in Kt/V
caused by weight loss (lower V) in a dialysis
patient with malnutrition likely is a false improvement in dialysis dose. No universally accepted
adjustments currently are available to eliminate
this potential error, but nephrologists should be
aware of the pitfall and consider offering additional dialysis for patients with evidence of malnutrition. Because V is a measure of lean body
mass and although using V as the denominator
eliminates potential errors that might result from
substituting weight in obese patients (presuming
that fat is not a source of uremic toxins), it does
not eliminate the potential error in malnourished
patients. Similarly, an increase in edema fluid or
possibly even muscle mass (if edema and muscle
S23
Table 4A. Preferred Measures of the Delivered Dose (in Order of Preference)
For 2 or 3 dialysis treatments per wk
Single pool Kt/Vurea determined by:
Urea kinetic modeling
Simplified multivariable equation
Equilibrated Kt/V (eKt/V)
Bloodless measurements of dialyzer clearance using ionic conductance or dialysate urea monitoring
URR
Double pool Kt/Vurea by formal kinetic modeling (used only for research purposes)
Solute removal index (SRI) from dialysate collections
For more frequent dialysis: a continuous equivalent of kidney clearance

Standard Kt/Vurea
Normalized Kt/Vurea
do not influence the generation of uremic toxins)

is expected to decrease Kt/V, although toxin
levels in the patient are not affected. Although
some experts are opposed to the notion that
delivered dialysis dose be scaled to patient size,80
it seems intuitive that a one-sized dialysis prescription does not fit all patient ages and sizes.
However, it also is possible that the rate of toxin
generation has more to do with diet or other
factors than body size.
The patients native kidneys provide functions

that cannot be duplicated by the dialyzer and that
contribute to patient survival.81 These benefits,
most of which are poorly understood, are not
reflected in small-solute clearances, even when
adjusted for intermittence.
As dialysis frequency is increased, fluctuations
in solute concentration are diminished, reducing
the power of urea kinetic modeling and favoring
dialysate methods for measuring the dose.
GUIDELINE 3. METHODS FOR POSTDIALYSIS

BLOOD SAMPLING
When dialysis adequacy is assessed by using
predialysis and postdialysis BUN measurements, blood samples should be drawn by
using certain acceptable procedures.
3.1 Both samples (predialysis and postdialysis) should be drawn during the same
treatment session. (A)
3.2 The risk of underestimating predialysis
BUN level because of saline dilution or by
sampling the blood after treatment has
begun should be avoided. (A)
3.3 The risk of underestimating the postdialysis BUN level because of access recirculation (AR) should be avoided by first
slowing the blood flow through the dialyzer to a rate at which AR is expected to
be minimal (100 mL/min) for a period
long enough to ensure that unrecirculated
blood has advanced to below the sampling
port (usually 15 seconds). (A)
3.4 An alternative method is to stop the
dialysate flow for a period long enough to
increase the dialysate outlet BUN level
close to that of the blood inlet BUN level
(3 minutes) before obtaining the postdialysis sample. (A)
BACKGROUND
Summary of Updated Changes
The proper methods of sampling blood for
urea nitrogen before and after an HD treatment
were detailed in Guidelines 7 through 9 of the
previously published KDOQI 2000 HD Adequacy Guidelines.6 These updated guidelines,
3.1, 3.2, and 3.3, are largely unchanged from the
2000 guidelines, except for minor details. When
sampling blood from venous catheters, the volume of the initial aspirate is specified more
precisely, and a recommendation is made to
discardinstead of routinely reinfusingthe aspirated blood sample. Guideline 3.4, acknowledging the alternative use of the dialysate-stop-flow
method, is new.
RATIONALE
As reviewed in the 2000 guidelines,6 there are
3 components of postdialysis urea nitrogen reS24
bound (see Fig 3). The first is caused by AR,

which resolves within seconds after stopping dialysis (point B), the second is caused by CAPR, which
resolves within 1 to 2 minutes after stopping dialysis (point C), and the third is caused by entry of
urea from relatively undialyzed tissues and body
compartments, which we term remote-compartment (RC) rebound. The latter resolves within 30
to 60 minutes after stopping dialysis (point D).
The first focus of these blood-drawing guidelines is to limit the effect of AR on the postdialysis BUN sample because AR causes large overestimations of the true delivered dose and can
result in true delivered Kt/V values less than 0.8
(at which level mortality risk is strongly increased) in patients with apparent Kt/V values of
1.4 or greater.83 Since the KDOQI 2000 guidelines were published, it has become clear that the
later rebound caused by CAPR is small84 and
effects of RC rebound are relatively predictable
based on the rate of dialysis.84,85 In addition,
some studies showed that sampling blood about
30 minutes before the end of dialysis can predict
the BUN level 30 minutes after the end of
dialysis.86 This method is not recommended in
adults because of its relative complexity and
because RC rebound is relatively predictable
based on the rate of dialysis,84,85 andmost
importantlybecause in the presence of AR, the
dialysis dose can still be markedly underestimated unless a slow-flow method is used to draw
the sample 30 minutes before the end of dialysis.
Predialysis Blood Sampling Procedure (CPG
3.1 and 3.2, see Table 5)
The predialysis BUN sample must be drawn
before dialysis is started to prevent this sample
from reflecting any impact of dialysis. Dilution
of the predialysis sample with saline or heparin
must be avoided. Underestimating the predialysis BUN level will result in underestimation of
delivered Kt/V or URR, which is not particularly
dangerous; however, nPCR then will be underestimated.
Postdialysis Blood-Sampling Procedure (CPG
3.3, see Table 6)
Proper timing for acquisition of the postdialysis BUN sample is critical.6,83 Immediately upon
METHODS FOR POSTDIALYSIS BLOOD SAMPLING
S25
BU N (mg/dl)
36
32
RC
rebound
28
C APR
24
AR
20
16
Fig 3. Components of postdialysis urea

(BUN) rebound. See text for explanation.
Reprinted with permission.82
-4 0
completion of HD, if AR was present, some of

the blood remaining in the access and extracorporeal circuit actually is recirculated blood. If the
blood sample is drawn immediately upon completion of dialysis, just-dialyzed blood that has
recirculated into the access will dilute the sample.
The consequence of sampling this admixture is a
falsely decreased BUN value and artificially elevated Kt/V and URR.6,83 Therefore, the amount
of dialysis delivered will be overestimated.
Early urea rebound (3 minutes after dialysis)
may be viewed as a 2-component process.89-91
The first component is caused by blood recirculation within the access or catheter and is not
present in patients without AR. If AR is present,
urea rebound from recirculation begins immediately upon completion of HD and resolves in less
than 1 minute, usually within 20 seconds. The
second component of early urea rebound is caused
by CAPR that begins approximately 20 seconds
-2 0
20
40
60
time (minutes postdialysis)
after stopping HD and is completed 2 to 3 minutes

after slowing or stopping the blood pump.90
CAPR refers to the routing of just-dialyzed blood
through the veins to the heart, through the pulmonary circuit, and back to the access without the
passage of the just-dialyzed blood through any
urea-rich tissues.90-93 It should not occur with a
venous access because venous (rather than arterial) blood is sampled; however, some increase
in urea concentration during the initial 3-minute
time frame may occur because of mixing of urea
returning from different organs. The late phase
of urea rebound (3 minutes) is completed
within 30 to 60 minutes after the cessation of
dialysis. The late phase is a consequence of
flow-volume disequilibrium (perfusion or parallel-flow model)94 and/or delayed transcellular
movement of urea (diffusion model)92,95 (see
CPG 2, Methods of Measuring and Expressing
the HD Dose).
S26
Why the Blood Pump Should Be Slowed Before

Sampling
Decreasing blood flow to 100 mL/min reduces
the entry of cleared blood into the access and
stops AR (unless there is needle reversal, in
which case it still greatly reduces AR). The dead
space of the blood tubing attached to the access
needle usually is about 3 mL. The dead space in
most venous catheters is similar, albeit somewhat less, in the range of 1 to 2 mL. The dead
space between the tip of the dialyzer inlet (arterial) blood tubing and sampling port area usually
is about 7 to 12 mL, giving a total dead space of
10 to 15 mL, although this should always be
measured and known for a given set of blood
tubing because in some blood tubing, the sampling port is farther removed from the patient
connection. A flow rate of 100 mL/min is about

1.6 mL/s. Therefore, waiting 15 seconds at such
a flow rate will ensure that the column of undiluted blood will have moved 1.6 15 24 mL
into the blood tubing during the time of reduced
blood flow. As long as the volume of tubing
between the patient connection and sampling site
is substantially less than this 24 mL, the sampled
blood should not be contaminated with outflow
blood.
In situations in which the blood is drawn not
from a sampling port on the inflow blood tubing,
but by attaching a Luer-Lock connector (Becton
Dickinson and Co., Franklin Lakes, NJ, USA) to
either the venous catheter or arterial needle blood
tubing, the dead-space volume to the sampling
site is only 2 to 3 mL. However, for simplicity,
METHODS FOR POSTDIALYSIS BLOOD SAMPLING
S27
Fig 4. Stop-dialysate method for postdialysis blood sampling. Mean arterial and
venous blood urea concentrations after
stopping dialysate flow are expressed as a
fraction of the blood urea concentration in
the contralateral arm at time zero (n 10).
The data suggest that, for practical purposes, 3 minutes after stopping dialysate
flow, equilibration has occurred between
inlet and outlet blood. Reprinted with permission.96
the Work Group recommended keeping the slowflow period the same regardless of the site from
which blood is sampled.
Stopping Dialysate Flow Before Sampling
A new method for postdialysis blood sampling
introduced since the KDOQI 2000 Guideline
update was reviewed by the Work Group.96,97
When dialysate flow is stopped, the dialysate
outlet urea concentration starts to approach the
blood inlet level, and AR (if present) has a
progressively lower dilutional effect on inlet
blood flow. With this method, as outlined in
Table 7, blood flow must not be reduced because
the dialysate, now trapped in the dialyzer,
needs to equilibrate with blood as quickly as
possible. Two studies showed that 5 minutes was
adequate to equilibrate the arterial and venous
blood tubing samples.96,97 The Work Group recommendation is to follow the method of Geddes
et al.96 It should be realized that 3 minutes after
stopping dialysis, the CAPR component of rebound will be complete and RC rebound will
have begun. Hence, a postdialysis BUN sample
drawn by using this dialysate method will be

slightly higher than that obtained when using the
blood method because with the latter, the sample
is obtained only 15 seconds after the end of
dialysis. This means that the spKt/V obtained by
using the stop-dialysate-flow method will (theoretically) be slightly lower in comparison to the
slow-the-blood-flow method.
Use of a 5-minute waiting period resulted in a
2% decrease in measured value for URR (Fig 4).96
Because of the rebound considerations discussed
and based on data in Fig 4, the Work Group
decided that a 3-minute waiting period was sufficient. By that time, dialyzer inlet and outlet
samples have nearly equilibrated.
LIMITATIONS
The stop-dialysate-flow method has not been
validated during pediatric dialysis. If a large
dialyzer is used at a relatively lower blood flow
rate, the dialyzer outlet blood may still have a
substantially lower urea concentration than inlet
blood after 3 minutes of stopping dialysate flow.
GUIDELINE 4. MINIMALLY ADEQUATE HEMODIALYSIS

4.1 Minimally adequate dose:
The minimally adequate dose of HD given 3
times per week to patients with Kr less than
2 mL/min/1.73 m2 should be an spKt/V
(excluding RKF) of 1.2 per dialysis. For
treatment times less than 5 hours, an alternative minimum dose is a URR of 65%. (A)
4.2 Target dose:
The target dose for HD given 3 times per
week with Kr less than 2 mL/min/1.73 m2
should be an spKt/V of 1.4 per dialysis not
including RKF, or URR of 70%. (A)
4.3 In patients with residual urea clearance
(Kr) greater than or equal to 2 mL/min/1.73
m2, the minimum session spKt/V can be
reduced. One method of minimum dose
reduction is described in CPR 4.4. In such
patients, the target spKt/V should be at
least 15% greater than the minimum dose.
(B)
4.4 Missed and shortened treatments:
Efforts should be made to monitor and
minimize the occurrence of missed or
shortened treatments. (B)
RATIONALE
Minimally Adequate Dose (CPG 4.1)
The present adequacy guideline for a minimally
adequate dose remains unchanged from the previous (2000) guidelines.6 In deciding whether this
guideline needed to be changed, the committee
considered 3 lines of evidence. The first was
results of the primary analysis of the NIH HEMO
Study, published in 2002.1 The committee also
had access to as-treated results of the HEMO
Study, which were published at the time the draft
guidelines were released in November 2005.98
This report was judged to be of some importance
because it identified a dose-targeting bias in the
analysis of delivered therapy versus mortality in
cross-sectional data sets, which potentially impacts on the weight of evidence derived from
such data sets. The second was a series of articles
suggesting that dosing of dialysis should not be
based on URR or its derivative, Kt/V (which
essentially is volume of blood cleared divided by
the modeled urea volume, V), but on the volume
of blood cleared (Kt) only.78,99-101 The third was
a series of analyses of delivered dose (ie, URR)
S28
versus mortality based on either the USRDSMedicare data set or the Fresenius Medical Care
subset of these data.102-104
HEMO Clinical Study: Primary
(Randomized) Results
Primary results of the HEMO Study, which
randomized patients to a delivered eKt/V of 1.16
versus 1.53, equivalent to URR values of about
63% versus 75% or spKt/V values of about 1.3
versus 1.7, revealed little evidence to support
increasing the dose of dialysis beyond the current (2000) KDOQI recommendations, respectively.6 The lack of benefit, without even a trend
that was close to statistical significance, appeared not only in the primary outcome of mortality, but also in a variety of main secondary
composite outcomes relating to various causes of
hospitalization combined with mortality. Furthermore, analysis of minor secondary composite
outcomes dealing with nutritional measures
including changes in weight and serum albumin
levels,105 as well as QOL measures106also
failed to support a beneficial effect of increasing
the dose of dialysis. Of all trials evaluated, the
HEMO Study was by far the largest, and its
randomized design and measurement of hard
outcomes were given an enormous weight in
determining whether the 2000 KDOQI HD Adequacy Guidelines needed to be changed. The
Work Group realized that the recently published
European guidelines recommended substantially
higher minimal doses of HD based on an eKt/V
measure, corresponding to spKt/V minimum targets of about 1.4 to 1.5.12
HEMO Clinical Study: As-Treated Results
The HEMO dose-versus-mortality question
also was assessed within each treatment arm,
measuring the effects of actual delivered dose
over time versus mortality.98 This study identified a dose-targeting bias and suggested that
patients in a cross-sectional analysis receiving
less dialysis are also at greater risk for death.
This increased death risk was of a high magnitude and was incompatible with a biological
effect of dose. Although conditions of the 2
HEMO Study arms were not representative of
how dialysis is prescribed in the field, documentation of such a strong potential dose-targeting
MINIMALLY ADEQUATE HEMODIALYSIS
bias (which may be operative in cross-sectional

studies, albeit to a lesser degree) convinced the
Work Group members to place less weight on
dose-versus-mortality relationships derived from
observational studies despite the large numbers
of patients included in such studies.
Studies Advocating Alternate Measures of
Urea-Based Adequacy
These studies are discussed in more detail in
CPG 2, Methods for Measuring and Expressing
the HD Dose. Since the 2000 KDOQI HD Adequacy Guidelines were published, 1 group of
investigators in particular, using data derived from
Fresenius Medical Care North America patients in
the United States, argued that dose of dialysis
should not be factored by modeled V.78,100,101 The
arguments against using URR or its derivative
Kt/V fall into 2 general categories: (1) doing so
may result in relative underdialysis of women
and small patients of both sexes, and (2) because
modeled V is itself a predictor of mortality, use
of dialysis dose factored by V may confound
dialysis dose-versus-mortality relationships found
in cross-sectional studies in complex and not
always predictable ways. A secondary analysis
of the intent-to-treat results of the HEMO Study
suggested that the higher dose of dialysis may
result in better survival in women, who also
tended to be smaller than the men in that particular trial.13 The Work Group decided, based on
suggestive evidence, that more dialysis (beyond
2000 KDOQI levels) may be better for women
and, perhaps, smaller patients, but that the level
of evidence did not reach a point at which the
existing guideline should be changed. Hence, 2
CPRs were derived suggesting that more dialysis
in women and/or in smaller patients might be
beneficial (see Section II). Despite the theoretical arguments, as well as attempts to address
confounding effects of V in cross-sectional data
sets, the committee believed that, at present, the
data are not compelling enough to depart from
the 2000 recommendation to follow smallmolecule clearance using Kt/V.
Given the increased use of conductivity to
measure clearance during the dialysis session,
the Work Group also considered using an anthropometric volume as the clearance denominator
when clearance was measured by conductivity.
Using an anthropometric volume as denominator
S29
was speculated to result in a more stable denominator, less affected by errors in predialysis and postdialysis urea nitrogen determinations. For example,
(Kecn T/Vant, where Vant anthropometricallyestimated total body water distribution volume)
could be used instead of Kt/V urea. The Work
Groups conclusion was that there were not sufficient data comparing sequential dialysis adequacy measures by using both conductivity and
urea kinetics in the same patients to make such a
major revision, although it was recognized that
from a quality-assurance perspective, it would be
less challenging to ensure a constant dialysis
dose given a more constant denominator. Concerns also were raised about altered modeled to
anthropometric urea volume ratios in individual
patients, although given the relative flatness of
the adequacy to mortality curve, this issue may
be of secondary importance.
Another potential strategy discussed was to normalize the dialysis amount to a denominator based
on BSA as opposed to urea volume, whether the
latter was derived from modeling or anthropometrics. For example, this is accomplished easily by
multiplying the target Kt/V value by 3.27
V/V0.667 (V raised to the 2/3 power). Such a correction method (developed by the Frequent HD Network investigators) gives the same dialysis dose
when V 35 L, but then augments the dose when
V is less than this amount and reduces the dose
when V is larger, giving, in effect, a dose based on
BSA instead of V. Again, for lack of definitive
clinical outcomes evidence supporting this approach, it was left for perhaps a future revision of
the guidelines when more data might be available.
Dose-Related Mortality in Large Observational
Data Sets
Since the KDOQI 2000 HD Adequacy guidelines were published, a number of studies, including analyses of USRDS Annual Data Reports,
continued to examine the relationship between
dose of dialysis and mortality. Most, but not all,
observational studies reported dose in terms of
either spKt/V or URR. The dose-versus-mortality relationship was examined as a function of
race and sex57,104 and as influenced by various
measures of body size102,103 and nutritional status.99 Because the general median spKt/V increased over time, these analyses included much
larger samples of patients receiving higher doses
S30
S31
Table 9. Fraction of Treatments With an spKt/V Greater Than 1.2 When Targeting 1.2 to 1.4
per Dialysis
Achieved Kt/V averaged over k treatments*
Target Kt/V
k=1
k=2
k=3
k=4
1.20
1.25
1.30
1.35
1.40
0.51
0.66
0.79
0.87
0.92
0.48
0.68
0.82
0.90
0.95
0.47
0.68
0.84
0.93
0.97
0.47
0.69
0.84
0.93
0.97
Data shown for a single treatment (k = 1) and for averaging over k treatments.
*Greene et al. Proceedings of the XVth International Congress of Nephrology, Buenos Aires, Argentina, May 2 through 6, 1999.106A
of dialysis. Most of these analyses suggested that

increasing the dose of dialysis above the target
recommended in the 2000 guidelines to levels
targeted in the high-dose arm of the HEMO
Study (spKt/V 1.7) should decrease mortality
by a substantial amount (Table 8). However, the
lack of concordance between these observational
results and negative results of the HEMO Study,
coupled with the dose-targeting bias identified in
the as-treated analysis of HEMO Study patients,
restrained the Work Group from recommending
a global increase in recommended spKt/V for
patients dialyzed 3 times per week.
Renal Clearance Compared With the 2000
Guidelines
The 2000 KDOQI HD Adequacy Guidelines
were applied to patients with a Kr less than
5 mL/min/1.73 m2, for which Kr is defined as
the average of urea and creatinine clearances.
In the present guidelines, the committee decided to use urea clearances for the purpose of
specifying minimally adequate urea fractional
removal. This allows more accurate measurement of protein catabolism in patients with
significant Kr and an opportunity to combine
Kr with Kd (see CPG 2). Urea clearance of 3
mL/min corresponds approximately to an average of urea and creatinine clearances of 5
mL/min. In the present guidelines, this number
was reduced to 2 mL/min of normalized urea
clearance to enable some decrease in dialysis
dose for patients with moderate degrees of
RKF, as discussed in the accompanying CPR.
A more complete discussion of why this step
strategy was adopted, rather than the addition
of residual clearance as a continuous function,
is detailed in the accompanying CPR.
Target Dose (CPG 4.2)

The KDOQI 2000 HD Adequacy Guidelines
specified a target spKt/V of 1.3, with a minimally
adequate dose of 1.2 per dialysis given 3 times
per week. During the course of measuring the dose
of therapy many times in each patient enrolled in
the HEMO Study, the variability of modeled volume and hence of spKt/V was determined accurately. The within-patient coefficient of variation
for single-pool V in the HEMO patient data set was
close to 10%. The relationship between target Kt/V
and subsequent achieved Kt/V is shown in Table 9.
As shown in Table 9, the previous recommendations to target 1.3 would result in about 21%
of treatments at any given time apparently
being less than the Kt/V minimum target of
1.21 (the fraction 1.2 is 0.79, so 0.21, or
21%, would be 1.2). Thus, it appears that
targeting 1.3 would result in needless prescription modifications and/or troubleshooting. Targeting therapy at an spKt/V of 1.4 and averaging results from 3 monthly measurements of
adequacy results in a much greater proportion
of treatments (in the range of 97%), greater
than the minimum 1.2 adequacy target. Setting
the target dose of dialysis to 1.4, rather than
1.3, also seemed to be justified given suggestive results (not yet qualifying for guidelinegenerating status) that subsets of patients might
benefit from higher doses of dialysis.
Avoiding Missed Treatments (CPG 4.3)
Measurement of fractional urea removal during a single dialysis treatment obviously is not
a monthly average of dialysis adequacy and
has validity only if dialysis treatments are
delivered reliably 3 times per week on a regular basis. A number of studies document that
S32
the number of missed and/or shortened dialysis treatments in US dialysis patients (4%
missed treatments per month) is more than the
number missed by their counterparts in other
countries, such as Japan. 107 Whereas the
KDOQI 2000 HD Adequacy Guidelines suggested increasing the frequency of measuring
Kt/V or URR in patients for whom treatments
frequently were shortened or missed, they did
not address the issue of monitoring and minimizing the occurrence of missed and shortened
treatments. A number of studies suggested that
poor compliance in HD, especially in terms of
number of missed treatments, is an important predictor of mortality and hospitalizations.14-16 For
this reason, the Work Group believed that every
dialysis center should have a mechanism in place to
monitor and minimize the occurrence of missed
and shortened dialysis treatments.
LIMITATIONS
The main limitation to recommending adequate
dosing of dialysis in patients following a thriceweekly schedule is the difficulty performing randomized studies, as well as multiple confounding
issues related to analysis of dose-mortality relationships in observational studies. In the Work Groups
opinion, data from the HEMO Study suggested that
the dose-benefit relationship for values of spKt/V
in the current clinical setting are relatively flat at
greater than the recommended minimum value of
1.2 thrice weekly. Many patient subgroups and
perhaps all patients might benefit from more dialysis, but it seems that benefits would be derived
primarily from extending dialysis treatment time
markedly or moving to a more frequent dialysis
schedule, as opposed to simply increasing urea
Kt/V.
GUIDELINE 5. CONTROL OF VOLUME AND

BLOOD PRESSURE
There is ample evidence in the non-CKD
population that optimal control of blood pressure influences mortality. In the HD population, available evidence indicates that control
of a patients fluid volume influences outcome.
Volume and blood pressure are linked; thus, it
is important to optimize ultrafiltration and
dry weight to control blood pressure in an
effort to improve patient outcome.
5.1 The ultrafiltration component of the HD
prescription should be optimized with a
goal to render the patient euvolemic and
normotensive. This includes counseling
the patient on sodium and fluid restriction, adequate ultrafiltration, and the use
of diuretics in patients with RKF. (A)
5.2 Daily dietary sodium intake should be restricted to no more than 5 g of sodium
chloride (2.0 g or 85 mmol of sodium). (A)
5.3 Increasing positive sodium balance by
sodium profiling or using a high dialysate sodium concentration should be
avoided. (B)
RATIONALE
The volume status of a maintenance dialysis
patient is mainly a function of sodium intake,
water intake, urine output, and removal of excess
fluid by ultrafiltration during dialysis. Because
cellular membranes are freely permeable to water, the osmotic gradient generated by the addition of dietary sodium to the ECF compartment
causes water to move from cells into the ECF
space, thus expanding ECF volume at the expense of the intracellular fluid compartment. The
increase in ECF osmolality stimulates the thirst
center of the hypothalamus, increasing water
intake. Thus, the combined influence of both
positive sodium and water balances causes expansion, primarily of the ECF volume.108 Such volume expansion can be especially marked in dialysis patients with poor RKF.
Poor volume control can exacerbate hypertension and its myriad detrimental effects on the
cardiovascular system.109-112 Early reports of
risks associated with excessive sodium and water
were inconclusive, but analysis of USRDS Waves
3 and 4, when adjusted for comorbidity, showed
that weight gain between dialyses of more than

4.8% (ie, 3.4 kg in a 70 kg person), a reflection of
excessive sodium and water intake, is associated
with increased mortality.113 Although a precise
definition of dry weight is not possible in each
patient, methods have been described for controlling volume and blood pressure and are reviewed
here. A thorough examination of the approach to
deriving a true dry weight is beyond the scope
of the Work Group. The reader is referred to
standard dialysis texts for detailed information.
Achievement of Optimal Dry Weight
(CPG 5.1)
A patients true dry weight, defined as the
weight when fluid volume is optimal, can be
determined accurately, but the method is not
readily available in clinical settings (eg, use of
multiple-frequency bioimpedance spectroscopy).114 Instead, dry weight usually is determined clinically by evaluating level of blood
pressure, evidence of fluid overload, and the
patients tolerance of ultrafiltration aimed to arrive at the estimated target weight.115 It should
be noted that a patient can have fluid excess in
the absence of gross clinical evidence of volume
expansion,116 a phenomenon termed silent overhydration.117 During dialysis, as the patients
dry weight is approached, the rate at which the
vascular compartment refills from fluid in the
adjacent tissue spaces is reduced.118 If UFR is
reduced toward the end of dialysis, the reduced
compensatory refilling process may be adequate
to support the patients depleted blood volume,
thereby avoiding hypotension and muscle cramping. When the blood volume is refilled and blood
pressure improves, more rapid ultrafiltration can
be resumed. For a fluid-overloaded dialysis patient, this step-by-step process of identifying, or
probing, for the true dry weight through ultrafiltrationbut without inducing hypotension
should be accomplished gradually over a number
of dialysis treatments (usually over 4 to 12 weeks,
but it may require as long as 6 to 12 months) until
evidence of fluid overload is in abeyance.119-121
For patients with diabetes mellitus (autonomic
dysfunction) or cardiomyopathy, this process of
approaching the dry weight may take longer
S33
S34
because plasma refilling can be low even in the

presence of an expanded volume.
From the very beginning of the dialysis therapy,
concomitant with ultrafiltration probing, dietary
sodium should be restricted and use of a high
dialysate sodium concentration and sodium profiling should be avoided. While decreasing the
patients fluid volume, net fluid losses ideally
should not exceed 1 to 2 kg/wk, and by restricting dietary sodium and fluid intake, weight gain
between dialyses should not exceed 1 kg during
the week and 1.5 to 2 kg during the weekend.121
It should be noted that during this dry weight
probing stage, in 90% of patients, ECF volume
becomes normal within a few weeks, but the
elevated blood pressure continues to decrease for
another 8 months or longer. See Fig 5 for a
description of this lag phenomenon.122-125
As patients lose excess fluid and their hypertension improves, therapy with antihypertensive
medications can be systematically tapered or
discontinued.121
Tolerance to ultrafiltration varies among patients. The slow approach to achievement of dry
weight is appropriate for most patients, but for
patients with cardiac failure or severe complication-associated hypertension, more aggressive
ultrafiltration may be required acutely.126 Some
patients may require slow ultrafiltration during a
longer time than 4 hours 3 times weekly.115 To
improve fluid removal during dialysis and reduce
morbidity, monitoring blood volume during HD
has been recommended. However, use of moni-
toring devices has met with varying degrees of

success; some investigators have obtained satisfactory results,127-130 whereas other have had
disappointing results.131 Further studies are required to clarify this important issue.
Hypotension during dialysis has many adverse
effects and potential life-threatening consequences. By impairing tissue perfusion, low blood
pressures can compromise dialysis adequacy.132
Hypotension induced by overzealous ultrafiltration also may contribute to loss of RKF and, in
predisposed patients, coronary and/or cerebral
ischemia.121 To avoid hypotension, dry weight
should be systematically reevaluated after each
dialysis treatment. It was suggested that a dialysis log summarizing the relevant information,
such as body weights, blood pressures, and intradialytic incidents, is essential to provide a longitudinal dynamic view of ECF volume and blood
pressure changes.133 Dry weight may change, for
example, when a newly dialyzed patient becomes less uremic, regains appetite, and gains
muscle and nonfluid weight (reflected by an
increase in serum creatinine level), or when a
patient has an intercurrent illness and loses muscle
and tissue weight.
Hypertension: Prevalence, Pathogenesis,
and Risks (CPG 5.1)
It is noteworthy that 60% to 90% of maintenance
HD patients have hypertension.41,109,134-138 Despite the use of multiple medications, hypertension in these patients often is poorly con-
Fig 5. Illustration of the lag phenomenon. The secondary decrease in blood pressure seen at 5 months
unassociated with a change in ECV was observed in all 8 patients studied. Reprinted with permission.125
CONTROL OF VOLUME AND BLOOD PRESSURE
trolled.109,111,124,136,139 For example, among the

first 1,238 maintenance HD patients enrolled in the
HEMO Study, less than 30% had blood pressures
that were considered normotensive by the Joint
National Committee (JNC) VI standards.111 In another study of 2,535 clinically stable adult HD
patients, 86% were found to be hypertensive. Within
this hypertensive group, only 30% had their blood
pressure under adequate control, 58% were inadequately treated, and 12% were not treated at all.109
With regard to the pathogenesis, it generally is
recognized that the majority of hypertensive HD
patients develop hypertension because of fluid
overload secondary to sodium and water retention.123,133,140-142 A high predialysis or interdialysis blood pressure may be related to excessive
sodium and water ingestion during the interdialysis period,126,136 a high dialysate sodium
level,143,144 or sodium profiling,145 whereas a
high postdialysis blood pressure may reflect inadequate achievement of dry weight.113,146 There
may be exceptions to these simple explanations
of the effects of sodium and water retention on a
patients blood pressure. For example, blood
pressures in a small number of patients with
CKD stage 5 were found to respond less readily
compared with the majority when challenged
with similar degrees of fluid retention.112,134
Conversely, reduction of fluid excess in a hypervolemic and hypertensive dialysis patient may
not bring about a prompt decrease in blood
pressure until ECV is less than a certain threshold value. These clinical observations suggest
that the relationship between ECV and blood
pressure in some patients may be sigmoidal,
rather than linear, and that volume overload
leads to an increase in blood pressure only when
physiological autoregulation can no longer cope
with the fluid excess.147
For some patients, the conventional dialysis
time is too short for their ultrafiltration requirements to be readily fulfilled. Attempts to accelerate ultrafiltration in these patients may precipitate hypovolemia and hypotension. Normal saline
frequently is administered and ultrafiltration is
slowed or discontinued, at least temporarily. As a
consequence, at the end of the dialysis session,
not only has the originally targeted fluid excess
not been removed, but the infused saline also has
expanded ECV further. More sodium and water
will accumulate during the succeeding interdialy-
S35
sis period, contributing further to a chronic state

of baseline volume expansion in association with
persistent hypertension.
It should be noted that each 10 mm Hg increase in mean arterial blood pressure is correlated independently with the development of
progressive concentric LVH, de novo ischemic
heart disease, and de novo congestive cardiac
failure.148 The leading cause of death in maintenance HD patients is CVD,149 which is responsible for at least 50% of HD deaths in the United
States.112 Apart from fluid overload, there are
other significant pathogenic factors for hypertension in dialysis patients,150 such as arterial stiffness151,152 caused by arteriosclerosis, salt-related reduction in nitric oxide formation,153-155
sympathetic nervous system overactivity,156 activation of the renin-angiotensin system,157 presence of other vasoconstrictors,126 lack of vasodilators,126 erythropoietin therapy,158 genetic
predisposition,112 and other as yet poorly defined
causes. Although it is generally recognized that
hypertension requires control in hypertensive
dialysis patients,110,147,159,160 the ideal target
blood pressure is unknown at present.161 In patients with reduced vascular and cardiac compliance, blood pressure goals may need to be higher.
Vigorous contraction of plasma volume in such
patients should be avoided to allow adequate
tissue perfusion during ultrafiltration when hypotension is prone to occur.161 However, some
have recommended that attempts be made to
decrease these high pressures as much as possible to achieve optimal survival.162 Finally, some
dialysis patients with low predialysis blood pressures also have a high mortality rate.148,163,164
Risk for death in these patients may reflect cardiac failure, coronary artery disease, malnutrition, inadequate dialysis, or other serious illnesses that can decrease blood pressure.110,161,165
It is likely that the cardiovascular problems in
some of these patients result from poorly treated
prior hypertension. Thus, there is every incentive
to control blood pressure as early as possible
before cardiac damage leads to permanent hypotension and an almost certain early death.166
In a small number of patients, blood pressure
paradoxically increases after dialysis. The mechanism of this elevation is not fully understood.147
Some hypertensive patients for whom blood pressure increases while fluid is removed during
S36
dialysis may respond to still more fluid removal

by undergoing repeated isolated ultrafiltration
sessions, with eventual better blood pressure
control.167 However, attempts to remove excess
fluid from these patients by using ultrafiltration
should be conducted with special care.147
Recommended Sodium Intake (CPG 5.2)
The normal daily sodium chloride intake in
the United States varies from 5.8 to 17.4 g (2.3 to
6.9 g [100 to 300 mmol] of sodium),168 while
both the American Heart Association169,170 and
Institute of Medicine171 recommend a daily tolerable upper intake level for sodium chloride of no
more than 5.8 g (2.3 g [100 mmol] of sodium) for
the average healthy adult. The Institute of Medicine also recommends that because older individuals, African Americans, and people with
chronic diseases, including hypertension, diabetes, and kidney diseases, are especially sensitive
to the blood pressureincreasing effects of salt,
they should consume less than the tolerable upper intake level. The European Society of Hypertension and European Society of Cardiology recommend a daily sodium chloride intake of 4.7 to
5.8 g (1.8 to 2.3 g [80 to 100 mmol] of sodium)
for patients with arterial hypertension.172 Finally, use of a low-sodium chloride diet, namely,
less than 5.8 g (2.3 g [100 mmol] of sodium) also
was found to decrease blood pressure in individuals without hypertension.173
Thus, the daily sodium chloride intake suggested for dialysis patients (namely, no more
than 5 g [ie, 2.0 g [85 mmol] of sodium]) is
consistent with recommendations for healthy adults
by US health research groups and for patients with
essential hypertension by European health organizations. It also is recommended for dialysis patients
by various investigators.133,141,174-176 A 5-g sodium chloride diet in a 70 kg anuric compliant
patient should bring about a 1.5-kg average interdialysis weight gain on a conventional thriceweekly regimen.141 Most dialysis patients should
be able to tolerate this degree of ultrafiltration
requirement. A more stringent daily sodium chloride limitation amounting to 2.5 to 3.8 g (1 to
1.5 g [43 to 65 mmol] of sodium) has been
recommended for hypertensive dialysis patients.121,126 In patients who happen to lose appreciable amounts of sodium through either RKF or
extrarenal routes, sodium restriction can be modi-
fied and tailored to those losses. Patients who are

accustomed to a more liberal sodium intake
might lose their appetites and become malnourished if sodium restriction is instituted too
abruptly and too strenuously. In such patients,
sodium limitation can be introduced gradually to
provide ample time for taste adjustments. Most
patients find that they do not miss the sodium if
they cut back gradually.176A For patients who
cannot tolerate sodium restriction at all, to combat sodium and water excess, more prolonged
and/or more frequent dialysis treatments (including periodic isolated ultrafiltration) may be required (see Prolonging Dialysis Treatments).
When observing a low-sodium diet, in addition to refraining from adding salt during cooking and at the dining table, canned, processed,
and salty-tasting food should be avoided.172,175
A low-sodium diet does not equate to tasteless
food. Many varieties of flavor enhancers are
available to make food more appealing and palatable.143 Moreover, after exposure to salt restriction for 8 to 12 weeks, the appeal of low-sodium
foods in both normotensive and hypertensive
individuals is enhanced.177 Sodium restriction
does not require a reduced intake of other essential nutrients.178
Sodium Restriction and Blood Pressure
Control (CPG 5.2)
That excessive sodium intake can aggravate
hypertension and adequate sodium restriction
can prevent or ameliorate hypertension is well
known.169 As early as the middle of the last
century, limiting daily sodium intake of nonCKD hypertensive patients with a rice and fruit
diet was shown to reduce ECF volume and blood
pressure during a period of weeks as excess
sodium was excreted in urine.179 This observation pertaining to the benefit of sodium limitation
may relate to the rarity of hypertension among
individuals of populations living in very remote
areas who consume a low-sodium diet (median
daily intake, 17 to 51 mmol).180
Among dialysis patients, myriad observational
and interventional studies of patients with CKD
have shown that restricting sodium intake is an
essential tool for volume and blood-pressure control.124,125,140,141,165,175,181-192 Apart from its effect
in nonuremic hypertensive patients, a sodium-poor
rice and fruit diet also was shown to improve the
hypertension of patients with renal failure.193,194

These observations echo those in PD patients, for
whom decreasing sodium in the diet is crucial for
the achievement of dry weight and effective control
of blood pressure.195
Since infancy, most of us are accustomed to
consuming a larger quantity of salt than we
need.196 Restricting salt intake in HD patients is
tantamount to requiring them to change their
customary lifestyle. Changing ones lifestyle is
always a difficult undertaking. However, moderating ones sodium intake is a small price for a
patient with CKD to pay if one wishes to avoid
the devastating effects of relentless excess sodium and water accumulation on morbidity and
mortality.
Prolonging Dialysis Treatments
Elevated blood pressures can be decreased
satisfactorily with aggressive ECF volume control, achieved by limiting sodium intake and
performing adequate ultrafiltration.182 Success
using this strategy has been reported in studies
from Tassin, France, showing that hypertension
is improved substantially with a combination of
dietary sodium limitation (85 to 100 mmol/d of
sodium) and dialyzing slowly for 8 hours 3 times
per week.197 Sodium limitation decreased patients average weight gain between dialyses to
1.7 kg, less than 3% of mean BW.133 Both the
limited weight gain (ie, ultrafiltration requirement) and long period of ultrafiltration combined
to ensure that symptoms during dialysis were
minimized and dry weight was achieved.133 Upon
initiation of HD treatments, 89% of patients were
hypertensive despite therapy with antihypertensive medications. However, after 3 months of the
described strategy, only 5% of those patients still
required the use of such medications.197 Of
course, because the Tassin patients were dialyzed
longer than patients treated with a conventional
regimen, it could be argued that these patients fared
better because they had better removal of small and
middle molecules, improved nutrition, and better
phosphate control. However, a comparison study of
mortality rates in conventionally dialyzed patients
from Nottingham, United Kingdom, concluded that
the improved control of blood pressure was the
most likely and predominant cause of better results
shown by the Tassin patients.198
S37
It should be noted that adequate control of

blood pressure as a consequence of dietary sodium restriction (100 mmol/d of sodium) and
appropriate ultrafiltration with175 or without185,199
a low-sodium dialysate (135 mmol/L) also was
shown in patients treated with a conventional
thrice-weekly (4 to 5 hours per treatment) dialysis regimen. In addition to blood pressure control, patients also showed regression of LVH and
a decrease in left atrial and left ventricular systolic and diastolic pressures.185,199
For conventionally dialyzed patients (3 sessions per week, 4 hours per session) who are
still overloaded despite maximally tolerable
ultrafiltration, the recently proposed: (1) shortdaily (2 to 3 hours for each treatment, 6 or 7
treatments per week) regimen;200-202 (2) long
(8 hours for each session) nocturnal thriceweekly regimen;197,203 and (3) long (8 hours
for each session) nocturnal (6 to 7 nights per
week) regimen204,205 all were reported to remove excess fluid and improve hypertension
satisfactorily.110 A longer weekly treatment time
(5 hours per session, 3 times per week) also was
shown to cause less hypotension during dialysis
and less postdialysis postural hypotension compared with its shorter counterpart (4 hours per
session, 3 times per week).206 Alternatively, periods of isolated ultrafiltration can be added to a
standard treatment regimen.199
Dietary Water Restriction
When a patient is advised to restrict sodium
intake, does he or she need to be advised to limit
water intake too? It was suggested that attempts
at water restriction commonly are futile if sodium limitation is not observed simultaneously.
Reducing a patients water intake alone is not
prudent most of the time because the increased
ECF osmolality brought about by the excessive
sodium ingestion stimulates thirst, followed by
water consumption and hence isotonic fluid
gain.207,208 Advising patients to limit their water
intake without curtailing their sodium intake will
cause suffering from unnecessary thirst. Some of
these patients may even feel guilty if they fail to
resist the urge to drink in the face of marked
thirst.143 However, although excessive water intake accompanies the ingestion of excess salt,
other factors can have a role in stimulating drinking. Such factors include hyperglycemia, el-
S38
evated blood angiotensin levels, and ingestion of

such drugs as clonidine.209 Thus, to ensure complete safety, patients should be watched carefully
to make sure they do not accumulate more fluid
than recommended.
Pathogenesis of the Lag Phenomenon
The exact mechanism responsible for the
lag phenomenon is still not fully understood.122,125,174 Its occurrence may be related to
the appearance of lower peripheral vascular resistance caused by relaxation of endothelial smooth
muscle.174 In this regard, it was shown that p38
mitogen-activated protein kinase (p38MAPK)
promotes the formation of asymmetric dimethylarginine (ADMA). The latter, in turn, can inhibit
the action of nitric oxide synthase and hence the
production of nitric oxide. Sodium chloride was
suggested to bring about p38MAPK release and
hence ADMA synthesis.153 The consequent decrease in endothelial nitric oxide formation leads to
failure of arteriolar muscle to relax. It should be
noted that high ADMA concentrations have been
found in plasma of patients with CKD stage 5.154,155
In recent studies involving experimental animals
with chronic renal failure, high sodium chloride
intake decreased nitric oxide synthase expression in certain areas of the brain, resulting in
activation of the sympathetic nervous system and
hypertension.210 In addition, there is evidence
that sodium overload may cause reversal of the
inhibition of Na, K-ATPase through endogenous ouabain. This step would bring about an
increase in intracellular sodium and calcium concentrations, subsequently causing an increase in
vascular tone and blood pressure.211 Sodium
restriction should lead to the opposite effects.
The contention that sodium limitation can cause
vascular relaxation is consistent with the observation that long-term dialysis patients maintained
for years on a low-salt diet have peripheral
vascular resistance that is lower than that of
healthy controls.212 Thus, it is entirely possible
that sodium restriction may work in ways other
than that of simple ECF volume contraction.
Use of Diuretics
To promote loss of sodium and water from
dialysis patients, large doses of potent loop diuretics, such as furosemide, bumetanide, or torsemide,
can be administered.213-216 However, diuretic
therapy is effective only when RKF is high

enough to provide daily urine output of at least
100 mL.217 The effectiveness of this therapy may
not last long,209 possibly because of a further
inevitable decline in renal function. Loop diuretics should be used with caution because of the
possibility of ototoxicity.218,219 The incidence
of ototoxicity appears to be greater with furosemide and much less with bumetanide or
torsemide.213,214
Dialysate Sodium Concentration (CPG 5.3)
High concentrations of sodium in dialysate
reduce the removal of sodium during dialysis
and ultrafiltration.143,144 In the 1960s, when a
dialysis treatment typically lasted 6 hours, dialysate sodium levels were in the realm of 135
mmol/L.144 However, since the early 1970s, with
the advent of shorter treatments (3 times per
week for 4 hours per treatment), removal of the
required amount of excess fluid became more
difficult. To overcome this difficulty, it became
necessary to increase dialysate sodium to a greater
concentration (eg, to the region of 140 mmol/L
in the 1990s).143,220 Although increasing dialysate sodium concentration can decrease morbidity both during and between treatments, such
dialysates can aggravate thirst, fluid gain, and
hypertension.143,144,220,221 Similar consequences
were found in patients treated with sodium profiling, a technique that increases dialysate sodium
concentration early in treatment (eg, 145 to 155
mmol/L), followed by a progressive decrease
(linear, step, or logarithmic) to a lower value (eg,
135 to 140 mmol/L) at the end of dialysis.145 It
should be noted that the patients postdialysis
serum sodium concentration is a function of the
time-averaged dialysate level, not the terminal
level of sodium in dialysate.222 Reviews of the
large volume of literature on this topic showed
that sodium profiling is of uncertain benefit.144,145,223 Some investigators had satisfactory experiences with a dialysate sodium concentration of 138 mmol/L in a large number of
patients. During these studies, the dosage of
antihypertensive medications often had to be
decreased or discontinued.
CONCLUSION
Use of appropriate ultrafiltration techniques,
dietary sodium restriction, and lower dialysate
sodium concentrations160,224 has been instrumental in attaining a true dry weight and amelioration
of hypertension in many maintenance HD patients.133 Reembracing the time-honored and useful, yet inexpensive, tool of dietary salt restriction should serve to promote the health of HD
patients. During the process of controlling ECF
volume and decreasing predialysis weight, the
development of hypotension during dialysis or
hypertension between dialysis treatments should
not be construed as a failure of volume control to
normalize blood pressure. The lag phenomenon
noted previously should be taken into consideration when evaluating patients with persistent
hypertension.112 To more easily control hypertension in most dialysis patients, use of a high
S39
dialysate sodium concentration and sodium profiling should be discouraged.

Finally, application of appropriate ultrafiltration with every dialysis treatment, the incessant vigilance to target and subsequently to
maintain a true dry weight (which is subject to
change because of loss or gain of nonfluid
body tissue), and confirmation that a patient is
compliant with a sodium-restricted diet combine to demand a considerable amount of time
from members of the health care team. However, to obtain favorable results, an intense,
totally committed, and prolonged effortwith
a high degree of motivationis required from
caregivers, as well as from the patients themselves.112
GUIDELINE 6. PRESERVATION OF RESIDUAL

KIDNEY FUNCTION
Prospective randomized trials and observational studies have confirmed that the presence of RKF is one of the most important
predictors of a patients survival.
6.1 One should strive to preserve RKF in HD
patients. (A)
6.2 Methods for preserving RKF differ among
patients (see CPR 6). (B)
BACKGROUND
When HD therapy is first initiated, most patients have small and significant (but inadequate)
levels of RKF, and many have normal or even
high rates of urine output. This level of RKF may
persist for many months and years, adding continuous solute clearance and other kidney functions to the intermittent clearances provided by
dialysis treatments. The volume of urine produced each day allows more fluid intake, reducing the otherwise larger fluctuations in body fluid
volumes between dialysis treatments that contribute to volume overload syndromes, hypertension, and cardiac hypertrophy. Unlike hemodialyzer clearance, RKF is subject to temporary or
permanent reduction caused by numerous toxic
insults that often confront patients with CKD
stage 5.
RATIONALE
The impact of residual function on duration
of life and QOL has been evaluated extensively in PD patients,68,225-227 but only recently has attention been given to it in HD
patients (see Table 10).81 This difference is
especially striking because the number of longterm HD patients in the United States is more
than 10 times as large as the number receiving
PD. Possible reasons for ignoring RKF include a
lack of RKF measurements in HD patients, complacency because of confidence in the larger dose
of dialysis possible with HD, previous rapid
decrease in urine output after HD therapy is
begun, and the added inconvenience and expense
of collecting urine. Measurement of RKF in HD
patients also likely was ignored because, in contrast to PD, nearly all KRT is managed for the
S40
patient by nurses and technicians. Selecting a

subgroup of patients who prefer self-care (PD)
also selects for willingness to perform selfmeasurements of RKF. There also has been concern that PD is minimally adequate; thus, RKF may
play a more essential role. Earlier studies showed
that RKF decreased more rapidly in patients initially treated with HD compared with continuous
ambulatory PD (CAPD).228 However, recent studies showed that RKF is preserved better in HD
patients than in the past, possibly because of the
use of more biocompatible membranes, discontinuation of acetate as a bicarbonate precursor,
high-flux dialysis, and the earlier initiation of
dialysis therapy, especially in patients with
diabetes.81,229-231 More recent studies suggest
that with the use of ultrapure water to dilute
concentrated dialysate, RKF decreases at a rate
indistinguishable from that in CAPD patients.232
The protective role of RKF for preserving life
and extending longevity in PD patients is well
recognized68,226,227; previous KDOQI guidelines promoted the preservation of RKF in this
population.233 More recent data show that RKF
in HD patients affords many of the same benefits, including a lower dialysis dose requirement
and improved patient survival.234 The reduced
need for dietary potassium and fluid restriction
and reduced requirement for fluid removal during HD can enhance QOL and reduce the frequency of hospitalizations. In HD patients, the
continuous nature of RKF contrasts with the
intermittent schedule of dialysis, whereas for PD
patients, both are nearly continuous. Evidence
that includes mathematical analysis of solute
kinetics and comparison of outcomes in PD
versus HD patients suggests that continuous clearance is more efficient than intermittent clearance.235 Such arguments have been used, for
example, to explain the much lower weekly
dialysis clearance requirement in PD compared
with HD patients despite nearly equal outcomes,
especially in the first year of treatment. If this
difference in efficiency is accepted, the contribution of RKF to overall kidney plus dialyzer
function is greater than the simple addition of
time-averaged clearances would suggest.
PRESERVATION OF RESIDUAL KIDNEY FUNCTION
S41
Because it appears that RKF can be preserved,

every effort should be made to protect existing
renal function in HD patients, especially if daily
urine volume exceeds 100 mL. When measures
are taken to protect RKF after initiation of HD
therapy, patients may continue to experience
long-term benefits, even at very low GFRs.
Suggested methods to protect RKF are detailed in CPR 6.
LIMITATIONS
Data that support reducing the dose of dialysis
in patients with significant residual function are
all observational. The recent randomized trial of
HD dose1 intentionally excluded patients with
significant residual function; therefore, little dosing information for patients with RKF is available. It is possible that patients with residual
function can derive more benefit from doses of
dialysis targeted for anephric patients compared
with the downward adjusted dose; therefore, a
firm recommendation to reduce the dose is not
possible at this time.
In rare cases, persistence of nephrotic-range
proteinuria may necessitate renal embolization
or removal of the kidneys. Occasionally, renal
endocrine function (eg, renin secretion) contributes to hypertension, necessitating ablation or
removal of the native kidneys. This scenario is
much less common today compared with 40
years ago because potent antihypertensive agents
are readily available. Occasionally, removal of
residual kidney mass may be required to manage
bacterial pyelonephritis. Before transplantation, removal of obstructed kidneys or kidneys
with stones or cysts causing infections that
cannot be completely eradicated with antibiotics
may be warranted. In these cases, careful timing
of the transplantation and nephrectomy can maximize benefit from RKF while also reducing the
risk of transplantation. In some cases, removal of
a transplanted kidney is warranted to eliminate
symptomatic inflammation caused by continued
allograft rejection.
GUIDELINE 7. QUALITY IMPROVEMENT PROGRAMS

The continuous quality improvement (CQI)
process has been shown to improve clinical
outcomes in many disciplines, including CKD.
It presently is conducted at both the facility
level and local network level.
7.1 For HD adequacy, each dialysis clinic
should continue to monitor the processes
related to the delivery of dialysis, such as
Kt/V, reuse standards, etc. (A)
7.2 Consideration should be given to providing resources and training for expanding
the assessment of clinical outcomes beyond mortality to include hospitalization
rates, QOL, patient satisfaction, and transplantation rates, recognizing that without
adequate resources and training, these
outcomes are unlikely to be valid, and the
efforts to collect such information may
adversely affect patient care. (B)
7.3 Quality improvement programs should
include representatives of all disciplines
involved in the care of HD patients, including physicians, physician assistants, nurse
practitioners, nurses, social workers, dietitians, and administrative staff. (B)
BACKGROUND
The CQI process has been shown to improve
process and clinical outcomes in many disciplines, including CKD and particularly CKD
stage 5.236
Improvement in both QOL and longevity are
goals of Healthy People 2010, the strategic plan
for the nations health (www.healthypeople.gov;
accessed May 1, 2006).236A Kidney disease is 1
of 18 focus areas for Healthy People 2010. For
patients with CKD stage 5 receiving dialysis
therapy, the ongoing process to improve clinical
outcomes is linked inextricably to the assessment
of dialysis adequacy, and the need for programs
to continuously assess and improve care remains
as great as ever.237
RATIONALE
With regard to HD adequacy guidelines, data
from the HEMO Study support a plateau at the
level of the existing recommended HD adequacy
targets for the current practice of thrice-weekly
treatments. There is no compelling evidence that
S42
additional increases in dialysis dose within the

presently recommended range improve such clinical outcomes as patient mortality, hospitalization
rates, QOL, patient satisfaction, and/or transplantation rates.1 However, as the global care for
dialysis patients evolves, it is reasonable to assume that so may the most effective thresholds
for delivery of dialysis. Therefore, continuing
monitoring of outcomesincluding not only delivered dose of dialysis, but also other key aspects of established and emerging factors that
impact on both QOL and longevity of life for
dialysis patientswill be critical for the continuing improvement of care for the dialysis patient.
Domains of clinical outcomes to be monitored
(in addition to mortality) when sufficient resources exist and validated standards have been
created might include:
Hospitalization rates
QOL
Patient satisfaction
Transplantation rates
Key to this process is the commitment to an

evidence-based approach that will build upon,
and not detract from, the existing limited resources.237 This would contribute to the creation
of a system in which clinical outcome trends
could be tracked and then meaningfully compared with regional outcome data (eg, from the
CKD Stage 5 Network), national data, international data, and historical data from the facility
itself. These findings could build upon the existing evidence-based recommendations for PD and
HD, anemia management, and vascular access.
Comparison with regional or national data
may be difficult because of limitations in adjusting for the case-mix of patients at individual
centers and variations in quality of data collection to capture the adequate case-mix description. Thus, facilities that have fewer resources
and less trained staff and/or more linguistically
diverse patient populations are more likely to be
unable to capture a complete clinical profile and
more likely to underestimate case-mix severity,
providing an overestimate of adjusted mortality
or hospitalization rates.
For the overall care of dialysis patients, there
likely will be value in tracking selected associ-
QUALITY IMPROVEMENT PROGRAMS
ated clinical outcomes to assess the role of HD,

such as those related to reuse systems and frequent dialysis strategies. Many investigators and
facilities already assess the former (eg, mortality) and the NIH is assessing the latter in a
prospective study (www.clinicaltrials.gov/show/
NCT00264758; accessed May 1, 2006).237A-239
The establishment of highly functional systems
and well-trained dedicated staff (including those
listed next) to ensure the quality and uniformity
of data collection, as well as the ability to extract
which component(s) contribute to clinical outcomes, will be critical to this process.
Quality improvement program representatives
should include:
Physicians
Physician assistants
Nurse practitioners
Nurses
Social workers
Dietitians
Administrative staff
Hospitalization Rates
The large number of patients hospitalized at
multiple facilities creates a tremendous task in
the collection of accurate and valid data. Moreover, differences in similar procedures performed in an inpatient and outpatient setting vary
geographically and across health care systems.
This information would need to be clarified and/or
appropriately adjusted to capture meaningful data.
Quality of Life
One of the more commonly used tools to
assess health-related QOL (HRQOL) for patients
with CKD stage 5 is the Kidney Disease and
Quality of Life Short Form (KDQOL-SF).240
There is evidence that the physical, psychological, and/or mental components of HRQOL predict death and hospitalization among HD patients.32,241-243 Unfortunately, the area of QOL
assessment is still limited by the use of multiple
tools, challenging attempts at maintaining uniformity in QOL data collection. Although the
KDQOL-SF has been translated and used in
culturally, geographically, and linguistically diverse populations, it does not appear to have
been validated in these settings. This is critical
because there may be significant sex, genera-
S43
tional, and/or racial/ethnic variations in perceivedand therefore, reportedQOL.244-247 In

addition, many of the interventions shown to
improve QOL have not been validated simultaneously to decrease the risk for adverse clinical
outcomes.
Patient Satisfaction
Multiple factors influence patient satisfaction.
Specific to HD, one key factor influencing patient satisfaction, time on dialysis therapy, is
related inversely to achieving a higher dose of
dialysis, higher phosphate clearance, less rapid
volume removal, and other factors linked to
improved clinical outcomes. This may place facilities in the situation in which patient satisfaction and clinical outcomes are in conflict, and
there are no national standards for arbitrating this
situation.248
Similar to QOL assessments, there also are
multiple tools actively being used for assessing
patient satisfaction that vary across and even
within facilities. Without standard tools and validation of the tools, the utility of such surveys at
present is insufficient to meet a clinical guideline
standard. However, the continuing development
and refinement of these tools is crucial to the
continued improvement of care and the foundation of future guidelines.
Transplantation Rates
There are no data linking the delivery of
dialysis doses within the recommended range to
renal transplantation. Multiple factors influence
transplantation rates, including, but not limited
to, case-mix, geography, insurance status, and
patient and provider bias.249,250 While the monitoring of trends is valuable, assessment of the
impact of these factors needs to be isolated,
standardized, and validated into an appropriate
analytical model before including dialysis transition rates to renal transplantation as a potential
standard.
LIMITATIONS
These guidelines for achieving the broad clinical outcome goals of improved QOL and enhanced longevity are a summation of ongoing
best practices that supplement the existing
KDOQI HD Guidelines. These best practices and
the robust evidence required to support the rigor
S44
of a CPG are still evolving. This will require a

methodologically sound foundation with standards that are generalizable. Future data collection will require assessments using prespecified
approaches to data analysis that include all these
factors and other related confounders (eg, demographics, case-mix, and medical therapeutics)
into a clinically valid multivariable statistical
model. Otherwise, the ability to ascertain the
evidence of the contribution of existing clinical
outcome best practices versus the achievement
of recommended guidelines becomes a statistical/
logistical impossibility. Such a consideration is

an intense undertaking and should not be initiated without total commitment to the resources
needed to address each of these issues and create
the valid models needed to monitor improved
care in a meaningful way. If this is not done,
interpretation of partially collected or invalid
data would: (1) be unable to determine the root
cause of changes in clinical outcomes, (2) not be
valid across and/or within facilities, and (3) add
limited value above the present outcome analyses.
GUIDELINE 8. PEDIATRIC HEMODIALYSIS PRESCRIPTION

AND ADEQUACY
8.1 Initiation of HD:
8.1.1 Dialysis initiation considerations
for the pediatric patient should
follow the adult patient guideline of a GFR less than 15 mL/
min/1.73 m2. (A)
8.1.2 For pediatric patients, GFR can be
estimated by using either a timed
urine collection or the Schwartz
formula. (A)
8.1.3 Dialysis therapy initiation should
be considered at higher estimated
GFRs when the patients clinical
course is complicated by the presence of the signs and symptoms
listed in Table 11, CPR 1 for adult
patients, as well as malnutrition
or growth failure for pediatric patients. Before dialysis is undertaken,
these conditions should be shown
to be refractory to medication
and/or dietary management. (A)
8.2 Measurement of HD adequacy:
8.2.1 spKt/V, calculated by either formal urea kinetic modeling or the
second-generation natural logarithm formula, should be used for
month-to-month assessment of delivered HD dose. (B)
8.2.2 Assessment of nutrition status is an
essential component of HD adequacy measurement. nPCR should
be measured monthly by using either formal urea kinetic modeling
or algebraic approximation. (B)
8.2.3 Principles and statements regarding slow-flow methods for postdialysis sampling and inclusion of
RKF (or lack thereof) outlined in
the adult guidelines also pertain
to pediatric patients. (B)
8.3 Prescription of adequate HD:
8.3.1 Children should receive at least the
delivered dialysis dose as recommended for the adult population. (A)
8.3.2 For younger pediatric patients, prescription of higher dialysis doses
and higher protein intakes at 150%
of the recommended nutrient intake for age may be important. (B)

8.4 Nondose-related components of adequacy:
Accurate assessment of patient intravascular volume during the HD
treatment should be provided to
optimize ultrafiltration. (B)
BACKGROUND
Provision of evidence-based pediatric HD adequacy guidelines is hampered by a number of
epidemiological issues. Stage 5 CKD remains a
relatively uncommon disease, and renal transplantation is still the predominant and preferred KRT
modality for children. In addition, PD is a viable
modality option for many pediatric patients. Finally, children with CKD stage 5 show significantly better survival rates compared with adult
patients. As a result of these factors, no longterm pediatric outcome study comparable to the
HEMO Study or the National Cooperative Dialysis Study (NCDS) would be adequately powered
to detect an effect of delivered HD dose on
pediatric patient outcome. Nevertheless, some
recent pediatric data exist to describe the most
accurate methods for quantifying urea removal,
correlate delivered dose of dialysis with inflammation, and examine other components of the
dialysis prescription, including ultrafiltration and
nutrition provision. These data can serve as the
basis for CPRs in caring for children receiving
HD. For areas in which no pediatric data exist,
CPGs and CPRs for adult patients should serve
as a minimum standard for pediatric patients.
RATIONALE
Although the Schwartz formula overestimates
GFR, especially at lower GFR levels, recent
pediatric data show that GFR estimated by using
the Schwartz formula of 15 mL/min/1.73 m2 or
less had excellent negative predictive value for a
measured GFR of 20 mL/min/1.73 m2 by
iothalamate clearance.21,251 Because 24-hour
urine collections often are not possible for smaller
nontoilet-trained children, reliance on serum
creatininebased formulas is essential in this
subset. As with the MDRD equation, use of the
S45
S46
Schwartz formula is simple and does not depend

upon collection of urine samples. The Schwartz
formula contains a cofactor that accounts for
patient sex and age to incorporate estimates of
lean muscle mass.
Modality choice is governed by a number of
factors, including patient size, availability of a
caregiver to competently perform home dialysis,
and the expected length of waiting time for a
renal allograft. Children weighing less than 10
kg are better suited for PD because HD in very
small children requires extensive nursing expertise. Also, because infants require greater nutritional needs to promote growth on a per-kilogram basis, thrice-weekly HD often is insufficient
to maintain acceptable fluid, potassium, and electrolyte balances. HD should be strongly considered for patients who do not have one, and
preferably two, caregivers who are competent
and motivated to provide home PD. For patients
who have a consenting living renal allograft
donor available and who have substantial urine
output and electrolyte control, initiation of maintenance dialysis therapy may be avoided if a
preemptive transplantation can be scheduled expeditiously.
Monthly solute clearance and nutrition status measurement using urea as the surrogate
small molecule are essential to assess the dose
of dialysis in pediatric patients because patients receiving optimal dialysis should grow
and gain weight through adolescence. Thus,
assessment of Kt/V will guide the practitioner
to increase dialyzer size, blood flow rates, or
dialysis treatment time as patients grow. Singlecenter pediatric data exist that show the Daugirdas formula reliably estimates spKt/V derived
by using formal urea kinetic modeling.252 An
essential component of adequacy measurement is nutrition status assessment because
recent pediatric data show that increased delivered dialysis dose does not in and of itself lead
to improved nutritional intake.253 Pediatric data
show that nPCR is more sensitive than serum
albumin concentration as a marker of proteinenergy malnutrition in a small group of malnourished children receiving HD.254,255
No large-scale studies exist to validate a target
spKt/V or eKt/V as adequate for the pediatric HD
population, although methods for accurate measurement of each have been validated in children.254,256
Certainly, because infants and young children have

greater nutritional requirements to support growth,
pediatric patients should receive at least the minimum dialysis dose as prescribed for adults. A study
showed that pediatric patients who receive a thriceweekly Kt/V of 2.0 and 150% of the recommended
daily allowance of protein were able to show
catch-up linear growth without the use of recombinant growth hormone.257 Chronic inflammatory
mediator levels seem to be inversely proportional
to eKt/V in pediatric HD patients,258 although an
optimal eKt/V level has not been established to
mitigate chronic inflammation, which is related in
large part to dialysis vintage. Thus, a case can be
made for providing pediatric patients with a Kt/V
greater than the adult-based guideline of 1.2, but a
larger scale study is warranted to determine an
optimal Kt/V target. Such a strategy will ensure
that smaller growing pediatric patients receive
enough nutrition and adequate waste product clearance. Observational pediatric data exist showing
that older, larger, and African-American children
are less likely to receive an spKt/V greater than 1.2
consistently259; therefore, practitioners should be
informed to make specific efforts to ensure the
provision of adequate dialysis in these vulnerable
populations.
Management of pediatric HD patient fluid status
is especially difficult because children are expected
to grow and gain weight from infancy through
adolescence. Thus, distinguishing between real
weight accretion versus fluid overload is critical to
prevent a chronic fluid-overloaded state that can
lead to chronic hypertension and resultant CVD.
Given the relative high ultrafiltration rate to dialysis treatment time ratio and the relative inability of
younger patients to accurately verbalize symptoms
from overly rapid ultrafiltration, the means to accurately assess patient intravascular volume can help
optimize ultrafiltration to attain patient true target
dry weight while minimizing intradialytic symptoms. Noninvasive monitoring (NIVM) of hematocrit during the dialysis treatment uses an in-line
sensor to reflect the change in patient blood volume
as an inverse change in patient hematocrit during
fluid removal. Ultrafiltration guided by NIVM algorithms that adjust UFRs and targets based on hourly
NIVM blood volume changes have been shown to
decrease patient symptoms, hospitalization, extra
treatments for fluid overload and hypertension,
antihypertensive medication requirements, and
PEDIATRIC HEMODIALYSIS PRESCRIPTION AND ADEQUACY
fourth weekly HD treatments for pediatric patients

receiving HD.260-262
LIMITATIONS
Any pediatric study to determine either an adequate or optimal delivered dialysis dose requires
S47
practical end points to be valid. Whereas death and

hospitalization rates are easily measurable end
points, their relative infrequency in the pediatric
HD population and the low prevalence of pediatric
CKD stage 5 make an adequately powered study
using these end points a virtual impossibility.
II. CLINICAL PRACTICE RECOMMENDATIONS

FOR HEMODIALYSIS ADEQUACY
CLINICAL PRACTICE RECOMMENDATION FOR

GUIDELINE 1: INITIATION OF DIALYSIS
Certain complications of kidney failure justify initiation of dialysis treatment in patients
for whom estimated GFR has not yet decreased to 15 mL/min/1.73 m2 (Table 11).
Table 11. Complications That May Prompt Initiation of Kidney Replacement Therapy
Intractable ECV overload
Hyperkalemia
Metabolic acidosis
Hyperphosphatemia
Hypercalcemia or hypocalcemia
Anemia
Neurological dysfunction (eg, neuropathy, encephalopathy)
Pleuritis or pericarditis
Otherwise unexplained decline in functioning or well-being
Gastrointestinal dysfunction (eg, nausea, vomiting, diarrhea, gastroduodenitis)
Weight loss or other evidence of malnutrition
Hypertension
S49
CLINICAL PRACTICE RECOMMENDATIONS FOR

GUIDELINE 2: METHODS FOR MEASURING AND
EXPRESSING THE HEMODIALYSIS DOSE
For patients managed with HD, both dialyzer and native kidney function can be measured periodically to assess the adequacy of
replacement therapy. Urea clearance is the
preferred measure of both (see Guideline 2).
2.1 Residual kidney urea clearance (Kr) is
measured best from a timed urine collection.
2.2 For purposes of quality assurance, the
delivered dose should be measured and
compared with the prescribed dose each
month.
BACKGROUND
Failure to include Kr in the model of urea
kinetics will not harm the patient provided the
dose of dialysis is adequate. Inclusion of Kr is
advantageous because it allows accurate measurement of G and nPCR (or nPNA), which
otherwise are underestimated in patients with
significant RKF and are helpful to assess dietary
adequacy. Inclusion of Kr also allows a potential
reduction in the duration and frequency of dialysis as a means of improving QOL by extending
time off dialysis. Limiting time and reducing the
intensity of dialysis may benefit some more than
others, depending on lifestyle and treatment tolerance. Mathematical analysis of solute kinetics
during and between HD treatments shows that
average and peak solute levels are controlled
better by continuous (compared with intermittent) clearance, and that increasing the frequency
of a given weekly clearance also lowers levels of
dialyzable solutes. Comparison of delivered dose
with prescribed dose of dialysis adds another
dimension to the analysis of adequacy that can
spot problems with the blood access device and
dialysis equipment, including blood and dialysate pumps. This function is independent of the
determination of adequacy.
RATIONALE
Adding RKF to Dialyzer Clearance
If Kr is included in the dialysis prescription,
it becomes important to measure Kr frequently
to avoid prolonged periods of underdialysis as Kr
S50
is lost. The rate of loss may vary among patients.

In some patients, monthly measurements are
advised, whereas in others with good urine output, quarterly measurements will suffice. If infrequent measurements are chosen, the patient and
dialysis staff must be alert to changes in urine
output and exposure to toxic insults (see Table
16, CPR 6). Urine output roughly correlates with
RKF, but it should not be used as the sole
determinant because it does not predict RKF
accurately in individual patients.81 Patients with
potentially recoverable renal function represent a
special group in whom regular measurements of
RKF are especially advantageous. Failure to follow up RKF closely may lead to unnecessary
prolongation or perpetuation of dialysis in a
patient with adequate native kidney function
who does not require dialysis.
For both PD and HD, the preferred measure of
RKF is urea clearance. This differs from recommended measures of kidney function in patients
with CKD stages 1 to 4, for whom creatinine
clearance has been the traditional index, as well
as the serum creatininebased estimate of GFR
derived from the MDRD Study.263 Reasons for
recommending urea clearance as opposed to other
techniques include the following:
Unlike creatinine clearances, measurements of

urea clearance are not confounded by renal
tubular secretion.
Native kidney urea clearances are lower than
the kidneys GFR, so the patient is protected.
Conversely, creatinine clearances are always
higher than GFR.
MDRD estimates of GFR based on serum
creatinine level are not valid in patients managed with dialysis.
Inclusion of native kidney urea clearances in
kinetic modeling programs allows accurate
calculation of G and nPCR as an aid to diet
assessment.
When Kr is included in the expression of
overall excretory function, the method for combining intermittent dialyzer clearance with continuous Kr requires some effort. Methods for
adding Kr to Kd should take into account the
additional clearance that RKF provides between

dialysis treatments and the increased efficiency
of continuous (compared with intermittent) clearance. Suggested methods for combining Kr with
Kd can be found in Appendix. Caution must be
exercised when using any of the methods found
in the Appendix to adjust the dialysis dose for Kr
values above 2 mL/min. Other potentially vital
benefits of dialysis must be considered when
contemplating a reduction in dose based solely
on urea kinetics. An alternative simplified method
(using a table) for adjusting spKt/V in patients
with Kr 2 mL/min/1.73 m2 can be found in
CPR 4, Minimally Adequate Hemodialysis.
It is important to note that the adequacy standards described in these guidelines and CPRs
that refer to dialysis-session-based spKt/V values do not include an adjustment for the continuous component of residual urea clearance.
One of the disadvantages of adjusting the HD
dose according to RKF is the patients perception of worsening health when the ultimate decrease in native kidney function requires longer
treatment times. Successive prolongations of dialysis can contribute to psychological depression
that further compromises the patients QOL and,
possibly, survival.32 Incremental dosing while
counseling the patient to anticipate the increase
in treatment time as renal function is lost is the
Work Groups preferred approach.
How to Measure More Frequent Dialysis
The correction for rebound at the end of
dialysis (see previous discussion of eKt/V) reduces, but does not eliminate, the effect of intermittence and disequilibrium on dialysis efficiency. Efficiency is defined as the effect of
lowering solute concentration achieved for a
given level of dialysis dose. Because the dose is
defined as a clearance, the solute level is inversely proportional to the dose and the relationship between the 2 is curvilinear, eventually
reaching a plateau of effectiveness as dialysis
dose is increased. Intermittent dialysis therefore,
in contrast to continuous dialysis, has a selflimiting aspect that diminishes its efficiency. If
the efficiency of continuous dialysis is defined as
unity, then the efficiency of thrice-weekly dialysis has been estimated as 0.7 or less, depending
on the solute. The greater the solute disequilibrium, the lower the efficiency of intermittent
S51
dialysis. Increasing the frequency, ie, moving

toward a more continuous pattern, increases efficiency. An adjustment in dose therefore theoretically is necessary to account for the improvement in efficiency for dialysis schedules that are
more frequent than 3 times per week. This concept is inherent in the already accepted dictum
that the same weekly dose given once or twice
weekly will not suffice to maintain HD adequacy.
The recommended method for normalizing
and expressing the dose of dialysis independent of frequency is to reduce the expressed
delivered dose to a continuous equivalent clearance.202,264,265 This method relies on calculated
average or peak concentrations of the index solute
and assumes a weekly steady state of generation
and removal. Under such conditions, the solute
removal rate will equal the generation rate. In
addition, the well-known relationship between clearance and concentration dictates that the average
solute level will be proportional to the generation
rate and inversely proportional to the continuous
equivalent clearance (Kce):
Cav = G/Kce
Kce = G/Cav
where C av is average concentration
The value of Kce for urea is calculated easily
by using formal urea modeling that produces
both G and time-averaged C (TAC).264 However,
the resulting clearance is significantly higher
than a consensus-derived continuous equivalent
clearance for PD. This observation led 2 groups
to propose using the average peak or average
predialysis urea concentrations as the target instead of mean concentration.265,266 This substitution of a higher concentration than Cav in the
expressions resulted in a lower average clearance, more in keeping with the accepted continuous peritoneal clearances for CAPD. The resulting quasiclearance was called standard K and
standard Kt/V (stdKt/V).265 Another proposed
approach is to model the kinetics of other
solutes because almost all other small and large
dialyzable solutes have greater disequilibrium
than urea.267,268 As noted, the inefficiency of
intermittent dialysis is accentuated by disequilibrium. All these methods produced a set of curves
S52
RECOMMENDATIONS FOR HEMODIALYSIS ADEQUACY
relating spKt/V to stdKt/V or normalized Kt/V

that were similar, partially because parameters
were chosen in each case to force the resulting
continuous equivalent clearance to match the
accepted values for continuous PD (CAPD).
stdKt/V is calculated easily by using formal urea
kinetic modeling and has been chosen by the
NIH-sponsored Frequent HD Network as the
frequency-normalized expression to monitor dialysis doses in their study of daily HD outcomes.
Conversion of spKt/V to stdKt/V can be approximated by using an explicit equation that
assumes a symmetric weekly schedule of dialyses, no Kr, and a fixed volume (V). This method
was presented first by Gotch in 1998 and later
refined by Leypoldt in 200471:
1 e eKt/V
t
stdKt/V =
1 e eKt/V 10080
+
1
Nt
spKt/V
10080
where N is number of treatments per week and

eKt/V is derived from spKt/V by using 1 of the
expressions in Table 4. It should be noted that
stdKt/V calculated using this equation may differ
slightly from stdKt/V calculated using the more
exact method described previously that takes
into account other variables, such as ECF volume expansion/contraction, asymmetry of the
weekly schedule, and Kr.
The complexities of normalizing more frequent HD to a continuous equivalent clearance
perhaps have contributed to a lack of consensus
about dose expressions for the increasingly popular schedule of 4 treatments per week. The extra
dialysis treatment often helps with management
of larger patients, patients with refractory anemia, and patients with excessive fluid gains.
Most of these methods require formal kinetic
modeling and modeling programs that are not
locked into 3 treatments per week. In addition,
regulatory agencies have not caught up with
these concepts and continue to demand a minimum Kt/V of 1.2 per dialysis as if they are given
3 times per week. If an extra dialysis treatment is
given, a simple mathematical calculation shows
that the minimum dose per dialysis required if
the minimum for 3 times per week is 1.2 per
dialysis is 0.9 per dialysis to achieve the same
weekly clearance. This calculation assumes that

all dialysis treatments are equal and the extra
treatment produces no gain in efficiency. This
conservative calculation will provide more dialysis for the patient than is apparent from the
expressed dose, which effectively protects the
patient from underdialysis. Alternatively, the dialysis clinic can simply multiply the measured
Kt/V by 4 and divide by 3 to obtain the equivalent of Kt/V for 3 treatments per week.
Quality Assurance
The Work Group continues to recommend
comparisons of prescribed with delivered doses
as a quality assurance aid. Guideline 4 provides a
minimum Kt/V threshold below which action
should be taken to prevent underdialysis. However, even if the dose is adequate, comparison
of prescribed with delivered dose has potential
additional benefit for the patient. If significantly
different (15% difference), troubleshooting
should be done to detect other problems that may
impact on future dosing, such as AR or a faulty
blood pump. In practice, comparison of prescribed with delivered dose is accomplished by
comparing modeled V with real V. The latter is
determined preferably by averaging previous values of modeled V, but also can be determined by
using an anthropometric formula, eg, Watson.269
If a problem exists with delivery, usually modeled V is significantly greater than real V. Because urea modeling provides a ratio of K/V, the
inflated V is caused by an inordinately high
prescribed K compared with delivered K. Prescribed K is determined from the dialyzer specification, K0A, and flow rates, whereas modeled
K/V is determined mainly from changes in BUN
levels during the dialysis. Comparison of modeled V with a previously determined patientspecific value for V is equivalent to comparing
delivered with prescribed clearance. When V is
too high, efforts should be made to detect such
problems as AR, an error in dialysis timing,
inadequate blood pump occlusion or calibration,
faulty dialysate pump, error in blood sampling,
or inadequate performance of the dialyzer (eg,
because of clotting during dialysis or excessive
reuse).
CLINICAL PRACTICE RECOMMENDATIONS FOR GUIDELINE 4:

4.1 High-Flux Membrane:
When methods to achieve good dialysate water quality are available, highflux HD membranes should be used,
defined as those providing 2-microglobulin (2M) clearance of at least
20 mL/min under conditions of actual
use.
4.2 Minimum dose with hemofiltration or
hemodiafiltration:
The recommended minimum delivered dose target, measured by
using pretreatment and posttreatment BUN levels, is the same as that
for HD.
4.3 Minimum spKt/V levels for different dialysis schedules:
4.3.1 Two to 6 treatments per week are
appropriate for certain patients.
4.3.2 Twice-weekly HD is not appropriate
for patients with Kr less than 2
mL/min/1.73 m2.
4.3.3 Minimum spKt/V targets for 2-, 4-,
and 6-times-per-week dialysis schedules logically should be different
from that for the thrice-weekly
schedule. In the absence of doseranging outcomes data, minimum
spKt/V targets for different schedules can be based on achieving a
minimum stdKt/V of 2.0 per week.
4.3.4 The target spKt/V dose should be at
least 15% higher than the listed
minimum dose because of the variability in measuring Kt/V, as discussed in Guideline 4.
4.4 RKF (measured by Kr):
4.4.1 The minimally adequate dose of dialysis can be reduced in patients with Kr
greater than 2 mL/min/1.73 m2.
4.4.2 In the absence of dose-ranging outcomes data, the minimum spKt/V
target for patients with substantial
RKF can be reduced, but the reduced target should be no lower
than 60% of the minimum target
for patients with no residual renal
function (the reduction depends on
4.5
4.6
4.7
4.8
dialysis frequency), per values provided in Table 13.

4.4.3 When the minimally adequate dose
is reduced because of substantial
RKF, Kr should be monitored at
least quarterly and as soon as possible after any event that might
have acutely reduced RKF.
Increase in minimally adequate dose for
women and smaller patients:
An increase in the minimally adequate dose of dialysis should be
considered for the following groups
of patients:
4.5.1 Women of any body size.
4.5.2 Smaller patients, for example,
patients with values for anthropometric or modeled V of
25 L or lower.
Dialysis adequacy for patients who are malnourished and/or losing weight:
An increase in the minimally adequate dose of dialysis and/or a
change to a more frequent dialysis
schedule should be considered for
the following groups of patients:
4.6.1 Patients whose weights are
20% less or lower than their
peer body weights.
4.6.2 Patients with recent otherwise
unexplained and unplanned
weight loss.
Dialysis adequacy for patients with hyperphosphatemia or chronic fluid overload and
other categories of patients who might
benefit from more frequent dialysis:
A change to a more frequent dialysis schedule should be considered
for the following groups of patients:
4.7.1 Patients with hyperphosphatemia.
4.7.2 Patients with chronic fluid
overload with or without refractory hypertension.
A change to a more frequent dialysis
schedule may be beneficial to a broader
group of patients in terms of improving
S53
S54
QOL and quality of sleep, reducing sleep

apnea, and improving sensitivity to erythropoietin.
4.9 Minimum dialysis treatment time for
thrice-weekly schedules:
The minimum HD treatment time
for thrice-weekly dialysis in patients
with Kr less than 2 mL/min should
be at least 3 hours.
RATIONALE
High-Flux Membrane (CPR 4.1)
The 2M molecule has an important role in
the pathogenesis of dialysis-related amyloidosis,
which is seen primarily in HD patients who have
been dialysis dependent for more than 5 years.
An important question is whether use of membranes that clear 2M gives rise to superior
outcomes over shorter periods, especially in terms
of such hard outcomes as mortality and hospitalization. The primary results of the HEMO Study
suggested that assignment to dialysis using a
high-flux membrane had no significant effect on
patient mortality or a variety of main secondary
outcomes that combined mortality with either
hospitalization or decrease in serum albumin
levels.1 However, in contrast to results of dose
randomization (for which the mean effect size of
dose on mortality or secondary outcomes was
close to zero) in the flux analyses, the mean
effect size for mortality, as well as for several of
the secondary outcomes, was fairly consistently
close to a 10% benefit, although the 95% confidence intervals (CIs) included zero. Further analysis of the HEMO Study data showed that assignment to high-flux dialysis improved mortality (as
well as main secondary outcomes) in higher
vintage patients, ie, those dialyzed longer than
the median time of 3.7 years at baseline.270 This
analysis in higher vintage patients was predefined at the outset of the HEMO Study before
beginning the trial. Furthermore, some of the
secondary outcomesin particular, composites
focusing on cardiovascular death and/or cardiovascular hospitalizationswere improved in the
group assigned to high-flux therapy.271
During the KDOQI HD update period, 2000 to
2005, no other randomized trials assessing hard
end points (mortality and/or hospitalization) in patients undergoing high-flux versus low-flux dialy-
sis were published. Several randomized trials looked

at the effects of high-flux dialysis on predialysis
2M levels, and all found a measurable effect
(reduction in level with high-flux dialysis), including the HEMO Study (see Table 12).270,272,273
Additional observational studies suggested that
the mortality rate might be decreased in patients
dialyzing with high-flux membranes (see Leypoldt,
1999,274 and Woods, 2000275 in Table 12). After
results of the HEMO Study were disclosed, analysis of mortality versus flux data from the 1999
to 2000 USRDS, published in abstract form, found
a small mortality risk reduction (relative risk [RR],
0.972; 95% CI, 0.950 to 0.995) in prevalent patients, and an RR of 0.951 (CI, 0.937 to 0.966) in
incident patients dialyzed with high-flux
membranes.277A However, this abstract has not
been published as an article in a peer-reviewed
journal.
In a large European cohort of patients making
up the Lombardi registry, mortality and risk for
carpal tunnel surgery were compared in patients
undergoing (mostly low-flux) HD, hemodiafiltration, and hemofiltration.278 A 10% mortality risk
reduction was found in patients treated with
either hemodiafiltration or hemofiltration compared with mostly low-flux HD, but the CI included zero. However, the investigators found a
significant risk reduction for carpal tunnel surgery in the hemodiafiltration/hemofiltration
groups.
The most recent European Best Practice Guidelines include recommendations for the use of
high-flux membranes, supported by level B evidence (Guideline II.2.1) and also recommend the
addition of a convective component to enhance
middle-molecule removal, also with level B evidence (Guideline II.2.2).279 However, a recent
Cochrane group review, looking at a metaanalysis of RCTs studying the effect of dialysis
membrane on outcome, concluded that it was too
soon to make a definitive recommendation.273
The Work Group ultimately decided that the
evidence for benefits of high-flux membrane
use in terms of hard outcomes was suggestive,
but not definitive enough to be formulated as
a guideline, taking a more conservative approach than the European group. However, the
Work Group decided that the evidence for
mortality reduction was strong enough for a
CPR encouraging high-flux dialysis. The evi-
S55
S56
dence is incontrovertible that high-flux dialysis decreases predialysis serum 2M levels

(Table 12),270,272,273 and lower predialysis 2M
levels were linked to improved outcome. Furthermore, reduced long-term consequences of
2-amyloidosis with the use of high-flux membranes was reported by 2 groups,280,281 confirming a much earlier report.282
The Work Group also specified a definition of
high-flux dialysis. In the HEMO Study, 2M
clearances were measured in vivo, and a clearance of at least 20 mL/min was defined as
adequate for a dialyzer to be considered high flux
(the low-flux dialyzers used had 2M clearance
indistinguishable from zero). Because the manufacturing industry has learned how to expand
2M clearances while minimizing albumin leakage, current dialyzers are available with much
greater 2M clearances, and the clearance can be
increased still further by the use of hemodiafiltration and/or novel dialyzer designs. The value of
20 mL/min was adopted for these guidelines
because it corresponded to the minimum level
obtained in the HEMO Study, which provided
much of the evidence for this CPR.
Minimum Dose With Hemofiltration or
Hemodiafiltration (CPR 4.2)
Urea is a surrogate adequacy molecule for
measuring clearance of a large family of uremic
toxins, some of which may have a much higher
molecular weight. Because convective removal
accelerates removal of larger (5 kd), yet permeable, solutes during extracorporeal therapy, it
might be argued that with hemofiltration, the
ratio of removal of these larger molecular-weight
toxins to urea removal is higher; hence, minimal
adequacy parameters based on urea removal either do not apply or existing minimal adequacy
guidelines based on urea removal should be
lower when hemofiltration is used. No dosefinding studies of hemofiltration that report hard
outcomes could be identified by the Work Group.
In the absence of data to the contrary, the Work
Group decided to maintain recommended minimum adequacy standards for urea removal for
both hemofiltration- and hemodiafiltration-based
therapies. With hemodiafiltration, urea removal
usually is unchanged or slightly enhanced by the
supplemental filtration, so this was a somewhat
moot issue. However, for some forms of primar-
ily hemofiltration-based dialysis therapy (in which

limited amounts of replacement fluid are used),
the recommended minimum levels of urea removal may be difficult to achieve. The Work
Group decided, on the basis of current evidence
and lack of an interaction between urea-based
adequacy and flux in the HEMO Study, that it
would be prudent to recommend the same minimum levels of spKt/V for HD, hemofiltration,
and hemodiafiltration.
Minimum spKt/V Levels for Different Dialysis
Schedules (CPR 4.3)
gave adequacy recommendations only for thriceweekly HD schedules. Since the last update, 1
important cross-sectional study appeared suggesting that survival in patients treated with twiceweekly HD was no worse (and was possibly
better) in a USRDS patient sample.234 Given
these data and with earlier initiation of dialysis in
patients with higher levels of RKF, the Work
Group decided that thrice-weekly HD as a minimum frequency level was no longer appropriate.
Based on solute kinetics (discussed later), the
Work Group was comfortable recommending a
twice-weekly dialysis schedule, but only for patients with substantial RKF.
Also, since the KDOQI 2000 update, a large
set of studies was published regarding the potential advantages of giving dialysis treatments more
often than 3 times per week. The number of
treatments ranges from an additional fourth treatment per week in patients who have problems
controlling volume283 to offering short daily
dialysis treatments ranging from 1.5 to 3 hours
(or longer) 4 to 6 times per week. An alternative
method of extending therapy is to greatly increase dialysis treatment time (from the usual 2.5
to 5 hours) to 7 to 10 hours by giving dialysis at
night. Various frequency schedules for nocturnal
dialysis have been reported, from 3 to 6 times per
week.284 Simple avoidance of the 2-day interdialysis interval by giving dialysis every other
day also has been advocated.285
At the time of the present guideline update, no
RCTs have been conducted to measure hard
outcomes (mortality and/or hospitalization) comparing conventional thrice-weekly dialysis with
either short-daily or nocturnal HD. Also, no
dose-finding RCTs have appeared comparing fre-
quent short dialysis with longer nocturnal regimens in an effort to achieve varying degrees of
solute removal.
Given the lack of maturity of the research data
in this field, the Work Group decided to refrain
from making specific recommendations about
the usefulness of these therapies in terms of a
guideline or from proposing guidelines regarding minimally adequate therapy given more frequently than 3 times per week.
How to measure adequacy of more frequent
therapies is not established. One of the main
benefits of more frequent therapies may be ridding the body of solutes that are difficult to
remove, such as phosphate, 2M, or some still
unknown uremic toxins. Another benefit may be
in better control of salt and water balance, which
may impact on patient survival as much as solute
control. In particular, the Work Group was impressed with observational data linking hard outcomes to calcium-phosphorus product,286 as well
as better control of serum phosphorus levels with
more intensive daily dialysis schedules200 and
most nocturnal dialysis schedules.284 Because 2,
4, 5, and 6 treatments per week (nocturnal and/or
short-daily therapies) increasingly are prescribed,
the Work Group decided that some guidance was
needed in terms of minimally adequate doses.
Although an argument could be made that
urea is not the only solute to use for measuring
doses in a more frequent dialysis setting, control
of small-solute levels in patients is vital to survival, so the Work Group decided to base recommendations for this CPR on urea. Potential alternative solutes, such as 2M, are not as clearly
linked to outcome. Phosphate, while clearly
linked to outcome, has complex and as yet poorly
defined kinetics, and serum levels are affected
not only by dialysis, but also by diet and consumption of phosphorus binders. One of the
major disadvantages of urea is the rapidity of its
diffusion among body compartments (high intercompartmental mass transfer area coefficient).
This limitation can be minimized by using the
stdKt/V construct, as described in detail in CPR 2
and in the Appendix. When the dialysis dose is
expressed as stdKt/V, it seeks to control the mean
pre-dialysis BUN, but, alternatively, it can be considered to model a well-cleared, but highly sequestered, solute with a low intercompartmental mass
transfer area coefficient. Because highly seques-
S57
tered solutes will have a large rebound after dialysis, the time-averaged blood level will be close to
the mean predialysis level. stdKt/V also has the
quality of reflecting advantages of a more frequent
dialysis schedule that more efficiently removes
sequestered solutes, such as phosphorus, but also
possibly including a whole range of dialyzable
solutes in the 100 to 1,000 d molecular-weight
range.
In developing this CPR, the Work Group decided to target a minimum dialysis dose equivalent to an stdKt/V level of 2.0 per week. This is
the level obtained when one dialyzes using a
thrice-weekly schedule to an spKt/V of approximately 1.2 per treatment over 3.5 hours (Table 19).
In the absence of RKF, it is not possible to
reach an stdKt/V of 2.0 by using a twice-weekly
schedule. Kinetic modeling was used to examine
the levels of spKt/V per treatment that would be
required to reach a weekly stdKt/V value of 2.0
for twice-weekly to 7-times-weekly schedules
by using dialysis treatment times ranging from 2
to 8 hours. The simulation was performed both in
the absence of RKF and when Kr was 2 mL/min.
This simulation was used to arrive at the recommended minimum values in Table 13.
These spKt/V values should be considered
minimum values, not target values. It is especially important to note that extending dialysis
time is much more effective for controlling solute levels when frequency is increased to 4 to 7
treatments per week. Particularly in short-daily
therapies, longer treatment times markedly improve phosphate removal.
From Table 19, similar spKt/V values can be
determined for 8-hour treatments more typical of
nocturnal HD. Usually the Kt/V for an 8-hour
treatment, even at reduced dialysate and bloodflow rates, will be greater than 1.0; hence, the
Work Group did not believe that adequacy determined by predialysis or postdialysis BUN monitoring is appropriate for nocturnal HD schedules.
Target spKt/V Values per Treatment for
More-Frequent Therapies
In contrast to thrice-weekly schedules, for
which there are good data regarding the variance in Kt/V on repeated measurements, no
such data have been published for short-daily
dialysis, although there is no reason to assume
that it would be much different from the 10%
S58
variance found in the HEMO Study. For this

reason, the Work Group recommended targeting an spKt/V value that is about 15% higher
than the recommended minimum targets in
Table 19 in the Appendix.
Residual Kidney Function (CPR 4.4)
left unspecified any adequacy recommendations
for patients with substantial RKF (GFR 5.0
mL/min/1.73 m2, defined as the average of urea
plus creatinine clearance). Given the trends and
recommendations for earlier institution of dialysis therapy and perhaps the more successful
preservation of RKF in the past several years, a
large number of currently dialyzed patients have
substantial RKF. A consideration of solute kinetics shows that even low levels of RKF can
account for removal of large amounts of solute,
including such large-molecular-weight solutes as
2M, in addition to helping maintain salt and
water balance. Although there are no reliable
outcome data suggesting that the delivered dose
of dialysis might safely be reduced in patients
with substantial RKF, reduction of the extracorporeal dose makes sense from a solute-kinetics
viewpoint. The HEMO Study deliberately excluded patients with Kr for urea greater than 1.5
mL/min and hence cannot be of guidance. Observational studies suggested a benefit of even small
levels of RKF in terms of survival and other
secondary outcome measures, so it is clear that
all possible efforts should be expended to maintain RKF (see Guideline 6).
The Work Group was of the opinion that, at
the present state of incomplete knowledge, the
best way to adjust for residual renal urea clearance is to add it to the weekly stdKt/V. Residual
urea clearance of 2 mL/min is approximately

20 L/wk of clearance; accordingly, in a patient
with V 30 L, it represents about a 0.67 weekly
Kt/V unit. Table 13 shows spKt/V values per
treatment corresponding to a weekly stdKt/V
value of 2.0 in patients undergoing 2 to 6 treatments per week after adjusting (or not) for a
weekly Kr of 2 mL/min. In discussing adjustments
for Kr, the Work Group had 2 broad areas of
concern.
First, the kinetic effect of RKF is so powerful that in patients with Kr greater than 2
mL/min, an equivalent reduction in spKt/V
would result in very low recommended values.
The Work Group believed this was undesirable
for 2 reasons: (1) very low Kt/V values, especially for the twice-weekly or thrice-weekly
schedules, would limit other potential beneficial effects of dialysis, including salt and water
control; and (2) RKF sometimes can decrease
precipitously. Patients who were receiving a
markedly reduced dose of dialysis because of a
higher Kr then might be underdialyzed for a
few months until the reduction in Kr was
recognized and acted upon. For these reasons,
the Work Group developed an alternative
scheme that limited the downward adjustment
in spKt/V for Kr to 2 mL/min, even for patients
with higher levels of Kr. The decision to cap
the reduction in session Kt/V was based on the
lack of outcomes data in patients who have
higher levels of RKF and receive very low
amounts of dialysis Kt/V. Maintaining a minimum total Kt/V value of 1.2, using an exact
calculation of the required dialysis spKt/V as
described in the Appendix, would allow reduction of the dialysis dose down to near zero at
levels of RKF that are below the threshold for
initiating dialysis. The wisdom of recommending this fully incremental approach was intensely debated in the Work Group. Opinions
differed, so it was decided to leave further
reductions in dialysis dose, below values suggested in Table 13, to the discretion of the
clinician. One single study81, addressed this
issue but there are few other studies of outcomes in patients with RKF hemodialyzed
using an incremental dialysis schedule. This
remains a critical area where more research is
recommended.
Second, it was recommended that in patients
for whom treatments are reduced because of Kr
of 2.0 or greater, Kr should be rechecked at least
quarterly (every 3 months) and after any event
suspected to be associated with a sudden decrease in Kr. However, because the Work Group
did not want to impose a burden of verifying Kr
for all patients in a dialysis clinic, the recommendation is to verify it only in patients for whom
the target dialysis dose is reduced.
Increase in Minimally Adequate Dose for
Special Populations (CPR 4.5)
One potential area of concern relates to selected subgroups of patients who may require
more dialysis. During the design phase of the
HEMO Study, 7 such subgroups were postulated,
including patients with high comorbidity scores,
patients with diabetes, high-vintage patients, Caucasian patients, and women. Based on HEMO
Study results plus results from subsequent crosssectional studies plus clinical judgment and common sense, the Work Group recommended possibly increasing the target dose of dialysis in 2
groups of patients: women and small patients.
Women
Of the 7 high-risk groups identified during
the design phase in the HEMO Study, an interaction with dose group assignment was present for
only women (Table 8).13 Women assigned to the
higher dose of dialysis (URR 75%, on average)
had better survival than those assigned to URR
of about 63%. The overall benefit for men and
women was close to zero because an opposite
nonsignificant trend for increased mortality in
men assigned to the higher dose of dialysis
also was found. As best could be determined,
the sex-dose-mortality interaction was not
S59
caused by body size, although most women in

the HEMO Study had a smaller body size,
determined by using a variety of measures,
with little overlap with the men in the study.
While the HEMO Study was in progress, others identified a similar sex-dose interaction,57
and after HEMO Study results were reported,
another group reported a similar association in
the USRDS-Medicare database.104
To complicate matters, the dose-targeting bias
(discussed in more detail in Guideline 4) appeared to be enhanced in women compared with
men.98 This means that observational data should
not necessarily be considered confirmatory of the
intent-to-treat sex-dose-mortality interaction identified in the HEMO Study. However, because
both randomized and observational data suggested that a higher dose of dialysis might be
beneficial for women, the Work Group was comfortable with issuing a CPR for considering a
higher dialysis target dose in women. For the
most part, this happens naturally because most
women have a smaller value for V; thus, the
same prescription applied to a man and a woman,
even considering patients of equal weight, will
result in a higher Kt/V in the woman.
Body Size
There are, of course, multiple reasons why a
patient can be small. A patient can be short,
small boned, or simply thin, all without being
malnourished. Most data examining body size
versus dose versus mortality interactions looked
at anthropometric measures in which body size
was derived from weight and heighteg, body
mass index (BMI)and, in some studies (in
which Watson V was used), sex, and age. It
appears that most of the mortality effect in these
studies is related to BW because the Work Group
was not able to find data in which patient height
was a predictor of mortality (nor was height a
predictor of mortality in the HEMO Study). It is
then presumed that patients with lower BMI or
Watson V primarily are underweight patients
who are malnourished.
A separate issue is whether smaller nonundernourished patients who are at or near their expected weight might require more dialysis. Here,
the argument has to do with sizing delivered dose
of therapy based on body water, which is a factor
of BW to the 1.0 power (usually V some factor
S60
multiplied times the postdialysis weight). GFR

usually is sized according to BSA, which is a
factor multiplied times BW raised to the 0.667
(2/3) power. If Kt was normalized to BSA or
some factor multiplied by V0.667 and a single
target value was assigned for all values of weight,
the result would be that more dialysis would be
assigned to smaller patients than with the current
Kt/V strategy, and less dialysis would be assigned to very large patients. The argument has
been made that V is determined substantially by
skeletal muscle mass, which may be relatively
quiescent in terms of generation of uremic toxins.
Although women or less muscular men may have a
smaller V than similar-height controls, it does not
necessarily mean they require less dialysis.
The Work Group noted and reviewed a number of studies in this field, examining the relationship of Kt and various measures of body size.
Most of these analyzed the Fresenius North America patient data set.78,101
The Work Group also looked at an analysis of
survival by various body size parameters in the
HEMO Study,13 in which various measures of
body size were not found to interact with delivered
dose. The Work Group concluded that there was
not sufficient evidence to abandon the concept of
sizing of dialysis dose according to V for the
moment because cross-sectional survival analyses
of dose versus mortality have so many biases
thatat presentthe effects of individual confounding factors have not been completely clarified. Furthermore, there is great simplicity in being
able to monitor delivered dialysis dose based on
URR and then combine this with weight loss and
other information to compute a delivered Kt/V.
The compromise solution for the present update
was to keep the dose as spKt/V and the minimum
dose unchanged, as per the KDOQI 2000 guidelines, but to issue this CPR, which recommends
that one consider increasing minimum dialysis dose
targets in both women and small patients.
Several logical questions arise:
By how much should the targets be increased?

Should targets be increased for both large
women and small women?
In small women who also are small in terms
of their size, should the increase in dose be
greater than the increase for small men?
The Work Group decided to leave these decisions up to the practitioner, although an increased minimum dose of 25% was the range of
increase in dose envisaged for either women or
small patients (eg, to an spKt/V of 1.5 for a
thrice-weekly schedule with Kr 2).
Dialysis Adequacy for Patients Who Are
Malnourished and/or Losing Weight (CPR 4.6)
Because nutrition tends to deteriorate even at
relatively well-preserved levels of renal function,288 the notion is prevalent in the dialysis community that increasing the amount of dialysis may
help improve nutritional status. A variety of nutritional parameters were measured in the HEMO
Study, and the higher-dose group did not show
improvement in any of the nutritional parameters
measured, including serum albumin, anthropometrics, or food intake. However, patients treated with
longer (8-hour) periods of dialysis given 3 times
per week or patients following 6-times-per-week
short-daily dialysis regimens or nocturnal-dialysis
regimens sometimes reported marked benefits in
terms of food intake, serum albumin level (although this is confounded by blood volume changes
caused by hemoconcentration), and increase in dry
BW.284
For these reasons, the Work Group issued the
present CPR, which recommends that practitioners
consider increasing the dose of dialysis in a thriceweekly framework in patients who are judged to be
malnourished by BW criteria, subjective global
assessment, or other means. The lack of a beneficial
effect on nutritional parameters in the HEMO Study
of increasing spKt/V from 1.3 to 1.7 suggests that
perhaps a more useful strategy in such patients is to
increase dialysis frequency, although it is recognized that such therapies are not uniformly available at all centers.
Dialysis Adequacy for Patients Who Are
Hyperphosphatemic or With Refractory
Volume Overload and Other Categories of
Patients Who Might Benefit From More
Frequent Dialysis (CPR 4.7)
Patients With Hyperphosphatemia
Serum phosphorus level appears to be a robust
predictor of mortality in dialysis patients, as well
as patients with CKD.286 Phosphorus control is
dependent on phosphorus intake, compliance with
phosphorus-binder intake, and HD prescription.
Because serum phosphorus level decreases to a

low level early in dialysis, increases in Kt/V in a
thrice-weekly framework while holding treatment time constant (eg, by increasing blood flow
rate or dialyzer urea clearance) or slight increases in dialysis treatment time are expected to
have only a mild to negligible effect on serum
phosphorus levels. With short-daily dialysis
schedules, the initial 30 minutes of each treatment occurs while serum phosphorus levels are
still high, but overall serum phosphorus control
has been disappointing, especially using short
(1.5- to 2-hour) treatments. Patients undergoing
short-daily dialysis sometimes increase their food
or protein (and therefore phosphorus) intake,
which may compensate or even override the
small additional amount of phosphorus removal.
A recent nonrandomized study in which 3-hour
treatments were given 6 times per week showed
a decrease in serum phosphorus levels.200 However, it is not clear to what extent patients would
tolerate 3-hour treatments given 6 days per week
or if alternative measures to control serum phosphorus might be equally or more effective.
An increase in total weekly hours of dialysis,
probably more than 24 h/wk, distributed over at
least 3 treatments per week appears to be needed
to control phosphorus levels in most dialysis
patients. In the Tassin experience (8 h/wk 3
24 h), approximately one third of patients no
longer required phosphate binders (B. Charra,
personal communication, February 2005). Using
an every-other-night nocturnal dialysis strategy (28 h/wk) should give results similar to
those in the Tassin experience. Nocturnal dialysis given 5 to 6 times per week appears to
remove the need for phosphorus binders, adequately controls phosphorus levels in almost all
patients, and often requires the addition of phosphorus to the dialysate to prevent
hypophosphatemia.284
Volume-Overloaded Patients
Control of patient volume and blood pressure
are reviewed in detail in Guideline 5. In addition
to the recommendations discussed in Guideline 5
regarding sodium balance, one of the most reliable methods to help achieve volume control is
to extend total weekly dialysis time. In cases in
which this cannot be done practically in a thriceweekly framework, a 4-times-per-week schedule
S61
has proved useful. Additional benefits may be

obtained by moving to a short-daily or not-soshort daily 6-times-per-week schedule, and ultimate control would be expected using a nocturnal HD schedule.
Other Categories of Patients for Whom More
Frequent Dialysis May Be Beneficial
At the present time, other patient subgroups
that might benefit from more frequent dialysis
are not as clearly identified. It remains possible
that almost all patients might benefit, although
practical and reimbursement issues, as well as
the present incomplete state of knowledge, clearly
preclude such a recommendation. Small largely
uncontrolled studies suggest thatin addition to
improved nutritional status, serum phosphorus,
and volume controlmore frequent dialysis may
improve erythropoietin sensitivity, quality of
sleep, and sleep apnea, as well as overall QOL.
The Minimum Dialysis Treatment Time for 3
Treatments per Week With Kr Less Than 2
mL/min Should Be 3 Hours (CPR 4.8)
This guideline evolved from 2 considerations.
The first is the concept of attempting to maintain
stdKt/V close to 2.0 per week as a minimum
amount of dialysis across all schedules. For a
2-hour dialysis treatment, an spKt/V of at least
1.4 is required to achieve an stdKt/V of 2.0. The
second consideration is that it is difficult to
achieve good control of salt and water balance
with very short treatment times. The outcomes
evidence for this CPR is not particularly strong;
in the HEMO Study, the minimum treatment
time was 2.5 hours and there was no randomized
evaluation of treatment time; thus, the HEMO
Study is not applicable here. A study that compared conventional dialysis (3- to 4-hour treatments) with ultrashort high-efficiency hemodiafiltration found no difference in level of blood pressure
control.289
Very recent studies, including 1 RCT, suggested that dialysis treatment time has an impact
on outcomes.72A Cross-sectional data showed
that dialysis treatment time was related inversely
to mortality, but much of this effect disappeared
when patient BSA was included in the model.101
It was the Work Groups belief that a minimum
treatment time of 3 hours reflects clinical prac-
S62
tice and was especially important in patients with

a low Kr (2 mL/min).
LIMITATIONS
Given the difficulty conducting RCTs in the
HD population, many of the questions addressed
by the present CPRs will not be answered definitively with Level A evidence for many years. It
takes approximately 2,000 patients to run a randomized trial powered to detect a change in
mortality (eg, the HEMO trial), and even then,
the power to detect smaller effects is limited.
The level of 2M clearance in the HEMO Study
was modest, and it is unclear whether more definitive benefits of convective and/or high-flux treatment might be seen with high-substitution volume
hemodiafiltration, in which levels of 2M clearance substantially greater than those obtained in the
HEMO Study can be achieved.
The Work Group believes that given the dosetargeting bias identified in the HEMO database98
and the multiple confounding factors present in

assignment of dialysis dose, modeled volume,
and different survival effects caused by body
size, it is difficult to draw valid conclusions
about how best to target dialysis therapy based
on body size. The present guidelines address the
issue of increasing the amount of minimal dialysis for smaller patients. They do not address the
issue of reducing the amount of minimal dialysis
for very large patients, for which technical and
time issues become burdensome for both staff
and patient.
With regard to more frequent therapies, the
Work Group understands that their use is growing markedly. The present time should be one of
experimentation in terms of finding the best
combination of schedules and treatment times,
and the Work Group was accordingly restrained
in terms of its recommendations for how best to
deliver such therapies.
CLINICAL PRACTICE RECOMMENDATION 5: DIALYZER

MEMBRANES AND REUSE
Selection of dialyzer membranes and reuse
practices are not included in the prescription
of small-solute clearance, yet they can be important determinants of patient survival and
QOL.
5.1 When dialyzers are reused, they should be
reprocessed following the Association for
the Advancement of Medical Instrumentation (AAMI) Standards and Recommended
Practices for reuse of hemodialyzers.291
5.2 Dialyzers intended for reuse should have a
blood compartment volume not less than
80% of the original measured volume or a
urea (or ionic) clearance not less than 90%
of the original measured clearance.
5.3 The use of poorly biocompatible, unmodified cellulose dialyzer membranes for HD
is discouraged.
RATIONALE
Hemodialyzer Reprocessing and Reuse
(CPR 5.1)
Thorough examination of data pertaining to
the impact of reused dialyzers on patient safety
was beyond the scope of the HD Adequacy Work
Group. Therefore, the Work Group takes no position for or against the practice of dialyzer reuse.
Reprocessing dialyzers for reuse in the same
patient was popularized 2 to 3 decades ago to
allow widespread use of the more biocompatible
and higher flux dialyzers that are more expensive
than their less biocompatible and lower flux
counterparts. Reuse of the former more expensive dialyzers remains a common practice in the
United States today.41,292-297 In 2002 in the
United States, 78% of HD clinics reprocessed
dialyzers,41 butlargely as a result of declining
prices and the recent decision of a major dialysis
provider (Fresenius Medical Care, US) to discontinue reusefewer US dialysis patients are enrolled in reuse programs today.
Reprocessing of disposable medical devices
designed for single use as a cost-saving measure
has been debated, not only for dialyzers, but also
for sundry and other medical devices.297 In the
case of dialyzer reuse, the main concern has been
the risk to life, but other issues have been raised,
such as risk for infection and pyrogenic reactions, toxicity from disinfectants, reduced dialyzer performance,297 impaired removal of large
molecules,294 and the validity of the dialyzer
blood volume measurement as a criterion for
assessing dialyzer function.292,298
Over the years, a plethora of publications have
addressed the possible cause-and-effect relationship between reuse and mortality. Conclusions
reported in earlier publications were conflicting,
possibly because reuse-related morbidity and
mortality is a moving target (Table 14). Practice
patterns, reuse procedures, dialyzer membranes,
comorbidity, age difference, nature of the primary disease, disease severity, ethnic make-up,
and other potentially confounding influences have
evolved over time. For example, high-flux synthetic membranes have almost completely replaced low-flux cellulosic membranes. Whereas
the number of times that a dialyzer is reused
varies from clinic to clinic, the average number
of reuses per dialyzer is higher (15) in recent
years compared with earlier years (10).294 The
sterilant used also has varied from clinic to clinic
and over time. During 1983 to 2002, the percentage of centers using formaldehyde for reprocessing dialyzers decreased from 94% to 20%, whereas
the percentage using a peracetic acid preparation
increased from 5% to 72%. In 2002, a total of 4%
of centers used heat or glutaraldehyde to disinfect
dialyzers between reuses.295 Also, the number of
times that a dialyzer is reused varies from clinic to
clinic. Because of these various confounding factors, research data obtained from decades-old studies may have less present-day clinical relevance.
In one of the largest retrospective analyses,
1- to 2-year follow-up data were examined in a
representative sample of 12,791 patients treated
in 1,394 dialysis facilities from 1994 through
1995.297 After adjustment for other risks, RR for
mortality did not differ for patients treated in
clinics that reused dialyzers compared with patients from single-use clinics. In addition, among
patients at clinics that reused dialyzers, high-flux
synthetic membranes were associated with lower
mortality risk, particularly when exposed to
bleach.297 However, a recent study found a patient
survival advantage when the patient was switched
S63
S64
from reuse to single use.299 It was suggested that

because the cost of biocompatible membranes
has decreased of late, it might be time for dialysis clinics to consider abolition of the reuse
practice.300 However, the cost of single-use biocompatible dialyzers is still considerable, and
most investigators continue to maintain that the
practice of reuse is safe,301,302 provided it is
performed according to recognized reuse protocols, including the dialyzer manufacturers instructions.292,295,296,303
In an analysis of 49,273 incident Medicare
patients from 1998 to 1999, no significant differences in mortality or first hospitalization risk
were found among patients treated with singleuse dialyzers compared with dialyzers cleansed
by using different reprocessing techniques.238 In
a recent review of published reports, adjusted
Medicare and Centers for Disease Control data
from the early to mid-1990s showed no measurable mortality risk from reuse.239 In accordance,
recent Medicare data also showed no survival
advantage associated with single use in incident
US patients during 2001.304 In addition, no differences in mortality were found among for-profit,
not-for-profit, hospital-based, and free-standing
clinics. To date, no prospective RCTs of dialyzer
reuse have been carried out.
The delivered dose of dialysis may decrease as
a result of dialyzer reuse.306-310 The previous
Work Group was particularly concerned by the
apparent dialysis centerspecific effect of reuse
on delivered Kt/V, suggesting that the process of
dialyzer reuse and/or its monitoring may be
problematic. Recently, more encouraging results
generated by the HEMO Study showed that average loss of urea clearance was only 1% to 2% per
10 reuses for both low-flux and high-flux membranes reprocessed with different germicidal regimens.310 Focusing on larger molecule removal,
the same study showed that reuse of high-flux
dialyzers made of different membrane materials
and reprocessed with different germicides brought
about widely disparate clearances of 2M.310
For example, 2M clearances increased markedly by using high-flux polysulfone dialyzers
reprocessed with bleach, whereas reprocessing
the same dialyzer with peracetic acid appeared to
have the opposite effect.310
The Work Group recommends that dialysis
facilities choosing to reuse dialyzers follow the
DIALYZER MEMBRANES AND REUSE
AAMI recommendations for reprocessing while

remaining alert to the possibility that reuse may
adversely affect adequacy of the delivered dialysis dose. AAMI recommendations were prepared
by a panel of experts and offer practical reuse
procedures that have been adopted by the CMS,
formerly Health Care Financing Administration.
These recommendations represent the best guidance available on dialyzer reuse procedures.
Monitoring Reuse (CPRs 5.1 and 5.2)
Because small-solute clearance is the major
function of the dialyzer and clot formation within
the blood compartment reduces clearance, sometimes irreversibly, a method for monitoring clearance with each reuse is required to avoid underdialyzing the patient. Dialyzer blood compartment
volume, sometimes called total cell volume
(TCV) or fiber bundle volume, is an indirect
measure of the total membrane surface area
available for diffusive transport. It is measured
easily by displacement of air or water during the
reprocessing procedure.291 As surface area is lost
because of clotting, solute clearances decrease,
putting the patient at risk for underdialysis. This
risk would go undetected in a clinic that does not
measure clearances or TCV with each reuse.306,308-311 Changes in TCV were shown to
correlate well with changes in small-solute transport characteristics of hollow-fiber dialyzers,
although the relationship is not linear.307,312,313
A 20% loss of TCV correlates with only a 10%
loss of clearance because the (now) higher velocity in the remaining functioning fibers leads to an
increase in average diffusion rate within each
fiber.291,313,314 To allow accurate measurement
of these changes, TCV should be measured before the first use and during each subsequent
reuse processing. The first measurement is required because of possible variability among
dialyzers and dialyzer lots. The Work Group did
not consider using the average volume among
dialyzers of a given model or lot as an acceptable
substitute for this measurement before first use.
In vitro determination of TCV may not detect
loss of surface area caused by clotting during
dialysis.315 However, during routine dialysis in a
representative group of patients who underwent
adequate anticoagulation during each dialysis
treatment, no differences were found between
TCV values measured by using an ultrasound
S65
detection method applied during dialysis and

conventional volume displacement measurement
after dialysis.316
In the place of TCV as an indirect yardstick of
dialyzer function, direct measurements of ionic
clearance (also known as conductivity or sodium
clearance) or urea clearances also can be used to
evaluate dialyzer function because results of these
clearance values correlate closely with one another and TCV results.74,291,317-323 A variety of
dialysate delivery systems have the capacity to
perform noninvasive, automated, on-line determination of a dialyzers ionic clearance.318,319,323
The Work Group agrees with the AAMI that
TCV, ionic clearance, and urea clearance can all
be used to assess the function of either fresh or
reused dialyzers.76,317
Because a 10% decrease in urea clearance could
lead to inadequate dialysis if the dialysis prescription was marginal to begin with, the Work Group
agrees with the position of the AAMI that a change
in urea clearance of 10% is acceptable as long as
the patients dialysis prescription takes into account the 10% loss in such clearance (20% loss
in TCV) that may occur with dialyzer reuse.291
This criterion of 10% clearance change also
should apply to ionic clearances when they are
used as yardsticks because ionic clearance was
shown to correlate closely with urea clearance.291 Finally, monitoring relevant patient data
is recommended to ensure that all parameters
relating to dialyzer clearance are being met.
Specifically, examination of Kt/V and/or URR
over time is needed. The failure of these results
to meet the expectations of the dialysis prescription should be investigated.291
When TCV measurements are used to evaluate dialyzer function before the first use, the
rinsing associated with the reprocessing procedure may help remove undesirable dialyzer residuals (such as ethylene oxide,324 bore fluids,
potting compound [eg, polyurethane] fragments,
dialyzer membrane fragments, plastic components, and other noxious substances remaining
after dialyzer manufacture). In this regard, it is
now a not-uncommon practice for centers (regardless of whether practicing dialyzer reuse) to
preprocess dialyzers before their first use to
minimize the introduction of harmful manufacturing residuals into the bloodstream.300
S66
Dialyzer Membranes (CPR 5.3)

Dialyzer membranes can be classified into lowflux or high-flux varieties in accordance with their
ultrafiltration coefficient (Kuf) and large-molecule
clearance. The HEMO Study suggested that membranes with 2M clearance less than 10 mL/min
be regarded as low flux, whereas those with 2M
clearance greater than 20 mL/min and Kuf of
14 mL/h/mm Hg or greater may be classified as
high flux.270 Another classification recommended
that dialyzers with Kuf between 4 and 8 mL/
h/mm Hg be regarded as low flux, whereas those
with Kuf greater than 20 mL/h/mm Hg be regarded
as as high flux.325 Both cellulose and synthetic
membranes can be either low flux or high flux.
A thorough examination of all available data
concerning the pros and cons of the use of the
myriad varieties of dialyzer membranes was beyond the scope of the Work Group. The reader is
referred to standard texts and relevant publications for more information.
In the past, most cellulose membranes were
primarily hydrophilic and synthetic membranes
were primarily hydrophobic. However, more recent synthetic membranes can possess mixed
hydrophobic-hydrophilic structures.325 Unmodified cellulose dialyzers had enormous popularity
in the past, mainly because of their availability
and low cost, but their use has been associated
with a variety of abnormal biochemical changes
in the blood.326 One of the main causes for these
unfavorable changes centers on activation of the
alternate complement pathway with the resultant
formation of detrimental anaphylatoxins.327 Other
adverse effects involve impairment of granulocyte function, including phagocytosis, adhesion,
and formation of reactive oxygen species,328
and, in the presence of other factors, facilitation
of cytokine production by peripheral-blood mononuclear cells. An example of the latter phenomenon is depicted as follows: unmodified cellulose
membranes and certain modified cellulose membranes allow, by diffusion, more ready passage
of pyrogens (eg, endotoxins and their fragments)
into the blood from contaminated dialysate than
such synthetic high-flux membranes as those of
polyamide, polyacrylonitrile, and polysulfone
despite the larger pore size of the high-flux membranes.329,330 Pyrogens can promote the formation
of deleterious cytokines by circulating peripheral-
blood mononuclear cells that previously were

stimulated by exposure to unmodified cellulose
membranes.331,332
With regard to the possible impact of the use
of unmodified cellulose membranes on patient
morbidity and mortality, suffice it to say that
investigations carried out to date provided conflicting results.333 A number of studies suggested
that low-flux unmodified cellulose membranes
are inferior to high-flux synthetic ones in terms
of patient mortality.297,328,334,335 Conversely, no
differences in mortality were found in certain
comparative studies.280,336 Furthermore, the Cochrane Database of Systematic Reviews did not
find evidence of benefit when synthetic membranes were compared with cellulose or modified
cellulose membranes with regard to mortality
and dialysis-related adverse effects.273 Finally,
in patients dialyzed with unmodified cellulose
membranes, no acute clinically detectable ill
effects that could be related to complement activation were observed.337,338 Investigations that
control for the confounding influences of age, sex,
race, duration of renal failure, duration and type of
prior dialysis treatments, primary disease, RKF,
nutrition status, degree of fluid overload, calcium phosphorus product, hyperparathyroidism,
hyperlipidemia, acidosis, anemia, comorbidities
(such as diabetes, hypertension, heart failure,
and other cardiovascular ailments), dialyzer single
use or reuse (if reuse, method of sterilization),
membrane flux, dialysis adequacy, and so on are
difficult to perform. Such confounders might
help explain the conflicting results encountered
to date. In summary, to date, no unequivocal
evidence has come forward supporting the notion that biocompatible synthetic membranes are
definitely superior to their less biocompatible
cellulose-derived counterparts.
Not all cellulose membranes behave in the
same manner when interacting with the body.
For example, unmodified cellulose membranes
activate complement to a greater extent than
modified cellulose membranes, such as those of
various cellulose acetates, whereas some of the
modified cellulose membranes tend to activate
complement to a greater extent than synthetic
membranes.339,340 Because of differences in the
biological behavior of the various categories of
cellulose membranes, data derived from the use
DIALYZER MEMBRANES AND REUSE
of functionally diverse dialyzers should be evaluated separately.

Many synthetic membranes have the capacity
to adsorb endotoxins and 2M to various extents. Adsorption of endotoxins is related to the
provision of binding sites for bacterial products
by the hydrophobic domains of the synthetic
membranes.329 Adsorption of 2M by membranes made of polysulfone, polyacrylonitrile,
polyamide, polymethylmethacrylate, and polycarbonate279 is believed to be a function of the
electrical charges distributed both at the surface
and in the substance of the membrane.341,342 It
should be noted that high-flux membranes
(whether cellulose or synthetic), because of their
greater porosity, remove such large molecules
as 2M (molecular weight, 11,815 d)
to a greater extent than low-flux cellulose or
low-flux synthetic membranes, often decreasing serum levels.277,280,343-346 Accumulation of
2M in high concentrations promotes its polymerization to cause 2M amyloidosis.
Use of high-flux synthetic polyacrylonitrile
membranes has brought about a lesser incidence
of the amyloid-associated carpal tunnel syndrome and cystic bone lesions than the use of
low-flux cellulose membranes.282 Furthermore,
high-flux dialysis using polysulfone membranes
was reported to postpone clinical manifestations
S67
of dialysis-related amyloidosis.347 In 1 study,

prolonged use of high-flux synthetic membranes
led to improvement in carpal tunnel syndrome
and patient mortality.348 In the HEMO Study,
although high-flux membranes did not cause a
statistically significant improvement in mortality, predialysis serum 2M levels were found to
be a good predictor of mortality.349
Because unmodified cellulose membranes have
no known advantages over synthetic membranes
other than lower cost, and unmodified cellulose
membranes can markedly activate complement
and bring about other potentially adverse effects
in the blood, it would seem prudent to dialyze
patients with the more biocompatible and less
complement-activating membranes.279 This suggestion is strengthened because long-term effects
of intense complement activation and other untoward interactions with blood are largely unknown. However, it equally could be argued that
because of their lower costs, unmodified cellulose dialyzers would allow the implementation
of otherwise cost-prohibitive, but life-saving,
dialysis therapy in some developing countries.350
Because synthetic membranes are more biocompatible, cause less complement activation, and
can adsorb endotoxins and 2M, their use is
favored.
CLINICAL PRACTICE RECOMMENDATIONS FOR GUIDELINE

6: PRESERVATION OF RESIDUAL KIDNEY FUNCTION
Several actions and precautions are recommended to preserve and enhance RKF.
6.1 Angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) are agents of choice in HD
patients with significant RKF and who
need antihypertensive medication. Other
measures to protect native kidneys are
listed in Table 15.
6.2 Insults known to be nephrotoxic (eg, see
Table 16) in patients with normal or
impaired kidney function should be assumed, in the absence of direct evidence,
to be nephrotoxic for the remnant kidney
in HD patients and therefore should be
avoided.
6.3 Prerenal and postrenal causes of decrease
in RKF should be considered in the appropriate clinical setting.
BACKGROUND
Although the contribution of RKF to survival
is well documented for patients managed with
PD, the impact is less clear for those requiring
HD. Most studies assumed that RKF is negligible and report survival as a function of delivered Kt/Vurea, ignoring the potential benefits associated with RKF. However, recent data support
the notion that RKF is an important predictor of
survival and delivered Kt/Vurea can be adjusted
to reflect the presence of renal function.81,230
RATIONALE
RKF is an important contributor to dialysis
adequacy, and adequacy was shown to impact on
morbidity and mortality in patients with CKD
stage 5.53 In contrast to HD, RKF provides
continuous clearance of both small and large
solutes and helps attenuate the large fluctuations
in fluid balance and blood pressure that are more
pronounced in anuric patients. Urine volume
permits more fluid and potassium intake, relaxing overall dietary restrictions and reducing the
fluctuations in body fluid volumes between dialysis treatments that contribute to volume overload
syndromes, hypertension, and cardiac hypertrophy.351 Preservation of residual renal mass also
has the potential to provide beneficial endocrine
S68
and potentially other functions that are not yet

discovered.
To measure RKF, Kr can be calculated from a
24-hour urine collection for urea clearance. As
for PD, 24-hour urine collections should be obtained at least every 4 months or when a decrease
in RKF is suspected (eg, decreasing urine output
or recent exposure to a nephrotoxin). Precautions
and actions that have been recommended to
preserve RKF are listed in Table 15.
The nephrotoxic insults listed in Table 16 are
well known to cause injury to normal kidneys
and kidneys damaged by a variety of diseases. It
is reasonable to presume that these insults also
are harmful to the remnant kidney and should be
avoided if RKF is to be preserved for as long as
possible. Please refer to the Guideline for Preservation of RKF in PD patients in the NKF KDOQI
PD Adequacy Guidelines for further discussion
of this topic.
Episodes of intravascular volume depletion
that frequently occur during HD probably contribute to more rapid loss of RKF; therefore, efforts
to maintain hemodynamic stability should be
routine. Strategies to minimize hypotension during HD include avoidance of excessive ultrafiltration, maintaining the target hematocrit, reduction
in dialysate temperature, increasing dialysate sodium concentration, and predialysis administration of an agonist, such as midodrine. Avoidance of hypotension also helps ensure delivery of
adequate dialysis and minimize symptoms during HD. Paradoxically, loop diuretics, which are
implicated as a cause of worsening renal function when used overzealously in patients with
CKD, probably benefit HD patients because they
reduce the requirement for fluid removal during
dialysis.
The more prolonged preservation of RKF in
HD patients observed in more recent years has
been attributed to numerous factors, including
more widespread use of biocompatible membranes, high-flux dialysis, and use of bicarbonate
instead of acetate buffers. There is general disagreement about which of these factors, if any,
plays a role (Table 17). A recent prospective randomized study suggested that ultrapure water, when
combined with high-flux dialysis, may benefit
native kidney function.232,352 Another study of

high-flux biocompatible membranes with bicarbonate buffer and ultrapure water showed a decrease in RKF similar to that in a contemporary
group of CAPD patients.229 The more prolonged
exposure to membranes during nocturnal and
daily-dialysis regimens hopefully will shed more
light on membrane contributions.
Despite some early concerns about irreversible drug-induced renal disease,353 it is now
generally accepted that the decrease in renal
function observed in most patients treated with
ACE inhibitors and ARBs is reversible and renoprotective, even in patients with CKD stage 5.230
However, the drug-induced decrease in GFR
causes an increase in levels of BUN, creatinine,
and other solutes and may decrease urine output;
thus, consequences in HD patients are not all
benign. Irreversible loss of renal function may
occur in patients with ischemic renal disease
treated with ACE inhibitors.
Severe hypertension is well known to damage
normal kidneys acutely (malignant hypertension)
and can cause ongoing damage over a period of
years (hypertensive nephrosclerosis). In addition,
most kidney diseases, especially those like diabetes that target the kidney vasculature or glomeruli, are exacerbated by hypertension. In some
S69
patients initiating HD therapy, the kidneys may

have been damaged more acutely by severe hypertension. Control of hypertension after initiating dialysis therapy has been associated with
improvement in RKF, sometimes allowing discontinuation of dialysis therapy.354 These patients should be identified from the beginning,
and special attention should be given to controlling blood pressure for the purpose of preserving
and possibly improving RKF.
The Work Group encourages PD as a first
choice of modality for patients initiating KRT for
reasons outlined in the NKF KDOQI PD Adequacy Guidelines, but also as a means of preserving RKF. However, most patients are not candidates for self-dialysis outside of a clinic; thus,
HD remains the most common initial modality
choice for new patients. The same attention that
is given to RKF in PD patients should be directed
to this much larger group of HD patients.
LIMITATIONS
Use of the nephrotoxic agents listed in Table
16 is not always contraindicated because they
may be required in special circumstances to
relieve pain (eg, nonsteroidal anti-inflammatory
drugs), treat a difficult problem (eg, ultrafiltration during dialysis), or complete a vital diagnostic test (eg, coronary angiogram).
S70
III. RESEARCH RECOMMENDATIONS

RANKING OF RECOMMENDATIONS
Research recommendations have been grouped
into 3 categories: critical research, important
research, and research of interest. These rankings
were made by the Work Group based on current
evidence and the need for research to provide
additional evidence for the current CPGs and
CPRs. No attempt was made to rank research
recommendations within each of the 3 research
categories.
CRITICAL RESEARCH
RECOMMENDATIONS
Guideline 1: Initiation of HD
It has been well shown that education and
planning for kidney failure can improve patient
outcomes, but optimal approaches have not been
established. Answers to certain questions could
help improve clinical outcomes while reducing
costs. These questions include the approaches to
education and planning for kidney failure in
different demographic and cultural groups and
their relative costs. How effective are video and
internet-based educational materials? Are computer-interactive programs helpful? How can
nephrologists, nurses, social workers, dietitians,
pharmacists, other professionals, and patient volunteers work together most effectively to educate new kidney patients and families? What is
the best training for kidney patient educators?
How much of the educational role should nephrologists delegate? For example, can earlier teaching about dietary potassium allow more extensive treatment with ACE inhibitors and ARBs in
patients with CKD? Can new approaches to early
dietary education yield improved volume and
phosphorus control when patients reach kidney
failure? What are the psychological and behavioral consequences of early education about the
prospect of eventual organ failure and the shortened life expectancy associated with kidney failure?
Estimation equations for GFR (Table 1, Guideline 1) should be examined in patients who
produce unusually little creatinine, in particular,
the elderly and patients with other chronic illnesses. A second important clinical group for
which current estimating equations have not been
validated is those with significantly decreased
kidney perfusion, as occurs in patients with advanced heart failure.

Studies of the time to initiate replacement
therapy are needed to determine the consequences of timing on survival, morbidity, and
cost. Results of the IDEAL Study will be critical,
but it seems unlikely to be definitive for all
clinical subgroups. In view of racial differences
in dialysis mortality rates, it seems plausible that
response to early treatment might vary by race.
The HEMO Study finding of differential dose
effects in women also suggests the possibility
that the response to early initiation also might
vary by sex. Because of longer exposure to
uremia, do patients with a slower decrease in
GFR benefit from earlier initiation of kidney
replacement therapy? Do patients with primary
tubular disorders benefit from initiation of KRT
at a higher level of GFR than patients with
primary glomerular disorders? These questions
should be addressed in particular groups of interest, including children and the elderly.
Guideline 2: Methods for Measuring and
Expressing HD Dose
The ongoing Frequent HD Network will provide data that should be used to evaluate potential benefits of short-daily or nocturnal dialysis.
If published uncontrolled studies showing better
QOL are confirmed, efforts must be directed to
provide more frequent dialysis in a less encumbering manner.
The conductivity method promises to eliminate the need for drawing blood before and after
dialysis and can be applied to each dialysis
treatment. Objective studies are needed to correlate the delivered dose measured by using conductivity (ionic) dialysate methods with both eKt/V
and spKt/V determined by using classic bloodbased methods. Testing is needed to show whether
this method is a reliable substitute for the present
technique.
Guideline 3: Methods for Postdialysis Blood
Sampling
Because the amount of blood drawn from
dialysis patients should always be minimized, it
is desirable to minimize the volume of the discard sample when drawing blood from a venous
catheter. Studies of how the ratio of discarded
S71
S72
volume to catheter lumen volume affects BUN

concentration would be of practical interest.
Because timing may be different in smaller
patients with shorter circuit pathways, validation
of the stop-blood-flow method and stop-dialysateflow method for determining dialysis dose in
children requires future research.
Guideline 4: Minimally Adequate HD
There are no reliable data regarding mortality
that are not extremely susceptible to patient
selection, and no RCT comparing mortality rates
is foreseen in the near future. Whether more
frequent dialysis reduces hospitalization rates
may be answered by an RCT currently in progress
(NIH Frequent HD Network trial), although this
trial is underpowered to detect other than a very
large reduction. However, it is powered to detect
improvements in both QOL measures and left
ventricular mass index; the latter is strongly
related to hard cardiovascular outcomes.
An alternative measure of dialysis dose in
units measuring conductivity is Kecn T/Vant,
where Kecn is the conductivity-derived dialyzer
clearance, T session length, and Vant anthropometric volume. Studies are needed to determine whether adequacy determined serially using a conductivity standard is more or less
variable, and more or less reliable, than adequacy determined based on classical urea kinetics with predialysis vs. postdialysis BUN measurements. Studies are also needed to determine
whether much of the same information gleaned
from monthly pre- and postdialysis BUN measurements in terms of PCR could be obtained
using monthly predialysis BUN measurements
only, and quarterly pre/post BUN values.
Further study would look at the ratio of modeled to anthropometric volume, both crosssectionally, and serially in large numbers of
patients, and the possibility of dosing dialysis
based on Kecn T/BSA, where BSA is body
surface area multiplied by a correction factor
such that it would vary to the 2/3 power and in
effect, reflect dosing based on body surface area.
Guideline 5: Volume and Blood Pressure
Control
The cost of dialyzer and blood tubing disposal
has a direct impact on reuse, which reduces this
provider burden. Aside from the biological haz-
ard, recycling of dialyzer and tubing materials

could reduce the requirement for disposal site
space. Studies of the potential economic benefits
are needed.
Reuse of dialyzers and blood tubing may influence patient exposure to spallated particles, plasticizers, bore fluid, ethylene oxide, and other
noxious manufacturing residuals from newly
manufactured dialyzers. Studies should compare
these exposures with the single-use situation
when dialyzers and tubing are reused.
Guideline 6: Preservation of RKF
Additional comparative studies of outcome in
patients with and without RKF are needed.355 At
the present time, many dialysis clinics do not
measure RKF routinely and some do not measure it at all. Such studies would help resolve the
critical question about the importance of RKF
measurements. Perhaps even more helpful would
be a controlled clinical trial in which the prescribed dialysis dose is adjusted or not in patients
with significant RKF.
Some studies have implicated contamination
of the water used to prepare dialysate as a cause
of dialysis morbidity and mortality. Other studies
suggested that ultrapure dialysate helps preserve
RKF.232 Additional confirmatory studies are
needed to determine whether introduction of
ultrapure dialysate into routine clinical practice
would help preserve RKF and improve such
clinical outcomes as blood pressure control, nutritional status, and QOL.
A trial of ACE inhibitors or ARBs should be
done to evaluate the effectiveness of such agents
in preserving RKF.
After dialysis therapy has started, diuretics
often are prescribed for patients with good urine
output to help with potassium balance and avoid
excessive fluctuations in ECF volume and blood
pressure. This practice may or may not help
preserve RKF. Studies should address the effectiveness of various diuretic doses and whether
diuretics should be advocated in patients with
significant urine output to help preserve RKF.
For patients in whom the targeted prescribed
dialysis dose is based on RKF, there is an obvious need to measure RKF, but the optimum
frequency of measurements has not been determined. The optimum frequency may depend on
RESEARCH RECOMMENDATIONS
the type of kidney disease and the patients

history of its progression.
Guideline 7: Clinical Outcome Goals
Additional studies are needed to validate the
tools currently used to measure QOL and patient
satisfaction within the diverse CKD stage 5 population. Interventions used to improve QOL and
patient satisfaction should be evaluated to determine success in improving QOL, patient satisfaction, and clinical outcome. As standards of care
are modified and new care strategies are introduced, there is need for periodic reassessment of
the presently recommended dose of dialysis and
its effect on patient mortality, hospitalization
rates, QOL, patient satisfaction, and transplantation rates.
Guideline 8: Pediatric HD Prescription and
Adequacy
The high rates of young adult HD patient
cardiovascular mortality and morbidity,356,357
psychological illness, and unemployment358 compel pediatric HD patient study in the areas of
inflammation, cardiovascular fitness, nutrition assessment and malnutrition treatment, and healthrelated QOL. Because many young adult patients
are treated in pediatric programs and have the
potential to develop morbidities in their pediatric
years, there is a need to study these areas in
pediatric patients. Measurement of HD smallsolute clearance, preferably using either measured or validated estimated eKt/V, and nutrition,
using nPCR, are critical to control for the dose of
delivered dialysis and nutrition status in any
pediatric HD outcome study. Recent recommendations from the European Pediatric Dialysis
Working Group359 provide an excellent basis in
terms of the current state of the art in pediatric
HD practice, from which future research should
emanate to improve the care of pediatric HD
patients.
IMPORTANT RESEARCH
RECOMMENDATIONS
Guideline 1: Initiation of HD
Less critical questions include measurement
of patients preferences (in the technical sense of
utility) for the states of education vs. ignorance
regarding prognosis and choices. It also would
be important to understand demographic and
S73
cultural determinants of preference variation. Finally, work is needed on the ethical implications
of therapeutic attempts to influence patient preferences. These issues are all less critical as research priorities, not because they are less important, but because the findings are less likely to
influence practice and policy in the short term.
Guideline 2: Methods for Measuring and
Expressing the HD Dose
Tests of variance are needed for Kt/V measured in patients receiving daily dialysis treatments. Theoretically, the variance will be larger
because measured BUN values will be considerably lower and excursions from predialysis BUN
to postdialysis BUN also will be lower, which
reduces the power of kinetic modeling. How
much lower and how much variance have not
been determined in an experimental setting. This
study can be done simply by drawing predialysis
and postdialysis blood samples several days in
succession. If blood-based measurements of Kt/V
are found to be less reliable in these patients,
dialysate methods may be required to measure
the delivered dose. However, dialysate methods
are intrinsically less accurate for measuring Kt/V
than blood-based methods,364 so additional comparative studies will be required if the bloodbased methods are found to be inadequate.
Guideline 3: Methods for Postdialysis Blood
Sampling
A study of needlestick injuries in dialysis
clinics might help promote the use of bloodsampling procedures that do not involve use of
exposed needles. This is an area of obvious
importance and interest for which very few data
are available.
Guideline 5: Volume and Blood Pressure
Control
More research should be devoted to reprocessing techniques for various types of dialyzer membranes made by different manufacturers, especially with regard to approaches involving heat
and more biocompatible chemicals, such as citric
acid.
Guideline 6: Preservation of RKF
Observational studies should include data to
determine whether RKF serves to reduce fluctuations in serum potassium and bicarbonate concen-
S74
trations and reduce ECF volume and blood pressure fluctuations.

Some patients with slowly progressive kidney
disease might benefit from incremental dialysis
frequency (initiation of HD at a frequency 3
times per week). Studies are needed to determine
whether such a practice would help preserve
RKF in patients with significant urine output and
those with a marginally functional renal allograft.
RKF imparts a stronger survival advantage
than dose of dialysis. Investigations should explore potential kidney synthetic functions that, if
preserved in the remnant kidney, may provide
survival benefits not explained by level of GFR.
Guideline 7: Clinical Outcome Goals
There is a need for analysis of data linking
clinical outcomes to recommended processes
within the target goals. This would include analysis of the impact of specific KDOQI processes
adjusting for established factors (eg, blood pressure control, hemoglobin A1c [HbA1c], lipid management, pharmacological therapy) that strongly
influence clinical outcomes of HD patients. Periodically, there is a need for refining case-mix
adjustments over time to reflect changes in relative contribution of traditional, nontraditional,
and emerging risk factors as standards of care
change.
Guideline 8: Pediatric HD Prescription and
Adequacy
Recent data from a small pediatric study
showed benefits of daily nocturnal HD in chil-
dren. Additional study of daily HD treatment

schedules and technologies should be undertaken in children.
OF INTEREST
Less critical issues include the development of
prediction instruments to allow estimation of
time to symptomatic kidney failure on the basis
of serial GFR estimates.
Less critical questions include measurement
of patient preferences about the tradeoffs between the burdens and benefits of earlier therapy.
Investigation of dialysis creatinine kinetics
would help assess the effect of muscle mass on
outcome and compare somatic with visceral body
mass as risk factors for survival.
Studies of large patient populations to correlate urine output with RKF would help determine
whether urine volume-related cutoff values for
ignoring RKF are useful.
Although the potential insults listed in CPR
Table 16 are known to injure normal and partially damaged native kidneys, studies are required to indict each insult in patients with CKD
stage 5. It is unlikely that controlled clinical
trials will appear in the near future; therefore,
observational studies are encouraged.
The benefits of RKF may relate more to renal
mass than urine volume. This possibility should be
considered in outcome studies. Also, it would be
helpful to correlate kidney size with RKF to determine whether RKF is predictable based on size.
APPENDIX. METHODS FOR ADDING RESIDUAL CLEARANCE

TO HEMODIALYZER CLEARANCE
Because the duration is short and the clearance
is relatively low, RKF contributes little to the
decrease in BUN levels during dialysis. The
effect of residual urea clearance (Kr) is seen
during the long interdialysis interval when it
serves to decrease the predialysis BUN level, as
shown in Fig 6. When Kr is zero, the interdialysis
rise in the BUN level is linear in the absence of
fluid gain. If Kr is greater than zero, the increase
in BUN level between dialyses is curvilinear and
concave downward, resulting in a lower predialysis BUN level, so less HD is required to maintain
the same average BUN level.
In addition, the continuous nature of Kr provides a more efficient clearance, so simply adding the time-averaged Kr to time-averaged Kd
underestimates the contribution of Kr to overall
clearance. A quantitative relationship between
Kr, Kd, and overall urea clearance can be developed by applying a mathematical model of urea
kinetics. The goal is to determine how much of a
decrease in Kd can be allowed to achieve the
same level of BUN when Kr is added. The
following simplified formula depicts the relationship between dialyzer clearance (Kd) in the absence of Kr, and lower dialyzer clearance (Kd=)
permitted in the presence of Kr.360,361
kKr = Kdt Kd t
Kr, Kd and Kd= are expressed in milliliters per

minute; t is the duration of HD in minutes.
In this formula, k relates Kr to the difference
between Kd and Kd=, or the decrease in dialysis
dose that is possible while still achieving the same
BUN level that would be expected when there is no
Kr. The parameter k has units of mL/(mL/min) and
when multiplied by Kr permits an expression of Kr
in equivalent dialysis units than can be spared. It
can also be considered as a time or duration of Kr
analogous to dialysis duration (t), but always is
higher than the average interval between dialyses
(ti) because Kr is more efficient than Kd. When
expressed per dialysis, the relationship among the
reduced dialysis dose (Kd=t/V), the required dose in
the absence of Kr (Kdt/V), and the residual native
kidney clearance (kKr/V), is expressed by:
Kd t/V = Kdt/V _ kKr/V
where V is the patients volume of urea distribution

in milliliters.
In the absence of kinetic modeling, Kd=t/V can
be solved by substituting the interdialysis interval (10,080 min per wk/frequency) for k in this
expression. Note that this approach, shown in the
first data column in Table 18, ignores the improved efficiency of the continuous RKF, but it is
considered safe for the patient because it underestimates the effect of Kr.
Another method to incorporate Kr into Kt/V is
based on the equivalent clearance (EKR),264
which represents the continuous equivalent of
the patients intermittent urea clearance and can
be calculated as follows:
EKR = G/TAC
(G = urea generation rate;
TAC = time-averaged BUN)
The result can be normalized to a typical V of

35 L and expressed in terms of nPCR and TAC
using the equation for nPCR.362
nEKR = [35 (nPCR 0.17)]/(5.42 TAC)
Fig 6. Effect of residual native kidney clearance

(Kr). The increase in BUN levels from the post-BUN
level to the next pre-BUN level is modulated by Kr, as
shown in the lower curve. The result is a pre-BUN level
that is lower when compared to the pre-BUN level in
the absence of Kr (upper line).
EKR is a total clearance that includes RKF,

but the dialyzer component can be extracted by
subtracting Kr. EKR is the continuous clearance
necessary to maintain the equivalent TAC at the
patients nPCR. The EKR of intermittent HD can
be directly compared to the EKR of patients
S75
S76
Table 18. Values for k at Different Dialysis Frequencies and BUN Targets
Targeted BUN to hold constant
using
T
alone
i
Frequency
Time-Averaged*
Average Predialysis*
2
3
4
5
6
7
5040
3360
2520
2016
1680
1440
6500
4000
2850
2200
1780
1500
9500
5500
3700
2700
2100
1700
* The underlined numbers have been published.360,362 The remainder were derived from urea kinetic modeling.
dialyzed at any frequency or with the clearance

of continuously functioning native kidneys. Routinely solving these equations requires the use of
computational software.
The use of EKR has been criticized because it
fails to fully account for the improvement in
efficiency associated with the continuous clearance of native kidneys or continuous dialysis. 267
Apparently, equating average urea concentrations ignores other more toxic solutes for which
the difference in removal by continuous compared with intermittent clearance is greater than
for urea. Equating standard clearances using
the average peak BUN instead of TAC in the
previous equation has been offered as a solution

to this apparent problem.265
Instead of inflating Kr to match the relatively
inefficient non-continuous dialyzer clearance as
described above, an alternative method, favored
by the Work Group, reduces the dialyzer clearance to a continuous equivalent clearance, based
on normalizing the predialysis BUN. This continuous equivalent of a dialyzer clearance, also
known as standard clearance265 (stdK) is the
continuous clearance that maintains the BUN at
a constant value equal to the average predialysis
BUN achieved during intermittent dialysis. Because the pre-dialysis BUN is targeted, this ap-
Table 19. Minimum spKt/Va Required To Achieve a stdKt/Vb of 2.0 per Week
Kr = 0
Td (hr)
No. per Week
2.0
3.5
8.0
2
3
4
5
6
7
No. per Week

2
3
4
5
6
7
---1.22
0.87
0.77
0.64
0.57
0.51
0.45
0.42
0.38
Kr = 2 mL/min/1.73 m2
3.00
1.06
0.68
0.51
0.40
0.34
2.0
Td (hr)
3.5
8.0
---0.94
0.62
0.46
0.37
0.31
1.93
0.85
0.56
0.42
0.34
0.28
1.68
0.77
0.52
0.39
0.31
0.26
a. Dialyzer clearance only, expressed per dialysis

b. Calculated using a 2-compartment mathematical model. Assumptions: Patient with V = 35 L (should
not matter); Td is constant; Kd varies; ultrafiltration rate is 7 L/wk; nPCR is 1 g/kg/d (should not
matter); dialyzed compartment is 1/3 of total V; Kr(urea) is 0 or 2 mL/min; symmetric schedule.
It is important to note that the minimum values for spKt/V shown in this table do not take into account
reported improvements in outcome from increasing Kt/V when dialysis frequency is increase to more
than 3x/week.
APPENDIX. METHODS FOR ADDING RESIDUAL CLEARANCE TO HEMODIALYZER CLEARANCE
proach gives results similar to that depicted in

the third data column of Table 18. After normalizing the dialyzer clearance to stdK, Kr can
simply be added to it because both can be considered continuous clearances. Dialyzer clearances
(spKt/V) required to achieve a stdKt/V of 2.0
volumes per week are shown in Table 19 for
S77
treatment times that vary from 2 to 8 hours and

for schedules from 2 to 7 treatments per week.
These values were determined using a formal
2-compartment mathematical model of urea kinetics but similar results are obtained using the
simplified equation for stdKt/V shown in section
CPR2.
WORK GROUP BIOGRAPHIES

John T. Daugirdas, MD (Co-Chair), is a
Clinical Professor of Medicine at the University
of Illinois College of Medicine. His areas of
interest include dialysis adequacy and dialysis
hypotension. He is a member of the American
Society of Nephrology and the International Society of Nephrology and a founding member of
the International Society of Hemodialysis. He
was the Principal Investigator of one of the 15
Clinical Centers participating in the HEMO Study
and currently is a Consultant to the Data Coordinating Center for the Frequent Hemodialysis
Network trial of short-daily and nocturnal hemodialysis. Dr Daugirdas is one of the editors of the
Handbook of Dialysis and is founding editor of
the electronic journal, Hypertension, Dialysis,
and Clinical Nephrology. He has received grants
from Watson, American Regent, Aksys, Nephros, RRI, HDC Medical, Advanced Renal Technologies, Amgen, Ortho Biotech, Shire, Roche,
Astra Zeneca, and Neurochem.
Thomas A. Depner, MD (Co-Chair), is a
Professor of Medicine in the Department of
Internal Medicine, Division of Nephrology, at
the University of California, Davis School of
Medicine. He trained at the University of Portland
in Oregon, at Johns Hopkins University Medical
School in Baltimore, and at Case Western Reserve
University, where he completed his residency in
internal medicine at University Hospitals in Cleveland. He is a practicing board-certified nephrologist with a long-standing interest in hemodialysis. He currently is the director of dialysis services
at the University of California, Davis, and has
authored a textbook on the prescription of hemodialysis. He is a member of the American Society
of Nephrology, the International Society of Nephrology, the American Society for Artificial
Internal Organs, and a founding member of the
International Society of Hemodialysis. He was
involved as a Principal Investigator during the
HEMO Study and similarly is involved in the
NIH-Clinical Trial: Frequent Hemodialysis Network clinical trial. He has been a member of the
board of trustees for the American Society for
Artificial Internal Organs since 1997 and is a past
president of that organization. He has served on
the dialysis advisory council for the American
S78
Society of Nephrology and on the editorial board

of NephSAP.
Stuart Goldstein, MD, is an Associate Professor of Pediatrics at the Baylor College of Medicine in Houston, TX. He is Medical Director of
the Dialysis Unit at the Texas Childrens Hospital and Administrative Director of the Pheresis
Service at the Texas Childrens Hospital, both of
Houston. He is a member of the American Academy of Pediatrics, the American Society of Nephrology, the International Pediatric Nephrology
Association, the American Society of Pediatric
Nephrology, the International Society of Nephrology, and the Society for Pediatric Research. In
addition, he is on the Medical Review Board for
the End-Stage Renal Disease Network of Texas,
the Pediatric Nephrologist Representative for the
International Society of Nephrology Commission of Acute Renal Failure, on the Clinical
Affairs Committee for the American Society of
Pediatric Nephrology, on the Dialysis Advisory
Group for the American Society of Nephrology,
and on the Training/Certification Committee of
the American Society of Pediatric Nephrology.
He has received grants from Gambro Renal Products, Dialysis Solutions Inc, Baxter Healthcare,
B. Braun Inc, Amgen Inc, Abbott Laboratories,
and Toray Inc. He has also lectured for Genentech. Dr Goldstein has received research funds,
grants, or contracts from American Academy of
Pediatrics, Baxter Healthcare, Dialysis Solutions, Inc., Gambro Renal Products, Genentech,
Luitpold Pharmaceuticals, NxStage Inc., and The
University of Missouri.
Todd S. Ing, MD, joined the Hines Veterans
Affairs Hospital as a nephrologist and the Loyola
University Chicago Stritch School of Medicine
as a faculty member in 1976, after a number of
years in private practice. Committed to medical
education, he is an editor of the Handbook of
Dialysis. Topics of special interest to him include
the formulation of dialysates, bicarbonate-buffered peritoneal dialysis, first-use syndrome, peritoneal sclerosis, peritoneal fluid eosinophilia,
dialysis ascites, and dialysis-associated pericarditis. Dr Ing has received research funds, grants, or
contracts from Abbott Laboratories and Aksys
Ltd.
Victoria Kumar, MD, is Associate Professor

of Medicine, Department of Internal Medicine,
Division of Nephrology, University of California
Davis Medical Center. Dr Kumars fellowship
was at University of California Davis Medical
Center. Dr Kumar also is staff physician at the
Kaiser Permanente Medical Group.
Klemens B. Meyer, MD, is Associate Professor of Medicine at Tufts University School of
Medicine. He serves as Director of Dialysis
Services, Chair of the Health Information Committee, and Division of Nephrology Webmaster
at Tufts-New England Medical Center. He
founded Dialysis Clinic Incs (DCIs) Outcomes
Monitoring Program and serves as DCIs Medical Director for Information Technology. He has
chaired both the Medical Review Board and the
Board of Directors for End-Stage Renal Disease
Network 1. He participated in the design and
execution of the HEMO and CHOICE Studies. He
is an active participant in the NKF KEEP programs
and other regional chronic kidney disease screening and education programs. Dr Meyers particular
interests include informatics and decision sup-
S79
port in chronic kidney disease stages IV and V

and clinical applications of measures of patient
experience. Dr Meyers has received research
funds, grants, or contracts from Primary Insight
Contributor Network, MEDA Corp/Leerink
Swann & Co., and Gerson Lehram Healthcare
Council.
Keith Norris, MD, is board certified in internal medicine and nephrology and is a certified
hypertension specialist. He is the director of the
Clinical Research Center at the Charles R. Drew
University of Medicine and Science in Los Angeles, CA, where he also serves as the VicePresident of Research. He serves as a continuing
quality improvement and quality assurance advisor to industry and has published more than 100
articles and book chapters. He is the principal
investigator for a National Institutes of Health
comprehensive center for health disparities in
chronic kidney disease. Dr Norris has received
research funds, grants, or contracts from Abbott
Laboratories, Amgen, Genzyme/Bone Care International, Merck, and Pfizer.
REFERENCES
1. Eknoyan G, Beck GJ, Cheung AK, et al: Effect of
dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 347:2010-2019, 2002
2. Eknoyan G, Levey AS, Beck GJ, et al: The Hemodialysis (HEMO) Study: Rationale for selection of interventions.
Semin Dial 9:24-33, 1996
3. Centers for Medicare & Medicaid Services. 2003
Annual Report: End Stage Renal Disease Clinical Performance Measures Project. Am J Kidney Dis 44:S1-S92, 2004
(suppl 1)
4. Consensus Development Conference Panel: Morbidity and mortality of renal dialysis: An NIH consensus
conference statement. Ann Intern Med 121:62-70, 1994
5. Renal Physicians Association: Clinical Practice Guideline on Adequacy of Hemodialysis. Washington, DC, Renal
Physicians Association, 1993
6. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy, 2000. Am J
Kidney Dis 37:S7-S64, 2001 (suppl 1)
7. Goodkin DA, Young EW, Kurokawa K, Prutz KG,
Levin NW: Mortality among hemodialysis patients in Europe, Japan, and the United States: Case-mix effects. Am J
Kidney Dis 44:16-21, 2004
8. Hall YN, Sugihara JG, Go AS, Chertow GM: Differential mortality and transplantation rates among Asians and
Pacific Islanders with ESRD. J Am Soc Nephrol 16:34613463, 2005
9. Wong JS, Port FK, Hulbert-Shearon TE, et al: Survival advantage in Asian American end-stage renal disease
patients. Kidney Int 55:2515-2523, 1999
10. Collins AJ, Kasiske B, Herzog C, et al: Excerpts
from the United States Renal Data System 2004 Annual
Data Report. Am J Kidney Dis 45, 2005 (suppl 1)
11. Shlipak MG, Massie BM: The clinical challenge of
cardiorenal syndrome. Circulation 110:1514-1517, 2004
12. European Best Practice Guidelines Expert Group on
Hemodialysis, European Renal Association: Section II.
Haemodialysis adequacy. Nephrol Dial Transplant 17:S16S31, 2002 (suppl 7)
13. Depner T, Daugirdas J, Greene T, et al: Dialysis dose
and the effect of gender and body size on outcome in the
HEMO Study. Kidney Int 65:1386-1394, 2004
14. Held PJ, Port FK, Wolfe RA, et al: The dose of
hemodialysis and patient mortality. Kidney Int 50:550-556,
1996
15. Leggat JE Jr, Orzol SM, Hulbert-Shearon TE, et al:
Noncompliance in hemodialysis: Predictors and survival
analysis. Am J Kidney Dis 32:139-145, 1998
16. Saran R, Bragg-Gresham JL, Rayner HC, et al:
Nonadherence in hemodialysis: Associations with mortality,
hospitalization, and practice patterns in the DOPPS. Kidney
Int 64:254-262, 2003
17. Plantinga LC, Fink NE, Sadler JH, et al: Frequency
of patient-physician contact and patient outcomes in hemodialysis care. J Am Soc Nephrol 15:210-218, 2004
18. Cockcroft DW, Gault MH: Prediction of creatinine
clearance from serum creatinine. Nephron 16:31-41, 1976
19. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N,
Roth D: A more accurate method to estimate glomerular
S80
filtration rate from serum creatinine: A new prediction

equation. Modification of Diet in Renal Disease Study
Group. Ann Intern Med 130:461-470, 1999
20. Levey AS, Greene T, Kusek JW, Beck GJ, Group
MS: A simplified equation to predict glomerular filtration
rate from serum creatinine. J Am Soc Nephrol 11:155A,
2000 (abstr)
21. Schwartz GJ, Brion LP, Spitzer A: The use of plasma
creatinine concentration for estimating glomerular filtration
rate in infants, children, and adolescents. Pediatr Clin North
Am 34:571-590, 1987
22. Stevens LA, Levey AS: Measurement of kidney
function. Med Clin North Am 89:457-473, 2005
23. Mohler JL, Barton SD, Blouin RA, Cowen DL,
Flanigan RC: The evaluation of creatinine clearance in
spinal cord injury patients. J Urol 136:366-369, 1986
24. Gonwa TA, Jennings L, Mai ML, Stark PC, Levey
AS, Klintmalm GB: Estimation of glomerular filtration rates
before and after orthotopic liver transplantation: Evaluation
of current equations. Liver Transpl 10:301-309, 2004
25. Sherman DS, Fish DN, Teitelbaum I: Assessing renal
function in cirrhotic patients: Problems and pitfalls. Am J
Kidney Dis 41:269-278, 2003
26. Jafar TH, Schmid CH, Levey AS: Serum creatinine
as marker of kidney function in South Asians: A study of
reduced GFR in adults in Pakistan. J Am Soc Nephrol
16:1413-1419, 2005
27. Moss AH: Shared decision-making in dialysis: The
new RPA/ASN guideline on appropriate initiation and withdrawal of treatment. Am J Kidney Dis 37:1081-1091, 2001
28. Galla JH: Clinical practice guideline on shared
decision-making in the appropriate initiation of and withdrawal from dialysis. The Renal Physicians Association and
the American Society of Nephrology. J Am Soc Nephrol
11:1340-1342, 2000
29. Moss AH: Too many patients who are too sick to
benefit start chronic dialysis: Nephrologists need to learn to
just say no. Am J Kidney Dis 41:723-727, 2003
30. Moss AH, Holley JL, Davison SN, et al: Palliative
care. Am J Kidney Dis 43:172-173, 2004
31. Levin A, Lewis M, Mortiboy P, et al: Multidisciplinary predialysis programs: Quantification and limitations
of their impact on patient outcomes in two Canadian
settings. Am J Kidney Dis 29:533-540, 1997
32. Lopes AA, Bragg J, Young E, et al: Depression as a
predictor of mortality and hospitalization among hemodialysis patients in the United States and Europe. Kidney Int
62:199-207, 2002
33. Arora P, Obrador GT, Ruthazer R, et al: Prevalence,
predictors, and consequences of late nephrology referral at a
tertiary care center. J Am Soc Nephrol 10:1281-1286, 1999
34. Astor BC, Eustace JA, Powe NR, et al: Timing of
nephrologist referral and arteriovenous access use: The
CHOICE Study. Am J Kidney Dis 38:494-501, 2001
35. Avorn J, Bohn RL, Levy E, et al: Nephrologist care
and mortality in patients with chronic renal insufficiency.
Arch Intern Med 162:2002-2006, 2002
36. Avorn J, Winkelmayer WC, Bohn RL, et al: Delayed
nephrologist referral and inadequate vascular access in
REFERENCES
patients with advanced chronic kidney failure. J Clin

Epidemiol 55:711-716, 2002
37. Levey AS, Coresh J, Balk E, et al: National Kidney
Foundation practice guidelines for chronic kidney disease:
Evaluation, classification, and stratification. Ann Intern Med
139:137-147, 2003
38. Keshaviah PR, Emerson PF, Nolph KD: Timely
initiation of dialysis: A urea kinetic approach. Am J Kidney
Dis 33:344-348, 1999
39. Nolph KD: Rationale for early incremental dialysis
with continuous ambulatory peritoneal dialysis. Nephrol
Dial Transplant 13:S117-S119, 1998 (suppl 6)
40. Tattersall J, Greenwood R, Farrington K: Urea
kinetics and when to commence dialysis. Am J Nephrol
15:283-289, 1995
41. US Renal Data System: USRDS 2004 Annual Data
Report. The National Institutes of Health, National Institute
of Diabetes and Digestive and Kidney Diseases, Bethesda,
MD, 2004
42. Ellis PA, Reddy V, Bari N, Cairns HS: Late referral
of end-stage renal failure. QJM 91:727-732, 1998
43. Ifudu O, Dawood M, Homel P, Friedman EA: Timing
of initiation of uremia therapy and survival in patients with
progressive renal disease. Am J Nephrol 18:193-198, 1998
44. Roubicek C, Brunet P, Huiart L, et al: Timing of
nephrology referral: Influence on mortality and morbidity.
Am J Kidney Dis 36:35-41, 2000
45. Sesso R, Belasco AG: Late diagnosis of chronic renal
failure and mortality on maintenance dialysis. Nephrol Dial
Transplant 11:2417-2420, 1996
46. Fink JC, Burdick RA, Kurth SJ, et al: Significance of
serum creatinine values in new end-stage renal disease
patients. Am J Kidney Dis 34:694-701, 1999
47. Korevaar JC, Jansen MA, Dekker FW, et al: When to
initiate dialysis: Effect of proposed US guidelines on
survival. Lancet 358:1046-1050, 2001
48. Traynor JP, Simpson K, Geddes CC, Deighan CJ,
Fox JG: Early initiation of dialysis fails to prolong survival
in patients with end-stage renal failure. J Am Soc Nephrol
13:2125-2132, 2002
48A. The Renal Association UK Renal Registry. The Sixth
Annual Report, Dec. 2003. Available at: www.renalreg.
com/Report%202003/Cover3_Frames.htm. Accessed May 1,
2006
MD, 2003
50. Curtis BM, Barret BJ, Jindal K, et al: Canadian
survey of clinical status at dialysis initiation 1998-1999: A
multicenter prospective survey. Clin Nephrol 58:282-288,
2002
51. Cooper BA, Branley P, Bulfone L, et al: The
Initiating Dialysis Early and Late (IDEAL) Study: Study
rationale and design. Perit Dial Int 24:176-181, 2004
52. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure. Am J
53. Lowrie EG, Laird NM, Parker TF, Sargent JA: Effect
of the hemodialysis prescription of patient morbidity: report
S81
from the National Cooperative Dialysis Study. N Engl J Med

305:1176-1181, 1981
54. Owen WF Jr, Lew NL, Liu Y, Lowrie EG, Lazarus
JM: The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Engl J Med 329:1001-1006, 1993
55. Hakim RM, Breyer J, Ismail N, Schulman G: Effects
of dose of dialysis on morbidity and mortality. Am J Kidney
Dis 23:661-669, 1994
56. Parker TF III, Husni L, Huang W, Lew N, Lowrie
EG: Survival of hemodialysis patients in the United States is
improved with a greater quantity of dialysis. Am J Kidney
Dis 23:670-680, 1994
57. Owen WF Jr, Chertow GM, Lazarus JM, Lowrie EG:
Dose of hemodialysis and survival: Differences by race and
sex. JAMA 280:1764-1768, 1998
58. Collins AJ, Ma JZ, Umen A, Keshaviah P: Urea
index and other predictors of hemodialysis patient survival.
Am J Kidney Dis 23:272-282, 1994
59. Renkin EM, Gilmore JP: Glomerular filtration, in
Orloff J, Berliner RW (eds): Handbook of Physiology
Renal Physiology. Washington, DC, American Physiology
Society, 1973, pp 185-248
60. Singer MA, Morton AR: Mouse to elephant: Biological scaling and Kt/V. Am J Kidney Dis 35:306-309, 2000
61. Colton CK, Lowrie EG: Physical principles and
technical considerations, in Brenner BM, Rector FC (eds):
The Kidney. Philadelphia, PA, Saunders, 1981, pp 24252489
62. Depner TA: Single-compartment model, in Prescribing Hemodialysis: A Guide to Urea Modeling. Boston, MA,
Kluwer, 1991, pp 65-89
63. Daugirdas JT, Greene T, Depner TA, Gotch FA, Star
RA: Relationship between apparent (single-pool) and true
(double-pool) urea distribution volume. Kidney Int 56:19281933, 1999
64. Depner TA: Multi-compartment model, in Prescribing Hemodialysis: A Guide to Urea Modeling. Boston, MA,
Kluwer, 1991, pp 91-126
65. Daugirdas JT: Second generation logarithmic estimates of single-pool variable volume Kt/V: An analysis of
error. J Am Soc Nephrol 4:1205-1213, 1993
66. Depner TA, Daugirdas JT: Equations for normalized
protein catabolic rate based on two-point modeling of
hemodialysis urea kinetics. J Am Soc Nephrol 7:780-785,
1996
67. Depner TA: Estimation of Kt/V from the URR for
varying levels of dialytic weight loss: A bedside graphic aid.
Semin Dial 6:242, 1993
68. Bargman JM, Thorpe KE, Churchill DN: Relative
contribution of residual renal function and peritoneal clearance to adequacy of dialysis: A reanalysis of the CANUSA
Study. J Am Soc Nephrol 12:2158-2162, 2001
69. Daugirdas JT: Simplified equations for monitoring
Kt/V, PCRn, eKt/V, and ePCRn. Adv Ren Replace Ther
2:295-304, 1995
70. Tattersall JE, DeTakats D, Chamney P, Greenwood
RN, Farrington K: The post-hemodialysis rebound: Predicting and quantifying its effect on Kt/V. Kidney Int 50:20942102, 1996
S82
71. Leypoldt JK, Jaber BL, Zimmerman DL: Predicting

treatment dose for novel therapies using urea standard Kt/V.
Semin Dial 17:142-145, 2004
72. Held PJ, Levin NW, Bovbjerg RR, Pauly MV,
Diamond LH: Mortality and duration of hemodialysis treatment. JAMA 265:871-875, 1991
72A. Saran R, Bragg-Gresham JL, Levin NW, et al:
Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the DOPPS.
Kidney Int 69:1222-1228, 2006
73. Petitclerc T, Goux N, Reynier AL, Bene B: A model
for non-invasive estimation of in vivo dialyzer performances
and patients conductivity during hemodialysis. Int J Artif
Organs 16:585-591, 1993
74. Polaschegg HD: On-line dialyser clearance using
conductivity. Pediatr Nephrol 9:S9-S11, 1995 (suppl)
75. Di Filippo S, Pozzoni P, Manzoni C, Andrulli S,
Pontoriero G, Locatelli F: Relationship between urea clearance and ionic dialysance determined using a single-step
conductivity profile. Kidney Int 68:2389-2395, 2005
76. Gotch FA, Panlilio FM, Buyaki RA, Wang EX,
Folden TI, Levin NW: Mechanisms determining the ratio of
conductivity clearance to urea clearance. Kidney Int Suppl
89:S3-S24, 2004
77. Daugirdas JT, Greene T, Depner TA, Chumlea C,
Rocco MJ, Chertow GM: Anthropometrically estimated
total body water volumes are larger than modeled urea
volume in chronic hemodialysis patients: Effects of age,
race, and gender. Kidney Int 64:1108-1119, 2003
78. Lowrie EG, Li Z, Ofsthun N, Lazarus JM: The online
measurement of hemodialysis dose (Kt): Clinical outcome
as a function of body surface area. Kidney Int 68:1344-1354,
2005
79. Brimble KS, Onge JS, Treleaven DJ, Carlisle EJ:
Comparison of volume of blood processed on haemodialysis
adequacy measurement sessions vs regular non-adequacy
sessions. Nephrol Dial Transplant 17:1470-1474, 2002
80. Lowrie EG, Chertow GM, Lew NL, Lazarus JM,
Owen WF: The urea [clearance x dialysis time] product (Kt)
as an outcome-based measure of hemodialysis dose. Kidney
Int 56:729-737, 1999
81. Termorshuizen F, Dekker FW, van Manen JG, Korevaar JC, Boeschoten EW, Krediet RT: Relative contribution
of residual renal function and different measures of adequacy to survival in hemodialysis patients: An analysis of
the Netherlands Cooperative Study on the Adequacy of
Dialysis (NECOSAD)-2. J Am Soc Nephrol 15:1061-1070,
2004
82. Depner TA: Assessing adequacy of hemodialysis:
Urea modeling. Kidney Int 45:1522-1535, 1994
83. Daugirdas JT, Burke MS, Balter P, Priester-Coary A,
Majka T: Screening for extreme postdialysis urea rebound
using the Smye method: Patients with access recirculation
identified when a slow flow method is not used to draw the
postdialysis blood. Am J Kidney Dis 28:727-731, 1996
84. Daugirdas JT, Greene T, Depner TA, et al: Factors
that affect postdialysis rebound in serum urea concentration,
including the rate of dialysis: Results from the HEMO
85. Daugirdas JT, Depner TA, Gotch FA, et al: Comparison of methods to predict equilibrated Kt/V in the HEMO
Pilot Study. Kidney Int 52:1395-1405, 1997
86. Jean G, Charra B, Chazot C, Laurent G: Quest for
postdialysis urea rebound-equilibrated Kt/V with only intradialytic urea samples. Kidney Int 56:1149-1153, 1999
87. Lew JK, Hutchinson R, Lin ES: Intra-arterial blood
sampling for clotting studies. Effects of heparin contamination. Anaesthesia 46:719-721, 1991
88. McLaren G, Hanna C, Mills L, Bourdeau J, Cowin
R: Comparison of sampling methods for obtaining accurate
coagulation values in hemodialysis patients with heparinized central venous catheters. Nephrol Nurs J 28:632-636,
2001
89. Hakim RM, Depner TA, Parker TF III: Adequacy of
hemodialysis. Am J Kidney Dis 20:107-123, 1992
90. Schneditz D, Kaufman AM, Polaschegg HD, Levin
NW, Daugirdas JT: Cardiopulmonary recirculation during
hemodialysis. Kidney Int 42:1450-1456, 1992
91. Schneditz D, Polaschegg HD, Levin NW, et al:
Cardiopulmonary recirculation in dialysis. An underrecognized phenomenon. ASAIO J 38:M194-M196, 1992
92. Cappello A, Grandi F, Lamberti C, Santoro A:
Comparative evaluation of different methods to estimate
urea distribution volume and generation rate. Int J Artif
Organs 17:322-330, 1994
93. Sherman RA: Recirculation revisited. Semin Dial
4:221-223, 1991
94. Schneditz D, Van Stone JC, Daugirdas JT: A regional
blood circulation alternative to in-series two compartment
urea kinetic modeling. ASAIO J 39:M573-M577, 1993
95. Pedrini LA, Zereik S, Rasmy S: Causes, kinetics and
clinical implications of post-hemodialysis urea rebound.
Kidney Int 34:817-824, 1988
96. Geddes CC, Traynor J, Walbaum D, Fox JG, Mactier
RA: A new method of post-dialysis blood urea sampling:
The stop dialysate flow method. Nephrol Dial Transplant
15:517-523, 2000
97. Wu MJ, Feng YF, Shu KH, Cheng CH, Lian JD:
Another simpler bypassing dialysate technique for measuring post-haemodialysis BUN. Nephrol Dial Transplant 12:
2124-2127, 1997
98. Greene T, Daugirdas J, Depner T, et al: Association
of achieved dialysis dose with mortality in the Hemodialysis
Study: An example of dose-targeting bias. J Am Soc
Nephrol 16:3371-3380, 2005
99. Chertow GM, Owen WF, Lazarus JM, Lew NL,
Lowrie EG: Exploring the reverse J-shaped curve between
urea reduction ratio and mortality. Kidney Int 56:1872-1878,
1999
100. Lowrie EG, Li Z, Ofsthun N, Lazarus JM: Body
size, dialysis dose and death risk relationships among
hemodialysis patients. Kidney Int 62:1891-1897, 2002
101. Lowrie EG, Li Z, Ofsthun N, Lazarus JM: Measurement of dialyzer clearance, dialysis time, and body size:
death risk relationships among patients. Kidney Int 66:20772084, 2004
102. Port FK, Ashby VB, Dhingra RK, Roys EC, Wolfe
RA: Dialysis dose and body mass index are strongly
associated with survival in hemodialysis patients. J Am Soc
Nephrol 13:1061-1066, 2002
REFERENCES
103. Wolfe RA, Ashby VB, Daugirdas JT, Agodoa LY,

Jones CA, Port FK: Body size, dose of hemodialysis, and
mortality. Am J Kidney Dis 35:80-88, 2000
104. Port FK, Wolfe RA, Hulbert-Shearon TE, McCullough
KP, Ashby VB, Held PJ: High dialysis dose is associated with
lower mortality among women but not among men. Am J
Kidney Dis 43:1014-1023, 2004
105. Rocco MV, Dwyer JT, Larive B, et al: The effect of
dialysis dose and membrane flux on nutritional parameters
in hemodialysis patients: Results of the HEMO Study.
Kidney Int 65:2321-2334, 2004
106. Unruh M, Benz R, Greene T, et al: Effects of
hemodialysis dose and membrane flux on health-related
quality of life in the HEMO Study. Kidney Int 66:355-366,
2004
106A. Greene T, Daugirdas J, Beck G, Depner T, Ornt D,
Schulman G, Star R, Eknoyan G, and the HEMO Study:
Statistical basis for performance standards for achieving a
minimum spKt/V goal based on variability observed in the
NIH HEMO Study. Proceedings of the XVth International
Congress of Nephrology, Buenos Aires, Argentina, 1999, p
419
107. Bleyer AJ, Hylander B, Sudo H, et al: An international study of patient compliance with hemodialysis. JAMA
281:1211-1213, 1999
108. Schrier RW, Gurevich AK, Abraham WT: Renal
sodium excretion, edematous disorders, and diuretic use, in
Schrier RW (ed): Renal and Electrolyte Disorders. Philadelphia, PA, Lippincott Williams & Wilkins, 2003, pp 64-114
109. Agarwal R, Nissenson AR, Batlle D, Coyne DW,
Trout JR, Warnock DG: Prevalence, treatment, and control
of hypertension in chronic hemodialysis patients in the
United States. Am J Med 115:291-297, 2003
110. Horl MP, Horl WH: Hemodialysis-associated hypertension: Pathophysiology and therapy. Am J Kidney Dis
39:227-244, 2002
111. Rocco MV, Yan G, Heyka RJ, Benz R, Cheung AK:
Risk factors for hypertension in chronic hemodialysis patients: Baseline data from the HEMO Study. Am J Nephrol
21:280-288, 2001
112. Wilson J, Shah T, Nissenson AR: Role of sodium
and volume in the pathogenesis of hypertension in hemodialysis. Semin Dial 17:260-264, 2004
113. Foley RN, Herzog CA, Collins AJ: Blood pressure
and long-term mortality in United States hemodialysis
patients: USRDS Waves 3 and 4 Study. Kidney Int 62:17841790, 2002
114. De Lorenzo A, Deurenberg P, Andreoli A, Sasso GF,
Palestini M, Docimo R: Multifrequency impedance in the
assessment of body water losses during dialysis. Ren
Physiol Biochem 17:326-332, 1994
115. Sherman RA: Modifying the dialysis prescription to
reduce intradialytic hypotension. Am J Kidney Dis 38:S18S25, 2001 (suppl 4)
116. Mitch WE, Wilcox CS: Disorders of body fluids,
sodium and potassium in chronic renal failure. Am J Med
72:536-550, 1982
117. Dorhout Mees EJ, Ozbash C, Akcicek F: Cardiovascular disturbances in hemodialysis patients: The importance
of volume overload. J Nephrol 8:71-78, 1995
S83
118. Koomans HA, Geers AB, Mees EJ: Plasma volume

recovery after ultrafiltration in patients with chronic renal
failure. Kidney Int 26:848-854, 1984
119. Chazot C, Charra B, Vo Van C, et al: The Janusfaced aspect of dry weight. Nephrol Dial Transplant
14:121-124, 1999
120. Zucchelli P, Santoro A, Zuccala A: Genesis and
control of hypertension in hemodialysis patients. Semin
Nephrol 8:163-168, 1988
121. Mailloux LU, Fields S, Campese VM: Hypertension in chronic dialysis patients, in Nissenson AR, Fine RN
(eds): Dialysis Therapy. Philadelphia, PA, Hanley & Belfus,
2002, pp 341-358
122. Charra B, Bergstrom J, Scribner BH: Blood pressure control in dialysis patients: Importance of the lag
phenomenon. Am J Kidney Dis 32:720-724, 1998
123. DAmico M, Locatelli F: Hypertension in dialysis:
Pathophysiology and treatment. J Nephrol 15:438-445, 2002
124. Fishbane SA, Scribner BH: Blood pressure control
in dialysis patients. Semin Dial 15:144-145, 2002
125. Comty C, Rottka H, Shaldon S: Blood pressure
control in patients with end-stage renal failure treated by
intermittent haemodialysis. Proc Eur Dial Transplant Assoc
1:209-213, 1964
126. Campese VM, Tanasescu A: Hypertension in dialysis patients, in Henrich WL (ed): Principles and Practice of
Dialysis (ed 3). Philadelphia, PA, Lippincott Williams &
Wilkins, 2004, pp 227-256
127. Jabara AE, Mehta RL: Determination of fluid shifts
during chronic hemodialysis using bioimpedance spectroscopy and an in-line hematocrit monitor. ASAIO J 41:M682M687, 1995
128. Leypoldt JK, Cheung AK, Steuer RR, Harris DH,
Conis JM: Determination of circulating blood volume by
continuously monitoring hematocrit during hemodialysis.
J Am Soc Nephrol 6:214-219, 1995
129. Rodriguez HJ, Domenici R, Diroll A, Goykhman I:
Assessment of dry weight by monitoring changes in blood
volume during hemodialysis using Crit-Line. Kidney Int
68:854-861, 2005
130. Goldstein SL, Patel HP, Mahan JD, Flynn JT:
Prospective evaluation of a non-invasive monitoring of
hematocrit (NIVM) algorithm to improve cardiovascular
(CV) parameters in pediatric (ped) hemodialysis (HD)
patients (Pt). J Am Soc Nephrol 16:725A, 2005 (abstr)
131. Reddan DN, Szczech LA, Hasselblad V, et al:
Intradialytic blood volume monitoring in ambulatory hemodialysis patients: A randomized trial. J Am Soc Nephrol
16:2162-2169, 2005
132. Schneditz D, Zaluska WT, Morris AT, Levin NW:
Effect of ultrafiltration on peripheral urea sequestration in
haemodialysis patients. Nephrol Dial Transplant 16:994998, 2001
133. Charra B, Terrat JC, Vanel T, et al: Long thrice
weekly hemodialysis: The Tassin experience. Int J Artif
Organs 27:265-283, 2004
134. Salem M: Hypertension in the hemodialysis population? High time for answers. Am J Kidney Dis 33:592-594,
1999
S84
135. Raine AE, Margreiter R, Brunner FP, et al: Report

on management of renal failure in Europe, XXII,
1991. Nephrol Dial Transplant 7:S7-S35, 1992 (suppl 2)
136. Grekas D, Bamichas G, Bacharaki D, Goutzaridis
N, Kasimatis E, Tourkantonis A: Hypertension in chronic
hemodialysis patients: Current view on pathophysiology and
treatment. Clin Nephrol 53:164-168, 2000
137. Levey AS, Eknoyan G: Cardiovascular disease in
chronic renal disease. Nephrol Dial Transplant 14:828-833,
1999
138. Mittal SK, Kowalski E, Trenkle J, et al: Prevalence
of hypertension in a hemodialysis population. Clin Nephrol
51:77-82, 1999
139. Cheigh JS, Milite C, Sullivan JF, Rubin AL, Stenzel
KH: Hypertension is not adequately controlled in hemodialysis patients. Am J Kidney Dis 19:453-459, 1992
140. Scribner BH: A personalized history of chronic
141. Shaldon S: What clinical insights from the early
days of dialysis are being overlooked today? Semin Dial
18:18-19, 2005
142. Cohen EP: Dialysis hypertension: Dry weight and
dialysis time. Nephrol Dial Transplant 13:554-555, 1998
143. Charra B, Chazot C: The neglect of sodium restriction in dialysis patients: A short review. Hemodial Int
7:342-347, 2003
144. Flanigan M: Dialysate composition and hemodialysis hypertension. Semin Dial 17:279-283, 2004
145. Stiller S, Bonnie-Schorn E, Grassmann A, Uhlenbusch-Korwer I, Mann H: A critical review of sodium
profiling for hemodialysis. Semin Dial 14:337-347, 2001
146. Agarwal R: Hypertension in hemodialysis, in Nissenson AR, Fine RN (eds): Clinical Dialysis (ed 4). New
York, NY, McGraw-Hill, 2005, pp 755-769
147. Zoccali C, Dunea G: Hypertension, in Daugirdas
JT, Blake PG, Ing TS (eds): Handbook of Dialysis. Philadelphia, PA, Lippincott Williams & Wilkins, 2001, pp 466-476
148. Foley RN, Parfrey PS, Harnett JD, Kent GM,
Murray DC, Barre PE: Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease.
Kidney Int 49:1379-1385, 1996
149. Collins AJ: Cardiovascular mortality in end-stage
renal disease. Am J Med Sci 325:163-167, 2003
150. Luik AJ, Kooman JP, Leunissen KM: Hypertension
in haemodialysis patients: Is it only hypervolaemia? Nephrol Dial Transplant 12:1557-1560, 1997
151. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar
ME, London GM: Impact of aortic stiffness on survival in
end-stage renal disease. Circulation 99:2434-2439, 1999
152. Klassen PS, Lowrie EG, Reddan DN, et al: Association between pulse pressure and mortality in patients undergoing maintenance hemodialysis. JAMA 287:1548-1555,
2002
153. Fujiwara N, Osanai T, Kamada T, Katoh T, Takahashi K, Okumura K: Study on the relationship between
plasma nitrite and nitrate level and salt sensitivity in human
hypertension: Modulation of nitric oxide synthesis by salt
intake. Circulation 101:856-861, 2000
154. MacAllister RJ, Rambausek MH, Vallance P, Williams D, Hoffmann KH, Ritz E: Concentration of dimethyl-
L-arginine
in the plasma of patients with end-stage renal

failure. Nephrol Dial Transplant 11:2449-2452, 1996
155. Vallance P, Leone A, Calver A, Collier J, Moncada
S: Accumulation of an endogenous inhibitor of nitric oxide
synthesis in chronic renal failure. Lancet 339:572-575, 1992
156. Converse RL Jr, Jacobsen TN, Toto RD, et al:
Sympathetic overactivity in patients with chronic renal
failure. N Engl J Med 327:1912-1918, 1992
157. Agarwal R, Lewis R, Davis JL, Becker B: Lisinopril therapy for hemodialysis hypertension: Hemodynamic and
endocrine responses. Am J Kidney Dis 38:1245-1250, 2001
158. Abraham PA, Macres MG: Blood pressure in
hemodialysis patients during amelioration of anemia with
erythropoietin. J Am Soc Nephrol 2:927-936, 1991
159. Agarwal R: Hypertension and survival in chronic
hemodialysis patientsPast lessons and future opportunities. Kidney Int 67:1-13, 2005
160. London G, Marchais S, Guerin AP: Blood pressure
control in chronic hemodialysis patients, in Jacob C, Kjellstrand CM, Koch KM, Winchester JF (eds): Replacement of
Renal Function by Dialysis. Dordrecht, The Netherlands,
Kluwer, 1996, pp 966-989
161. Agarwal R: Exploring the paradoxical relationship
of hypertension with mortality in chronic hemodialysis.
Hemodial Int 8:207-213, 2004
162. Schomig M, Eisenhardt A, Ritz E: Controversy on
optimal blood pressure on haemodialysis: Normotensive
blood pressure values are essential for survival. Nephrol
Dial Transplant 16:469-474, 2001
163. Zager PG, Nikolic J, Brown RH, et al: U Curve
association of blood pressure and mortality in hemodialysis
patients. Medical Directors of Dialysis Clinic, Inc. Kidney
Int 54:561-569, 1998
164. Port FK, Hulbert-Shearon TE, Wolfe RA, et al:
Predialysis blood pressure and mortality risk in a national
sample of maintenance hemodialysis patients. Am J Kidney
Dis 33:507-517, 1999
165. Scribner BH: Can antihypertensive medications
control BP in haemodialysis patients: Yes or no? Nephrol
166. Levin NW, Blagg CR, Twardowski ZJ, Shaldon S,
Bower JD: What clinical insights from the early days of
dialysis are being overlooked today? Semin Dial 18:13-15,
2005
167. Cirit M, Akcicek F, Terzioglu E, et al: Paradoxical
rise in blood pressure during ultrafiltration in dialysis
patients. Nephrol Dial Transplant 10:1417-1420, 1995
168. Eaton SB, Konner M: Paleolithic nutrition. A
consideration of its nature and current implications. N Engl
J Med 312:283-289, 1985
169. Appel LJ, Brands MW, Daniels SR, Karanja N,
Elmer PJ, Sacks FM: Dietary approaches to prevent and treat
hypertension: A scientific statement from the American
Heart Association. Hypertension 47:296-308, 2006
170. Krauss RM, Deckelbaum RJ, Ernst N, et al: Dietary
guidelines for healthy American adults. A statement for
health professionals from the Nutrition Committee, American Heart Association. Circulation 94:1795-1800, 1996
171. Dietary Reference Intakes: Water, Potassium, Sodium, Chloride and Sulfate. Washington, DC, Institute of
Medicine, National Academy Press, 2004
REFERENCES
172. 2003 European Society of Hypertension-European

Society of Cardiology: Guidelines for the management of
arterial hypertension. J Hypertens 21:1011-1053, 2003
173. Sacks FM, Svetkey LP, Vollmer WM, et al: Effects
on blood pressure of reduced dietary sodium and the Dietary
Approaches to Stop Hypertension (DASH) diet. DASHSodium Collaborative Research Group. N Engl J Med
344:3-10, 2001
174. Khosla UM, Johnson RJ: Hypertension in the
hemodialysis patient and the lag phenomenon: Insights
into pathophysiology and clinical management. Am J Kidney Dis 43:739-751, 2004
175. Krautzig S, Janssen U, Koch KM, Granolleras C,
Shaldon S: Dietary salt restriction and reduction of dialysate
sodium to control hypertension in maintenance haemodialysis patients. Nephrol Dial Transplant 13:552-553, 1998
176. Rostand SG, Rutsky EA: Cardiac disease in dialysis
patients, in Nissenson AR, Fine RN, Gentile DE (eds):
Clinical Dialysis. Norwalk, CT, Appleton & Lange, 1995, pp
652-698
176A. Kaplan NM: Patient information. Hypertension
and diet and weight. UpToDate, version 13.3, UptoDate Inc.,
Waltham, MA, September 2005
177. Mattes RD: The taste for salt in humans. Am J Clin
Nutr 65:S692-S697, 1997 (suppl 2)
178. Korhonen MH, Jarvinen RM, Sarkkinen ES, Uusitupa MI: Effects of a salt-restricted diet on the intake of
other nutrients. Am J Clin Nutr 72:414-420, 2000
179. Kempner W: Treatment of hypertensive vascular
disease with rice diet. Am J Med 8:545-577, 1948
180. Carvalho JJ, Baruzzi RG, Howard PF, et al: Blood
pressure in four remote populations in the INTERSALT
Study. Hypertension 14:238-246, 1989
181. Ahmad S: Dietary sodium restriction for hypertension in dialysis patients. Semin Dial 17:284-287, 2004
182. Blumberg A, Nelp WB, Hegstrom RM, Scribner
BH: Extracellular volume in patients with chronic renal
disease treated for hypertension by sodium restriction.
Lancet 2:69-73, 1967
183. Mailloux LU: The overlooked role of salt restriction in dialysis patients. Semin Dial 13:150-151, 2000
184. Maduell F, Navarro V: Dietary salt intake and blood
pressure control in haemodialysis patients. Nephrol Dial
Transplant 15:2063, 2000
185. Ozkahya M, Toz H, Qzerkan F, et al: Impact of
volume control on left ventricular hypertrophy in dialysis
patients. J Nephrol 15:655-660, 2002
186. Shaldon S: Dietary salt restriction and drug-free
treatment of hypertension in ESRD patients: A largely
abandoned therapy. Nephrol Dial Transplant 17:1163-1165,
2002
187. Shaldon S: Salt restriction and not length of dialysis
is the key to drug free blood pressure control in ESRD
patients. J Nephrol 16:159, 2003
188. Shaldon S: Is salt restriction more important than
the length of dialysis in the miracle of Tassin? Int J Artif
Organs 27:813-814; author reply 27:815, 2004
189. Hegstrom RM, Murray JS, Pendras JP, Burnell JM,
Scribner BH: Two years experience with periodic hemodialysis in the treatment of chronic uremia. Trans Am Soc Artif
Intern Organs 8:266-280, 1962
S85
190. Shaldon S, Rae AI, Rosen SM, Silva H, Oakley J:

Refrigerated femoral venous-venous haemodialysis with
coil preservation for rehabilitation of terminal uraemic
patients. Br Med J 5347:1716-1717, 1963
191. Scribner BH: Adequate control of blood pressure in
patients on chronic hemodialysis. Kidney Int 41:1286, 1992
192. Abuelo JG: Large interdialytic weight gain. Causes,
consequences and corrective measures. Semin Dial 11:2532, 1998
193. Kempner W: Treatment of kidney disease and
hypertensive disease with rice diet. N C Med J 5:125-133,
1944
194. Kempner W: Treatment of heart and kidney disease
and of hypertensive and arteriosclerotic vascular disease
with the rice diet. Ann Intern Med 31:821-856, 1949
195. Gunal AI, Duman S, Ozkahya M, et al: Strict
volume control normalizes hypertension in peritoneal dialysis patients. Am J Kidney Dis 37:588-593, 2001
196. Ritz E: SaltFriend or foe? Nephrol Dial Transplant [Epub ahead of print, http://ndt.oxfordjournals.org/cgi/
reprint/gfi256v1] Dec 29, 2005
197. Charra B, Calemard E, Ruffet M, et al: Survival as
an index of adequacy of dialysis. Kidney Int 41:1286-1291,
1992
198. Innes A, Charra B, Burden RP, Morgan AG, Laurent G: The effect of long, slow haemodialysis on patient
survival. Nephrol Dial Transplant 14:919-922, 1999
199. Ozkahya M, Ok E, Cirit M, et al: Regression of left
ventricular hypertrophy in haemodialysis patients by ultrafiltration and reduced salt intake without antihypertensive
drugs. Nephrol Dial Transplant 13:1489-1493, 1998
200. Ayus JC, Mizani MR, Achinger SG, Thadhani R,
Go AS, Lee S: Effects of short daily versus conventional
hemodialysis on left ventricular hypertrophy and inflammatory markers: A prospective, controlled study. J Am Soc
Nephrol 16:2778-2788, 2005
201. Buoncristiani U: Fifteen years of clinical experience with daily haemodialysis. Nephrol Dial Transplant
13:S148-S151, 1998 (suppl 6)
202. Depner TA: Why daily hemodialysis is better:
Solute kinetics. Semin Dial 12:462-471, 1999
203. Alloatti S, Molino A, Manes M, Bonfant G, Pellu V:
Long nocturnal dialysis. Blood Purif 20:525-530, 2002
204. Lockridge RS Jr, Spencer M, Craft V, et al:
Nocturnal home hemodialysis in North America. Adv Ren
Replace Ther 8:250-256, 2001
205. Pierratos A, Ouwendyk M, Francoeur R, et al:
Nocturnal hemodialysis: Three-year experience. J Am Soc
Nephrol 9:859-868, 1998
206. Brunet P, Saingra Y, Leonetti F, Vacher-Coponat H,
Ramananarivo P, Berland Y: Tolerance of haemodialysis: A
randomized cross-over trial of 5-h versus 4-h treatment time.
Nephrol Dial Transplant 11:S46-S51, 1996 (suppl 8)
207. Tomson CR: Advising dialysis patients to restrict
fluid intake without restricting sodium intake is not based on
evidence and is a waste of time. Nephrol Dial Transplant
16:1538-1542, 2001
208. Rigby AJ, Scribner BH, Ahmad S: Sodium, not
fluid, controls interdialytic weight gain. Nephrol News
Issues 14:21-22, 2000
S86
209. Feinstein EI: Nutritional therapy in maintenance

hemodialysis, in Nissenson AR, Fine RN (eds): Dialysis
Therapy. Philadelphia, PA, Hanley & Belfus, 2002, pp
281-285
210. Campese VM, Mozayeni P, Ye S, Gumbard M:
High salt intake inhibits nitric oxide synthase expression and
aggravates hypertension in rats with chronic renal failure. J
Nephrol 15:407-413, 2002
211. Hamlyn JM, Hamilton BP, Manunta P: Endogenous
ouabain, sodium balance and blood pressure: A review and a
hypothesis. J Hypertens 14:151-167, 1996
212. Luik AJ, Charra B, Katzarski K, et al: Blood
pressure control and hemodynamic changes in patients on
long time dialysis treatment. Blood Purif 16:197-209, 1998
213. Dunn CJ, Fitton A, Brogden RN: Torasemide. An
update of its pharmacological properties and therapeutic
efficacy. Drugs 49:121-142, 1995
214. Flamenbaum W, Friedman R: Pharmacology, therapeutic efficacy, and adverse effects of bumetanide, a new
loop diuretic. Pharmacotherapy 2:213-222, 1982
215. Medcalf JF, Harris KP, Walls J: Role of diuretics in
the preservation of residual renal function in patients on
continuous ambulatory peritoneal dialysis. Kidney Int 59:
1128-1133, 2001
216. Wilcox CS: New insights into diuretic use in
patients with chronic renal disease. J Am Soc Nephrol
13:798-805, 2002
217. Khandelwal M, Oreopoulos DG: Is there a need for
low sodium dialysis solution for peritoneal dialysis patients?
Adv Perit Dial 20:156-162, 2004
218. Schwartz GH, David DS, Riggio RR, Stenzel KH,
Rubin AL: Ototoxicity induced by furosemide. N Engl
J Med 282:1413-1414, 1970
219. Humes HD: Insights into ototoxicity. Analogies to
nephrotoxicity. Ann N Y Acad Sci 884:15-18, 1999
220. Van Stone JC, Bauer J, Carey J: The effect of
dialysate sodium concentration on body fluid compartment
volume, plasma renin activity and plasma aldosterone
concentration in chronic hemodialysis patients. Am J Kidney Dis 2:58-64, 1982
221. Locatelli F, Di Filippo S, Pontoriero G: Fluid and
electrolyte balance during extracorporeal therapies, in Ronco
C, Bellomo R (eds): Critical Care Nephrology. Dordrecht,
The Netherlands, Kluwer, 1998, pp 249-259
222. Mann H, Stiller S: Urea, sodium, and water changes
in profiling dialysis. Nephrol Dial Transplant 11:S10-S15,
1996 (suppl 8)
223. Sang GL, Kovithavongs C, Ulan R, Kjellstrand
CM: Sodium ramping in hemodialysis: A study of beneficial
and adverse effects. Am J Kidney Dis 29:669-677, 1997
224. Horl MP, Horl WH: Drug therapy for hypertension
in hemodialysis patients. Semin Dial 17:288-294, 2004
225. Menon MK, Naimark DM, Bargman JM, Vas SI,
Oreopoulos DG: Long-term blood pressure control in a
cohort of peritoneal dialysis patients and its association with
residual renal function. Nephrol Dial Transplant 16:22072213, 2001
226. Shin SK, Noh H, Kang SW, et al: Risk factors
influencing the decline of residual renal function in continuous ambulatory peritoneal dialysis patients. Perit Dial Int
19:138-142, 1999
227. Singhal MK, Bhaskaran S, Vidgen E, Bargman JM,

Vas SI, Oreopoulos DG: Rate of decline of residual renal
function in patients on continuous peritoneal dialysis and
factors affecting it. Perit Dial Int 20:429-438, 2000
228. Lysaght MJ, Vonesh EF, Gotch F, et al: The
influence of dialysis treatment modality on the decline of
remaining renal function. ASAIO Trans 37:598-604, 1991
229. McKane W, Chandna SM, Tattersall JE, Greenwood RN, Farrington K: Identical decline of residual renal
function in high-flux biocompatible hemodialysis and CAPD.
Kidney Int 61:256-265, 2002
230. Moist LM, Port FK, Orzol SM, et al: Predictors of
loss of residual renal function among new dialysis patients.
J Am Soc Nephrol 11:556-564, 2000
231. Van Stone JC: The effect of dialyzer membrane and
etiology of kidney disease on the preservation of residual
renal function in chronic hemodialysis patients. ASAIO J
41:M713-M716, 1995
232. Schiffl H, Lang SM, Fischer R: Ultrapure dialysis
fluid slows loss of residual renal function in new dialysis
233. National Kidney Foundation: K/DOQI Clinical
Practice Guidelines for Peritoneal Dialysis Adequacy, 2000.
Am J Kidney Dis 37:S65-S136, 2001 (suppl 1)
234. Hanson JA, Hulbert-Shearon TE, Ojo AO, et al:
Prescription of twice-weekly hemodialysis in the USA.
Am J Nephrol 19:625-633, 1999
235. Depner TA: Daily hemodialysis efficiency: An
analysis of solute kinetics. Adv Ren Replace Ther 8:227235, 2001
236. Sugarman JR, Frederick PR, Frankenfield DL,
Owen WF Jr, McClellan WM: Developing clinical performance measures based on the Dialysis Outcomes Quality
Initiative Clinical Practice Guidelines: Process, outcomes,
and implications. Am J Kidney Dis 42:806-812, 2003
236A. Healthy People 2010. Available at: www.
healthypeople.gov. Accessed May 1, 2006
237. Owen WF Jr: Patterns of care for patients with
chronic kidney disease in the United States: Dying for
improvement. J Am Soc Nephrol 14:S76-S80, 2003 (suppl
2)
237A. Available at: www.clinicaltrials.gov/show/
NCT00264758. Accessed May 1, 2006
238. Collins AJ, Liu J, Ebben JP: Dialyser reuseassociated mortality and hospitalization risk in incident
Medicare haemodialysis patients, 1998-1999. Nephrol Dial
Transplant 19:1245-1251, 2004
239. Robinson BM, Feldman HI: Dialyzer reuse and
patient outcomes: What do we know now? Semin Dial
18:175-179, 2005
240. Hays RD, Kallich JD, Mapes DL, Coons SJ, Carter
WB: Development of the Kidney Disease Quality of Life
(KDQOL) instrument. Qual Life Res 3:329-338, 1994
241. DeOreo PB: Hemodialysis patient-assessed functional health status predicts continued survival, hospitalization, and dialysis-attendance compliance. Am J Kidney Dis
30:204-212, 1997
242. Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH: Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis. J Am Soc Nephrol 12:2797-2806, 2001
REFERENCES
243. Mapes DL, Lopes AA, Satayathum S, et al: Healthrelated quality of life as a predictor of mortality and
hospitalization: The Dialysis Outcomes and Practice Patterns Study (DOPPS). Kidney Int 64:339-349, 2003
244. Bakewell AB, Higgins RM, Edmunds ME: Does
ethnicity influence perceived quality of life of patients on
dialysis and following renal transplant? Nephrol Dial Transplant 16:1395-1401, 2001
245. Hicks LS, Cleary PD, Epstein AM, Ayanian JZ:
Differences in health-related quality of life and treatment
preferences among black and white patients with end-stage
renal disease. Qual Life Res 13:1129-1137, 2004
246. Kutner NG, Brogan D, Fielding B, Hall WD:
Black/white differences in symptoms and health satisfaction
reported by older hemodialysis patients. Ethn Dis 10:328333, 2000
247. Unruh M, Miskulin D, Yan G, et al: Racial differences in health-related quality of life among hemodialysis
248. Bass EB, Wills S, Fink NE, et al: How strong are
patients preferences in choices between dialysis modalities
and doses? Am J Kidney Dis 44:695-705, 2004
249. Ayanian JZ, Cleary PD, Keogh JH, Noonan SJ,
David-Kasdan JA, Epstein AM: Physicians beliefs about
racial differences in referral for renal transplantation. Am J
Kidney Dis 43:350-357, 2004
250. Ayanian JZ, Cleary PD, Weissman JS, Epstein AM:
The effect of patients preferences on racial differences in
access to renal transplantation. N Engl J Med 341:16611669, 1999
251. Seikaly MG, Loleh S, Rosenblum A, Browne R:
Validation of the Center for Medicare and Medicaid Services
algorithm for eligibility for dialysis. Pediatr Nephrol 19:893897, 2004
252. Goldstein SL: Hemodialysis in the pediatric patient: State of the art. Adv Ren Replace Ther 8:173-179,
2001
253. Marsenic O, Peco-Antic A, Jovanovic O: Effect of
dialysis dose on nutritional status of children on chronic
hemodialysis. Nephron 88:273-275, 2001
254. Goldstein SL, Baronette S, Gambrell TV, Currier H,
Brewer ED: nPCR assessment and IDPN treatment of malnutrition in pediatric hemodialysis patients. Pediatr Nephrol 17:531534, 2002
255. Orellana P, Juarez-Congelosi M, Goldstein SL:
Intradialytic parenteral nutrition treatment and biochemical
marker assessment for malnutrition in adolescent maintenance hemodialysis patients. J Ren Nutr 15:312-317, 2005
256. Goldstein SL, Brewer ED: Logarithmic extrapolation of a 15-minute postdialysis BUN to predict equilibrated
BUN and calculate double-pool Kt/V in the pediatric
hemodialysis population. Am J Kidney Dis 36:98-104, 2000
257. Tom A, McCauley L, Bell L, et al: Growth during
maintenance hemodialysis: Impact of enhanced nutrition
and clearance. J Pediatr 134:464-471, 1999
258. Goldstein SL, Currier H, Watters L, Hempe JM,
Sheth RD, Silverstein D: Acute and chronic inflammation in
pediatric patients receiving hemodialysis. J Pediatr 143:653657, 2003
259. Frankenfield DL, Neu AM, Warady BA, Watkins
SL, Friedman AL, Fivush BA: Adolescent hemodialysis:
S87
results of the 2000 ESRD Clinical Performance Measures

Project. Pediatr Nephrol 17:10-15, 2002
260. Goldstein SL, Smith CM, Currier H: Noninvasive
interventions to decrease hospitalization and associated
costs for pediatric patients receiving hemodialysis. J Am Soc
Nephrol 14:2127-2131, 2003
261. Jain SR, Smith L, Brewer ED, Goldstein SL:
Non-invasive intravascular monitoring in the pediatric hemodialysis population. Pediatr Nephrol 16:15-18, 2001
262. Michael M, Brewer ED, Goldstein SL: Blood
volume monitoring to achieve target weight in pediatric
hemodialysis patients. Pediatr Nephrol 19:432-437, 2004
263. Levey AS, Greene T, Schluchter MD, et al: Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes
Control and Complications Trial Research Group. J Am Soc
Nephrol 4:1159-1171, 1993
264. Casino FG, Lopez T: The equivalent renal urea
clearance: A new parameter to assess dialysis dose. Nephrol
265. Gotch FA: The current place of urea kinetic modelling with respect to different dialysis modalities. Nephrol
266. Keshaviah PR, Nolph KD, Van Stone JC: The peak
concentration hypothesis: A urea kinetic approach to comparing the adequacy of continuous ambulatory peritoneal dialysis
(CAPD) and hemodialysis. Perit Dial Int 9:257-260, 1989
267. Depner TA: Benefits of more frequent dialysis:
Lower TAC at the same Kt/V. Nephrol Dial Transplant
13:S20-S24, 1998 (suppl 6)
268. Depner TA, Bhat A: Quantifying daily hemodialysis. Semin Dial 17:79-84, 2004
269. Watson PE, Watson ID, Batt RD: Total body water
volumes for adult males and females estimated from simple
anthropometric measurements. Am J Clin Nutr 33:27-39,
1980
270. Cheung AK, Levin NW, Greene T, et al: Effects of
high-flux hemodialysis on clinical outcomes: Results of the
HEMO Study. J Am Soc Nephrol 14:3251-3263, 2003
271. Cheung AK, Sarnak MJ, Yan G, et al: Cardiac
diseases in maintenance hemodialysis patients: Results of
the HEMO Study. Kidney Int 65:2380-2389, 2004
272. Locatelli F, Andrulli S, Pecchini F, et al: Effect of
high-flux dialysis on the anaemia of haemodialysis patients
[see comment]. Nephrol Dial Transplant 15:1399-1409,
2000
273. MacLeod AM, Campbell M, Cody JD, et al:
Cellulose, modified cellulose and synthetic membranes in
the haemodialysis of patients with end-stage renal disease.
Cochrane Database Syst Rev CD003234, 2005
274. Leypoldt JK, Cheung AK, Carroll CE, et al: Effect
of dialysis membranes and middle molecule removal on
chronic hemodialysis patient survival. Am J Kidney Dis
33:349-355, 1999
275. Woods HF, Nandakumar M: Improved outcome for
haemodialysis patients treated with high-flux membranes.
Nephrol Dial Transplant 15:S36-S42, 2000 (suppl 1)
276. Schiffl H, Fischer R, Lang SM, Mangel E: Clinical
manifestations of AB-amyloidosis: Effects of biocompatibility and flux. Nephrol Dial Transplant 15:840-845, 2000
S88
277. Leypoldt JK, Cheung AK, Deeter RB: Rebound

kinetics of beta2-microglobulin after hemodialysis. Kidney
Int 56:1571-1577, 1999
277A. Ebben JP, Liu J, Collins AJ: Membrane associated
morbidity in incident and prevalent hemodialysis patients.
J Am Soc Nephrol 13:614A, 2002 (abstr)
278. Locatelli F, Marcelli D, Conte F, Limido A, Malberti F, Spotti D: Comparison of mortality in ESRD patients
on convective and diffusive extracorporeal treatments. The
Registro Lombardo Dialisi E Trapianto. Kidney Int 55:286293, 1999
279. European Best Practice Guidelines for Haemodialysis (Part 1): Section III. Biocompatibility. Nephrol Dial
Transplant 17:S32-S44, 2002 (suppl 7)
280. Locatelli F, Mastrangelo F, Redaelli B, et al: Effects
of different membranes and dialysis technologies on patient
treatment tolerance and nutritional parameters. The Italian
Cooperative Dialysis Study Group. Kidney Int 50:12931302, 1996
281. Nakai S, Iseki K, Tabei K, et al: Outcomes of
hemodiafiltration based on Japanese dialysis patient registry.
282. van Ypersele de Strihou C, Jadoul M, Malghem J,
Maldague B, Jamart J: Effect of dialysis membrane and
patients age on signs of dialysis-related amyloidosis. The
Working Party on Dialysis Amyloidosis. Kidney Int 39:10121019, 1991
283. Twardowski Z: Effect of long-term increase in the
frequence and/or prolongation of dialysis duration on certain
clinical manifestations and results of laboratory investigations in patients with chronic renal failure. Acta Med Pol
16:31-44, 1975
284. Pierratos A, McFarlane P, Chan CT: Quotidian
dialysisUpdate 2005. Curr Opin Nephrol Hypertens 14:
119-124, 2005
285. Diaz-Buxo JA: Beyond thrice-weekly hemodialysis. Hemodial Int 9:309-313, 2005
286. Block GA, Klassen PS, Lazarus JM, Ofsthun N,
Lowrie EG, Chertow GM: Mineral metabolism, mortality,
and morbidity in maintenance hemodialysis. J Am Soc
Nephrol 15:2208-2218, 2004
287. Salahudeen AK, Dykes P, May W: Risk factors for
higher mortality at the highest levels of spKt/V in hemodialysis patients. Nephrol Dial Transplant 18:1339-1344, 2003
288. Kopple JD, Greene T, Chumlea WC, et al: Relationship between nutritional status and the glomerular filtration
rate: Results from the MDRD Study. Kidney Int 57:16881703, 2000
289. Velasquez MT, von Albertini B, Lew SQ, Mishkin
GJ, Bosch JP: Equal levels of blood pressure control in
ESRD patients receiving high-efficiency hemodialysis and
conventional hemodialysis. Am J Kidney Dis 31:618-623,
1998
290. Kurella M, Chertow GM: Dialysis session length
(t) as a determinant of the adequacy of dialysis. Semin
Nephrol 25:90-95, 2005
291. Association for Advancement of Medical Information (AAMI): American National Standard. Reuse of Hemodialyzers (ANSI/AAMI RD47:2002 & RD47:2002/A1:
2003). Arlington, VA, AAMI, 2003
292. National Kidney Foundation: Report on dialyzer

reuse. Task Force on Reuse of Dialyzers, Council on
Dialysis, National Kidney Foundation. Am J Kidney Dis
30:859-871, 1997
293. Agodoa LY, Wolfe RA, Port FK: Reuse of dialyzers
and clinical outcomes: Fact or fiction. Am J Kidney Dis
32:S88-S92, 1998 (suppl 4)
294. Clark WR, Scott MK, Leypoldt JK: Reuse of
dialyzers: Methods and complications of dialyzer reuse, in
Nissenson AR, Fine RN (eds): Dialysis Therapy. Philadelphia, PA, Hanley & Belfus, 2002, pp 199-203
295. Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino
MJ: National surveillance of dialysis-associated diseases in
the United States, 2002. Semin Dial 18:52-61, 2005
296. Light PD: Reuse of hemodialysis membranes in
chronic dialysis therapy, in Henrich WL (ed): Principles and
Practice of Dialysis (ed 3). Philadelphia, PA, Lippincott
Williams & Wilkins, 2004, pp 16-27
297. Port FK, Wolfe RA, Hulbert-Shearon TE, et al:
Mortality risk by hemodialyzer reuse practice and dialyzer
membrane characteristics: Results from the USRDS Dialysis Morbidity and Mortality Study. Am J Kidney Dis
37:276-286, 2001
298. Vinhas J, Pinto dos Santos J: Haemodialyser reuse:
Facts and fiction. Nephrol Dial Transplant 15:5-8, 2000
299. Lowrie EG, Li Z, Ofsthun N, Lazarus JM: Reprocessing dialysers for multiple uses: Recent analysis of death
risks for patients. Nephrol Dial Transplant 19:2823-2830,
2004
300. Robinson BM, Feldman HI, Kobrin SM: Dialyzer
reuse, in Nissenson AR, Fine RN (eds): Clinical Dialysis
(ed 4). New York, NY, McGraw-Hill, 2005, pp 274-291
301. Kaufman AM, Levin NW: Dialyzer reuse, in Daugirdas J, Blake PG, Ing TS (eds): Handbook of Dialysis (ed
3). Philadelphia, PA, Lippincott Williams & Wilkins, 2001,
pp 169-181
302. Murthy BV, Pereira BJ: Effects of reuse on dialyzer
function. Semin Dial 13:282-286, 2000
303. Petersen J, Jani A: Effects of reuse on dialyzer
function. Semin Dial 13:289-290, 2000
304. Fan Q, Liu J, Ebben JP, Collins AJ: Reuseassociated mortality in incident hemodialysis patients in the
United States, 2000 to 2001. Am J Kidney Dis 46:661-668,
2005
305. Collins AJ, Ma JZ, Constantini EG, Everson SE:
Dialysis unit and patient characteristics associated with
reuse practices and mortality: 1989-1993. J Am Soc Nephrol
9:2108-2117, 1998
306. Sherman RA, Cody RP, Rogers ME, Solanchick JC:
The effect of dialyzer reuse on dialysis delivery. Am J
Kidney Dis 24:924-926, 1994
307. Farrell PC, Eschbach JW, Vizzo JE, Babb AL:
Hemodialyzer reuse: Estimation of area loss from clearance
data. Kidney Int 5:446-450, 1974
308. Garred LJ, Canaud B, Flavier JL, Poux C, PolitoBouloux C, Mion C: Effect of reuse on dialyzer efficacy.
Artif Organs 14:80-84, 1990
309. Murthy BV, Sundaram S, Jaber BL, Perrella C,
Meyer KB, Pereira BJ: Effect of formaldehyde/bleach
reprocessing on in vivo performances of high-efficiency
REFERENCES
cellulose and high-flux polysulfone dialyzers. J Am Soc

Nephrol 9:464-472, 1998
310. Cheung AK, Agodoa LY, Daugirdas JT, et al:
Effects of hemodialyzer reuse on clearances of urea and
beta2-microglobulin. The Hemodialysis (HEMO) Study
Group. J Am Soc Nephrol 10:117-127, 1999
311. Delmez JA, Weerts CA, Hasamear PD, Windus
DW: Severe dialyzer dysfunction undetectable by standard
reprocessing validation tests. Kidney Int 36:478-484, 1989
312. Deane N, Bemis JA: Multiple Use of Hemodialyzers (a report to the National Institute of Arthritis, Diabetes,
Digestive and Kidney Disease). New York, NY, Manhattan
Kidney Center, 1981
313. Gotch FA: Solute and water transport and sterilant
removal in reused dialyzers, in Deane N, Wineman RJ,
Bemis JA (eds): Guide to Reprocessing of Hemodialyzers.
Boston, MA, Nijhoff, 1986, pp 39-61
314. Dialyzers transport properties and germicidal elution, in Seminar on the Reuse of Hemodialyzers and
Automated and Manual Methods. New York, NY, National
Nephrology Foundation, 1984
315. Krivitski NM, Kislukhin VV, Snyder JW, et al: In
vivo measurement of hemodialyzer fiber bundle volume:
Theory and validation. Kidney Int 54:1751-1758, 1998
316. Narsipur SS: Measurement of fiber bundle volume
in reprocessed dialyzers. Clin Nephrol 61:130-133, 2004
317. Di Filippo S, Manzoni C, Andrulli S, et al: How to
determine ionic dialysance for the online assessment of
delivered dialysis dose. Kidney Int 59:774-782, 2001
318. Steil H, Kaufman AM, Morris AT, Levin NW,
Polaschegg HD: In vivo verification of an automatic noninvasive system for real time Kt evaluation. ASAIO J 39:M348M352, 1993
319. Lindsay RM, Bene B, Goux N, Heidenheim AP,
Landgren C, Sternby J: Relationship between effective ionic
dialysance and in vivo urea clearance during hemodialysis.
Am J Kidney Dis 38:565-574, 2001
320. Mercadal L, Ridel C, Petitclerc T: Ionic dialysance:
Principle and review of its clinical relevance for quantification
of hemodialysis efficiency. Hemodial Int 9:111-119, 2005
321. Petitclerc T, Bene B, Jacobs C, Jaudon MC, Goux
N: Non-invasive monitoring of effective dialysis dose
delivered to the haemodialysis patient. Nephrol Dial Transplant 10:212-216, 1995
322. Rahmati MA, Rahmati S, Hoenich N, et al: On-line
clearance: A useful tool for monitoring the effectiveness of
the reuse procedure. ASAIO J 49:543-546, 2003
323. Gotch FA: On-line clearance: Advanced methodology to monitor adequacy of dialysis at no cost, in Ronco C,
La Greca G (eds): Hemodialysis Technology. Basel, Switzerland, Karger, 2002, pp 268-271
324. Ing TS, Daugirdas JT: Extractable ethylene oxide
from cuprammonium cellulose plate dialyzers: Importance
of potting compound. ASAIO Trans 32:108-110, 1986
325. Ronco C, Levin NW, Polaschegg HD: Technical
problems during hemodialysis, in Nissenson AR, Fine RN
(eds): Dialysis Therapy (ed 3). Philadelphia, PA, Hanley &
Belfus, 2002, pp 156-165
326. Cheung AK, Leypoldt JK: The hemodialysis membranes: A historical perspective, current state and future
prospect. Semin Nephrol 17:196-213, 1997
S89
327. Craddock PR, Fehr J, Dalmasso AP, Brighan KL,

Jacob HS: Hemodialysis leukopenia. Pulmonary vascular leukostasis resulting from complement activation by dialyzer
cellophane membranes. J Clin Invest 59:879-888, 1977
328. Himmelfarb J, Hakim RM: Biocompatibility and
risk of infection in haemodialysis patients. Nephrol Dial
Transplant 9:S138-S144, 1994 (suppl 2)
329. Lonnemann G: Should ultra-pure dialysate be mandatory? Nephrol Dial Transplant 15:S55-S59, 2000 (suppl 1)
330. Smollich BP, Falkenhagen D, Schneidewind J,
Mitzner S, Klinkmann H: Importance of endotoxins in
high-flux dialysis. Nephrol Dial Transplant 6:S83-S85, 1991
(suppl 3)
331. Lonnemann G, Koch KM: Beta(2)-microglobulin
amyloidosis: Effects of ultrapure dialysate and type of
dialyzer membrane. J Am Soc Nephrol 13:S72-S77, 2002
(suppl 1)
332. Schindler R, Linnenweber S, Schulze M, et al:
Gene expression of interleukin-1 beta during hemodialysis.
Kidney Int 43:712-721, 1993
333. Churchill DN: Clinical impact of biocompatible
dialysis membranes on patient morbidity and mortality: An
appraisal of the evidence. Nephrol Dial Transplant 10:S52S56, 1995 (suppl 10)
334. Hakim RM, Held PJ, Stannard DC, et al: Effect of
the dialysis membrane on mortality of chronic hemodialysis
335. Hornberger JC, Chernew M, Petersen J, Garber AM:
A multivariate analysis of mortality and hospital admissions
with high-flux dialysis. J Am Soc Nephrol 3:1227-1237, 1992
336. Bonomini V, Coli L, Scolari MP, Stefoni S: Structure of dialysis membranes and long-term clinical outcome.
Am J Nephrol 15:455-462, 1995
337. Bergamo Collaborative Dialysis Study Group: Acute
intradialytic well-being: Results of a clinical trial comparing
polysulfone with cuprophan. Kidney Int 40:714-719, 1991
338. Skroeder NR, Jacobson SH, Lins LE, Kjellstrand
CM: Biocompatibility of dialysis membranes is of no
importance for objective or subjective symptoms during or
after hemodialysis. ASAIO Trans 36:M637-M639, 1990
339. Chenoweth DE: Complement activation during
hemodialysis: Clinical observations, proposed mechanisms,
and theoretical implications. Artif Organs 8:281-290, 1984
340. Ivanovich P, Chenoweth DE, Schmidt R, et al:
Symptoms and activation of granulocytes and complement
with two dialysis membranes. Kidney Int 24:758-763, 1983
341. Chanard J: [Membrane biocompatibility in dialysis:
The role of absorption]. Nephrologie 24:359-365, 2003
342. Chanard J, Caudwell V, Valeire J, et al: Kinetics of
131I-beta2 microglobulin in hemodialysis patients: Assessment
using total body counting. Artif Organs 22:574-580, 1998
343. Acchiardo S, Kraus AP Jr, Jennings BR: Beta
2-microglobulin levels in patients with renal insufficiency.
344. Hoenich NA, Woffindin C, Matthews JN, Goldfinch
ME, Turnbull J: Clinical comparison of high-flux cellulose
acetate and synthetic membranes. Nephrol Dial Transplant
9:60-66, 1994
345. Mrowka C, Schiffl H: Comparative evaluation of beta
2-microglobulin removal by different hemodialysis membranes: A six-year follow-up. Nephron 63:368-369, 1993
S90
346. Zingraff J, Beyne P, Urena P, et al: Influence of

haemodialysis membranes on beta 2-microglobulin kinetics:
In vivo and in vitro studies. Nephrol Dial Transplant
3:284-290, 1988
347. Kuchle C, Fricke H, Held E, Schiffl H: High-flux
hemodialysis postpones clinical manifestation of dialysisrelated amyloidosis. Am J Nephrol 16:484-488, 1996
348. Koda Y, Nishi S, Miyazaki S, et al: Switch from
conventional to high-flux membrane reduces the risk of
carpal tunnel syndrome and mortality of hemodialysis
349. Cheung AK, Rocco MV, Yan G, et al: Serum beta-2
microglobulin levels predict mortality in dialysis patients:
Results of the HEMO Study. J Am Soc Nephrol 17:546-555,
2006
350. Ivanovich P, Rosner K: A case for cellulosic membrane hemodialyzers. Semin Dial 13:409-411, 2000
351. Chandna SM, Farrington K: Residual renal function: Considerations on its importance and preservation in
dialysis patients. Semin Dial 17:196-201, 2004
352. Ward RA: Ultrapure dialysate. Semin Dial 17:489497, 2004
353. Devoy MA, Tomson CR, Edmunds ME, Feehally J,
Walls J: Deterioration in renal function associated with
angiotensin converting enzyme inhibitor therapy is not
always reversible. J Intern Med 232:493-498, 1992
354. James SH, Meyers AM, Milne FJ, Reinach SG: Partial
recovery of renal function in black patients with apparent
end-stage renal failure due to primary malignant hypertension.
Nephron 71:29-34, 1995
355. Kuno T, Matsumoto K: Clinical benefit of preserving residual renal function in patients after initiation of
dialysis. Blood Purif 22:S67-S71, 2004 (suppl 2)
356. Chavers BM, Li S, Collins AJ, Herzog CA: Cardiovascular disease in pediatric chronic dialysis patients. Kidney Int 62:648-653, 2002
357. Sarnak MJ, Levey AS: Cardiovascular disease and
chronic renal disease: A new paradigm. Am J Kidney Dis
35:S117-S131, 2000 (suppl 1)
358. Reynolds JM, Morton MJ, Garralda ME, Postlethwaite RJ, Goh D: Psychosocial adjustment of adult survivors
of a paediatric dialysis and transplant programme. Arch Dis
Child 68:104-110, 1993
359. Fischbach M, Edefonti A, Schroder C, Watson A:
Hemodialysis in children: General practical guidelines.
Pediatr Nephrol 20:1054-1066, 2005
360. Gotch FA: Kinetic modeling in hemodialysis, in
Nissenson AR, Fine RN, Gentile DE (eds): Clinical Dialysis.
Norwalk, CT, Appleton and Lange, 1995, pp 156-188
361. Yeun JY, Depner TA: Principles of hemodialysis, in
Pereira BJ, Sayegh MH, Blake P (eds): Chronic Kidney
Disease, Dialysis, and Transplantation. Philadelphia, PA,
Elsevier Saunders, 2005, pp 307-340
362. Depner TA: Prescribing Hemodialysis: A Guide to
Urea Modeling. Boston, MA, Kluwer, 1991
363. Sargent JA, Gotch FA: Mathematic modeling of
dialysis therapy. Kidney Int 18:S2-10, 1980 (suppl 10)
364. Depner TA, Greene T, Gotch FA, Daugirdas JT,
Keshaviah PR, Star RA: Imprecision of the hemodialysis
dose when measured directly from urea removal. Hemodialysis Study Group. Kidney Int 55:635-647, 1999
Peritoneal Dialysis Adequacy 2006

John M. Burkart, MD
Wake Forest University
Winston-Salem, NC
Beth Piraino, MD
University of Pittsburgh
Pittsburgh, PA
Work Group
Joanne Bargman, MD, FRCPC

Toronto General Hospital
Toronto, ON, Canada
Peter G. Blake, MD, FRCPC, MBBCh
London Health Sciences Center
London, ON, Canada
Fredric O. Finkelstein, MD
Hospital of St Raphael, Yale University
New Haven, CT
Thomas A. Golper, MD, FACP
Vanderbilt University Medical Center
Nashville, TN
Angellina Graham, RN
Wake Forest University Outpatient Dialysis
Kemp Center
Winston-Salem, NC
Susan Stark, MS, RD, CSR, LDN
UPMC Presbyterian Hospital
Pittsburgh, PA
Bradley A. Warady, MD
The Childrens Mercy Hospital
Kansas City, MO
Consultants:
Steven R. Alexander, MD, FACP
Stanford University School of Medicine,
Lucile Packard Childrens Hospital at Stanford
Stanford, CA
Michel Fischbach, MD
Hospital de Hautepierre
Strausbourg, France
Denis F. Geary, MB, MRCP(UK), FRCP(C)
The Hospital for Sick Children
Toronto, ON, Canada
Franz Schaefer, MD
University of Heidelberg Medical Center
Heidelberg, Germany
Cornelis H. Schrder, MD, PhD
Wilhelmina Childrens Hospital
Heijen, The Netherlands
Alan R. Watson, FRCP
Nottingham City NHS Trust
Nottingham, UK

National Kidney Foundation Center for Guideline Development and Implementation
at Tufts-New England Medical Center, Boston, MA
Amy Earley, BS
Rebecca Persson, BA
Gowri Raman, MD
Priscilla Chew, MPH

Stanley Ip, MD
Mei Chung, MPH

Tables
Table 1.
Table 2.
Table 3.
Table 4.
Table 5.
Table 6.
Table 7.
Table 8.
Table 9.
Table 10.
Table 11.
Table 12.
Table 13.
Table 14.
Table 15.
Table 16.
Table 17.
Table 18.
Table 19.
S92
Validated GFR-Estimating Equations.............................................................................. S100

Causes of Unusually Low or High Endogenous Creatinine Generation.......................... S100
Causes of Unusually Low or High Kidney Tubular Creatinine Secretion ....................... S101
Effect of Clearance on Patient Survival........................................................................... S105
Effect of Fluid Removal on Clinical Outcomes............................................................... S108
Effect of Clearance on Technique Survival ..................................................................... S110
Potential Insults to RKF in Patients on Dialysis .............................................................. S118
Effect of Pharmacological Interventions on RKF............................................................ S120
Various Domains to Be Considered for CQI Studies....................................................... S126
Complications That May Prompt Initiation of KRT ........................................................ S131
Possible Indications to Consider Increasing the Dose of Dialysis................................... S133
Possible Clinical Indications for Obtaining a 24-Hour RKF Collection ......................... S133
Clinical Indications for Measurement of Peritoneal or Kidney Clearance ...................... S134
Standardized Tests for Evaluating Peritoneal Membrane Transport/Function ................ S139
Clinical Indications for Repeat Peritoneal Membrane Transport Testing........................ S139
Mean Values of k ............................................................................................................. S149
Male Total Body Water (L) Nomograms ......................................................................... S152
Female Total Body Water (L) Nomograms...................................................................... S154
Body Surface Area........................................................................................................... S156

ACE
ADEMEX
APD
ARB
AV
BMI
BSA
CANUSA
CAPD
CCPD
CCr
CHF
CI
CKD
CMS CPM
COX-2
CPG
CPR
CQI
CRP
CVD
DBP
D/D0
DOQI
D/P
DPI
DV
EAPOS
ECF
GFR
HD
HR
IDEAL
IPP
KDOQI
KLS
KRT
Kt/Vurea
LBW
LVH
LVM
LVMI
MAP
MDRD
MTAC
NAPRTCS
nd
NECOSAD
NIPD
NKF
Angiotensin-converting enzyme
Adequacy of Peritoneal Dialysis in Mexico
Automated peritoneal dialysis
Angiotensin receptor blocker
Arteriovenous
Body mass index
Body surface area
Canada-United States Study
Continuous ambulatory peritoneal dialysis
Continuous cycling peritoneal dialysis
Creatinine clearance
Congestive heart failure
Confidence interval
Centers for Medicare and Medicaid Services Clinical Performance Measures Project
Cyclooxygenase-2
C-Reactive protein
Diastolic blood pressure
End dwell dialysate dextrose over initial dialysate dextrose
Dialysate to plasma ratio
Dietary protein intake
Drain volume of peritoneal effluent
European Automated Peritoneal Dialysis Outcome Study
Extracellular fluid
Hemodialysis
Hazard ratio
Initiating Dialysis Early And Late
Intraperitoneal pressure
Urea nitrogen clearance divided by volume of distribution of urea nitrogen
Low birth weight
Left ventricular mass
Left ventricular mass index
Mean arterial blood pressure
Modification of Diet in Renal Disease
Mass transfer area coefficients
North American Pediatric Renal Transplant Cooperative Study
No data reported
Netherlands Cooperative Study on the Adequacy of Dialysis
Nightly intermittent peritoneal dialysis
S93
S94
nPCR
nPNA
NS
NSAIDs
OR
pCCr
PCR
PD
PDC
PET
PNA
QOL
RCT
rGFR
RKF
ROC
RR
SBP
SD
SGA
SPA
TBW
TNa
TUF
UF
USRDS
UV
V
Normalized protein catabolic rate

Normalized protein equivalent of total nitrogen appearance
Not significant
Nonsteroidal anti-inflammatory drugs
Odds ratio
Peritoneal creatinine clearance
Protein catabolic rate
Peritoneal dialysis
Peritoneal dialysis capacity test
Peritoneal equilibration test
Protein equivalent of total nitrogen appearance
Quality of life
Residual glomerular filtration rate
Residual kidney function
Receiver operating characteristic
Relative risk
Systolic blood pressure
Standard deviation
Subjective global assessment
Standard peritoneal permeability analysis
Total body water
Total sodium removal
Total ultrafiltration
Peritoneal ultrafiltration
Urine volume
Volume of distribution of urea nitrogen
Foreword
his publication of the Clinical Practice

Guidelines (CPGs) and Clinical Practice
Recommendations (CPRs) for Peritoneal Dialysis Adequacy represents the second update of
guidelines established the importance of measuring the dose of dialysis in all long-term peritoneal dialysis patients. Several of these guidelines
have been selected as clinical performance measures by regulatory agencies to drive the process
of quality improvement in long-term dialysis
patients.
A number of important randomized clinical trials have been performed in long-term peritoneal
dialysis patients since the publication of the first
set of guidelines. The Adequacy of Peritoneal
Dialysis in Mexico (ADEMEX) Study, an industry-sponsored randomized clinical trial of
dialysis dose, is one of the largest studies to date
performed in long-term peritoneal dialysis patients. Other large clinical trials in peritoneal
dialysis patients have been conducted in Hong
Kong. The results of these and other studies of
long-term peritoneal dialysis patients have been
included in the literature review for this updated
set of guidelines and are reflected in new minimum levels for the dose of dialysis. In addition,
this update includes new guidelines on the preservation of residual kidney function, the management of volume status and blood pressure, and
the importance of patient education on all dialysis modalities.
practice recommendations, or CPRs. These
CPRs are opinion based and are based on the
expert consensus of the Work Group members. It
is the intention of the Work Group that the
guideline statements in Section I can be considered for clinical performance measures because
of the evidence that supports them. Conversely,
because the CPRs are opinion based, and not
evidence based, they should not be considered to
have sufficient evidence to support the development of clinical performance measures. The third

to combine all research recommendations for the
guidelines into 1 major section and also have
in how the research recommendations are presented is to provide a guidepost for funding agencies and investigators to target research efforts in
areas that will provide important information to
benefit patient outcomes.
This final version of the Clinical Practice Guidelines and Recommendations for Peritoneal Dialysis Adequacy has undergone extensive revision
in response to comments during the public review. While considerable effort has gone into
their preparation during the past 2 years and
every attention has been paid to their detail and
scientific rigor, no set of guidelines and clinical
practice recommendations, no matter how well
developed, achieves its purpose unless it is implemented and translated into clinical practice.
Implementation is an integral component of the
KDOQI process and accounts for the success of
its past guidelines. The Kidney Learning System
(KLS) component of the National Kidney Foundation is developing implementation tools that
will be essential to the success of these guidelines.
In a voluntary and multidisciplinary undertaking of this magnitude, many individuals make
contributions to the final product now in your
hands. It is impossible to acknowledge them
individually here, but to each and every one of
them, we extend our sincerest appreciation. This
limitation notwithstanding, a special debt of gratitude is due to the members of the Work Group
and their co-chairs, John Burkart from Wake
Forest University and Beth Piraino from The
University of Pittsburgh. It is their commitment
and dedication to the KDOQI process that has
made this document possible.

KDOQI Chair
KDOQI Vice-Chair
S95
Introduction
HIS publication represents the second revision of the Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines for Peritoneal Dialysis (PD) Adequacy. The revision was
precipitated in part by the publication of 2 prospective randomized trials that evaluated the
relationship between small-solute clearance and
short-term outcomes in patients on PD therapy.
These studies represent a higher level of evidence for guideline formation than were available to formulate the first 2 Dialysis Outcome
Quality Initiative (DOQI) and KDOQI Guidelines for PD Adequacy. The results of both studies suggested that improving survival on currently available PD therapies likely is related to
factors other than increasing small-solute clearances. Data continued to emerge that confirmed
the importance of maintaining residual kidney
function (RKF) and a guideline reflecting the
importance of RKF on patient outcomes was
added. In addition, there were preliminary data
suggesting that surrogates for cardiovascular risk
(peritoneal ultrafiltration and volume removal)
were predictive of relative risk (RR) for death in
cohort observational studies. Although the Work
Group acknowledges that these data are preliminary, we believed that recommendations for volume and blood pressure control in PD patients
could now be added.
In contrast to the second version of the KDOQI
Guidelines for PD Adequacy, the current guidelines represent a complete revision of the original. In addition to modifications of the actual
guidelines based on new medical evidence, clinical and practical experiences with use of the
original guidelines also were reviewed and, when
appropriate, incorporated. Most importantly, we
attempted to address issues related to experiences with implementation of the guidelines,
work load on dialysis unit staff, and use of the
guidelines for formulating clinical performance
measurements by some oversight bodies.
These guidelines are primarily for patients
on continuous ambulatory PD (CAPD) therapy.
There are limited data for automated PD (APD)
and no randomized controlled trials (RCTs).
Therefore, we cannot formulate guidelines for
APD, and any comments on this form of therapy
S96
are mainly opinion based. Further study is needed

in this area.
Because children are not small adults, guidelines for children have been separated into 1
section (Guideline 6). These mirror the adult
guidelines, but follow the pediatric literature. For
areas in which no pediatric-specific data exist,
the adult guidelines should serve as a minimum
standard for pediatric patients.
Despite voicing concerns in the original DOQI
publications, at times guidelines were used by
oversight bodies in a way not intended by the
Work Group andat other timesnot in keeping with the spirit in which the guidelines were
formulated. As a result, this publication is organized differently, into: (1) Clinical Practice Guidelines (CPGs); and (2) Clinical Practice Recommendations (CPRs). The guidelines are based on
available evidence such as it exists. Much more
information is needed; therefore, we would
strongly discourage oversight bodies from using
these CPGs for clinical performance measurements. The CPRs are based on weak evidence or
opinion and as such, should not be used for
clinical performance measurements. In particular, because of the absence of RCTs for patients
on APD therapy, no clinical performance measurements regarding this form of therapy are
appropriate. Guidelines are meant to inform, but
not replace, clinical judgment.
Finally, we must express some caveats and cautions about the guidelines. In contrast to the original guidelines, in which a target total solute clearance was recommended, in the present guidelines,
a minimal dose is recommended. When using a
target, even if a patient was below target, solute
clearance would still likely be adequate. Conversely, when using a minimal dose, there is less
room for error. All patients should be above the
minimal. Additionally, data from prospective randomized trials are based on relatively short-term
trials of patients on PD therapy in Mexico and
Hong Kong. These patients likely are on different
protein intakes and perhaps are more likely to be
adherent with the PD prescription than the typical
patient in the United States. As a result, the current
document emphasizes patient observations and adjustment of the PD prescription if the patient is not
doing well clinically. There is a paucity of knowl-
INTRODUCTION
edge regarding small-molecule clearance targets

and long-term complications, such as calciumphosphate product effects and uremic neuropathy.
Additional data are required to make recommendations for optimization of long-term health.
The prior publications recognized that there
was an absence of RCTs to answer important
S97
questions regarding PD adequacy and optimal

practice. The prior guidelines identified research needs, some of which have been met.
We hope that the present guidelines identify
questions that will stimulate further research,
improve patient outcomes, and advance the
clinical practice of PD.
I. CLINICAL PRACTICE GUIDELINES FOR PERITONEAL

DIALYSIS ADEQUACY
GUIDELINE 1. INITIATION OF DIALYSIS

1.1 Preparation for kidney failure:
Patients who reach chronic kidney disease (CKD) stage 4 (estimated glomerular filtration rate [GFR] < 30 mL/min/
1.73 m2) should receive timely education
about kidney failure and options for its
treatment, including kidney transplantation, peritoneal dialysis (PD), hemodialysis (HD) in the home or in-center, and
conservative treatment. Patients family
members and caregivers also should be
educated about treatment choices for
kidney failure. (B)
1.2 Estimation of kidney function:
Estimation of GFR should guide decision
making regarding dialysis therapy initiation. GFR should be estimated by using a
validated estimating equation (Table 1) or
by measurement of creatinine and urea
clearances, not simply by measurement of
serum creatinine and urea nitrogen. Table 2
and Table 3 summarize special circumstances in which GFR estimates should be
interpreted with particular care. (B)
1.3 Timing of therapy:
When patients reach stage 5 CKD (estimated GFR < 15 mL/min/1.73 m2), nephrologists should evaluate the benefits, risks,
and disadvantages of beginning kidney replacement therapy (KRT). Particular clinical considerations and certain characteristic complications of kidney failure may
prompt initiation of therapy before stage 5.
(B)
BACKGROUND
Optimum timing of treatment for patients with
CKD prevents serious and uremic complications,
including malnutrition, fluid overload, bleeding,
serositis, depression, cognitive impairment, peripheral neuropathy, infertility, and increased susceptibility to infection. However, all forms of
kidney replacement therapy entail important
trade-offs. As GFR decreases, patients and physicians must weigh many risks and benefits. Decision making is more complex for older and more
fragile patients. Together, patients and physicians must continually reconsider whether the
anticipated physiological benefits of solute clearance and extracellular fluid (ECF) volume con-
trol now outweigh the physical risks and psychosocial toll of therapy. In some cases, social and
psychological factors may militate to earlier dialysis therapy initiation, and, in some cases, to
later initiation. The initiation of dialysis therapy
remains a decision informed by clinical art, as
well as by science, and by the constraints of
regulation and reimbursement.
For some patients, conservative therapy without dialysis or transplantation is the appropriate
option.10-12 If the patient makes this choice, the
health care team should strive to maximize the
quality of life (QOL) and length of life by using
dietary and pharmacological therapy to minimize uremic symptoms and maintain volume
homeostasis. These include, but are not limited
to, use of low-protein diets, keto-analogs of
essential amino acids, loop diuretics, and sodium
polystyrene sulfonate. Nephrologists also should
be familiar with the principles of palliative care13
and should not neglect hospice referral for patients with advanced kidney failure.
RATIONALE
Preparation for Kidney Failure (CPG 1.1)
Timely Education in Stage 4 CKD
Timely patient education as CKD advances
can both improve outcomes and reduce cost.14
Planning for dialysis therapy allows for the initiation of dialysis therapy at the appropriate time
and with a permanent access in place at the start
of dialysis therapy. Planning for kidney failure
should begin when patients reach CKD stage 4,
for several reasons. The rate of progression of
kidney disease may not be predictable. There is
substantial variability in the level of kidney function at which uremic symptoms or other indications for dialysis appear. Patients vary in their
ability to assimilate and act on information about
kidney failure. Local health care systems vary in
the delays associated with patient education and
the scheduling of consultations, tests, and procedures. Results of access creation procedures vary,
and the success or failure of a procedure may not
be certain for weeks or months. Timely education will: (1) allow patients and families time to
assimilate the information and weigh the treatment options, (2) allow evaluation of recipients
and donors for preemptive kidney transplanta-
S99
S100
GUIDELINES FOR PERITONEAL DIALYSIS ADEQUACY
tion, (3) allow staff time to train patients who

choose home dialysis, (4) ensure that uremic
cognitive impairment does not cloud the decision, and (5) maximize the probability of orderly
and planned treatment initiation using the permanent access.
Predialysis education to inform the patient and
support persons about the relative value of various renal replacement modalities offers a freedom of choice that must be honored. Education
and choice of modality also are vital to the timely
placement of vascular or peritoneal access, training for home dialysis, and actual timing of the
initiation of the selected first modality. A comprehensive preemptive discussion of these issues
will enable patients and their support groups to
make rational decisions and will serve to involve
the patients as active participants in their personal health care. Playing an active role in ones
own health care, although thwarting the natural
defense mechanism of denial, reduces risks from
negligence and psychological depression that
have been associated with poor outcomes after
dialysis therapy is started.15
Contingency Plans
Optimal timing of vascular access creation
may depend on plans regarding transplantation
and/or PD treatment. Early attempts at native
vein arteriovenous (AV) fistula creation are particularly important in patients who are: (1) not
transplant candidates, or (2) lack potential living

kidney donors and also seem unlikely to perform
PD. For patients hoping to undergo preemptive
transplantation, avoiding dialysis treatment, the
decision about whether to attempt AV fistula
creation at CKD stage 4 (and, if so, when in stage
4) depends on the nephrologists estimate of the
likelihood that preemptive transplantation will
be accomplished. For patients interested in performing PD, the decision to attempt AV fistula
creation at CKD stage 4 depends on the nephrologists estimate of the probability that PD will be
successful. The benefits of planning for kidney
failure treatment are reflected in the literature
comparing the consequences of early and late
referral of patients with CKD to nephrologists.16-19
Education of Health Care Providers and Family
Members
Optimally, education in preparation for kidney
failure will include not only the patient, but also
other individuals who are likely to influence his
or her decisions. These may include family, close
friends, and primary care providers. Their understanding of such issues as the impact of interventions designed to slow progression, absence of
symptoms despite underlying kidney disease,
transplantation eligibility, choice between PD
and HD, and choice and timing of vascular
access may have critical consequences for the
patient.
Estimation of Kidney Function (CPG 1.2)
Use of GFR-Estimating Equations and
Clearances Rather Than Serum Creatinine to
Guide Dialysis Initiation
Variability in creatinine generation across the
population makes serum creatinine level alone
an inaccurate test for patients with kidney failure
Table 2. Causes of Unusually Low or High Endogenous Creatinine Generation

Condition
Vegetarian diet5
Muscle wasting5
Amputation5
Spinal cord injury6
Advanced liver disease7,8
Muscular habitus5
Asian race9
Creatinine Generation
Lo w
Lo w
Lo w
Lo w
Lo w
High
Lo w
INITIATION OF DIALYSIS
S101
Table 3. Causes of Unusually Low or High Kidney Tubular Creatinine Secretion

Drug or Condition
Trimethoprim5
Cimetidine5
Fibrates (except gemfibrizol) 5
Advanced liver disease8
likely to benefit from dialysis treatment. For

most patients in CKD stages 4 and 5, estimating
equations based on serum creatinine level and
other variables approximate GFR with adequate
accuracy. For most patients, measured clearance
does not offer a more accurate estimate of GFR
than prediction equations.20
Variation in Creatinine Generation
It is well established that creatinine generation
may be unusually low in patients with a number
of conditions and that it may be increased in
individuals of unusually muscular habitus (Table 2).
In these situations, GFR estimated by using creatinine and urea clearances may be substantially
more accurate (compared with radionuclide GFR)
than results of creatinine-based estimating equations. In patients for whom endogenous creatinine
generation is likely to be unusually low or high,
GFR should be estimated by using methods
independent of creatinine generation, such as
measurement of creatinine and urea clearances.
Variation in Tubular Creatinine Secretion
Several drugs are known to compete with
creatinine for tubular secretion, and advanced
liver disease has been associated with increased
tubular creatinine secretion (Table 3). Decreased
secretion will result in artifactually low GFR
estimates, and increased secretion will result in
overestimation of GFR by means of estimating
equations. In patients for whom tubular creatinine secretion is likely to be unusually low or
high, the consequent bias to all creatinine-based
measures should be considered in interpreting
GFR estimates.
Timing of Therapy (CPG 1.3)
Initiation of Kidney Replacement Therapy
This guideline is based on the assumption that
overall kidney function correlates with GFR.
Because the kidney has many functions, it is
Kidney Tubular
Creatinine Secretion
L ow
L ow
Lo w
High
possible that 1 or more functions will decrease

out of proportion to the decrease in GFR. Therefore, caregivers should be alert to signs of declining health that might be attributable directly or
indirectly to loss of kidney function and initiate
kidney replacement therapy (KRT) earlier in
such patients. However, they should consider
that dialysis is not innocuous, does not replace
all functions of the kidney, and that HD-related
hypotension may accelerate the loss of RKF.
This may particularly be true of HD.
Individual factorssuch as dialysis accessibility, transplantation option, PD eligibility, home
dialysis eligibility, vascular access, age, declining health, fluid balance, and compliance with
diet and medicationsoften influence the decision about the timing of when to start dialysis
therapy. It may be optimal to perform kidney
transplantation or begin home dialysis before
patients reach CKD stage 5. Even when GFR is
greater than 15 mL/min/1.73 m2, patients may
have a milder version of uremia that may affect
nutrition, acid-base and bone metabolism, calcium-phosphorus balance, and potassium, sodium, and volume homeostasis. Conversely,
maintenance dialysis imposes a significant burden on the patient, family, society, and health
system. This is complicated further by the potential risks of dialysis, especially those related to
dialysis access and dialysate. These considerations necessitate conservative management until GFR decreases to less than 15 mL/min/1.73
m2 unless there are specific indications to initiate
dialysis therapy. Thus, the recommended timing
of dialysis therapy initiation is a compromise
designed to maximize a patients QOL by extending the dialysis-free period while avoiding complications that will reduce the length and quality
of dialysis-assisted life.
Theoretical considerations support initiation
of dialysis therapy at a GFR of approximately 10
S102
mL/min/1.73 m2, and this was the recommendation of the 1997 National Kidney Foundation
NKF KDOQI HD Adequacy Guideline.21-23 In
2003, mean estimated GFR at the initiation of
dialysis therapy was 9.8 mL/min/1.73 m2. This
mean value reflects lower average values (7 to
9 mL/min/1.73 m2) for young and middle-aged
adults and higher average values (10 to 10.5
mL/min/1.73 m2) for children and elderly patients. Average GFR at initiation has increased in
all age groups since 1995; it has increased most
in the oldest patients.24
It is difficult to make a recommendation for
initiating KRT based solely on a specific level of
GFR. Several studies concluded that there is no
statistically significant association between renal
function at the time of initiation of KRT and
subsequent mortality.25-28 However, others suggested that worse kidney function at initiation of
KRT is associated with increased mortality or
morbidity.23,24,29 When corrections are made for
lead-time bias, there is no clear survival advantage to starting dialysis therapy earlier in comparative outcome studies of patients initiating
dialysis therapy at a higher versus lower GFR.30,31
Furthermore, it now is clear from observational registry data from the United States,
Canada, and the United Kingdom (www.renalreg.
com/Report%202003/Cover3_Frames.htm)31A
that patients with comorbidities initiate dialysis
therapy at higher levels of estimated GFR.24,32,33
It is reasonable to assume that this practice is
based on experience and the speculation, hope,
and/or impression that dialysis therapy may alleviate or attenuate symptoms attributed to the
combination of the comorbidity plus CKD. Because symptoms of early uremia are fairly nonspecific, one can expect that patients with symptoms associated with their comorbidities would
initiate dialysis therapy early. Healthy and hardy
patients with less comorbidity likely will develop symptoms at a later stage than a frailer
early-starting comparative group. Frail patients
who start dialysis therapy earlier do not live as
long as the hardy patients who start dialysis
therapy later. However, this remains merely an

interpretation of observational data. A more definitive answer may emerge from properly designed prospective trials. One such trial expects
to report in 2008. The Initiating Dialysis Early
And Late (IDEAL) Study from New Zealand and
Australia is a prospective multicenter RCT to
compare a broad range of outcomes in patients
starting dialysis with a Cockcroft-Gault GFR of
10 to 14 versus 5 to 7 mL/min/1.73 m2.34
In 2000, the NKF KDOQI Clinical Practice
Guideline on Nutrition in CKD advocated thatin
patients with CKD and estimated GFR less than
15 mL/min/1.73 m2 who are not undergoing maintenance dialysis therapyif: (1) protein-energy
malnutrition develops or persists despite vigorous attempts to optimize protein-energy intake,
and (2) there is no apparent cause for it other
than low nutrient intake, initiation of KRT should
be recommended.35 Furthermore, those guidelines set forth measures for monitoring nutritional status and identifying its deterioration.
Those guidelines are consistent with the present
recommendations.
LIMITATIONS
Individuals vary tremendously in the physiological response to uremia and to dialysis treatment. Patients expected to experience uremic
complications often survive much longer than
the physician anticipates, without apparent adverse consequences. Patients also vary in their
willingness and ability to adhere to a medical
regimen intended to forestall the need for dialysis treatment. Health care systems and providers
vary greatly in their capability to monitor patients with advanced kidney failure safely without dialysis treatment. At best, the decision to
initiate dialysis treatment or perform preemptive
transplantation represents a joint decision by
patient and physician, reflecting their mutual
understanding of the compromises and uncertainties. It requires clinical judgment based on clinical experience.
GUIDELINE 2. PERITONEAL DIALYSIS SOLUTE CLEARANCE

TARGETS AND MEASUREMENTS
Data from RCTs suggested that the minimally acceptable small-solute clearance for
PD is less than the prior recommended level
of a weekly Kt/Vurea of 2.0. Furthermore,
increasing evidence indicates the importance of RKF as opposed to peritoneal smallsolute clearance with respect to predicting
patient survival. Therefore, prior targets
have been revised as indicated next.
2.1 For patients with RKF (considered to
be significant when urine volume is >
100 mL/d):
2.1.1 The minimal delivered dose
of total small-solute clearance
should be a total (peritoneal and
kidney) Kt/Vurea of at least 1.7
per week. (B)
2.1.2 Total solute clearance (residual
kidney and peritoneal, in terms
of Kt/Vurea) should be measured
within the first month after initiating dialysis therapy and at least
once every 4 months thereafter. (B)
2.1.3 If the patient has greater than 100
mL/d of residual kidney volume and
residual kidney clearance is being
considered as part of the patients
total weekly solute clearance goal, a
24-hour urine collection for urine
volume and solute clearance determinations should be obtained at a
minimum of every 2 months. (B)
2.2 For patients without RKF (considered
insignificant when urine volume is <100
mL/d):
2.2.1 The minimal delivered dose of
total small-solute clearance should
be a peritoneal Kt/Vurea of at least
1.7 per week measured within the
first month after starting dialysis
therapy and at least once every 4
months thereafter. (B)
BACKGROUND
Previous studies suggested that improved
survival on PD therapy was associated with
higher total small-molecule clearances.36 Ex-
trapolations from the Canada-United States

(CANUSA) Study led to the prior guidelines
of a total weekly Kt/Vurea of 2.0 and creatinine
clearance (CCr) of 60 L/wk/1.73 m2 for CAPD
patients. Higher targets were chosen for continuous cycling PD (CCPD) and patients on
APD with no daytime dwell (dry day), and, in
the absence of data, based on theoretical considerations. Reanalysis of the CANUSA Study
showed that RKF, rather than peritoneal clearance, was associated with improved survival.37 Greater urine volume was a significant
and important predictor of better survival, as
well. Results of this reanalysis subsequently
were supported by the Adequacy of PD in
Mexico (ADEMEX) Study randomized trial of
CAPD patients comparing 2 levels of PD prescription.38 The 2 groups of patients had identical survival, indicating no benefit on survival
for greater small-molecule peritoneal clearance and confirming the benefit of RKF on
survival. Further support was supplied by another randomized trial of CAPD patients from
Hong Kong39 comparing 3 levels of total Kt/
Vurea in patients with small degrees of RKF,
with the lowest group randomized to a total
Kt/Vurea of 1.5 to 1.7, with no difference in
survival. Therefore, revision of the previous
guidelines is needed.
RATIONALE
Definitions
Total small-molecule clearance should be measured as Kt/Vurea and is based on a 24-hour
collection of urine (kidney Kt/Vurea; if volume
100 mL/d) and a 24-hour collection of effluent
for CAPD and APD, a sample of the effluent, and
the total drained effluent volume (peritoneal Kt/
Vurea; adding ultrafiltration with the infused dialysate volume). The term RKF is used to refer to
estimated GFR, measured as the average of CCr
and urea nitrogen clearance based on a 24-hour
urine collection. Urine volume in 24 hours of
100 mL or less is considered to represent negligible RKF, although there are few data to indicate at what level kidney function becomes negligible. The term delivered peritoneal Kt/
Vurea refers to the actual dose the patient is
S103
S104
receiving based on measurement using the described method. This is distinct from an estimated peritoneal Kt/Vurea using a kinetic modeling program. Delivered Kt/Vurea assumes that
the collection on the day the clearance is measured is representative of the patients typical
dialysis schedule and that the patient follows this
same prescription every day.
For patients with RKF (considered to be
significant when urine volume is >100 mL/d):
the minimal delivered dose of total smallsolute clearance should be a total (peritoneal
and kidney) Kt/Vurea of at least 1.7 per week.
(Moderately strong evidence). Table 4 summarizes the effect of clearance on patient survival.
In the ADEMEX Study, CAPD patients were
randomized to continue on 4 exchanges using 2
L per exchange or to an increase in the prescription to provide a peritoneal clearance of 60
L/wk/1.73 m2 by either an increase in exchange
volume or the addition of a nighttime exchange
or both.38 The 2 groups had identical overall
survival. Those with a mean total weekly Kt/
Vurea of 2.27 had patient and technique survival
equivalent to that of patients with a mean total
Kt/Vurea of 1.80.38 Peritoneal small-molecule
clearances bore no relationship to survival. In
this study, body mass indices (BMIs) in the 2
groups were 25.3 and 25.8 kg/m2, and 42% to
45% of patients had diabetes, respectively. Patients were followed up for a minimum of 2
years, with 2-year survival rates of 68.3% and
69.3%, respectively. Approximately one half the
patients had some RKF. The number of deaths in
the 2 groups was identical, although causes of
death varied slightly. In the ADEMEX Study, the
group randomized to the lower prescription had
slightly, but significantly, more deaths from congestive heart failure (CHF) and more deaths
ascribed to uremia and hyperkalemia. This was
balanced by an insignificantly higher number of
deaths in the intervention group caused by coronary artery disease and peritonitis (although peritonitis rates were not higher). Deaths caused by
CHF may have been greater in the control arm
because ultrafiltration was less in this group (130
mL/d less, which represents 3.9 L/mo), likely
because patients randomized to the higher prescription achieved this level through increased
exchange volume (which is associated with higher
ultrafiltration volumes) and, if necessary, a fifth
exchange using a nighttime exchange device.

Therefore, this difference in mortality caused by
CHF may be due to differences in fluid removal.
QOL also was assessed in the ADEMEX Study.
There were no significant differences between
the 2 groups at any time for physical composite
summary score, mental composite summary
score, or kidney disease component summary.40
Therefore, neither survival nor QOL was benefited by greater small-molecule clearances.
Results of the ADEMEX Study are consistent
with a subsequent randomized trial in Hong
Kong comparing total Kt/Vurea values of 1.5 to
1.7, 1.7 to 2.0, and greater than 2.0 in CAPD
patients.39 There were no differences in patient
survival in the 3 groups. All patients at the start
of the study had residual kidney Kt/Vurea of 1.0
or less, ensuring minimal RKF. Baseline residual
GFRs (rGFRs) were 2.38, 2.48, and 2.64 mL/min/
1.73 m2, respectively (representing kidney Kt/
Vureas of 0.44, 0.46, and 0.49 in the 3 groups,
respectively; not a significant difference). Average BMI was 22 kg/m2, somewhat smaller than
that of patients in the ADEMEX Study. The usual
prescription was three 2-L exchanges per day, as
opposed to four 2-L exchanges in the control arm
of the ADEMEX Study. During the course of the
2-year study, PD prescription was adjusted up or
down as RKF changed to stay within the randomized total Kt/Vurea category. By the end of the
study, residual kidney Kt/Vurea was at or less
than 0.1 in all 3 categories. Dialysis adequacy
was assessed every 6 months. Results of these 2
important studies highlight the need to look at
factors other than small-molecule clearance to
improve survival in PD patients because peritoneal small-molecule clearance was not a predictor of survival, hospitalization, or nutritional
state.
Observational studies support the findings of
these 2 randomized trials, indicating that RKF
(in those with RKF), rather than level of peritoneal small-molecule clearance, predicts survival,
as well as QOL.41 In a large group of US PD
patients (1,603 patients), age and serum albumin
level were predictors of death, as was RKF;
however, peritoneal clearance was not.42 Another study of 763 patients found that neither
peritoneal Kt/Vurea nor peritoneal CCr was predictive of 1-year mortality.43 This population consisted of 53% CAPD and 34% CCPD patients;
PERITONEAL DIALYSIS SOLUTE CLEARANCE TARGETS AND MEASUREMENTS
S105
S106
S107
the rest were on both modalities during the

6-month study period or information was missing. In a longitudinal study of 412 adult PD
patients (mean age, 52 years; 66.3% men, 15.3%
with diabetic nephropathy), survival was predicted by GFR (RR, 0.88; 95% confidence interval [CI], 0.79 to 0.99; P 0.039) and not
peritoneal CCr. Comorbidity, albumin level at
baseline, and age also were predictive of survival. Transport status was not a predictor of
survival in this cohort. Kidney rGFR also was
associated with multiple measures of better QOL,
in contrast to peritoneal clearance, which was not
associated with any component of QOL.44 In yet
another study,45 transport status was not associated with survival, but survivors had significantly more residual function than those who did
not survive (4.5 versus 2.8 mL/min/1.73 m2).
Low initial RKF was associated with greater
C-reactive protein (CRP) levels, indicating a
relationship between inflammation and loss of
RKF.
Observational studies suggest that volume status is closely linked to PD patient survival, as
shown in Table 5. In a study from The Netherlands of 118 consecutive new PD patients examined in a prospective observational multicenter
cohort study using Cox proportional hazards
regression, systolic blood pressure (SBP; RR,
1.42 for every 10 mm Hg increase in blood
pressure) was a predictor of survival, but peritoneal Kt/Vurea was not a predictor of survival, nor
was kidney rGFR.46 Another study from The
Netherlands examined poor outcomes (death or
at least 2 of the following: prolonged hospitalization, serum albumin 3 g/dL, or malnutrition) in
189 patients and found that a model including
comorbidity, serum albumin level, and physical
and mental QOL was predictive of poor outcome, with a receiver operating characteristic
(ROC) value of 0.84. A post hoc analysis excluding serum albumin level and QOL found that
mean arterial blood pressure (MAP) was a strong
predictor of poor outcome (MAP 107 mm Hg
had an 8.6 times greater risk compared with
MAP 107 mm Hg; P 0.005), but only in PD
patients, not HD patients.47 Similar results were
found in an observational study from Turkey
examining outcomes in 125 PD patients (who
had survived 6 months on PD therapy), 92% of
whom were on CAPD therapy. Comorbidity,
S108
serum creatinine level (likely a measure of nutrition), RKF, and hypertension (RR, 5.6; P
0.001), but not peritoneal clearance, were predictors of survival.48 Another study showed that
CRP level, RKF, and left ventricular mass index
(LVMI) were all predictive of both all-cause
mortality and cardiovascular death.49 An analysis of United States Renal Data System (USRDS)
Wave 2 data regarding blood pressure in PD
patients found that only low blood pressure (111
mm Hg) was predictive of death, clearly a reflection of poor cardiac function because the finding
was only present in those with a prior history of
CHF (positive or suspected, 68% of total
group).50 Of those with low blood pressurein
patients not administered antihypertensive medications (18% of total)there were no associations between blood pressure and mortality. It is
unclear whether this negative effect of low blood
pressure was caused by a harmful effect on RKF,
but this seems possible. All these studies suggest
that close attention to volume status and blood
pressure control are important in maximizing PD
patients chances of survival. Because of the
emerging evidence about the importance of euvolemia, the Work Group has added Guideline 4.
Serum albumin level has been shown repeatedly to be a predictor of survival in dialysis
patients. In a retrospective study from Turkey of
334 patients on CAPD therapy, survival was
predicted by age, serum albumin level, cormorbid conditions (including peripheral vascular disease), and functional status, but not by Kt/
Vurea.51 There are many causes of low albumin
levels, including poor intake, chronic inflammation, chronic liver disease, volume overload,
metabolic acidosis, and inadequate dialysis.52
There is little evidence that increasing smallmolecule clearance improves serum albumin
level. In neither the ADEMEX Study nor the
randomized study from Hong Kong did higher
peritoneal clearances lead to improvement in
nutritional status.
Other maneuvers appear to be more successful
in improving nutritional status. In a blinded randomized placebo-controlled trial of 60 CAPD
patients with a total Kt/Vurea of 1.91 to 1.93 at
the start of the study (and RKF of 1.78 to 1.91
mL/min), oral bicarbonate replacement was associated with an improvement in subjective global
assessment (SGA) score and a decrease in an-
S109
orexia.53 By the end of this 52-week study, total

average Kt/Vurea values were 1.77 (treatment)
and 1.78 (placebo). Three randomized trials examined the use of supplements to improve protein malnutrition.54-56 Protein powder (15 g
[equivalent to 11 g of high biological value
protein] administered twice daily) in CAPD patients with a total average Kt/Vurea of 1.7 to 1.8
was effective in improving SGA scores,55 whereas
an oral liquid protein supplement was not effective, in large part because of poor tolerance.56
Likewise, a randomized trial of amino acid tablets in PD and HD patients found that the supplement improved serum albumin levels in HD
patients, but not PD patients; adherence was poor
in PD patients.54
Overhydration also is a cause of hypoalbuminemia in PD patients.57 Twenty-one patients (15
patients, CAPD; 6 patients, CCPD) had an increase in serum albumin level, decrease in blood
pressure, and decrease in number of antihypertensive drugs after adjustment of the PD prescription to increase fluid removal. Therefore, the
existing evidence suggests that if Kt/Vurea is 1.8
or greater and serum albumin level is low, attention should be directed toward correcting metabolic acidosis and fluid overload and consideration should be given to a palatable protein
supplement. If Kt/Vurea is borderline (ie, 1.8),
consideration should be given to increasing the
dose of PD and to assessment of adherence with
the prescription.
Surprisingly few data are available regarding
the relationship between peritoneal small-molecule clearance and technique survival (Table 6).
In the ADEMEX Study, overall withdrawal from
the study and technique survival were similar for
the 2 groups on differing PD prescriptions.38
Cause of withdrawal varied, with more patients
in the control group withdrawing because of
uremia (compared with none in the intervention
group); however, by virtue of the study design,
neither patients nor physicians could be blinded
to the group. In the randomized trial from Hong
Kong,39 withdrawal from the study was 6%
because of inadequate dialysis and 8% because
of inadequate ultrafiltration for the group randomized to a total Kt/Vurea of 1.5 to 1.7 compared
with no patients withdrawn because of inadequate dialysis in the group randomized to a total
Kt/Vurea of 1.7 or greater. In an observational
S110
study, higher peritoneal Kt/Vurea was an independent predictor of better technique survival in a
group of patients with an average peritoneal
Kt/Vurea of 1.59.58 In another observational study
from the Netherlands Cooperative Study on the
Adequacy of Dialysis (NECOSAD)44 combining
patient and technique survival, there was no
effect of peritoneal clearance on outcome. In 413
patients at 3 months on dialysis therapy, renal
weekly Kt/Vurea was 0.82 and peritoneal weekly
Kt/Vurea was 1.52. At 36 months of follow-up, 31
patients remained in the cohort, with essentially
the same renal and peritoneal Kt/Vurea values.
These results taken together suggest that setting
the minimal total Kt/Vurea target at 1.7 should not
have a negative impact on technique survival.
Measured total Kt/Vurea is not always the
consistently delivered Kt/Vurea. Ultrafiltration
may vary considerably from day to day, urine
volume and GFR may fluctuate with volume
status, and the patient may change the timing of
the dialysis schedule or miss exchanges.59,60
Nonadherence with PD appears to vary by race
(patients of Asian extraction are very adherent,
for example), age (younger patients are more
nonadherent than older), employment status (employed patients are more nonadherent than unemployed), and, possibly, country, indicating cultural influences.61,62 Therefore, in a patient who
is not doing well on PD therapy, assessment of
performance of the PD should be done.
Adherence can be evaluated by talking to
patients and assessing inventory and use of supplies.63 In the ADEMEX Study, adherence was
assessed by consumption of dialysis solutions; in
the control group, 15.1 exchanges were missed
per patient compared with 18.6 exchanges missed
per patient in the intervention group.38 Because
follow-up was a minimum of 2 years, this indicates that less than 1 exchange was missed per
month, representing excellent adherence in these
Mexican patients. Adherence has not been reported in the studies from Hong Kong, but it is
possible that adherence with PD exchanges is
significantly and importantly better than in the
United States.
Close attention must be paid to the patients
commitment to fulfilling the prescription with
the new lower targets. Perceived decreased control over future health, depression, and concern
over restrictions that kidney disease imposes on
S111
daily life were all predictors of nonadherence.64

Few interventions have been done to decrease
nonadherence; this is a critical area for future
research.
To summarize, since the last guidelines were
published, 2 randomized trials examining different levels of small-molecule clearance have been
done in CAPD patients, showing no benefit of
the higher small-molecule clearances on patient
survival, nutritional status, hospitalization, or
QOL. Emerging data suggest that the focus to
improve survival in PD patients should be on
preserving RKF, controlling volume overload
(and thus blood pressure), treating metabolic
acidosis, and perhaps use of protein supplements. Therefore, the minimal target is changed
to a minimum Kt/Vurea of 1.7 per week, but
careful attention must be paid to adherence to the
prescription. The Work Group wishes to emphasize that this minimal target should not be interpreted as an average value for a program, but that
each patient should have a total Kt/Vurea at 1.7 or
higher.
For patients with RKF, total solute clearance
(residual kidney and peritoneal, in terms of
weekly Kt/Vurea) should be measured within the
first month after initiating dialysis therapy and
at least once every 4 months thereafter. If the
patient has greater than 100 mL/d of residual
kidney volume and residual kidney clearance is
being considered as part of the patients total
weekly solute clearance goal, a 24-hour urine
collection for urine volume and solute clearance determinations should be obtained at a
minimum of every 2 months. In the CANUSA
Study, RKF and peritoneal clearances were measured at baseline and every 6 months.65 During
this 2-year study, kidney CCr decreased from
38.8 to 14.3 L/wk/1.73 m2, a rate of decrease of 1
L/wk/1.73 m2/mo, or 0.1 mL/min/mo. The change
in total small-molecule clearance was caused
almost entirely by the gradual decrease in RKF
because few changes were made in PD prescription. Therefore, if small-molecule clearance is
dependent on RKF and the PD prescription,
close monitoring of kidney function appears warranted.
In the randomized trial from Hong Kong,
patients within each category had the prescription adjusted (either an increase or decrease) so
that total Kt/Vurea was within the target of each
S112
group (1.5 to 1.7, 1.7 to 2.0, and 2.0).39 Entry

criteria required an initial kidney Kt/Vurea less
than 1.0; average kidney Kt/Vurea values at the
start were 0.44, 0.46, and 0.49 (not significantly
different) for the 3 groups, and this number was
added to the peritoneal clearance. The PD prescription was, in turn, adjusted to reach the total
target. The first adequacy assessment was done
at 4 to 8 weeks after starting CAPD therapy, and
a reassessment was done 4 to 6 weeks after
adjusting the prescription. From that point on,
clearances were obtained every 6 months. During the course of the study, there was a steady
decrease in RKF in all 3 groups, such that by 37
months, average kidney Kt/Vurea was less than
0.1 in all 3 groups.
There is considerable variability in the rate of
RKF loss in PD patients.66 Therefore, to prevent
patients from falling below the minimum total
Kt/Vurea target of 1.7, when RKF is included in
the determination, it appears prudent to obtain a
24-hour urine measurement every 2 months. Because peritoneal Kt/Vurea does not change much
over time unless the prescription changes, every
4 months is believed to be adequate for measurement of peritoneal Kt/Vurea unless a change in
RKF is noted.
For patients without RKF (considered to be
insignificant for urine volume <100 mL/d), the
minimal delivered dose of total small-solute
clearance should be a peritoneal Kt/Vurea of at
least 1.7 per week measured within the first
month after starting dialysis therapy and at
least once every 4 months thereafter. There
are no RCTs of small-molecule clearance doses
that examine outcome in only anuric patients.
However, in the ADEMEX Study, anuric patients
(defined as GFR 1 mL/min and constituting
56% of the control group and 54% of the intervention group) were analyzed separately. There was
no survival benefit to increased small-molecule
clearance in anuric patients. Although values for
peritoneal Kt/Vurea are not given for this subset,
for all patients in the study, peritoneal Kt/Vurea
values were 1.58 and 1.59 at baseline and 1.62
and 2.13 averaged across the study duration,
respectively.38 The control CAPD prescription
was 2 L times 4 exchanges. These results suggest
that peritoneal Kt/Vurea of 1.62 in anuric CAPD
patients results in the same survival as for those
with Kt/Vurea of 2.1.
Most studies examining the relationship of

Kt/Vurea to outcome in anuric PD patients come
from Hong Kong. A descriptive study of a cohort
of 140 anuric Chinese CAPD patients showed a
relationship between small-molecule clearance
and patient survival.67 In this study, mean weekly
Kt/Vurea was 1.72 (confidence limits, 1.1 to 2.23,
indicating that a number of patients had low
peritoneal Kt/Vurea). The 2-year survival rate
was 68.8%, similar to the ADEMEX Study. Peritoneal Kt/Vurea was an independent predictor of
survival at this lower range of Kt/Vurea.67 The
usual prescription in these smaller patients (BMI,
23.4 kg/m2 on average) was 3 times 2 L/d, with
increased volume per exchange prescribed only
with poor ultrafiltration despite use of increased
dextrose dialysate.
Another retrospective analysis of Chinese
CAPD patients (n 168) compared 49 anuric
patients (GFR, 0.7 and 0.05 mL/min/1.73 m2)
with an average Kt/Vurea of 1.93 0.19 with 71
patients with Kt/Vurea of 1.38 0.22 and found
that 1-year survival rates were 91.8% and 87.3%;
hospitalization and technique survival were not
different, but normalized protein equivalent of
total nitrogen appearance (nPNA) decreased a bit
more in the group with the lower Kt/Vurea, although this difference was insignificant (delta,
0.02 versus 0.04 g/kg/d decrease). Of note, patients with the higher Kt/Vurea were on an average exchange volume of 8 L/d, whereas those
with the lower clearance were on 6 L/d.68 Anuric
CAPD patients not only have greater overall
mortality than nonanuric patients, the cause of
the increase can be attributed to sudden cardiac
death.69 These data suggest that Kt/Vurea of 1.7
(1 SD greater than the mean for the group with
the lower Kt/Vurea) should be sufficient in anuric
patients. Close attention must be paid to cardiac
risk factors to prevent sudden death in these
patients.
Another observational study from Hong Kong
suggests some benefit of increasing dose of dialysis, but with a plateau effect. The study examined
outcome and risk factors for death in 150 anuric
PD patients (defined as 24-hour urine 100
mL).70 After anuria developed (at a mean time
on PD therapy of 44.1 months, with subsequent
follow-up with anuria of 50.0 months), patients
with a baseline peritoneal Kt/Vurea less than 1.67
were more likely to die than those with perito-
neal clearance greater than this (RR, 1.985; P

0.01). Baseline Kt/Vurea at the start of anuria was
not predictive of mortality with Cox proportional
hazard survival analysis (RR, 0.919 for every 0.1
increase, 0.833 to 1.014; P 0.094). Survival
was identical for those with Kt/Vurea greater than
or less than 1.80 (P 0.98), but in the subpopulation with Kt/Vurea less than 1.8 at baseline
anuria, a subsequent Kt/Vurea greater than 1.76
resulted in better survival than for those with a
clearance less than this (P 0.033). In this
observational study, PD prescription was changed
to increase Kt/Vurea after anuria occurred.
Women, in particular, were at increased risk for
death with a Kt/Vurea less than 1.67.
An observational study compared CAPD patients with total Kt/Vurea of 2.03 because of
significant RKF with those with total Kt/Vurea of
1.93 and very little RKF (RKF 0.30 mL/min/
1.73 m2) with a third group with very little RKF
and total Kt/Vurea of 1.38 (RKF 0.29 mL/min/
1.73 m2).68 Patients in the 2 groups with equivalent Kt/Vurea (66% and 96% because of peritoneal rather than RKF, respectively) had equivalent
survival and nutritional status. The group with
the lower Kt/Vurea (1.38; 96% from peritoneal
and virtually no RKF) had equivalent survival,
hospitalization, and technique survival, but baseline normalized protein catabolic rate (nPCR;
grams per kilogram per day) and percentage of
lean body mass were worse for those patients
compared with both other groups.
A single dialysis center observational cohort
study of 270 CAPD patients followed up to 6
years with average total Kt/Vurea of 1.78 0.4
and peritoneal Kt/Vurea of 1.59 0.37 (0.82 to
2.33) showed in prevalent patients only (as opposed to incident) that an increase of 0.1 in
peritoneal Kt/Vurea was associated with 9% better survival (RR, 0.91; 0.85 to 0.98). Because
prevalent patients would have much lower (if
any) RKF, this study supports the hypothesis that
only at low levels of small-molecule clearance
does peritoneal clearance have an impact on
survival.58
The European Automated Peritoneal Dialysis
Outcome Study (EAPOS) was a prospective multicenter study of outcomes in anuric APD patients (n 177).71 One half the patients were
using icodextrin for the long exchange. Timeaveraged analyses showed that age, SGA grade
S113
C, and diabetic status predicted patient survival.

Time-averaged CCr and baseline solute transport
status had no effect on patient or technique
survival. The range of CCr (liters per week per
1.73 m2) was 55.2 to 76.6 in this study.71 At
baseline, 12% of patients had a body surface area
(BSA) greater than 2.0 m2, and mean CCr ranged
from 46 L/wk/1.73 m2 for low-average transporters to 75 L/wk/1.73 m2 for high transporters.
EAPOS results suggest that large anuric patients,
including those with low-average transport status,
can be maintained successfully on APD therapy.
The NECOSAD Study Group, a prospective
multicenter cohort study of new adult dialysis
patients, recently released results of a study examining the relationship between small-solute
clearances in anuric PD patients (n 130).72 At
the point of anuria, patients had been on PD
therapy (primarily CAPD) for an average of 13
months and peritoneal weekly Kt/Vurea was 1.8.
Mean BMI was 24.8 kg/m2. Anuria in this study
was defined as urine output less than 200 mL/d.
When Kt/Vurea was analyzed as a time-dependent
continuous variable correcting for age, Davies score,
SGA, time on dialysis therapy, serum albumin
level, and hemoglobin concentration, there was no
relationship with survival. When Kt/Vurea was analyzed as a dichotomous value (1.7 versus 1.7),
there was no relationship with survival. Only when
Kt/Vurea was analyzed as a dichotomous value
(1.5 versus 1.5) could a relationship with survival be seen (RR, 3.28; 95% CI, 1.25 to 8.60; P
0.02). These results are consistent with those of the
2 RCTs previously discussed, which did not show a
survival benefit of increased small-molecule clearance in PD patients.
To summarize, although data are limited, peritoneal weekly Kt/Vurea of 1.7 in anuric patients
on CAPD therapy appears to be an adequate
minimal target. Randomized trials assessing different levels of peritoneal Kt/Vurea in anuric
patients are needed. Randomized trials to assess
different targets in APD patients also are needed.
In patients who are anuric, the dose of total
small-solute clearance should be measured
within the first month after starting dialysis
therapy and at least once every 4 months thereafter. A retrospective analysis examined clearances in 115 anuric patients (89 patients, CAPD;
26 patients, APD).73 Anuria was defined as urine
output less than 100 mL/d or kidney CCr less
S114
than 1 mL/min. Clearance studies were obtained

every 3 months. This permitted adjustment in the
prescription in an attempt to meet KDOQI targets, which were Kt/Vurea of 2 or greater for
CAPD patients and 2.2 or greater for APD patients. Fifty-six percent of patients had a change
in prescription after the onset of anuria, and 25%
of these patients had an additional change based
on the collections. Therefore, frequent measurement of peritoneal Kt/Vurea in anuric patients
permits timely adjustment of the prescription.
A study assigned 100 anuric CAPD patients in
nonrandom fashion to either an increase (n 50)
or no change in prescription (n 50) and repeated the clearance at 6 months.74 Patients with
an increase in prescription (peritoneal Kt/Vurea
increased from 1.58 to 1.91) had an improvement in daily ultrafiltration, increase in nPNA
(from 0.91 to 1.10 g/kg), and increase in percentage of lean body mass (all significant) at 6
months, whereas there were no changes in any
parameters in control patients (Kt/Vurea 1.66
at month 0 and 1.69 after 6 months). This nonrandomized trial suggests that patients with Kt/Vurea
less than 1.7 may benefit from intervention.
Therefore, frequent collections appear warranted.
tients. Slightly more than one half the patients in

the ADEMEX Study were essentially anuric and
a subanalysis was performed, but the study was
not specifically designed to study this population.
There is even less information on levels of
prescribed dose for CCPD, and even more limited on APD with dry days. There are no randomized trials comparing different doses on CCPD
therapy or comparing CCPD with APD with a
dry day. Of particular interest are patients who
start PD with APD with a dry day and subsequently have a day exchange, and then 2 day
exchanges added, a form of incremental dialysis.
Theoretically, this might protect the peritoneal
membrane from 24-hour glucose exposure, but
middle-molecule clearance would be restricted
with such an approach if applied early in the
course of PD. In view of the very limited data
about APD clearances and outcomes, no guidelines are possible for small-molecule clearance
on APD therapy.
There are no randomized trials examining
middle-molecule clearances in PD patients. Because emerging data suggest a plateau effect of
small-molecule clearances on outcome in both
PD and HD patients, attention should be turned
to other uremic toxins. For example, there are no
randomized long-term trials examining risk for
neuropathy with these relatively low levels of
PD prescription because this may appear after
several years and the present studies examine 2
to 3 years. Longer term trials are necessary.
LIMITATIONS
There are only 2 randomized trials of dialysis
dose in PD patients. The study designs were
different in that the ADEMEX Study targeted a
higher level of peritoneal clearance (not quite
achieved), whereas the Hong Kong trial targeted
3 levels of total Kt/Vurea, combining kidney and
peritoneal clearance to achieve this and adjusting
the PD prescription to stay within the indicated
goal. Each study had a homogeneous ethnic
population (Mexican and Chinese, respectively).
Therefore, the ability to apply these results to
different ethnic groups and more culturally heterogeneous populations is limited and is the reason
that the evidence is listed as moderate, rather
than strong. Of particular concern is the variability in adherence to home prescription in other
cultures in which adherence was shown to be
problematic in some patients.
Data are limited in anuric patients. There are
no randomized trials examining different prescribed and delivered doses of peritoneal smallmolecule clearance in completely anuric pa-
IMPLEMENTATION ISSUES
The prescribed dose of PD, as is true of HD, is
not invariably the delivered dose. Patients adjust
the timing of exchanges, eliminate exchanges,
and change the dextrose of the dialysis solution,
resulting in variations in ultrafiltration that, in
turn, affect small-molecule clearance. Patients
are responsible for their dialysis delivery, yet
depression is common in PD patients, which may
impact on adherence.75,76 Close attention must
be paid to the patients ability to perform (mentally and physically) his or her dialysis.
Furthermore, RKF does not remain stable. It is
affected by volume status and tends to decrease
over time. Therefore, if including residual kidney clearance as part of total Kt/Vurea, the measured dose of Kt/Vurea may not precisely reflect
the delivered dose of Kt/Vurea, which will be less

in some cases. This means that the clinician should
err on the side of a higher prescribed dose when
possible.
Implementation of the goal of euvolemia in
PD patients involves close monitoring of urine
volume, ultrafiltration, and physical examination, including blood pressure. Both home records
and in-center measurements are needed. Frequent contact with the patient to supervise the
use of the appropriate dialysis dextrose solution
is necessary. The use of loop diuretics may be
indicated to increase urine volume as appropriate
(discussed later). Negative ultrafiltration with
the long exchange should be avoided by adjusting the prescription and dialysate dextrose solution.
COMPARISON TO OTHER GUIDELINES
In 1999, the Canadian Guidelines for Adequacy
and Nutrition in PD were published.77 For CAPD
and APD, the minimum weekly Kt/Vurea clearance
target was set at 2.0. CCr targets were 60 L/wk in
high and high-average peritoneal transporters and
50 L/wk in low and low-average peritoneal transporters. This was given as an opinion. Clearance
values for Kt/Vurea of 1.7/wk and CCr of 50 L/wk
were considered almost always unacceptable. The
recommendation was to perform a collection within
6 to 8 weeks of starting PD therapy and then,
ideally, every 6 months, unless the prescription was
changed or clinical status changed unexpectedly. A
cautionary note was to be aware of the potential for
noncompliance with exchanges. Clinic visits were
considered to be adequate every 2 to 3 months
unless the patient was not doing well. It was recommended to perform a peritoneal equilibration test
(PET) within 6 weeks of initiating PD therapy.
Special attention should be paid to state of hydration, serum albumin level, and nutritional status in
high transporters. The importance of controlling
volume overload and hypertension was emphasized.
The draft document from November 21, 2003,
of the Canadian Society of Nephrology Clinical
Practice Guidelines on PD Adequacy, not yet finalized, indicates that the term adequacy must be
defined more broadly, rather than limited to only
small-molecule clearances. The authors suggest
that adequate dialysis includes attention to volume
status and nutrition and cardiovascular risk reduc-
S115
tion. Focus on preservation of RKF also is necessary. The Canadian draft guidelines contain 6 sections. The first indicates that peritoneal Kt/Vurea
should be maintained at a minimum of 1.7 per
week in both CAPD and APD patients when kidney rGFR is less than 4 mL/min. In patients with
GFR greater than 4 mL/min, peritoneal Kt/Vurea
may be maintained at 1.0 to 1.7. If the patient
appears uremic, the peritoneal prescription should
be increased. The draft guidelines emphasize the
importance of considering lifestyle issues of the
patient and caretakers, if any, and the effect of
cumulative exposure to glucose. If peritoneal clearance is less than 1.7/wk because of dependence on
RKF, the recommendation is to measure GFR every 2 months. Peritoneal Kt/Vurea can be measured
every 6 months unless there is an unexpected
change in the patients condition. One section in
the draft document is devoted to volume status and
blood pressure. Emphasis is placed on appropriate
prescription (in particular, a reasonable dwell time
of at least 2 hours to permit sodium removal) and
use of icodextrin and diuretics, as appropriate. If
blood pressure is greater than 130/80 mm Hg, the
investigators recommend achieving euvolemia and,
if not effective, adding an antihypertensive, giving
preference to an angiotensin-converting enzyme
(ACE) inhibitor.
The Australian PD guidelines are published online (www.cari.org.au; last accessed 2/14/2006).77A
As evaluation of adequacy, the guidelines recommend including clinical assessment of well-being,
physical measurements, small-solute clearance, fluid
removal, and the impact of treatment on the individuals life. Clearances alone (either greater or
less than the target) should not be interpreted as
representing adequate or inadequate dialysis. For
CAPD and APD, weekly Kt/Vurea is recommended
as 2.0, with a minimum of 1.7/wk. Minimum CCr
target is given as 60 L/wk in high and high-average
transporters and 50 L/wk in low-average and low
peritoneal transporters. Kt/Vurea less than 1.7 and
corrected CCr of 50 L/wk should be considered
unacceptable for a patient with a BMI of 20 to 26
kg/m2. Emphasis is placed on not using smallsolute clearance alone, but interpreting results together with clinical and laboratory assessments,
including hydration status, blood pressure and lipid
control, bone disease, anemia, and nutrition.
The Renal Association (UK) Guidelines, published in August 2002, recommend a total
S116
weekly CCr, combining dialysis and RKF, of

50 L/wk/1.73 m 2 and/or weekly dialysis
Kt/Vurea of 1.7 or greater (www.renal.org/
Standards/RenalStandSumm02.pdf).77B These
should be measured by 6 to 8 weeks after the
start of dialysis therapy and repeated at least
annually, more often if RKF is rapidly decreasing. The suggestion is made that high or highaverage transporters and APD patients may
need higher targets.
The European Best Practice Guidelines for PD
were initiated in 1999 and published in 2005.78
The minimum peritoneal target for Kt/Vurea in
anuric patients is 1.7, identical to that in the
present guidelines, but in addition, the guidelines

recommend net ultrafiltration in anuric patients
of 1.0 L per day. This guideline is believed to be
evidence based (level B). No specific targets are
provided for those with RKF other than to note
that RKF can compensate when these peritoneal
targets are not achieved. A higher Kt/Vurea target
for APD was not recommended, with the rationale of the rapid diffusion of urea during short
cycles, such as occurs with the cycler at night.
However, the guidelines recommend achieving a
minimum CCr of 45 L/wk/1.73 m2, as well as a
minimum Kt/Vurea of 1.7 in patients on the
cycler (evidence level C).
GUIDELINE 3: PRESERVATION OF RESIDUAL

KIDNEY FUNCTION
Prospective randomized trials of dialysis
adequacy and many observational studies have
confirmed a strong association between the
presence of RKF and reduction of mortality in
patients on PD therapy.
3.1 It is important to monitor and preserve
RKF. (A)
3.2 In the patient with RKF who needs antihypertensive medication, preference should be
given to the use of ACE inhibitors or angiotensin receptor blockers (ARBs). (A)
3.3 In the normotensive patient with RKF,
consideration should be given to the use of
ACE inhibitors or ARBs for kidney protection. (B)
3.4 Insults to RKF (see Table 7) in patients
with CKD also should be considered
insults to RKF in PD patients and should
be avoided when possible. (B)
BACKGROUND
Studies of the adequacy of PD, measured by
small-solute clearance (Kt/Vurea and CCr), have
shown that in the presence of RKF, outcome is
driven by the kidney component only. In studies
in which both the kidney and peritoneal contribution to small-solute clearance are measured, RR
for mortality is related inversely to only the
kidney component.37,41,42,46,79 There is no significant association between peritoneal small-solute
clearance and outcome. It is only in studies of
anuric patients that peritoneal clearance parameters are associated with outcome,67,73 and even
then, peritoneal ultrafiltration may be more important than peritoneal small-solute clearance.71 The
mechanism(s) involved in the robust association
between RKF and reduction in mortality are
purely speculative.
One possible benefit of preserved kidney function may be the kidney excretion of salt and
water, which helps maintain euvolemia. In the
reanalysis of the CANUSA Study, residual urine
volume was more important than residual kidney
small-solute clearance in predicting outcome.37
Furthermore, other studies showed that preserved kidney function is associated with both
better blood pressure control and maintenance of
more normal cardiac geometry.48,87,88
Another explanation for the benefit of RKF is

that ongoing kidney clearance of uremic solutes
contributes in a more significant way to reduction in mortality than that afforded by peritoneal
clearance. Why kidney Kt/Vurea or CCr should
reduce mortality while peritoneal Kt/Vurea or CCr
does not very likely lies in other solutes cleared
by the kidneys and perhaps less well-cleared by
the peritoneal membrane. In other words, kidney
small-solute clearance parameters serve as a
marker of ongoing kidney function, but the benefit of the function is in the removal of other
unmeasured uremic toxins.
Another possibility is that the association of
preserved kidney function and better outcome is
not the direct result of any excretory function of
the kidney (eg, salt, water, small or large solutes). It may be that intrinsically healthier or
relatively uninflamed patients may have a
slower decrease in RKF. Studies have reported
comorbid disease to be associated with faster
decrease in RKF in patients on dialysis therapy89;
thus, the absence of comorbid disease would be
associated with relative preservation of kidney
function. Therefore, the better outcome in dialysis patients with more preserved kidney function
may be a marker of the relative absence of
comorbid disease in these patients, rather than a
particular life-prolonging function of the kidneys
themselves.
Large population studies showing an association between decrease in kidney function and
adverse cardiac events have led to the cardiorenal hypothesis. This hypothesis states that loss
of kidney function increases the chance of cardiac-associated mortality in a manner that is not
readily explained by traditional cardiac risk factors, such as lipid disorders. Healthy kidneys are
associated with an absence of inflammation, and
the increasing incidence of cardiac events with
even minor decrements in kidney function may
reflect the loss of this antiinflammatory function.
This has led to the observation that patients with
decreasing kidney function are more likely to die
of cardiac causes than to reach CKD stage 5.90
However, in those who reach the need for dialysis, the association of further decrease in RKF
with adverse events may simply reflect the same
S117
S118
cardiorenal process, albeit now at the dialytic

end of the spectrum of kidney function.
In the absence of certainty about which, if any,
aspect of kidney function is associated with the
improved outcome, it seems reasonable to try to
preserve kidney function for as long as possible
in patients on dialysis therapy.
general can be assumed to be nephrotoxic to

RKF. There are different levels of evidence to
support these assumptions.
RATIONALE
Definitions
RKF represents the function of the native
kidneys or the in situ kidney allograft. GFR is
estimated by the numerical average of the 24hour CCr and urea nitrogen clearance. Urine
volume is the volume of urine produced in a
24-hour collection period. Anuric patients are
those for whom 24-hour urine volume is considered insignificant, arbitrarily chosen as 100 mL/d
or less. However, as mentioned in Guideline 2, it
is unclear at what volume or GFR the contribution of RKF is considered negligible and the
patient is functionally anuric.
It is important to monitor and preserve
RKF. Although the explanation for the association of preserved RKF with survival is not
known (see Background), the association is so
robust in studies from around the world that
preservation of this function should be a major
objective in the management of dialysis patients. Furthermore, although the benefit of
increasing dialytic (HD or PD) clearance appears to plateau eventually,38,91 no such asymptotic function holds for RKF. The ultimate
extrapolation would be to normal kidney function, and survival in this group is many fold
greater than in those with no kidney function.92
It is reasonable to assume that interventions
that slow the decrease in kidney function in
patients with CKD also will slow the decrease in
RKF in patients on dialysis therapy. Furthermore, agents or events that are nephrotoxic in
In the patient with RKF who needs antihypertensive medication, preference should be given
to the use of ACE inhibitors or ARBs. The last
2 decades have seen a plethora of studies showing that control of blood pressure, particularly by
the use of ACE inhibitors and ARBs, is associated with a decrease in the slope of decline in
kidney function in patients with kidney disorders, particularly those with diabetic kidney disease or glomerulonephritis.93-97 In many studies,
the salutary effect of ACE inhibitors and especially ARB agents was seen with little or no
change in blood pressure control. Again, can the
assumption be made that interventions that slow
the decrease in GFR in patients with CKD also
work in dialysis patients?
A retrospective study of more than 200 PD
patients found that patients not administered antihypertensive drugs had a faster decrease in
their kidney function.89 In analysis of data from
the USRDS, use of an ACE inhibitor or calcium
channel blocker was associated with decreased
loss of RKF, defined as urine volume greater than
200 mL/d.98
These observations led to 2 RCTs that examined the effect of ACE inhibition and angiotensin
receptor blockade on RKF in PD patients. In the
first study, 60 PD patients were randomized to
receive 5 mg of ramipril or no treatment. Other
antihypertensive agents could be used. At the end
of 1 year, the subgroup administered the ACE
inhibitor had just less than 1 mL/min greater
GFR compared with those not administered the
drug.99 A similar study, albeit in even fewer
patients, showed that 40 to 80 mg/d of valsartan
was associated with a slower decrease in GFR
and urine volume at 24 months, without a difference in blood pressure.100 Although the number
of patients in each study was small, there is

consistency between the 2 studies and a believable physiological underpinning to the findings.
For this reason, the use of these agents is recommended when antihypertensive therapy is indicated for PD patients.
In the normotensive patient with RKF, consideration should be given to the use of ACE
inhibitors or ARBs for kidney protection. It is
not clear how much of the renoprotective effect
of ACE inhibitors or ARBs is related to their
antihypertensive effect versus other mechanisms.
Studies of nondialysis populations suggested
that the renoprotective effect is, in part, independent of effects on blood pressure. Therefore,
these agents often are used in patients with CKD,
especially those with glomerulonephritis or diabetic kidney disease, even if the patients are
normotensive. If this effect can be extrapolated
to patients on dialysis therapy, it would suggest
that these agents can slow the decrease in kidney
function even in those with normal blood pressure. In both studies of ACE inhibitors and
ARBs, the salutary effect of the drugs on RKF
was independent of changes in blood pressure.99,100 One study specifically targeted patients with a blood pressure of at least 120/70
mm Hg.99 Although average entry blood pressure was high, it is not clear whether normotensive patients were involved in these studies and
whether the agents had an effect in this subset of
patients (Table 8).
Insults (Table 7) to RKF in patients with
CKD also should be considered insults to
RKF in PD patients and should be avoided
when possible. Other drugs, events, and interventions that worsen kidney function in patients
with CKD also should be expected to worsen
RKF in patients on dialysis therapy. Potential
insults are listed in Table 7; this list should not be
considered all inclusive. Whereas it is reasonable
to make the assumption that exposure to these
potential nephrotoxins might harm RKF in PD
patients, there is little high-grade evidence to
prove it.
Retrospective analyses of RKF found that previous episodes of PD peritonitis are associated
with faster kidney decline.89,101 This could be
the result of the inflammation of the peritoneum
itself, drugs used to treat the infection, or associated ECF volume depletion. A general linear
S119
multivariate model also implicated the use of

aminoglycosides, separate from the rate of peritonitis, as an associated factor.89 A retrospective
study of RKF found that patients for whom
peritonitis was treated with aminoglycosides had
a greater decrease in kidney function compared
with those treated with other less-nephrotoxic
antibiotics.102 However, the most recent retrospective analysis could not detect a difference in
the slope of decrease in GFR in PD patients with
peritonitis treated with or without gentamicin.103
The data therefore are not strong and are somewhat contradictory. However, if an antibiotic
without the nephrotoxic potential of an aminoglycoside can be used in its place without compromising antibacterial efficacy, it is still recommended to do so.
Other agents that should be avoided are nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors. These
drugs may be particularly harmful under conditions of preexisting kidney insufficiency or diminished kidney blood flow. This setting, of course,
applies to RKF in patients on dialysis therapy;
thus, this may represent a group particularly
vulnerable to the nephrotoxic effects of COX-2
inhibitors. Conventional analgesia, such as acetaminophen, should be used in dialysis patients
with noninflammatory pain. Other drugs to consider are low-dose opiates (watching for constipation) and short courses of oral or intra-articular
corticosteroids for acute inflammatory noninfectious arthritis.
Intravenous or intra-arterial dye can be nephrotoxic, especially in patients with antecedent kidney dysfunction, particularly diabetic nephropathy. Again, there is no reason to expect that this
risk is less for RKF in patients on dialysis therapy.
In dialysis patients with kidney function, the
decision to administer a dye load should not be
taken lightly. The indication for the dye study
should be reviewed, and alternative studies that
do not use dye should be sought. The patient who
must undergo the study should be well hydrated
at the time, and the smallest volume of the least
nephrotoxic dye should be used. Whether pretreatment with N-acetylcysteine is helpful in decreasing the incidence and severity of dye nephrotoxicity is controversial in patients with CKD;
there are even fewer data for patients on dialysis
therapy.104,105 Furthermore, there are no studies
S120
examining volume expansion as a method of

protecting RKF in patients on dialysis therapy
who must undergo contrast studies. However,
given the low cost and favorable side-effect
profile of N-acetylcysteine, consideration should
be given to pretreating patients with this agent
before the dye study, and it also would seem
reasonable to ensure that volume depletion is not
present.
As in any patient with unexplained deterioration in kidney function, both prekidney and postkidney causes should be ruled out. Given that the
mean age of patients starting dialysis therapy is
increasing, prostatic hypertrophy with urinary obstruction must be considered in men with sudden
deterioration in function. Episodes of ECF volume depletion are associated with a decrease in
urine volume and function106,107 and should be
avoided unless necessary to keep the patient out
of CHF.
PD is associated with low bone turnover. In
PD patients, there is a good chance of hypercalcemia as a result of aggressive therapy with oral
calcium or calcitriol and vitamin D analogs. The
resulting increase in serum calcium concentration could be nephrotoxic; thus, hypercalcemia
should be avoided.
Finally, many patients who start on (or return
to) PD therapy after a failed kidney transplant
have significant residual function in the transplanted kidney. It is unclear whether patients should
continue to receive immunosuppressive therapy,
particularly with agents other than calcineurin inhibitors, in an attempt to prolong this RKF. A recent
S121
decision analysis suggested that the benefit of continued immunosuppression outweighed the risk
when CCr was greater than approximately 1.5 mL/
min.108 However, this conclusion remains to be
validated by clinical studies.
Whether urine volume, small-solute clearance, or some other kidney-related factor is responsible for the decrease in mortality associated
with RKF, it is important to have some measure
of this residual function. It is impracticable to
use exacting tests to calculate this, such as inulin
clearance or radionucleotide measurements. The
average of urea nitrogen and CCr has been shown
to have a reasonable approximation of RKF.109
However, the accuracy of this measurement depends on the careful collection of 24-hour urine.
Especially in patients with very little function,
inaccuracy in the timing of the collection can
lead to incorrect results. Accuracy perhaps can
be improved by the collection of a 72-hour
sample and dividing the result by 3110; however,
this is a time-consuming and cumbersome process. Patients will need to be instructed on the
careful collection of 24-hour urine and make it a
habit to bring these collections as part of the
regular clinic visit.
Use of ACE inhibitors and ARBs may add to
the cost of medications for patients. In addition,
there is a risk for cough, particularly with ACE
inhibitors. There also is a theoretical risk for
hyperkalemia, although this has not been found
in studies to date.
GUIDELINE 4. MAINTENANCE OF EUVOLEMIA

Volume overload is associated with CHF,
left ventricular hypertrophy (LVH), and hypertension; therefore, it is important to monitor ultrafiltration volume, dry weight, sodium
intake, and other clinical assessments of volume status.
4.1 Each facility should implement a program that monitors and reviews peritoneal dialysate drain volume, RKF, and
patient blood pressure on a monthly basis.
(B)
4.2 Some of the therapies one should consider
to optimize extracellular water and blood
volume include, but are not limited to,
restricting dietary sodium and water intake, use of diuretics in patients with
RKF, and optimization of peritoneal ultrafiltration volume and sodium removal. (B)
BACKGROUND
There is a high prevalence of coronary artery
disease, LVH, and CHF in patients with CKD
stage 5, including those on PD therapy.112 Cardiovascular disease (CVD) is the largest cause of
death in this population.112 In the general population without kidney failure, hypertension is a
major risk factor for all these conditions.113 In
patients with kidney failure, the literature is less
clear, but volume overload is widely believed to
be the major contributor to hypertension.114
Therefore, interventions to optimize volume status (and hence blood pressure) are considered
central to the management of these patients.
RATIONALE
There are no RCTs addressing the effect on
survival of interventions to improve blood pressure and volume control in PD patients, but there
is broad consensus, based on the general cardiovascular literature, that normalization of blood
pressure and volume status in these patients is
desirable.
There is circumstantial evidence from observational studies suggesting that better volume control may improve outcomes. This evidence includes the finding in a number of studies that low
transport status according to PET is associated
with improved outcome in CAPD patients; this
may reflect the beneficial effect of low transport
S122
status on peritoneal ultrafiltration and thus on

clinical outcome.36,81 Greater fluid removal (peritoneal plus kidney) also was found to be a
favorable predictor of outcomes in observational
studies of both CAPD and APD patients; again,
interpretation of this finding remains controversial because it is unclear whether greater fluid
removal indicates better or worse control of
volume status or it is just a marker of fluid
intake.48,71,115 The relationship between blood
pressure and survival in patients with CKD stage
5 is confounded by the high prevalence of cardiac failure, which is associated with both hypotension and greater mortality.116 However, 1 study
found that hypertension is associated with a
greater likelihood of de novo cardiac failure in
patients with CKD stage 5 treated with HD.117
Each facility should implement a program
that, each month, assesses patients blood pressure and volume status and evaluates their
drain volume, RKF, and dietary salt and water
intake. To ensure good control of blood pressure and volume status in PD patients, clinical
examination of the patient needs to be carried out
on a monthly basis. Less frequent examination
may be acceptable. An approach to the volume
overloaded patient has been developed by the
International Society for Peritoneal Dialysis and
was published elsewhere.218 In particular, this
should involve reevaluation of the patients target weight. Clinical examination will need to be
done more frequently in the initial weeks of PD
therapy when target weight is being established
for the first time. In stable well-established PD
patients with well-controlled blood pressure, less
frequent examination may be acceptable.
Key determinants of volume status in PD patients are salt and water intake, RKF, and net
peritoneal fluid removal; these also should be
reviewed on a monthly basis. Salt and water
intake is not routinely restricted in PD patients,
but should be evaluated if there is persistent
volume overload and hypertension. This can be
done by a dietitian or indirectly by measuring
salt and water removal by RKF and PD.
Salt and water removal are evaluated by measuring daily urinary volume and sodium content
and measuring the difference between the volume and sodium content over 1 day of the
MAINTENANCE OF EUVOLEMIA
dialysate effluent and infused dialysis solution.

In this calculation, it is important to remember
that PD solution bags routinely are overfilled to
allow for flushing of the tubing before infusion
of fluid into the peritoneal cavity.118 Total sodium and water removal by peritoneal and urinary routes can be considered a reasonable indicator of sodium and water intake, provided the
patient is clinically stable and sodium and water
losses by other routes are taken into account.
Particular attention should be given to the net
peritoneal fluid absorption that frequently occurs
with long duration dwells, such as the nocturnal
dwell in CAPD and diurnal dwell in APD, because this can be avoided by altering the PD
prescription.
Some of the therapies one should consider
implementing to optimize extracellular water
and blood volume include, but are not limited
to, restricting dietary sodium and water intake,
use of diuretics in patients with RKF, and
optimization of peritoneal ultrafiltration volume and sodium removal. As discussed, dietary advice can be given to reduce sodium and
water intake in the event of a persistent problem
with hypertension and/or fluid overload. In patients with RKF, a small RCT showed that urinary sodium and water removal can be enhanced,
or at least maintained for longer, on PD therapy
and that volume status can be improved with the
use of high-dose loop diuretics.119 Other RCTs
also showed urinary volume and clearance to be
maintained better in patients treated with ACE
inhibitors and also those treated with ARBs.99,100
Peritoneal fluid removal can be increased by
using a more hypertonic glucose solution or an
alternative osmotic agent, such as icodextrin.
Consistent use of hypertonic glucose solutions
raises concerns about damage to the peritoneal
membrane and the adverse effects of increased
systemic absorption of glucose. Concerns about
the role of glucose in membrane deterioration, in
particular, have been supported by recent studies.120,121 A preferred approach is to avoid longduration dwells that often are associated with
ineffective fluid removal or even net fluid resorption. In patients on APD therapy, this can be done
by either shortening the day dwell and leaving
the patient dry for a portion of the day or
draining out the day dwell and replacing it with
fresh dialysis solution partway through the day.
S123
In CAPD patients, it can be dealt with by switching to APD without a long day dwell or using a
night-exchange device to divide the nocturnal
dwell into 2 shorter dwells. An alternative strategy is to use icodextrin solution for the long
nocturnal dwell in CAPD patients and the long
day dwell in APD patients. This was shown in
RCTs to both increase peritoneal ultrafiltration
and decrease ECF volume.122,123 With icodextrin in place, there is no need to drain a day dwell
early to optimize ultrafiltration. However, some
patients may still request a shorter duration day
dwell (6 to 8 hours) to allow for a period of day
dry time, which some find more comfortable.
LIMITATIONS
While individual strategiessuch as loop diuretics, ACE inhibitors, ARBs, and icodextrin
have been shown to increase fluid removal and
decrease ECF volume in small RCTs, there have
been no trials of sufficient size to examine
whether these interventions impact on key patient outcomes, such as patient survival, technique survival, cardiovascular events, hospitalization, and QOL. The likelihood of such studies
being done is compromised by the large numbers
of patients that would be required to achieve
statistical power to answer these questions and
by the already widespread acceptance and use of
the strategies concerned.
With regard to studies that have been done,
use of fluid removal as an end point should be
questioned because it is possible that greater
fluid removal may simply lead to greater fluid
intake without a change in ECF volume status or
blood pressure. More weight therefore should be
given to studies that use direct and indirect
measures of volume status as end points, such as
echocardiographic indices, blood pressure, body
composition, and body compartment volume estimates.
The whole approach of optimizing blood
pressure and volume status as a means of improving patient outcome also has not been validated
in randomized trials and is justified only by
reference to the beneficial effect of decreasing
blood pressure that is evident from multiple
studies of patients without kidney failure. Again,
this strategy is so widely accepted and practiced
that it is unlikely to be tested in the PD or CKD
stage 5 population in a randomized trial. How-
S124
ever, there is a case to be made for carrying out

RCTs comparing more- and less-aggressive approaches to decreasing blood pressure because
there is no consensus about what appropriate
blood pressure targets are in the PD population.
There also is little evidence about which antihypertensives are best to use to optimize blood
pressure after volume status has been normalized, although benefits shown for high-dose loop
diuretics, ACE inhibitors, and ARBs support a
primary role for these agents.99,100,119
The question of whether greater use of hypertonic glucose damages the peritoneal membrane
has been controversial for many years. Recent
clinical studies have strengthened the evidence
for this hypothesis, but it is not conclusively
proven because studies are not randomized and
potentially are confounded by such factors as
RKF and inflammation.120,121 The question of
whether more use of hypertonic glucose causes
greater systemic harm to the patient with more
hyperglycemia, hyperlipidemia, hyperinsulinemia, obesity, and consequent cardiovascular effects has been more difficult to answer, although
it might appear intuitively logical that this is the
case. In this situation, an appropriate response
would be to give the patient the benefit of the
doubt and minimize hypertonic glucose exposure while at the same time ensuring that this is
not at the expense of volume overload and hypertension. Such a compromise would involve judicious use of salt and water restriction, loop
diuretics, and nonglucose PD solutions.
Some cautions have been voiced concerning
sodium and water removal in patients on APD. In
some patients who are performing multiple short
overnight dwells (4 exchanges over 8 hours)
the sodium sieving effect of short-duration APD
cycles, as well as the tendency for salt and water
resorption during the long day dwells may compromise BP and volume control with this modality.124,125 One study suggested superior SBP
control with CAPD compared with APD
therapy.125 However, this was not a randomized

study and previous studies, including a randomized study, did not show worse outcomes on
APD therapy.126 Also, although blood pressure
likely is an important surrogate or intermediate
outcome, it is not clear that salt and water removal is.115 It is important to note that blood
pressure control is multifactorial. Control of blood
pressure and euvolemia can be obtained in patients on APD if the prescription is individualized with attention to the UF profile on the long
dwell and minimization of sodium sieving during overnight dwells. Possible maneuvers to minimize this problem include: using less than four
overnight exchanges during 8 hours (average in
the United States is currently less than 4 exchanges/night time); shortening the day dwell by
draining and either doing an additional midday
exchange or having a dry time with no dialysate present; or by substituting icodextrin for
glucose solutions. At present, there is insufficient
evidence to justify recommending one PD modality over another, but it would be reasonable to
pay close attention to volume status and blood
pressure in APD patients.
Implementation of these guidelines requires
patients to have regular clinic visits and physical
examinations. These generally should be monthly
after the patient is established on PD therapy, but
should be more frequent during and in the first
weeks after initial training. Less frequent visits
may be acceptable if the patient is stable on PD
therapy with good blood pressure and volume
status.
Access to dietitian assistance will be required
to assess and advise patients about sodium and
fluid intake. Use of icodextrin requires access to
this solution, which is not available in some
jurisdictions and which is limited by cost considerations in others.
GUIDELINE 5: QUALITY IMPROVEMENT PROGRAMS

The continuous quality improvement (CQI)
process has been shown to improve outcomes
in many disciplines, including CKD stage 5.
5.1 Each home-training unit should establish
quality improvement programs with the
goal of monitoring clinical outcomes and
implementing programs that result in improvements in patient care. (B)
5.2 Quality improvement programs should
include representatives of all disciplines
involved in the care of the PD patient,
including physicians, midlevel practitioners, nurses, social workers, dietitians,
and administrators. (B)
5.3 Suggested domains of clinical activities
one should consider monitoring are listed
in Table 9. (B)
BACKGROUND
It is important that each facility establish a
CQI program because such programs have been
shown to improve outcomes in a variety of
disciplines, including the care of patients with
CKD stage 5. The domains to be examined need
to be considered carefully at each facility. Areas
that present particular problems at an individual
facility should receive special attention. Because
the CQI program will involve review of patientrelated activities from a variety of domains, it is
important that representatives of all disciplines
involved in the care of PD patients (physicians,
nurses, social workers, dietitians, and administrators) be included in the CQI process.
There are certain special domains that should
be considered for CQI examination for PD facilities, outlined in Table 9. These domains are in
addition to the standard therapeutic targets outlined in other parts of the KDOQI Guidelines,
which include adequacy measures, blood pressure and volume control, anemia and bone mineral metabolism management, lipid control, etc.
Technique failure is an important issue for PD
facilities.127-129 Technique failure is defined as
patients discontinuing PD for reasons other than
death or transplantation. It accounts for a variable percentage of the reasons that patients terminate PD therapy. The most common reasons
reported for technique failure include peritonitis,
catheter-related problems, psychosocial factors,
and problems with ultrafiltration or poor clearances.127-129 Programs are encouraged to evaluate the reasons that patients terminate PD therapy
and then develop strategies for improving outcomes.
Peritonitis remains a leading cause of morbidity for PD patients and has been associated with
mortality, hospitalizations, and termination of
PD therapy.130-132 Although peritonitis rates have
improved significantly during the past several
years, peritonitis remains a major issue for PD
units. It is important for facilities to develop
strategies for tracking peritonitis rates, assessing
the organisms responsible for peritonitis, and
developing strategies to better understand the
reasons for peritonitis. In addition, treatment
guidelines for peritonitis have been established
by the International Society of PD.130 Each facility needs to evaluate which treatment strategy is
best for its program; this depends on understanding the rate of peritonitis, organisms causing
peritonitis, and possible reasons for peritonitis.
Exit-site infections are a problem for PD patients
because these infections may be responsible for
peritonitis and lead to catheter removal.133-135 Treatment guidelines have been developed for the
management of exit-site care and infections.133,134
Facilities should evaluate their exit-site infection
rates and review whether their treatment practices provide acceptable levels of care.
A variety of catheters and insertion methods
have been used for PD patients. There is insufficient evidence to recommend one type of catheter or one catheter placement technique.136 Each
facility should examine catheter success rates
and methods of catheter insertion and track these
results over time.
QOL assessments for dialysis patients have
been the focus of several studies. A variety of
instruments have been used for these assessments; there is no generally agreed-upon or accepted instrument to perform these assessments.
However, it should be noted that various findings
on these QOL assessments have correlated significantly with morbidity and mortality rates in
patients with CKD stage 5 maintained on both
HD and PD therapy.137-141 Monitoring QOL may
be particularly important for a home-based
therapy.142 This is especially so because PD
S125
S126
therapy is associated with significant technique

failure rates and requires patient cooperation and
compliance. It should be noted that QOL assessments may present problems in terms of using
standardized instruments in geographically, linguistically, and culturally different groups. Although some domains of QOL problems are
amenable to therapy,76,143 it has not been shown
that interventions to improve QOL decrease adverse clinical outcomes.
Patient satisfaction with therapy for CKD stage
5 also has been attracting increased attention
recently.144,145 As treatment options for patients
with CKD stage 5 expand, it is important to
monitor how patients feel about their treatment
and their facility so that appropriate modifications can be made to improve patients perceptions of their therapy and care. This is an important issue to consider for all patients, but is
particularly relevant for patients on a homebased therapy, for whom adequate communication between the staff and the patient is essential.
There are no generally agreed-upon instruments
to assess patient satisfaction with care, but facilities are encouraged to consider examining methods of evaluating this domain.
LIMITATIONS
Although CQI programs generally are considered to be beneficial, there are no studies of PD
facilities that document the efficacy of such
programs on improving patient outcomes.
The institution of effective CQI programs requires that adequate information be made available and resources be provided to the facility to
effectively manage these programs. It is important for the facility to strive to provide the
materials necessary to permit CQI programs to
operate effectively.
Some of the areas suggested for CQI activity
in Table 9 do not have established standards or
instruments to assess these domains (eg, patient
satisfaction, QOL). Several studies attempted to
assess these domains, and each facility will need
to review these studies and select instruments
that it believes are appropriate.
GUIDELINE 6. PEDIATRIC PERITONEAL DIALYSIS

INTRODUCTION
The provision of evidence-based pediatric PD
adequacy guidelines is hampered by a number of
epidemiological issues. CKD stage 5 remains a
relatively uncommon disease in children, while
kidney transplantation is still the predominant
mode of KRT. In addition, HD is a viable modality option for many pediatric patients, especially
adolescents. Finally, children with CKD stage 5
show significantly better survival rates compared
with adult patients. As a result of these factors, no
long-term pediatric outcome study similar to the
ADEMEX Study is adequately powered to detect
an effect of the delivered PD dose on pediatric
patient outcome.38 Nevertheless, pediatric data exist, for example, to describe the most accurate
methods for assessing peritoneal membrane transport capacity and quantifying urea removal.146-148
These data and others can serve as a basis for CPGs
in children receiving PD. For areas in which no
pediatric-specific data exist, the CPGs and CPRs
for adult patients should serve as a minimum standard for pediatric patients, but the overall clinical
wellness of the individual pediatric patient should
be the primary factor that influences the quantity
and quality of the care provided.
6.1 Recommended laboratory measurements
for peritoneal membrane function:
6.1.1 The PET is the preferred approach to
the clinical assessment of peritoneal
membrane transport capacity in pediatric patients and should be performed to aid in the prescription
process. (A)
6.2 Maintenance of euvolemia and normotension:
6.2.1 The frequent presence of hypertension and associated cardiac abnormalities in children receiving PD
requires strict management of blood
pressure, including attention to fluid
status. (A)
6.3 Quality improvement programs:
6.3.1 The CQI process has been shown to
improve outcomes in many disciplines, including CKD stage 5. (A)
6.3.1.1 Each home training unit
should establish quality improvement programs with
the goal of monitoring clinical outcomes and implementing programs that result in improvements in patient
care. In children, growth and
school attendance/performance are clinical activities to be monitored in addition to those recommended
for adult patients.
6.3.1.2 Quality improvement programs should include representatives of all disciplines involved in the care of the
pediatric PD patient, including physicians, nurses, social
workers, dietitians, play
therapists, psychologists, and
teachers.
6.3.1.3 Single-center trends in pediatric clinical outcomes should
be compared with national
and international data.
RATIONALE
Recommended Laboratory Measurements
for Peritoneal Membrane Function
The PET is the most common technique used
clinically in children to assess peritoneal membrane transport capacity and guide the prescription process, although other means of membrane
assessment have been reported.146,147,149 Addition of a volume marker during the PET also can
provide valuable information regarding fluid handling. Institution of a standardized PET procedure for children has resulted from recognition
of the age-independent relationship between BSA
and peritoneal membrane surface area and the
resultant recommendation for use of a test exchange volume scaled to BSA when one conducts studies of peritoneal transport kinetics in
children.150-152 Based on 2 large-scale studies
and resultant normative data, the PET in children
should be performed with an exchange volume
of 1,000 to 1,100 mL/m2 BSA.146,147 Provision
of a smaller volume characteristically results in
more rapid equilibration of solute between blood
and dialysate and the artifactual appearance of an
inherently increased (more rapid) membrane
S127
S128
transport capacity.153 Repeated PET testing is

recommended when knowledge of the patients
current membrane transport capacity is necessary for determination of the patients PD prescription (eg, in the setting of suboptimal clearance), especially when clinical events have
occurred (eg, repeated peritonitis) that may have
altered membrane transport characteristics.154,155
Kinetic modeling programs have been developed
that use peritoneal membrane transport test data
from the standard PET and PD capacity (PDC)
tests to help in prescription management. These
have been validated for clinical use in pediatrics.151,156
ume overload appeared to be the most important

etiologic factor.162
Proper fluid management requires knowledge
and repeated monitoring of the patients daily
residual kidney volume and daily ultrafiltration
volume. Efforts to modify the dialysis prescription with the goal of enhancing ultrafiltration
with the lowest possible dialysate dextrose concentration are conducted best with knowledge of
the patients peritoneal membrane transport capacity as derived from the PET. If patients are
characterized as high/rapid transporters and are
unable to achieve the ultrafiltration necessary for
blood pressure control with standard dialysis
solutions, consideration should be given to the
use of an icodextrin-based dialysis solution.163,164
Whereas its use has been associated with enhanced ultrafiltration in pediatric patients, a recent report suggests that icodextrin-associated
fluid removal correlated significantly with age
and that icodextrin may behave differently in
young children in whom ultrafiltration may not
be as successful.165 This experience has not been
duplicated in other centers and requires confirmation.
Recommendations for antihypertensive therapy
in children are provided in the Fourth Report on
the Diagnosis, Evaluation, and Treatment of High
Blood Pressure in Children and Adolescents, as
well as in the KDOQI Clinical Practice Guidelines
on Hypertension and Antihypertensive Agents in
CKD.157,166
Finally, in some patients who are polyuric,
negative net daily ultrafiltration may be desirable
because of its potential to replenish decreased
intravascular volume and improve RKF. When
negative net daily ultrafiltration is not possible,
provision of additional fluids is recommended.
Maintenance of Euvolemia and Normotension

Hypertension is a common complication of
children receiving dialysis. As delineated in the
KDOQI CVD Guidelines, determination and
management of blood pressure in children should
follow recommendations by the Fourth Report
on the Diagnosis, Evaluation, and Treatment of
High Blood Pressure in Children and Adolescents.157,158 In that report, it is recommended
that the optimal (normal) SBP and DBP should
be less than the 90th percentile for age, sex, and
height.
A recent analysis of data from the North American Pediatric Renal Transplant Cooperative Study
(NAPRTCS) found that 56.9% of nearly 4,000
dialysis patients had uncontrolled hypertension
(blood pressure than the age-, sex-, and heightspecific 95th percentile) and an additional 19.7%
of patients had controlled hypertension (blood
pressure the 95th percentile with antihypertensive medication).159 In addition, marked echocardiographic changes have been documented in
pediatric patients at both the initiation of dialysis
therapy and during maintenance dialysis therapy.
A retrospective study of 64 long-term dialysis
patients found that 48 children (75%) had LVH,
including 26 of 38 children (68%) on PD
therapy.160 Similarly, another report showed increased left ventricular mass (LVM) and LVMI
in children receiving dialysis compared with a
healthy population.161 Whereas the cause of the
elevated blood pressure is multifactorial, others
found that high blood pressure and cardiac impairment were most frequent in the younger and
nephrectomized dialysis patients for whom vol-
Quality Improvement Programs

A CQI program should be instituted in all
dialysis facilities that care for children receiving
PD, based on evidence that improvements in
patient care are best achieved in this manner. In
addition to monitoring outcomes related to, for
example, complications related to infection,
achievement of solute clearance targets, adequacy
of nutrition, osteodystrophy, anemia management,
and QOL, school attendance/performance and
growth are key issues to be monitored in any
program caring for children receiving long-term
PEDIATRIC PERITONEAL DIALYSIS
dialysis. Not surprisingly, data collected by the

NAPRTCS showed that children receiving PD regularly show better school attendance than those on
HD therapy.167 However, differences exist in the
PD population when attendance is stratified by
race, an issue that requires attention and often
intervention. The recommendation for regular
growth assessment, as previously delineated in the
pediatric component of the KDOQI Nutrition
Guidelines, results from the negative impact that
CKD can have on height velocity and the association between poor growth and poor outcome in
children receiving dialysis.35,168 The use and influence of medical interventions (eg, correction of
acid-base abnormalities, control of secondary hyperparathyroidism and renal osteodystrophy, provision of adequate nutrition, and institution and effect
of recombinant human growth hormone therapy)
also should be monitored.168A-171
Although programs with varying levels of
pediatric expertise coordinate the care of children receiving long-term dialysis, ideally, a treatment facility should be able to provide the necessary multidisciplinary services required by
children and families through a team of specialists with pediatric experience. All these disciplines should be involved in the CQI process.172
S129
In view of the relatively small number of

children who receive PD in any one center, it is
imperative that single-center data be compared
with results contained in large pediatric databases to determine whether modification of a
centers program is deemed necessary. Organizations such as the NAPRTCS and USRDS provide
such data.24,173
LIMITATIONS
Although attention to fluid management likely
will benefit blood pressure control and help prevent the development of CVD in children receiving PD, no large-scale study of the pediatric
CKD stage 5 population has proved this to be
true.
Although CQI programs generally are considered to be beneficial, there are no studies of
pediatric PD facilities that document the efficacy
of such programs in terms of their ability to
improve patient outcomes.
While it is intuitively beneficial for the CQI
program to be multidisciplinary in nature, quality standards for some disciplines in terms of
their application to the pediatric PD population
have not yet been established.
II. CLINICAL PRACTICE RECOMMENDATIONS FOR

PERITONEAL DIALYSIS ADEQUACY
CLINICAL PRACTICE RECOMMENDATION FOR GUIDELINE 1:

INITIATION OF DIALYSIS
Certain complications of kidney failure justify
initiation of dialysis treatment in patients for
whom estimated GFR has not yet decreased to

15 mL/min/1.73 m2 (Table 10).
Table 10. Complications That May Prompt Initiation of KRT

Intractable extracellular volume overload
Hyperkalemia
Metabolic acidosis
Hyperphosphatemia
Hypercalcemia or hypocalcemia
Anemia
Neurological dysfunction (e.g., neuropathy, encephalopathy)
Pleuritis or pericarditis
Otherwise unexplained decline in functioning or well-being
Gastrointestinal dysfunction (e.g., nausea, vomiting, diarrhea, gastroduodenitis)
Weight loss or other evidence of malnutrition
Hypertension
S131

GUIDELINE 2: PERITONEAL DIALYSIS PRESCRIPTION
TARGETS AND MEASUREMENTS
In a PD prescription, there are certain general considerations.
etary protein intake (DPI; such as nPNA)

should be measured.
2.1 Regardless of delivered dose, if a patient

is not thriving and has no other identifiable cause other than possible kidney
failure, consideration should be given to
increasing dialysis dose (see Table 11).
2.2 In a patient with minimal RKF, a continuous (rather than intermittent) 24 h/d of
PD dwell PD prescription should be used
to maximize middle-molecule clearance.
2.3 If either peritoneal Kt/Vurea is at least 1.7
or 24-hour urine output is less than 100
mL, monitoring of RKF is not required
for monitoring the dose of PD. However,
periodic measurement of RKF may be of
value in this group of patients for the
reasons noted in Table 12.
2.4 All measurements of peritoneal solute
clearance should be obtained when the
patient is clinically stable and at least 1
month after resolution of an episode of
peritonitis.
2.5 More frequent measurements of either
peritoneal urea clearance or RKF should
be obtained when clinically indicated (see
Table 13).
2.6 When calculating Kt/Vurea , one should
estimate V from either the Watson or
Hume equation in adults. In the absence
of evidence, use of the patients ideal or
standard (rather than actual) weight
should be considered in the calculation of
V.
2.7 The determination of peritoneal CCr is of
little added value for predicting risk for
death; therefore, for simplicity, adequacy
targets are based on urea kinetics only.
Peritoneal creatinine excretion rate may
be used to monitor estimates of muscle
mass over time.
2.8 During the monthly evaluation of the PD
patient, nutritional status should be estimated. Serum albumin levels should be
monitored, and when obtaining 24-hour
total solute clearances, estimations of di-
RATIONALE
Regardless of delivered dose, if a patient is not
thriving and has no other identifiable cause other
than possible kidney failure, consideration should
be given to increasing the dialysis dose. There
are many reasons that a dialysis patient fails to
do well. Often, failure to do well on PD therapy
relates more to comorbidity174 or complications
(such as peritonitis) than to adequacy. However,
close examination of the 2 randomized trials of
CAPD patients comparing small-molecule clearances gives some support to increasing dialysis
in the symptomatic patient. In the ADEMEX
Study, lower prescription (total average Kt/Vurea
of 1.8 versus 2.27) resulted in more deaths from
CHF (13.4% versus 5.7% in the intervention
group; P 0.05) and uremia, hyperkalemia,
and/or acidosis (12.2% versus 5.1% in the intervention group; P 0.05). More patients in this
unblinded study were withdrawn because of uremia in the control group (5% versus none in the
intervention group). Another randomized trial
confirmed these results. Six percent of those in
the group with total Kt/Vurea of 1.5 to 1.7 were
withdrawn because of inadequate dialysis versus none in the groups with total Kt/Vurea of 1.7
to 2.0 and greater than 2.0 (P 0.002 comparing
all 3 groups). In addition, another 8% were
withdrawn because of inadequate ultrafiltration
in the group with Kt/Vurea of 1.5 to 1.7 versus 4%
and 1% in the groups with total Kt/Vurea of 1.7 to
2.0 and greater than 2.0, respectively (P 0.012).
The group with the lowest clearance also required more erythropoietin. In the opinion of the
Work Group, if a patient has symptoms possibly
attributable to inadequate dialysis, such as anorexia, nausea, anemia, and hyperkalemia, or if
volume overload is present, consideration should
be given to increasing the dialysis dose.
Two additional indications listed in Table 11
for increasing the dialysis dose are uremic pericarditis and neuropathy. Tradition suggests that
if a pericardial rub develops in a dialysis patient,
the intensity of dialysis should be increased. This
S132
PERITONEAL DIALYSIS PRESCRIPTION TARGETS AND MEASUREMENTS
is an area that is poorly studied. Uremic neuropathy also is not very well understood, but if it
develops, the dose of dialysis should be increased, with attention to removal of middle
molecules.
There are no convincing data to support increasing small-molecule clearance to improve
nutritional status or QOL. A study randomly
assigned CAPD patients on 3 CAPD exchanges
to continue on this prescription (n 42) or to
increase to 4 exchanges (n 40). Peritoneal
Kt/Vurea stayed constant at 1.56 in the 6-L group
and increased from 1.59 to 1.92 in the 8-L group.
Net ultrafiltration was better in the latter group, as
was nPNA, which increased from 1.10 to 1.24 (P
0.05), but there was no change in serum
albumin level.175 Another study increased the
prescribed PD in 23 patients with a subsequent
increase in peritoneal Kt/Vurea from 1.62 to 1.96,
which was associated with an increase in serum
albumin level from 3.55 to 3.83 g/dL.176 It was
unclear whether the increase in serum albumin
level was caused by improved volume status
(weight actually decreased and nPCR did not
change). Others found that increasing the PD prescription to offset the loss of RKF did not result in
an improvement in protein intake.177 The
NECOSAD reported that RKF correlated significantly with many parameters of the Kidney Disease-QOL (physical functioning, role limitations, social functioning, mental health, vitality,
S133
bodily pain, general health, symptoms, effect of

kidney disease on daily life, sleep disorders, and
overall health rating). Peritoneal clearances correlated with none of these.44 In the ADEMEX
Study, QOL was similar in the groups randomized to the higher small-molecule clearance relative to the lower target (total average Kt/Vurea of
1.8 versus 2.27).40 In addition, patients with a
serum albumin level less than 3 g/dL at the start
had similar survival whether administered the
higher or lower delivered dose. In confirmation
of these results, patients randomized to a total
Kt/Vurea of 1.5 to 1.7 had outcomes in respect to
composite nutritional index and serum albumin
level similar to patients with higher total Kt/
Vurea.39 In an observational study of anuric Chinese CAPD patients, serum albumin level did not
correlate with Kt/Vurea.67 Mean Kt/Vurea of these
patients was 1.72 to 1.73 during the course of the
2-year observation. Serum albumin level in PD
patients appears to be linked to inflammation and
volume overload.49,57,178,179
In summary, if the patient appears to have
uremic signs and symptoms, the PD prescription
can be changed to increase small-molecule clearance. However, there are no convincing data that
this will lead to better nutritional status, survival,
or QOL.
In a patient with minimal RKF, continuous
(rather than intermittent) (24 h/d of PD dwell)
S134
RECOMMENDATIONS FOR PERITONEAL DIALYSIS ADEQUACY
PD prescription should be used to maximize

middle molecule clearance. Middle-molecule
clearance, in contrast to small-molecule clearance, is much more a function of total time of
dialysis rather than dialysate flow rate. Because evidence suggests that middle molecules, such as -amyloid, contribute to joint
and bone disease in the long term, it seems
reasonable to maximize middle-molecule clearance in PD patients. 2-Microglobulin levels
increased over time in the CANUSA Study and
were associated with increased risk for death
and hospitalization. 65 Maximizing middlemolecule clearance is achieved best by performing continuous PD without dry periods. It is
unclear whether starting PD with a dry abdomen as a form of incremental dialysis in
patients with significant RKF has benefits (such
as protection of the peritoneal membrane
against continuous glucose exposure or potential enhancement of peritoneal immune function). Further research is needed in this area.
If either peritoneal Kt/Vurea is at least 1.7 or
24-hour urine output is less than 100 mL,
monitoring RKF is not required for monitoring
dose of PD. However, periodic measurement of
RKF may be of value in this group of patients
for the reasons noted in Table 12. A study of
anuric patients on APD therapy with a 24-hour
prescription71 found that predictors of survival
were age; SGA score of C, indicating malnutrition (RR, 6.97; P 0.006); and diabetes, but not
time-averaged total CCr. Anuria was carefully
defined in this study as 24-hour urine volume
less than 100 mL and GFR (determined by using
the average of urea and creatinine kidney clearance based on 24-hour collection of urine) less
than 1 mL/min/1.73 m2. Patients with any RKF
continued to provide 24-hour urine collections;
they had an average kidney clearance of 1.92
L/wk/1.73 m2 at the start of the study and 0.59
L/wk/1.73 m2 at 24 months. In this study, peritoneal clearances were repeated every 2 months
until the planned targets were reached, and then

every 6 months.
Similarly, in the ADEMEX Study, patients
brought in repeated clearances (urine and peritoneal) every 2 months until the target was achieved;
then the frequency was reduced to every 4
months.38 In the Hong Kong randomized trial,
after initial adjustment of the prescription to get
the patient into the target total Kt/Vurea range
(which, in some cases, required reducing the
peritoneal dose), the clearance (kidney and peritoneal) was repeated in 4 to 6 weeks, then every
6 months until the study ended (15 months after
the last patient recruitment).39 Average kidney
Kt/Vurea decreased steadily over time and was
less than 0.1 by the study end point in all 3 groups.
The CAPD prescription was continuously adjusted
upward to enable patients to stay within the total
Kt/Vurea targets of 1.5 to 1.7, 1.5 to 2.0, and greater
than 2.0.
In an observational study, urine volume was
determined every 2 months at clinic visits by
having the patient measure daily urine volume
for the 7 days before the visit; this was normalized to 1.73 m2.48 Actual measurement of kidney
and peritoneal clearance was performed every 6
to 12 months. Total fluid removal (ultrafiltration
plus urine volume) was a strong predictor of
survival (RR, 0.90 for every 100 mL/24 h; P
0.01). RKF also was a strong predictor of survival (RR, 0.41 for every increase in RKF of 1
mL/min/1.73 m2; P 0.01).
Because a total Kt/Vurea greater than 1.7 has
not been associated with clinical benefits, if this
goal is achieved through PD, there would seem
to be no need for measuring RKF. However,
given the importance of RKF for survival, measuring 24-hour urine volume may focus attention
on remaining kidney function. Furthermore, in
the opinion of the Work Group, for patients who
have persistent edema, measuring sodium losses
in urine and effluent may help in management.
However, there are few data for this.
There is considerable heterogeneity in the decrease in RKF in PD patients.89 Therefore, measurement of RKF seems warranted to monitor
this important predictor of outcome.89,101 Peritonitis may have a negative impact on RKF; therefore, reassessing RKF after an episode of peritonitis would appear reasonable.
All measurements of peritoneal solute clearance should be obtained when the patient is
clinically stable and at least 1 month after
resolution of an episode of peritonitis. Peritonitis transiently changes the patient to a high
transporter and decreases ultrafiltration per dextrose concentration used. Therefore, a dialysate
clearance obtained close to an episode of peritonitis may either overestimate (because of the
high transport status) or underestimate (because
of the decrease in convection from decreased
ultrafiltration) clearance of small molecules.
Therefore, it appears best to defer a collection
until 1 month or more after peritonitis. A change
in prescription may require time for the patient to
reach equilibrium; therefore, a delay in performing the collection is warranted.
More frequent measurements of either peritoneal urea clearance or RKF should be obtained
when clinically indicated (see Table 13). For a
patient with failure to thrive with no alternative
explanation, repeated clearance of urine and peritoneal effluent may determine whether uremia is
contributing to the problem. With the development of intravascular volume depletion, inadvertent use of NSAIDs, or other intercurrent events,
a PD patient may lose significant RKF such that
the PD prescription is no longer adequate. A
decrease in dialysate dextrose concentration may
result in decreased ultrafiltration and decreased
clearance, leading to uremia. Overzealous blood
pressure control also may lead to loss of RKF.
Last, the patient may change the timing of the
exchanges (ie, shortening some and lengthening
others excessively), leading to inadequate dialysis. Repeating the clearance, if clinically indicated, may uncover these potential problems.
Consideration should always be given to nonadherence with the prescription if the patient is not
doing well. Nonadherence may be investigated
by assessing the supplies ordered, as well as
home supply inventory and analysis of the cycler
memory system (if available).
S135
When calculating Kt/Vurea , one should estimate V from either the Watson or Hume equation in adults. In the absence of evidence, use of
the patients ideal or standard (rather than
actual) weight should be considered in the calculation of V. For the patient close to or at dry
weight, the Watson or Hume equation is acceptable.180,181 The Watson equations tend to underestimate total body weight.182,183 In underweight
patients, it also seems sensible to adjust the
clearance for ideal body weight. An international
cross-sectional study184 examined the nutritional
status of 224 CAPD patients, of whom 71 were
anuric, defined as no urine output. When parameters of severely malnourished patients were
adjusted to desired weight, nPCR was decreased
(0.76 versus 0.98 for well-nourished patients), as
was Kt/Vurea (1.40 versus 1.68). These results
suggest it is important to normalize V to calculate Kt/Vurea in malnourished patients. In amputees, total body water (TBW) must be calculated
by determining the percentage of body weight
lost in the amputation (using a nomogram) and
dividing actual weight by percentage of body
composition remaining, applying this weight with
the nonamputated height to the Watson formula
to determine the proportion of body water. This
proportion then is multiplied by actual weight to
obtain V.185
However, the correct determination of V for
overweight patients is unclear.186 The Watson
formula overestimates TBW in obese patients
and underestimates it in overhydrated patients.183
Body size does not affect dialysate to plasma
(D/P) ratio of small solutes.187
Determination of peritoneal CCr is of little
added value for predicting risk for death; therefore, for simplicity, adequacy targets are based
on urea kinetics only. Peritoneal CCr may be
used to monitor estimates of muscle mass over
time. Total CCr in patients with RKF is much a
reflection of RKF. In the absence of RKF, CCr
seems to add little to the use of urea clearance. A
study examined 912 PD patients by using the
USRDS data set, as well as by questionnaires
completed by centers, and found that kidney urea
clearance (but not dialysate urea clearance) was
predictive of 12-month mortality. Neither kidney
nor dialysate CCr were predictive.43 However,
peritoneal and kidney creatinine excretion is a
good measure of muscle mass and may be used
S136
to measure this sequentially if it seems appropriate.188,189

During the monthly evaluation of the PD
patient, nutritional status should be estimated.
Serum albumin levels should be monitored and
when obtaining 24-hour total solute clearances,
estimations of DPI (such as nPNA) should be
measured. Nausea, vomiting, and appetite suppression are acknowledged symptoms of uremia.
Uremic patients tend to have decreased DPI,190
and spontaneous DPI decreases as renal rGFR
decreases to less than 50 to 25 mL/min.191 These
tendencies may be exacerbated during the period
before the initiation of dialysis therapy when
many patients are not only anorexic, but also are
acidotic and often treated with low-protein renal protective diets. As a result, patients may
show signs of protein malnutrition when they
present for dialysis. Dialysis itself is associated
with unique metabolic and nutritional problems.
PD patients may have a decreased appetite and
early satiety192,193 and typically lose 5 to 15 g of
protein and 2 to 4 g of amino acids per day in
their dialysate.194 These losses amount to a net
loss equivalent to 0.2 g protein/kg/d and tend to
be higher in rapid transporters than low transporters. These losses are increased transiently during
episodes of peritonitis,195 at times doubling after
even a mild episode. Studies of patients with
CKD stage 5196-199 showed that some of the
most important predictors of patient risk for
death are such surrogates of nutritional status as
serum albumin level, SGA score, and DPI estimate. Hence, it would be appropriate to monitor
and maintain normal nutritional status in patients
on PD therapy. However, it is important to note
that there have been no prospective randomized
trials that evaluated a patients RR for death
when 2 different levels of a surrogate for nutritional status were compared as the target intervention.
A patients RR for death correlates with surrogates of nutritional status. It is well recognized
that such markers of nutritional status as serum
albumin level, estimation of DPI, and SGA
score200 are influenced by many additional clinical parameters other than nutrition-related ones;
therefore, they must be treated as imperfect surrogates for nutritional status of a patient. For
example, in an individual PD patient, the significance of an isolated serum albumin level must be
viewed with caution. An isolated level does not

necessarily predict nutritional status. Levels must
be followed up over time and interpreted in the
context of other patient-related issues, such as
peritoneal membrane transport type, total solute
clearance, volume status, presence of chronic
liver disease, presence of comorbid diseases, and
any inflammatory state.
Most (95%) nitrogen intake in humans is in
the form of protein. Therefore, when the patient
is in a steady state (not catabolic or anabolic),
total nitrogen excretion multiplied by 6.25 (there
are 6.25 g protein per gram of nitrogen) is
thought to be an estimation of DPI.201 Estimated
DPI is calculated from urea nitrogen appearance
in dialysate and urine. Multiple equations have
been derived, some of which have been validated
in CAPD (but not nightly intermittent PD [NIPD])
patients (protein equivalent of total nitrogen appearance [PNA] protein catabolic rate [PCR]
protein losses). These estimations initially were
called the PCR. However, PCR actually represents the amount of protein catabolism exceeding synthesis required to generate an amount of
nitrogen that is excreted, ie, PCR is a net catabolic equivalent. Thus, because these calculations are based on nitrogen appearance, the term
is more appropriately called the protein equivalent of nitrogen appearance, or PNA. Following
up a patients nPNA (discussed next) over time is
a way to estimate DPI over time to ensure
adequate nutritional status. A baseline PNA
should be obtained during training. These should
be recalculated every 4 to 6 months by using the
same 24-hour dialysate and urine collections
used to monitor solute clearances. One cause of a
decreasing nPNA would be decreasing DPI at
times because of suboptimal total solute clearance.
For comparison purposes, it is recommended
that PNA be normalized for patient size (ie,
nPNA). What patient weight (actual, standard,
ideal) to use for that normalization is controversial. Depending on the weight used in calculating
nPNA, there may or may not be a statistical
relationship between clinical evidence of malnutrition and nPNA values less than target. PNA
normalized by actual weight tends to be high or
may appear to be increasing over time in malnourished individuals if normalized (divided) by a
progressively smaller malnourished weight com-
pared with the patients baseline weight.202 It

therefore is the opinion of the Work Group that
ideal weight be used for the normalization process.
Data from the Centers for Medicare and Medicaid Services (CMS) Clinical Performance Measures (CPM) Project for the year 2000 found
that, in long-term PD patients, mean nPNA was
0.95 0.31 g/kg/d, normalized creatinine appearance rate was 17 6.5 mg/kg/d, and mean
percentage of lean body mass was 64% 17%
of actual body weight.203
There is some controversy about what amount
of DPI, in terms of grams of protein per kilogram
of body weight, is needed to maintain a positive
nitrogen balance in PD patients. Early studies suggested that DPI of at least 1.2 g/kg/d was needed to
maintain nitrogen balance,204,205 a value considerably higher than that recommended for healthy
individuals. The NKF KDOQI guidelines recently recommended DPI for long-term PD patients of 1.2 to 1.3 g/kg/d.35 Two cross-sectional
studies suggested that patients who show no
signs of malnutrition seem to eat less protein
(0.99206 and 0.88207 g/kg/d, respectively). Results likely are caused by variations in the patient
populations studied, historical dietary patterns,
and amounts of RKF present. Therefore, several
investigators proposed that daily protein intake
in these patients should be in the range of 0.9 to
1.1 g/kg/d.208,209 If values are less than this
amount, one should consider looking for potential causes of decreased DPI, such as intentional
low DPI, gastroparesis, comorbidity, chronic inflammation, and suboptimal small-solute removal.
There is little evidence from prospective RCTs
that increasing small-solute removal results in an
improvement in surrogate markers for nutritional
status. In both the ADEMEX Study and Hong
Kong trials, the intervention groups (higher smallsolute clearance) did not have an improvement in
surrogate measurements of nutritional status (albumin level and PNA). If surrogate markers for
nutritional status suggest that the patients nutri-
S137
tional state is declining, one should consider

evaluation for new comorbidity, additional dietary evaluation, dietary supplements, and, if no
other cause is identified, an increase in dialysis
dose.
LIMITATIONS
There is a marked lack of high-quality studies
of PD patients examining different doses of PD.
Only 2 randomized trials have been performed,
both in CAPD patients. There are no randomized
trials of different doses of small-molecule clearances in APD patients. There also are no studies
comparing initiation of PD therapy with a cycler
at night and a dry day versus CCPD. There are no
randomized trials targeting different levels of
blood pressure control. There are only 2 randomized trials of interventions to protect RKF and
none examining the effect of different prescriptions (especially APD versus CAPD) on RKF.
Control of middle molecules is believed to be
important to prevent long-term complications,
but studies of this are mostly lacking.
Obtaining a clearance in PD patients is very
dependent on the cooperation of the patient. The
patient must bring the used dialysate to the
dialysis unit. This may be difficult for elderly or
weak patients unable to lift heavy objects or
those with limited transportation. If the patient is
told to sample the effluent and record the weight
(for CAPD) or drain volume (for APD), the center
is dependent on the patient providing the correct
numbers. Furthermore, on the day of the clearance,
the patient is more likely to do the proper full
prescription. Therefore, the measurement, at best,
is that of that particular days dialysis and not
necessarily reflective of average clearance. To
some extent, use of a cycler with a mechanism of
monitoring the use of the cycler and time on the
cycler could be used.210 This cycler is not universally available and increases the cost of treatment.
CLINICAL PRACTICE RECOMMENDATIONS 3:

RECOMMENDED LABORATORY MEASUREMENTS FOR
PERITONEAL MEMBRANE FUNCTION AND
ULTRAFILTRATION VOLUME
Total solute clearance and peritoneal effluent volume ultimately are influenced by peritoneal membrane transport characteristics.
Multiple tests are documented to be efficacious for determining peritoneal membrane
transport. None of these tests has been shown
to be clinically superior to the others (see
Table 14).
3.1 Each center should choose one of these
tests to use when characterizing peritoneal transport in their patients.
3.2 Baseline peritoneal membrane transport
characteristics should be established after
initiating a daily PD therapy.
3.3 Data suggest that it would be best to wait
4 to 8 weeks after starting dialysis to
obtain this baseline measurement.
3.4 Peritoneal membrane transport testing
should be repeated when clinically indicated (see Table 15).
3.5 All measurements of peritoneal transport
characteristics should be obtained when
the patient is clinically stable and at least
1 month after resolution of an episode of
peritonitis.
BACKGROUND
After PD therapy is initiated, total solute removal is related to residual kidney and peritoneal
effluent volumes and the concentration of the
solute in question in each of those volumes. The
background for, definitions of, and frequency of
how and what to measure to determine total
solute removal or clearance are outlined in CPG
2 and CPR 2. During a typical PD dwell, peritoneal effluent drain volume and concentration of
solutes in that drain volume will vary from
patient to patient and are dependent on the individual patients peritoneal membrane transport
characteristics, infused volume/exchange, concentration and type of osmotic agent used, rates
of lymphatic absorption of fluid, and dwell time/
exchange.211 Although in our goal to replace lost
RKF, we have been focused on the movement of
solutes and fluid from blood to the peritoneal
S138
cavity (and ultimately, by draining the peritoneal

fluid, removal from the body), it is important to
note that solutes (ie, osmotic agents) and fluid
also potentially are absorbed from the peritoneal
cavity. To most efficiently optimize solute and
fluid removal in each patient, one must know and
understand each individuals peritoneal membrane transport characteristics and recognize that
there is potential that they may change over
time.212,213
RATIONALE
Definitions
Two of the typical laboratory measurements
routinely obtained in PD patients are: (1) those
used to quantify and document amount of solute
removed from the body (such as the weekly
Kt/Vurea or CCr described previously), and (2)
tests that classify peritoneal membrane transport
characteristics (described next). Tests that measure peritoneal membrane transport characteristics are designed to define or classify an individual patients rate of solute diffusion and
potential fluid removal, not quantify actual
amount of solute or volume of fluid removed.
After an individual patients peritoneal membrane transport characteristics are defined, one
can use such data to guide prescription management and predict what the delivered solute removal may be with a certain prescription. As
noted, it is recommended that dialysate and urine
be collected and solute removal be measured to
accurately quantify a patients delivered dose of
dialysis.
Each center should choose one of these tests
to use when characterizing peritoneal transport
in their patients. It is known that peritoneal
membrane transport characteristics vary from
patient to patient. To optimize solute removal
and ultrafiltration volumes, it is helpful to know
each patients individual peritoneal membrane
transport properties. Multiple tests have been
developed to evaluate various aspects of peritoneal membrane function (see Table 14). There
have been no prospective randomized trials designed to determine which test is best for prescrip-
LAB MEASUREMENTS FOR PERITONEAL MEMBRANE FUNCTION AND ULTRAFILTRATION VOLUME
S139
Table 14. Standardized Tests for Evaluating Peritoneal Membrane Transport/Function

Aspect of Peritoneal Function
Small solute transport
Ultrafiltration capacity
Ultrafiltration via water channels
Fluid absorption
Peritoneal blood flow
Permeability to macromolecules
PET
Method of Peritoneal Function Testing

SPA
D/P* creatinine
Drain volume
MTAC creatinine
Drain volume
D/P Na
Model for Na channel

Dextran 70
Restriction coefficients
PDC
Area permeability
Estimates ultrafiltration
coefficient
Derived
Large-pore flow
Abbreviations: SPA, standard peritoneal permeability analysis; MTAC, mass transfer area coefficient.
* Ratio of concentration of solutes in dialysate (D) to plasma (P).
tion management. Each test has its strengths and

weaknesses, and all are useful. These have been
reviewed recently.214
Traditionally, peritoneal membrane transport/
function has been assessed by using the standard
PET.211 The PET has been standardized both
procedurally and interpretably to classify peritoneal membrane function. It was designed and
initially used primarily to evaluate small-solute
transport characteristics, and although ultrafiltration properties of the peritoneal membrane are
linked, the original PET was not designed to
differentiate all the variations in peritoneal membrane transport/function that result in pathological alterations in ultrafiltration capacity.
A modification of the original PET using
1.36%/1.5% dextrose/dextran 70, called the standard peritoneal permeability analysis (SPA), was
developed to better evaluate mass transfer area
coefficients (MTAC) of small- and middlemolecular-weight solutes and also better determine residual volume and ultrafiltration kinetics.215 The 1.36%/1.5% dextrose/dextran 70
solutions were chosen so there would be less of
an osmotic gradient for ultrafiltration and therefore one would be able to better determine the
true diffusive MTAC characteristics of the mem-
brane in a situation in which there would be less

ultrafiltration and its associated convective removal of solutes.
The standard PET subsequently was modified,
and 3.86%/4.25% dextrose solutions were substituted to maximize crystalloid osmotic ultrafiltration and optimize the ability to evaluate pathological variations in ultrafiltration capacity.216 This
modification allows one to evaluate aquaporinmediated water transport and the sodium- versus
water-removal characteristics of peritoneal transport. The PET and SPA use single dwells and
direct measurements to characterize peritoneal
transport properties.
Another procedure, the PDC test, uses data
from multiple dwells (typically 5) performed
during a 24-hour period.217 Data are combined in
a mathematical model to estimate peritoneal transport characteristics. In addition to establishing
MTAC, the PDC test is better able to determine
peritoneal fluid absorption rates and macromolecule permeability.
There are geographic variations in the use of
tests for classifying peritoneal membrane function. The PET is the simplest procedure to perform and, as expected, has the most clinical
experience related to its use. There are no data to
S140
suggest that one test is better than another in

common clinical settings; hence, each center
should use the test they are most comfortable
with. The International Society for PD has recommended that a modified PET (3.86%/4.25% dextrose) dwell be used to optimally evaluate patients with ultrafiltration failure.218
Baseline peritoneal membrane transport
characteristics should be established after initiating a daily PD therapy. It is recognized that
to optimize solute removal and ultrafiltration volumes, one must understand peritoneal physiological processes and know each patients individual
peritoneal membrane transport characteristics. This
could be done by careful observations of such
clinical parameters as blood pressure, volume status, physical examination findings, well-being, and
serum chemistry test results, adjusting the peritoneal prescription as indicated. One is likely to be
better able to do this if one documents peritoneal
membrane transport characteristics in each patient. Once established, these data can be used to
guide prescription writing and predict clearances
and ultrafiltration volumes. Kinetic modeling programs have been developed that use peritoneal
membrane transport test data from the standard
PET to help in prescription management. These
have been validated for clinical use.
Data suggest that it would be best to wait 4 to
8 weeks after starting dialysis therapy to obtain
this baseline measurement. The initial instillation of dialysate into the peritoneal cavity and the
initiation of PD therapy is associated with mild
changes in local cytokine production, peritoneal
vascularity, and blood flow. These changes in
peritoneal anatomy and perfusion potentially can
influence peritoneal membrane transport. Historical data have suggested there is a small increase
in D/P ratio for small solutes during the first
month on PD therapy.219 This phenomenon recently was confirmed in a longitudinal analysis
of 50 new PD patients.220 One-week, 1-month,
and 1-year PET results from individual patients
were compared. Significant changes in D/P urea
(0.91 versus 0.94), D/P creatinine (0.55 versus
0.66), and end dialysate dextrose concentration
over initial dialysate dextrose concentration (D/
D0) glucose (0.38 versus 0.36) were noted. Onemonth PET results correlated better with 1-year
results than did 1-week PET results. D/D0 values
for glucose changed the least during the first
month, and 1-week D/D0 values better predicted

transport characteristics than 1-week drain value.
Based on these and historic data, it is recommended that the baseline peritoneal membrane
transport study is obtained after the first 4 to 8
weeks of starting dialysis. During training, one
could estimate peritoneal membrane transport
rate by measuring the drain volume from a 4-hour
dwell of 2.5% dextrose and comparing expected
D/P ratios of creatinine to the patients observed
drain volume. However, as noted, the observed
drain volume is not as predictive as other laboratory measurements. For most patients at the
initiation of dialysis therapy, there is some RKF
present. Therefore, estimating delivered clearance and ultrafiltration volumes from D/P ratio
predicted by drain volumes observed during training suffice until a formal PET and 24-hour dialysate collection can be obtained. Standard clinical
practice usually involves a timed 4-hour dwell
with 2.5% dextrose during training and a follow-up PET at about 1 month after initiating PD
therapy, at which time other issues regarding
prescription management can be reviewed.
Peritoneal membrane transport testing should
be repeated when clinically indicated (see Table
15). In general, peritoneal transport is stable
over time. However, small cohort studies that
evaluated peritoneal transport characteristics over
time, often with a short follow-up period, suggest that in some patients, peritoneal transport
changes.221 Impaired ultrafiltration is the most
frequent clinically noted abnormality. The prevalence of this change is dependent on dialysis
vintage. One review using a clinical definition
for ultrafiltration failure (defined as a need for
hypertonic exchanges) suggested it was present
in 3% of patients at 1 year and 31% after 6
years.222 In another cross-sectional study of patients on PD therapy for a median of 19 months
(range, 0.3 to 178 months) and using a laboratory
definition of ultrafiltration failure (ultrafiltration
400 mL after a 4-hour dwell with 4.25% dextrose), impaired ultrafiltration was noted in 23%
of patients.216 It appears (from these studies in
unselected patients) that over time, there tends to
be an increase in transport manifested by higher
MTACs, higher D/P ratios for small solutes,
decrease in ultrafiltration when using glucosecontaining fluids, and increased restriction to the
transport of macromolecules.223 These clinical
LAB MEASUREMENTS FOR PERITONEAL MEMBRANE FUNCTION AND ULTRAFILTRATION VOLUME
observations suggest there tends to be an increase in number of microvessels per unit of

peritoneal surface area, along with decreased
permeability to large-molecular-weight solutes.
The net result is that the diffusive rate of solute
transport tends to increase and drain volume/
dwell tends to decrease. However, in many patients, total solute removal/dwell often remains
stable because of these two offsetting phenomena.
As a result of the observed stability of peritoneal transport over time in most patients, one
does not need to routinely document individual
patients peritoneal membrane transport characteristics over time with routine laboratory measurement (peritoneal membrane transport testing). However, one needs to clinically assess
drain volume and clinical volume status in each
patient on a regular basis. Drain volume can be
assessed during a clinical visit by reviewing a
patients overnight (for CAPD) or daytime (for
APD) drain volume and assessing the patients
need to use hypertonic dialysate solutions to
maintain euvolemia. If one suspects a change in
clinical status, peritoneal membrane testing
should be repeated (see Table 15).
As noted, kinetic modeling programs have
been developed that use peritoneal membrane
transport test data from the standard PET to help
in prescription management, and they have been
validated for clinical use. As a result, most centers use the standardized PET as the baseline test
to characterize peritoneal membrane transport.
However, it now is recommended that one use a
3.86%/4.25% dextrose PET to work up a patient
suspected to have ultrafiltration failure.218 Part
of that evaluation includes comparison of current
D/P data to historical baseline data. The 2.27%/
2.5% dextrose PET and 3.86%/4.25% dextrose
PET were compared, and no clinical differences
between D/P ratios for such small solutes as
creatinine were found.224 Two studies compared
2.27%/2.5% dextrose with 3.86%/4.25% dextrose PET. Forty stable PD patients were found
to have little difference in D/P creatinine values,
but expected differences in ultrafiltration profile.225 A subsequent study of 154 patients compared the 2 tests, found little clinical differences
in D/P creatinine values, and established reference values for the 4.25% dextrose PET.226
These data suggest that in common clinical
practice, one could compare D/P ratios for small-
S141
solute transport between tests. If ultrafiltration

failure is suspected, the 3.86%/4.25% dextrose
PET would be most useful, even if a 2.27%/2.5%
PET was done at baseline.
All measurements of peritoneal transport characteristics should be obtained when the patient is
clinically stable and at least 1 month after resolution of an episode of peritonitis. Peritonitis is
associated with peritoneal inflammation, which,
in turn, is associated with hyperemia and changes
in peritoneal transport. These changes usually
are transient. The most striking clinical finding
noted during an episode of peritonitis is impaired
ultrafiltration.227 This is associated with an increase in peritoneal transport of low-molecularweight solutes and increased rates of glucose
absorption. These changes usually are transient
and typically resolve within a month after resolution of the peritonitis.228,229
LIMITATIONS
There have been no prospective randomized
trials comparing patient outcomes with the use of
various test methods. Therefore, one cannot be
recommended over the other. However, it is unlikely there will be differences among test methods,
and that study has not been recommended. These
tests are designed to classify and evaluate membrane function. Although suggested by the literature that peritoneal transport type may influence
patient outcome, it is controversial about whether
patients with different baseline transport characteristics have different clinical outcomes or need
to be on different types of PD therapies. Patients
with all types of peritoneal function have been
managed successfully on each of the different
types of PD modalities (CAPD versus APD). The
number of patients with ultrafiltration failure at
any one center is limited, and data are just
emerging on identifying them with use of 3.86%/
4.25% dextrose PET. Therefore clinical data for
outcomes after adjusting therapy based on PET
findings and the use of newer PD fluids are
lacking. With current therapies/solutions, it was
shown that longitudinal laboratory monitoring of
peritoneal transport of individual patients is not
indicated. It is possible that if routine testing is
no longer done as newer solutions are used, one
may not have the data to evaluate longitudinal
changes in transport and response to therapy
with the use of these solutions.
S142
IMPLEMENTATION
Most centers are already using standard PET
in clinical practice. Many are routinely monitoring transport changes over time (most on a yearly
basis, although the prior KDOQI PD Adequacy
Guidelines recommended more frequent monitoring). These CPRs are less demanding than the
original KDOQI PD Adequacy Guidelines
andas CPRs instead of CPGsshould make
implementation easier because there will be no

related performance measures.
COMPARISON TO OTHER GUIDELINES
The frequency of testing has been decreased
compared with prior KDOQI PD Adequacy
Guidelines. They are similar to anticipated revisions of the Canadian and European guidelines
for PD.
CLINICAL PRACTICE RECOMMENDATIONS 4: WRITING THE

PERITONEAL DIALYSIS PRESCRIPTION
The PD modality has an impact on adherence and QOL, which are important considerations in writing a PD prescription. Ultrafiltration, which is important in optimizing volume
control and thus patient survival, is dependent on the prescription and peritoneal membrane characteristics. Clearance of middle
molecules, while not proved to influence patient survival, should be an important consideration in the prescription.
CAPD and the daytime dwell(s) of

APD to maximize solute clearance
and ultrafiltration volume.
4.5.5 In patients who are hypertensive or
who show evidence of volume overload, ultrafiltration generally should
not be negative (ie, no absorption)
for any daytime or nighttime
exchanges.
4.1 The patients schedule and QOL should

be taken into account when prescribing
PD.
4.2 To optimize middle-molecule clearance in
patients who have minimal RKF, the PD
prescription should preferentially include
dwells for the majority of the 24-hour day.
This is recommended even if smallmolecule clearance is above target without the longer dwell.
4.3 As tolerated by the patient, to optimize
small-solute clearance and minimize cost,
one should first increase instilled volume
per exchange before increasing the number of exchanges per day. The exchange
volume of the supine exchange(s) should
be increased first because this position has
the lowest intra-abdominal pressure.
4.4 The patients record of PD effluent volume should be reviewed monthly, with
particular attention to the drain volume
from the overnight dwell(s) of CAPD and
the daytime dwell(s) of APD.
4.5 A number of techniques can be used to
optimize volume and blood pressure control.
4.5.1 To achieve the desired volume status, the lowest possible dialysate
dextrose concentration should be
used.
4.5.2 When appropriate, implement dietary sodium and fluid restriction.
4.5.3 In patients with RKF, to achieve dry
weight, diuretics may be preferred
to increasing dialysate dextrose concentration.
4.5.4 Drain volume should be optimized
during the overnight dwell(s) of
As explained in CPGs 2 and 4, the PD prescription requires frequent review to ensure that clearance- and volume statusrelated guidelines are
being implemented. In determining the PD prescription, the required clearances and the effect
on volume status are paramount, but other factors that need to be considered are potential
effects on middle-molecule clearance and on
QOL of patients and their caregivers.
BACKGROUND
RATIONALE
The patients schedule and QOL should be
taken into account when prescribing PD. The
PD prescription can be onerous for patients and
their caregivers. There is evidence that nonadherence is common and that it is more likely to
occur with more demanding prescriptions, such
as CAPD with 5 exchanges daily.61 Some patients find larger dwell volumes difficult to tolerate.38 Social factors and burnout are recognized as common problems in PD therapy and as
causes of technique failure.128 Accordingly, prescriptions should take the personal and social
circumstances of patients into account. The implications of additional dwells, increased dwell
volumes in CAPD and APD, and longer cycler
times in APD should be discussed with patients
and/or their caregivers with a view to designing a
prescription that can meet both medical and
social requirements and maintain reasonable
QOL.
To optimize middle-molecule clearance in
patients who have minimal RKF, the PD prescription should preferentially include dwells
for the majority of the 24-hour day. This is
recommended even if small-molecule clearance
is above target without the longer dwell. The
term middle molecule refers to molecules of
S143
S144
molecular weight greater than 1,000 kd. There

has long been controversy concerning their importance in uremic toxicity in patients with kidney failure generally and in both HD and PD
patients. To date, no high-level clinical study
has provided conclusive evidence that middlemolecule clearance determines important clinical outcomes in dialysis patients, although
there is some weak, but suggestive, evidence
for HD patients from the HEMO Study.91 In
PD patients, middle-molecule clearance is time
dependent and not significantly influenced by
dialysate flow rates or dwell volumes.230 Prescriptions, such as standard CAPD or APD
with full-duration day dwells, maximize
middle-molecule clearance, and this is thought
by some to be an advantage of PD over conventional intermittent HD. However, with the increase in popularity of APD in the past decade,
there has been widespread use of prescriptions
with short dwells or no day dwells at all,
particularly in patients with RKF. Such prescriptions may facilitate fluid removal or improve
patient QOL in that many APD patients tend to
prefer not to carry peritoneal fluid in the daytime.
However, there is concern that the dry day may
compromise middle-molecule clearance and thus
may be harmful to patients.
Such prescriptions often are used in patients
with substantial RKF because Kt/Vurea targets
can still be achieved easily. In such circumstances, middle-molecule clearance need not be
a concern because RKF is a far more substantial
contributor to middle-molecule clearance than
any PD prescription. If such prescriptions are
associated with low Kt/Vurea values, they need to
be altered anyway, in accordance with CPG 2.1.
The concern about middle-molecule clearance
only arises in patients with minimal residual
function and a dry day APD prescription that still
meets Kt/Vurea targets. This may occur because
the patient is small in body size or is a high
transporter. In this situation, the disparity between adequate small-solute clearance and low
middle-molecule clearance leads to concern.
There is no evidence in the PD literature to guide
prescriptions in this situation, but in the interests
of patient safety, it is recommended that at least
low-volume long-duration dwells be prescribed.
Given the lack of high-level evidence to support
this statement, implementation should be tem-
pered by QOL considerations for the patient and

by the risk for mechanical complications, both of
which may be affected negatively by long day
dwells.
As tolerated by the patient, to optimize smallsolute clearance in CAPD and minimize cost,
one should first increase instilled volume per
exchange before increasing the number of exchanges per day. The exchange volume of the
supine exchange(s) should be increased first
because this position has the lowest intraabdominal pressure. In CAPD, the principal
methods to increase peritoneal clearance are to
either increase dwell volumes, typically from 2
to 2.5 L to 3 L, or increase frequency of exchanges, typically from 4 to 5 daily.212 Both
strategies are similarly effective in increasing
peritoneal Kt/Vurea, and increased frequency
of exchanges may have a greater benefit in
enhancing ultrafiltration. However, increasing
the dwell volume generally is preferred unless
there are mechanical contraindications. This is
because adherence to CAPD prescriptions with
5 daily exchanges has been shown to be particularly poor and may be associated with worse
QOL. Also, the cost of increasing exchange
frequency is greater than the cost of increasing
dwell volumes. However, ultimately, patient preferences should be a major determinant of which
strategy is followed.
If patients have concerns about tolerating increased dwell volumes in either CAPD or APD,
consideration should be given to increasing nighttime dwell volumes initially. The rationale for
this strategy is that increases in intraperitoneal
pressure (IPP) are less for a given dwell volume
in the supine or recumbent position compared
with either sitting or standing.
The patients record of PD effluent volume
should be reviewed monthly, with particular
attention to the drain volume from the overnight dwell(s) of CAPD and daytime dwell(s) of
APD (see CPR 4.2).
A number of techniques can be used to optimize volume and blood pressure control (see
CPRs 4.5.1 to 4.5.5).
LIMITATIONS
None of these individual prescription strategies have been shown to produce superior outcomes in RCTs. However, their effects on clear-
WRITING THE PERITONEAL DIALYSIS PRESCRIPTION
S145
ance and fluid removal are well recognized from

clinical studies and clinical experience and are
not controversial. The relative merits of particular strategies in a given patient need to take into
account multiple personal and social factors that
will vary among patients. These are not easily
studied in clinical trials. In such situations, different strategies may need to be tried in a given
patient until an optimal compromise among clearance, ultrafiltration, and QOL requirements is
achieved.
With regard to the middle-molecule recommendation, there is too little evidence to offer a firm
guideline, but, just as when dealing with smallsolute clearances, the best principle is to give the
patient the benefit of the doubt and not provide

lower clearances than have been shown to be
safe by clinical studies. However, given the lack
of evidence, weight also should be given to other
factors, such as QOL and risk for mechanical
complications.
IMPLEMENTATION
Implementation of these recommendations requires only that patients be carefully evaluated
monthly. At the evaluations, ultrafiltration and
clearance requirements should be reviewed, with
particular attention to how the prescription is
affecting QOL and whether the patient is adherent to it. Appropriate changes could then be made.

6: PEDIATRIC PERITONEAL DIALYSIS
6.1 Dialysis initiation:
6.1.1 Dialysis initiation should be considered for the pediatric patient when
GFR is 9 to 14 mL/min/1.73 m2 BSA
and should be recommended when
GFR is 8 mL/min/1.73 m2 or less.
GFR can be estimated by either
averaging the measured creatinine
and urea clearances by using a timed
urine collection, using the Schwartz
formula, or using a timed urine
collection to determine CCr after a
dose of cimetidine. Dialysis therapy
initiation should be considered at
the greater estimated GFR levels
when the patients clinical course is
complicated by the presence of malnutrition, fluid overload, hypertension, hyperkalemia, hyperphosphatemia, acidosis, growth failure/
decreasing height velocity, or
neurological consequences of uremia. Before dialysis is undertaken,
these conditions should be shown to
be persistent and refractory to medication and/or dietary management.
6.2 Modality selection:
6.2.1 The decision regarding the selection
of PD as a dialysis modality for the
pediatric patient should take a variety of factors into account, including patient/family choice, patient
size, medical comorbidities, and
family support.
6.3 Solute clearance targets and measurements:
6.3.1 In the absence of definitive data
correlating solute removal and clinical outcome in children, current
recommendations for solute clearance in pediatric patients receiving
PD are as follows:
6.3.1.1 The pediatric patients clinical status should be reviewed
at least monthly, and delivery of the prescribed solute
clearance should render the
S146
patient free of signs and

symptoms of uremia.
6.3.1.2 All measurements of peritoneal solute clearance should
be obtained when the patient
is clinically stable and at least
1 month after resolution of an
episode of peritonitis.
6.3.1.3 More frequent measurements
of peritoneal solute clearance
and RKF should be considered when clinical events are
likely to have resulted in decreased clearance or when
new/worsening signs or symptoms of uremia develop.
6.3.1.4 Regardless of the delivered
dose of dialysis, if a patient
is not doing well and has no
other identifiable cause other
than kidney failure, a trial
of increased dialysis is
indicated.
6.3.2 For patients with RKF (defined as
urine Kt/Vurea > 0.1/wk):
6.3.2.1 The minimal delivered
dose of total (peritoneal and
kidney) small-solute clearance should be a Kt/Vurea of
at least 1.8/wk.
6.3.2.2 Total solute clearance should
be measured within the first
month after initiating dialysis and at least once every 6
months thereafter.
6.3.2.3 If the patient has RKF and
residual kidney clearance is
being considered as part of
the patients total weekly solute clearance goal, a 24hour urine collection for
urine volume and solute
clearance determinations
should be obtained at a minimum of every 3 months.
6.3.3 For patients without RKF (defined
as urine Kt/Vurea < 0.1/wk) or for
those in whom RKF is unable to be

measured accurately:
6.3.3.1 The minimal delivered
dose of small-solute clearance should be a peritoneal
Kt/Vurea of at least 1.8/wk.
6.3.3.2 The peritoneal solute clearance should be measured
within the first month after
starting dialysis and at least
once every 6 months
thereafter.
6.3.4 When calculating Kt/Vurea, one
should estimate V or TBW by using
the sex-specific nomograms based
upon the following equations:
Males: TBW = 0.010
(height weight)0.68
0.37 weight
Females: TBW = 0.14

(height weight)0.64
0.35 weight
6.4 Preservation of RKF:
6.4.1 Techniques that may contribute to
the preservation of RKF in pediatric patients receiving PD should be
incorporated as a component of
dialysis care whenever possible.
6.4.1.1 Nephrotoxic insults in
those with normal or impaired kidney function
should be assumed, in the
absence of direct evidence,
to also be nephrotoxic in
patients on PD therapy
who have RKF and therefore should be avoided.
6.4.1.2 Aminoglycoside antibiotics should be avoided
whenever possible to minimize the risk for nephrotoxicity, as well as ototoxicity and vestibular
toxicity.
6.4.1.3 Prekidney and postkidney causes of a decrease in RKF should be
considered in the appropriate clinical setting.
S147
6.4.1.4 Infections of the urinary

tract should be treated
promptly.
6.4.1.5 Diuretics should be used
to maximize urinary salt
and water excretion.
6.4.1.6 An ACE inhibitor or ARB
should be considered in a
PD patient who requires
antihypertensive medication and has RKF.
6.5 Writing the PD prescription:
6.5.1 In addition to solute clearance,
QOL, ultrafiltration/volume control, and possibly the clearance of
middle molecules should be considered when writing the PD prescription.
6.5.1.1 The patients dialysis
schedule and QOL as it
relates to such issues as
school and work attendance/performance should
be taken into account
when designing the dialysis prescription.
6.5.1.2 To optimize small-solute
clearance, minimize cost,
and possibly decrease the
frequency of exchanges,
one should first increase
the instilled volume per
exchange (target range,
1,000 to 1,200 mL/m2
BSA; maximum, 1,400
mL/m2 BSA), as tolerated
by the patient, before increasing the number of
exchanges per day. The
volume of the supine exchange(s) should be increased first because this
position has the lowest intra-abdominal pressure.
Objective evidence of patient tolerance may require assessment of IPP.
6.5.1.3 The patients record of PD
effluent volume should be
reviewed monthly, with
particular attention to the
S148
drain volume from the

overnight dwell of CAPD
and daytime dwell of
CCPD.
6.5.1.4 Factors to be considered
when attempting to optimize total body volume
include:
a. Dietary sodium and
fluid restriction may be
implemented in patients
unable to maintain euvolemia/normotension
with dialysis alone.
b. In patients with RKF,
diuretics may be preferred over increasing the dialysate dextrose concentration to
achieve euvolemia.
c. Drain volume should
be optimized after the
overnight dwell of
CAPD and the daytime dwell(s) of CCPD
to maximize solute
clearance and ultrafiltration volume.
d. In patients who are hypertensive or in whom
there is evidence of
volume overload, ultrafiltration generally
should be positive for
all daytime or nighttime exchanges.
e. An effort should be
made to determine the
lowest possible dialysate dextrose concentration required to
achieve the desired ultrafiltration volume.
6.5.1.5 To optimize middle-molecule clearance in patients
who have minimal RKF,
the PD prescription should
preferentially include the
use of CCPD with dwells
24 h/d or CAPD. This is
recommended even if
small-molecule clearance is
above target without the
longer dwell.
6.5.1.6 The use of NIPD (eg, no
daytime dwell) can be considered in pediatric patients who are clinically
well, whose combined dialysis prescription and
RKF achieves or exceeds
the target solute clearance, and who are without
evidence of hyperphosphatemia, hyperkalemia,
hypervolemia, or acidosis.
6.6 Other aspects of the care of the pediatric
PD patient:
6.6.1 All children on PD therapy with
anemia should follow the KDOQI
Guidelines for Management of Anemia that pertain to pediatrics.231
6.6.2 Management of dyslipidemias for
prepubertal children on PD therapy
should follow recommendations by
the National Cholesterol Expert
Panel in Children and Adolescents.232 Postpubertal children or
adolescents on PD therapy should
follow the pediatric recommendations provided in the KDOQI Clinical Practice Guidelines for Managing Dyslipidemia in CKD.233
6.6.3 All children on PD therapy should
follow the pediatric-specific recommendations provided in the KDOQI
Clinical Practice Guidelines for CVD
in Dialysis Patients and the KDOQI
Clinical Practice Guidelines on Hypertension and Antihypertensive
Agents in CKD.158,166
6.6.4 All children on PD therapy should
follow the recommendations provided in the KDOQI Clinical Practice Guidelines for Nutrition in
Chronic Renal Failure.35
RATIONALE
Dialysis Initiation
The gold standard for measurement of GFR is
inulin clearance, but this technique is impractical
to perform clinically. Whereas the use of such

radioisotopic measures as chromium-51,
iothalamate sodium 125I, and technetium 99DTPA are alternative measures to inulin, these
techniques are expensive, require multiple blood
samples, and are not ideal for frequent monitoring.234,235
A measured CCr requires a timed urine collection, most often 12 to 24 hours in duration. The
accuracy of the assessment as a means of estimating GFR is complicated by the need for a complete urine collection and that creatinine secretion results in overestimation of GFR, especially
at lower levels of kidney function.236,237 At lower
levels of GFR, accuracy is improved by measuring both creatinine and urea clearances on the
same timed urine collection and averaging the
values to obtain the estimated GFR.238,239
The accuracy of the GFR estimate by CCr can
be increased by the provision of cimetidine to the
patient before the timed urine collection.239 A
study of children showed that as a result of
cimetidines capacity to block the kidneys tubular secretion of creatinine, its use in a formal
outpatient protocol is associated with GFR results that approximate those obtained with inulin.240,241
The Schwartz formula also overestimates GFR,
especially at lower GFR levels, and provides a less
accurate means of estimating the target clearance
for dialysis consideration than what can be determined with a complete timed urine collection.242
However, recent pediatric data show that a GFR of
15 mL/min/1.73 m2 or less estimated by using the
Schwartz formula had an excellent negative predictive value for a measured GFR of 20 mL/min/1.73
m2 by using iothalamate clearance.243
Because a timed urine collection often is not
possible for smaller nontoilet-trained children,
reliance on a serum creatininebased formula,
such as the Schwartz formula, is essential in this
subset of patients. The Schwartz formula con-
S149
tains a cofactor that accounts for patient sex and

age to incorporate estimates of lean body mass.
The Schwartz formula is calculated in the following manner4,242:
GFR = kL/Pcr
where GFR is expressed in milliliters per
minute per 1.73 m2, L represents body length in
centimeters, Pcr is plasma creatinine in milligrams per deciliter, and k, a constant of proportionality, is a function of urinary creatinine excretion per unit of body size (see Table 16).
Finally, a variety of signs and symptoms may
be present in the pediatric patient with CKD
stage 4 (GFR, 15 to 29 mL/min/1.73 m2) that are
not routinely associated with the presence of
uremia, but that remain unresponsive to medical
and/or dietary therapy. A trial of dialysis may on
occasion result in marked clinical improvement.
Modality Selection
PD is the preferred initial long-term dialysis
modality worldwide for the pediatric patient with
CKD stage 5.244,245 Its use is particularly advantageous in the very small patient for whom
maintenance of a functional and complicationfree vascular access can be problematic. The
provision of PD, often in association with the use
of an automated cycling device, also facilitates
regular school attendance for most age-appropriate children.245 The use of PD is preferred over
HD when there are contraindications to the use
of anticoagulation, in children who have cardiovascular instability, and in children who live far
from a pediatric HD center.
However, there are absolute and relative contraindications to the use of PD in children that
include the following246:
Absolute contraindications:
Omphalocele
Gastroschisis
S150
Bladder extrophy
Diaphragmatic hernia
Obliterated peritoneal cavity
Peritoneal membrane failure
Relative contraindications:
Current clinical opinion supports the recommendation that the target delivered solute clearance in pediatric patients should meet or exceed
adult standards. The term delivered refers to
the actual dose the patient is receiving based on
measurement, in contrast to an estimated value
using a kinetic modeling program.151,156 Data
from pediatric and adult patients found serum
albumin level to be a predictor of patient survival, and a Kt/Vurea of 1.8 or greater in adult PD
patients has been associated with better serum
albumin values.55,249 The ADEMEX Study did
not show a clinical benefit associated with Kt/
Vurea greater than 1.7/wk in adult CAPD patients, whereas other studies provided evidence
for a recommended minimal Kt/Vurea greater
than 1.7/wk and an optimal Kt/Vurea of 1.8/wk
based on survival data in anuric adult CAPD
patients.38,39,70 No similar large-scale studies
have been performed in children. Pediatric studies have presented data suggestive of a correlation between patient outcome (especially growth)
and total solute clearance; however, the number
of patients in these and other pediatric studies is
small and the potential role of RKF can be
confounding, and thus data correlating solute
clearance to outcome cannot be considered definitive.250,251 Nevertheless, it is recommended that
solute clearance assessments take place at least
every 6 months in all cases and that more frequent assessments be conducted when dialysis
clearance may have been compromised (eg, after
peritonitis), there is a progressive loss of RKF, or
there is clinical evidence of inadequate dialysis.
Historically, both Kt/Vurea and CCr have served
as measures of dialysis clearance. In addition,
the averaged urea and CCr from a timed urine
collection has been recommended as the most
accurate means to estimate RKF and remains a
preferred approach to estimate GFR when considering dialysis therapy initiation.238,239 Nevertheless, determination of dialysis and urine Kt/Vurea
alone currently is recommended for follow-up
based upon the simplicity of the calculation and
because studies of adult patients on PD therapy
have not provided evidence of a benefit in terms
Inadequate living situation for home dialysis

Lack of appropriate caregiver
Impending/recent major abdominal surgery
Imminent living-related donor transplantation
(within 6 months of dialysis initiation)
Recognition of the burden of care for families

that coexists with the provision of this home
therapy is paramount so that appropriate support
systems may be put in place.247 Assessment of
the patients and caregivers perception of QOL
may aid in this process .246A
PD Solute Clearance Targets and
Measurements
The clinical status of the pediatric patient
should be monitored closely as an important
qualitative means of determining whether the
patient is receiving an adequate quantity of dialysis. Irrespective of the delivered dose of dialysis,
adequate dialysis likely is provided if the patients clinical status is characterized by adequate growth, blood pressure control, and nutritional status; avoidance of hypovolemia and
sodium depletion; and adequate psychomotor
development.246,248
Clinical manifestations of inadequate dialysis
may include the following:
CHF
Hyperphosphatemia/excessive serum calcium
phosphorus product
Uncontrolled hypertension/hypervolemia
Overt uremia (uremic pericarditis, pleuritis)
Repeated hyperkalemic episodes
Clinical or biochemical signs of malnutrition
or wasting
Poor school performance
Factors contributing to inadequate dialysis include:
Loss of RKF
Prescription inadequate for peritoneal membrane transport characteristics
Reduced peritoneal surface area caused by
extensive intra-abdominal adhesions
Loss of membrane solute transport/ultrafiltration capacity because of peritonitis

Noncompliance with PD prescription
Poorly functioning PD catheter
of patient outcome when expressing clearance in

any manner other than Kt/Vurea.252,253 The agerelated differences in the residual urine volume
of children with CKD stage 5 precludes duplication of the adult preference to universally characterize the presence of RKF as urine volume
greater than 100 mL/d.
Accurate estimation of TBW or V is a critical
component of the dialysis prescription in PD.
Because gold-standard isotope dilution techniques are laborious, cost-ineffective, and not
widely available, anthropometric prediction equations based on height and weight commonly are
used to determine TBW.254 During childhood,
complex changes in body composition occur that
necessitate the use of appropriate allometric formulae. Whereas such equations have been established in healthy populations, recent studies
showed that the use of these equations routinely
overestimates TBW in pediatric patients receiving PD.255-257 Conversely, the recent determination of TBW by heavy water (H2O18 or D2O)
dilution in 64 pediatric patients receiving PD has
allowed for the development of TBW prediction
equations that perform equally well in male and
female, North American and European, obese
and nonobese, and growth-retarded and normally
sized children.148
The sex-specific nomograms designed to estimate TBW, which are based upon the prediction
equations, are shown in Table 17 and Table 18.
Because the height weight parameter also
predicts BSA, use of the Gehan and George
equation for BSA allows for TBW-estimating
equations that can be simplified, but with slightly
less precision, compared with the best fitting
equations to:
Male: TBW = 20.88 BSA 4.29

Females: TBW = 16.92 BSA 1.81
Whereas several approaches to the calculation
of BSA are used in pediatrics, the Gehan and
George equation for BSA was derived from the
greatest number of study subjects.258,259 The
Gehan and George equation is as follows:
BSA (m2) = 0.0235 (height [cm]) 0.42246

(weight [kg]) 0.51456
S151
Based on this equation, BSA can be determined by height and weight by referring to Table
19.
Preservation of RKF
There are no large-scale studies in pediatrics
that provide evidence of a correlation between
RKF and patient outcome in children receiving
PD. However, in a single-center observation of a
pediatric PD population, it was shown that superior growth velocity occurred in a group of
children with RKF versus a group of children
without RKF despite the achievement of similar
mean total solute clearance in the 2 groups of
patients.250 Thus, it is possible that growth, as
well as achievement of solute clearance goals,
benefits from RKF and emphasizes the need to
prevent nephrotoxic insults whenever possible.
In addition, there is evidence that pediatric patients on PD therapy lose RKF at a slower rate
than patients on HD therapy.260
While there is no experience regarding the use
of ACE inhibitors or ARBs in children with CKD
stage 5 similar to that in adults, use of an ACE
inhibitor in children with CKD has been associated with marked slowing of kidney deterioration.99,100,261 In the setting of CKD stage 5, close
monitoring for the presence of hyperkalemia is
mandatory when an ACE inhibitor or ARB is
used.262
Writing the PD Prescription
Both CAPD and APD are used by children,
and the prescription designed for either modality
is best tailored to the needs of the individual
patient. APD is the preferred PD modality in
children, in large part because its use is characterized by freedom from procedures during the
daytime hours.245,263 The pediatric PD patients
QOL and the influence that the dialysis prescription has on it is an issue that should be reassessed
regularly because of the impact that CKD can
have on the childs overall development. Although there are not yet any validated measures
of QOL designed for the pediatric CKD stage 5
population, the PedsQL 4.0 Generic Core
Scales and the Child Health Questionnaire have
both been used successfully in the pediatric dialysis population.246A,264,265
Pediatric data have provided evidence that the
prescription of an exchange volume that results
S152
S153
S154
S155
S156
S157
S158
in an exceedingly high IPP may result in patient

intolerance and poor ultrafiltration.266 Whereas
the target range for the exchange volume of
patients older than 2 years is 1,000 to 1,200
mL/m2 BSA, the initial prescribed volume should
be somewhat lower for smaller infants (600 to
800 mL/m2 BSA). A stepwise increase in volume
as tolerated by the patient usually is possible.
While the limitation of dietary sodium in children may have a positive influence on total body
volume, this recommendation should be instituted with caution in patients with high RKF
and/or dialysis-related sodium losses. Salt depletion may result in hypotension and impaired
growth.267
The removal of middle molecules and lowmolecular-weight proteins ideally also should be
taken into account in the prescription process
because of the influence it may have on clinical
outcome, especially in patients without RKF.248
However, few data exist on the topic in pediatrics, prompting it to currently have a minor role
in prescription considerations for children.268
Although the PD prescription is characterized
most often by 24-hour dwells, in some circumstances, NIPD without the use of a daytime dwell
can be used effectively. Its use requires that the

patients clinical status be monitored closely and
consideration be given to a 24-hour dwell prescription if NIPD is not fully effective. This
recommendation has been made previously by
the European Pediatric PD Working Group.269
LIMITATIONS
No large-scale prospective study has been
conducted in children on PD therapy that correlates solute removal (PD and RKF) with patient
outcome. This precludes the ability to make an
evidence-based recommendation regarding the
target solute clearance.
Few data are available for children that compare the impact of RKF versus peritoneal solute
removal on patient outcome.
Although data are available from the adult
CKD stage 5 population showing the benefit of
ACE-inhibitor and ARB therapy as a means of
preserving RKF, no similar pediatric data are
available.
The ability to assess the QOL of the pediatric
PD patient and his or her family is limited by the
absence of a QOL tool that has been validated in
the pediatric CKD stage 5 population.
evidence and on the need for research to provide
additional evidence.
The recognized lack of prospective randomized trials and level A medical evidence was
noted when the original KDOQI Guidelines for
PD Adequacy were formulated. As a result, most
of the guidelines were opinion based, and important areas for research were identified. Some of
those questions have been answered with wellconducted, prospective, randomized trials so that
new guidelines can be formulated with grade A
and B medical evidence. Subsequent studies have
identified further questions and deficiencies in
current medical knowledge that will hopefully
stimulate further research.
CRITICAL RESEARCH
RECOMMENDATIONS
Guideline 1. Initiation of Dialysis
Although it is recognized that the patients
clinical condition at the start of KRT is an important predictor of outcome, there are no data to
confirm whether an earlier (in terms of kidney
progression) or a healthier (less advanced comorbidities) start results in a survival advantage
or just a lead-time bias. Furthermore, is the
answer to that question dependent on prior rate
of progression of kidney disease, cause of kidney
disease, the same for different ethnic groups, or
dependent on comorbidities present? Given the
cost of KRT to society, it is important to know
whether, in general, the timing of the start of
dialysis therapy improves total lifespan or only
increases time on dialysis therapy, but not total
lifespan. If it is the latter, data to show that the
patient otherwise would tend to be healthier with
less hospitalization, better QOL, or rehabilitation
also would be important to know.
Guideline 2. PD Solute Clearance Targets
and Measurements
It now is well documented that the presence of
RKF offers the typical patient on KRT an important survival advantage. What is not known is
S160
why that is true. Is it caused by better blood

pressure or volume control, more small-solute
removal, removal of middle molecules, or some
other poorly recognized function of metabolic or
paracrine function of the kidney tubules? Additional research to define the effects of RKF
would be most important. Results may influence
clinical practice, guidelines on initiation of dialysis therapy (can it be done in an incremental
manner?), and further determine how one best
includes the residual kidney component of total
solute clearance in dose calculations.
As noted in the text of these guidelines, 2 recent
prospective randomized trials suggested that, over
the range of solute clearance studies and using
current standard PD technologies (mainly CAPD),
trying to achieve higher solute clearance goals had
little clinical benefit for the population as a whole.
Therefore, considerably more research is needed in
the area of adequacy of PD. Additional randomized
trials, optimally multicentered, to examine different PD doses are needed to evaluate lower Kt/Vurea
in populations with larger patients with more comorbidity. A study that compares a group that maintains a peritoneal Kt/Vurea of 1.7 from the start of
dialysis therapy (disregarding RKF) with a group
that has a total Kt/Vurea of 1.7 (kidney plus peritoneal, which would require starting PD therapy with
a minimal prescription with subsequent adjustment
upward as RKF is lost) would be helpful. In addition, a randomized trial of different levels of smallmolecule clearances is needed specifically for anuric patients on PD therapy. Trials with a longer
follow-up than 2 years with assessment of nerve
conduction to evaluate for neuropathy would be
helpful. Markers of middle-molecule clearances
also should be obtained long term. A randomized
study to evaluate the influence of middle-molecule
clearance or of full- versus partial-duration day
dwells on patient outcomes would be valuable.
Trials are needed in APD, with both dry day
and wet days. A trial that compares outcomes
with beginning PD on APD with a dry day versus
beginning PD with a wet day (controlling for
peritoneal dose), with the subsequent adjustment
of the prescription (including the addition of a
wet day), would be informative in evaluating the
potential benefit of a dry abdomen for part of the
day on protection of the peritoneal membrane
and immune function. Such a study would need

to include markers of the peritoneal membrane,
as well as determination of middle molecules
and neuropathy.
Studies must be designed that separate the
effects of volume control from those of smallmolecule clearances. It is clear from the studies
that have been done that volume overload sometimes is a consequence of using a limited number
of exchanges in CAPD and perhaps a consequence of excessively short nighttime exchanges
in APD, in which the ultrafiltration volume is
likely to be 50% sodium free.
Because increasing small-molecule clearance
does not appear to be the path to improved survival,
studies investigating other maneuvers to decrease
mortality should be investigated. Attention should
be focused on specific causes of mortality. These
studies could include use of an ACE inhibitor in
combination with a lipid-lowering drug versus ACE
inhibitor alone, monthly follow-up to assess and
adjust the prescription to maximize volume status
versus less frequent visits, and to evaluate cardiovascular deaths. Anuric patients are more likely to
die a sudden death.69 Data from the same group
indicate that hypokalemia is a risk factor for death;
in this study, hypokalemia was defined by 3 measurements of potassium during 12 weeks, and sudden death was not more frequent in this group.270
Therefore, it seems possible that hypokalemia might
be more common in anuric patients, possibly because of dietary and nutritional issues, and contribute to sudden death, but this needs to be studied.
Another area that might prove fruitful to decrease morbidity and mortality is further research on decreasing the risk for, and managing,
peritonitis. The risk for death related to peritonitis is variable from a low of 3% of deaths in
Canada to 16.6% of deaths in Hong Kong.69
Aggressive catheter removal for refractory peritonitis versus delayed catheter removal (in an
attempt to decrease mortality related to peritonitis) may result in a decrease in peritonitis-related
deaths. Peritonitis remains the leading cause of
technique failure271 and affects peritoneal function during the first year on PD therapy.272 Additional research on training methods and exit-site
care may prove fruitful.
Last, studies of maneuvers to improve adherence with the prescription and diet are much
needed in PD patients, especially in such coun-
S161
tries as the United States, where adherence is less

than optimal. Such maneuvers might include
closer monitoring, treatment of depression, evaluation of supplies with home visits, etc.
Guideline 3. Preservation of RKF
Rigorous studies are needed to examine
whether the use of radiocontrast dye affects RKF
in dialysis patients and whether renoprotective
strategies in the nondialysis population also apply to those on dialysis therapy. Although controversial, it was suggested that the rate of decrease
in RKF in those on APD therapy compared with
those on CAPD therapy is faster. More data are
needed. Because of financial issues and ease of
administration, use of aminoglycoside antibiotics for the treatment of peritonitis has been
recommended. Therefore, data about whether
long- or short-term use of aminoglycosides is
associated with a more rapid decrease in RKF
would be helpful. The USRDS analysis80 showed
an association between use of ACE inhibitors
and also use of calcium channel blockers with
better preservation of RKF. Subsequent studies
examined ACE inhibitors and ARBs, but not the
use of calcium channel blockers; therefore, additional studies are needed. Clinical evaluation of
the continuing use of immunosuppressive therapy
(other than calcineurin inhibitors) to maintain
residual kidney allograft function in patients on
dialysis therapy is lacking. Also unclear is
whether the benefit of attaining normotension by
vigorous ultrafiltration is offset by the decrease
in RKF from the attendant volume depletion.
Guideline 4. Maintenance of Euvolemia
Randomized trials to determine optimal blood
pressure targets for PD patients are required.
Larger randomized trials looking at the effect of
newer dialysis solutions on important patient
outcomes also would be helpful. Studies looking
at the relationship between peritoneal hypertonic
glucose exposure and metabolic and cardiovascular outcomes, as well as patient survival, would
be valuable.
Guideline 5. Quality Improvement Programs
CQI programs were shown to improve specific
outcomes for subgroups of patients, such as
peritonitis rates, exit-site infection rates, technique failure rates, etc. It would be important to
develop a better understanding about which fac-
S162
tors also improve patient well-being and satisfaction with their modality. Current guidelines recommend assessing peritoneal transport status by
using PET. They subsequently recommend a
hypertonic dwell (4.25% dextrose) to work up a
patient with ultrafiltration failure. Studies that
compare 1.36%/1.5% dextrose or 2.27%/2.5%
dextrose PET with 3.86%/4.25% dextrose PET
are minimal. Because the 3.86%/4.25% test is
recommended for the workup of ultrafiltration
failure, more comparison data are needed. Furthermore, most kinetic modeling programs use
data from 2.27%/2.5% dextrose PET to predict
solute clearance and ultrafiltration. One needs to
evaluate whether current kinetic modeling programs are as accurate if 4.25% PET is used;
alternatively, if not, one may want to develop
programs that use 4.25% dextrose PET data
specifically. Once done, the standard PET may
be changed to a 4.25% dextrose PET.
Guideline 6. Pediatric PD
Pediatric data are sparse, in part because there
are few clinical trials using RR for death as an
outcome for adequacy. However, there are other
important aspects of overall patient care that
need to be considered and evaluated. These include the development of a simplified means to
estimate glomerular rate in children that precludes the need for urine collection and that is
accurate at low levels (stages 4 to 5 CKD) of
kidney function, determination of adequate and
optimal total solute clearance in children receiving PD, comparison of the impact of peritoneal
solute clearance versus RKF on patient outcome,
evaluation of PD and the longevity of dialysis
therapy on QOL of pediatric patients and their
families, determination of the ability of icodextrin-based dialysis solutions to enhance ultrafiltration across the age/size spectrum of pediatrics,
and evaluation of the safety and efficacy of
ACE-inhibitor, ARB, and diuretic therapy in children with CKD stage 5 receiving PD.
IMPORTANT RESEARCH
RECOMMENDATIONS
Much more research is needed regarding the
impact on the patient of the period leading up to
dialysis therapy and the period just after starting
dialysis therapy. Additional research is needed
on mood disorders, particularly depression and

anger, that may develop during this period and
the impact such disorders may have on outcomes
after dialysis therapy is initiated.
and Measurements
The presence of RKF was rather arbitrarily
defined in this document by the Work Group as
100 mL of urine output per day. This was chosen
because many of the studies on clearances chose
100 mL/d as the cutoff value. However, it is not
clear that this is the most appropriate level of
urine output to use, or even if urine volume,
rather than measured GFR, would be preferable.
Additional research is needed in this area.
Data for the effect of peritonitis on RKF are
contradictory. Studies examining the impact of
peritonitis, as well as the treatment approach, on
RKF are needed. In particular, the severity of
peritonitis may relate to loss of RKF with more
severe episodes (for example, fungal or those
caused by gram-negative bacilli) perhaps more
likely leading to loss of RKF.
Euvolemia in home dialysis patients is not always readily achieved because patients may not be
knowledgeable about this aspect of PD. A study
examining training methods emphasizing evaluation of euvolemia as done by the patient on
impact of blood pressure and volume status would
be worthwhile. In addition, there are few, if any,
studies of interventions to enhance patients abilities to follow a rather rigorous diet in regard to
sodium intake. Such studies should be undertaken.
Quality improvement programs are rather time
consuming and therefore costly. A cost analysis
of the impact of aggressive interventions by a
program on outcomes should be carried out.
CPR for Guideline 3
Current guidelines recommend assessing peritoneal transport status by using PET. They subsequently recommend a hypertonic dwell (4.25%
dextrose) to work up a patient with ultrafiltration
failure. Studies that compare 1.36%/1.5% dextrose or 2.27%/2.5% dextrose PET with 3.86%/
4.25% dextrose PET are minimal. Because the

3.86%/4.25% test is recommended for the workup
of ultrafiltration failure, more comparison data
are needed. Furthermore, most kinetic modeling
programs use data from 2.27%/2.5% dextrose
PET to predict solute clearance and ultrafiltration. One needs to evaluate whether current kinetic modeling programs are as accurate if 4.25%
PET is used; alternatively, if not, one may want
to develop programs that use 4.25% dextrose
PET data specifically. Once done, the standard
PET may be changed to a 4.25% dextrose PET.
OF INTEREST
It is unclear whether it is advisable to start
patients who chose cycler dialysis on therapy
with a dry day. Theoretically, this might enhance
long-term preservation of the peritoneal membrane, but there are no data concerning this. In
addition, it is unclear whether a patient who
wishes to dialyze at home using the cycler should
be started initially on CAPD. The Work Group
sees no reason for such an approach, but a study
might be carried out to investigate the impact of
each approach on QOL. Research on the desirability of placing a backup fistula in patients who
chose PD therapy would be of interest.
and Measurements
HD patients have a measure of small-solute
adequacy carried out each month. There is considerable controversy among PD experts about the
S163
desirable frequency of measurements of peritoneal

clearance, which tends not to change much over
time. Studies evaluating this more carefully are
warranted.
Because PD prescriptions often are dependent
on RKF, it is important that the health care team
recognize when RKF decreases. A study in which
the PD patient measures the volume of urine
output daily (such as transplant recipients historically were asked to do in the period immediately
after transplantation) as a marker of RKF and to
notify the dialysis program if there is a substantial change would be of some interest to see if
this approach impacts on earlier recognition of
an important change in RKF.
Patients on PD therapy traditionally are asked
to monitor their own blood pressure at home, at a
minimum daily. A study in which the patient
measures blood pressure more often and takes an
as-needed extra blood pressure medication for an
elevation would be of interest to determine if this
impacted on RKF or other outcomes.
Quality improvement programs traditionally
are multidisciplinary. However, it is unclear how
involved the physician or physician assistant
typically is in many programs in the CQI efforts.
An evaluation of the importance of having a
physician PD champion in the multidisciplinary CQI process would be of interest.

Joanne Bargman, MD, FRCPC, received her
MD cum laude at the University of Toronto in
1978. After medical residency in Toronto, she was
chosen as an exchange resident in Melbourne,
Australia, where she completed her postgraduate
year 3. She undertook nephrology training at
Stanford University and, as a fellow of the Medical Research Council of Canada, spent almost 3
years in physiology research examining mechanisms of urinary concentration. She assumed a
staff nephrologist position at the Toronto Western Hospital in 1985 and worked in the PD unit
with Dimitrios Oreopoulos. She has published
more than 120 articles and delivered more than
200 lectures internationally on subjects ranging
from PD to glomerulonephritis and systemic
lupus erythematosus. She is Director of the PD
Program and also Co-Director of the RenalRheumatology Lupus Clinic at the University
Health Network in Toronto. Dr Bargman is a
council member of the International Society of
Nephrology and the International Society of PD.
She is the recipient of major teaching awards at
the undergraduate and postgraduate levels at the
University of Toronto. Dr Bargman has received
research funds, grants, or contracts from Amgen,
Baxter Healthcare, Fresenius Medical Care, and
Gambro Healthcare.
Peter G. Blake, MD, FRCPC, MBBCh, is a
Professor of Medicine and Chair of the Division
of Nephrology at the University of Western Ontario and London Health Sciences Centre. He is a
member of the Canadian Society of Nephrology
Work Group on PD, was the editor of 2 major
textbooks in nephrology, and is Editor-in-Chief
of Peritoneal Dialysis International. His areas of
interest include dialysis with particular regard to
the development of PD, adequacy and nutrition
in PD, trends in patient outcomes, and the economics of dialysis. Dr Blake has received lecture
fees from Amgen, Baxter Healthcare, and Ortho
Biotech.
John M. Burkart, MD (Co-Chair), is Professor of Medicine/Nephrology at Wake Forest Baptist Medical Center in Winston-Salem, NC. He is
Corporate Medical Director of the Wake Forest
University Outpatient Dialysis Centers. He attended medical school at Rush Medical College
in Chicago, IL, and did his residency training and
S164
fellowship at the Bowman Gray School of Medicine of Wake Forest University. He has served on
the PD Adequacy Work Group since its formation, currently as the Co-Chair. He is treasurer of
the International Society for PD. He is a member
of the Centers for Medicare and Medicaid Services advisory council for reimbursement based
on case-mix. He has authored many chapters on
PD in major nephrology text books and parts of
Up to Date and is interested in all clinical aspects
of PD and hemodialysis. Dr Burkart has received
research funds, grants, or contracts from Baxter
Healthcare, Genzyme, and Fresenius Medical
Care.
Fredric O. Finkelstein, MD, is Chief of Nephrology, Hospital of St Raphael, and Clinical
Professor of Medicine at Yale University, New
Haven, CT. Dr Finkelstein has been involved in
continuous ambulatory PD since 1979, when he
started a freestanding continuous ambulatory PD
facility in New Haven, CT. He has written extensively on a variety of issues involving PD therapy.
He currently is a member of the Council of the
International Society of PD and is on the Editorial Board of Peritoneal Dialysis International.
Dr Finkelstein has received research funds, grants,
or contracts from Baxter Healthcare and Renal
Research Institute.
Thomas A. Golper, MD, FACP, trained at
Indiana University and the Oregon Health Sciences University and currently is Professor of
Medicine (Nephrology) at Vanderbilt University
Medical Center in Nashville, TN. He has held
positions on the Board of Directors of the Renal
Physicians Association and American Association of Kidney Patients, served as the PD Adequacy Work Group Chair for the first 2 versions
of KDOQI, and remains on the Work Group and
Steering Committee. He led the Network 9 Peritonitis and Catheter Survival Study and has served
on the International Society of PD Ad Hoc Committee for Peritonitis for many iterations of its
guidelines. His interests remain in the field of
dialysis and the administrative aspects of nephrology practice. Dr Golper has received research
funds, grants, or contracts from Amgen, Baxter
Healthcare, Genzyme, Ortho Biotech, and Roche.
Angellina Graham, RN, graduated in 1995
with an associate degree in nursing. She is cur-
rently employed by Wake Forest Outpatient Dialysis at Piedmont Dialysis Center, serving in the
role of Charge Nurse in the Hometraining Department and has also assisted with numerous clinical trials.
Beth Piraino, MD (Co-Chair), received her
BS from the University of Pittsburgh. She attended medical school at the Medical College of
Pennsylvania and graduated magna cum laude.
She did her subsequent training in Internal Medicine and Nephrology at the University of Pittsburgh Health Center, after which she joined the
faculty of the University of Pittsburgh School of
Medicine, rising through the ranks over the years
to her current position as tenured Professor of
Medicine and Associate Dean of Admissions. Dr
Pirainos major research interest has been to
improve outcomes of patients on PD therapy, in
particular, by decreasing infectious complications.
She has published widely in the area of PD, with
numerous presentations at national and international meetings. She was Secretary for the International Society of PD from 2001 to 2006. She is
Director of the PD Program at the University of
Pittsburgh and Co-Medical Director of Dialysis
Clinic Inc of Oakland. She received the prestigious Life Time Achievement Award at the 24th
Annual Dialysis Conference in February 2004
for contributions to the care of PD patients. Dr
Piraino has received research funds, grants, or
contracts from Paul Teschan Fund through Dialysis Clinic Inc. and Baxter Healthcare.
S165
Susan Stark, MS, RD, CSR, LDN, is a

dietitian specialist at the University of Pittsburgh
Medical Center, Presbyterian Hospital. She is a
member of the American Dietetic Association.
Bradley A. Warady, MD, is Chief of Nephrology and Director of Dialysis and Transplantation at The Childrens Mercy Hospital
and Professor of Pediatrics at the University of
Missouri-Kansas City School of Medicine. Dr
Waradys clinical and research focus is end-stage
renal disease, with particular emphasis on PD.
He established the Pediatric PD Study Consortium and is a member of the Board of Directors
of the North American Pediatric Renal Transplant Cooperative Study. He currently serves as
Co-Principal Investigator of the International Pediatric Peritonitis Registry and the National Institutes of Healthfunded Chronic Kidney Disease
in Children (CKiD) study. He co-edited the books
CAPD/CCPD in Children and Pediatric Dialysis
and has published more than 200 articles and
book chapters. He is a council member of the
International Society of PD and has been a member of the KDOQI PD Adequacy, Pediatric Nutrition, and Pediatric Bone Work Groups for the
National Kidney Foundation. Dr Warady also
serves as an Associate Editor for Peritoneal
Dialysis International and sits on the Editorial
Board of Pediatric Nephrology. Dr Warady has
received research funds, grants, or contracts from
Amgen and Watson Pharmaceuticals.
CONSULTANTS TO THE KDOQI PEDIATRIC PERITONEAL

DIALYSIS GUIDELINE AND CPRs
Steven R. Alexander, MD, FACP, is Chief of
Division of Nephrology at Department of Pediatrics at Stanford University School of Medicine.
Dr Alexander is the Founder and Director of the
Annual Symposium on Pediatric Dialysis and he
is serving on the Editorial Board for Pediatric
Transplantation and International Journal of Artificial Organs. Dr Alexander has received research funds, grants, or contracts from Amgen,
AstraZeneca Inc., Genentech Inc., National Institutes of Health, Southwest Pediatric Nephrology
Study Group (SPNSG), and Watson Pharmaceuticals.
Michel Fischbach, MD, is Chief of the Pediatric Department at the University Hospital of
Strasbourg and Professor of Pediatrics at the
University Louis Pasteur of Strasbourg, France.
Dr Fischbachs clinical and research focus is end
stage renal disease with a special interest in
hemodialysis and peritoneal dialysis. As a member of the European Pediatric Dialysis Work
Group (EPDWG), he published as a first author
on the European Peritoneal Dialysis Guidelines
(2002) for children. He is also the primary author
in more than 100 international articles on dialysis in children and he serves as an Associate
rently employed by Wake Forest Outpatient Dialysis at Piedmont Dialysis Center, serving in the
role of Charge Nurse in the Hometraining Department and has also assisted with numerous clinical trials.
Beth Piraino, MD (Co-Chair), received her
BS from the University of Pittsburgh. She attended medical school at the Medical College of
Pennsylvania and graduated magna cum laude.
She did her subsequent training in Internal Medicine and Nephrology at the University of Pittsburgh Health Center, after which she joined the
faculty of the University of Pittsburgh School of
Medicine, rising through the ranks over the years
to her current position as tenured Professor of
Medicine and Associate Dean of Admissions. Dr
Pirainos major research interest has been to
improve outcomes of patients on PD therapy, in
particular, by decreasing infectious complications.
She has published widely in the area of PD, with
numerous presentations at national and international meetings. She was Secretary for the International Society of PD from 2001 to 2006. She is
Director of the PD Program at the University of
Pittsburgh and Co-Medical Director of Dialysis
Clinic Inc of Oakland. She received the prestigious Life Time Achievement Award at the 24th
Annual Dialysis Conference in February 2004
for contributions to the care of PD patients. Dr
Piraino has received research funds, grants, or
contracts from Paul Teschan Fund through Dialysis Clinic Inc. and Baxter Healthcare.
S165
Susan Stark, MS, RD, CSR, LDN, is a

dietitian specialist at the University of Pittsburgh
Medical Center, Presbyterian Hospital. She is a
member of the American Dietetic Association.
Bradley A. Warady, MD, is Chief of Nephrology and Director of Dialysis and Transplantation at The Childrens Mercy Hospital
and Professor of Pediatrics at the University of
Missouri-Kansas City School of Medicine. Dr
Waradys clinical and research focus is end-stage
renal disease, with particular emphasis on PD.
He established the Pediatric PD Study Consortium and is a member of the Board of Directors
of the North American Pediatric Renal Transplant Cooperative Study. He currently serves as
Co-Principal Investigator of the International Pediatric Peritonitis Registry and the National Institutes of Healthfunded Chronic Kidney Disease
in Children (CKiD) study. He co-edited the books
CAPD/CCPD in Children and Pediatric Dialysis
and has published more than 200 articles and
book chapters. He is a council member of the
International Society of PD and has been a member of the KDOQI PD Adequacy, Pediatric Nutrition, and Pediatric Bone Work Groups for the
National Kidney Foundation. Dr Warady also
serves as an Associate Editor for Peritoneal
Dialysis International and sits on the Editorial
Board of Pediatric Nephrology. Dr Warady has
received research funds, grants, or contracts from
Amgen and Watson Pharmaceuticals.
CONSULTANTS TO THE KDOQI PEDIATRIC PERITONEAL

DIALYSIS GUIDELINE AND CPRs
Steven R. Alexander, MD, FACP, is Chief of
Division of Nephrology at Department of Pediatrics at Stanford University School of Medicine.
Dr Alexander is the Founder and Director of the
Annual Symposium on Pediatric Dialysis and he
is serving on the Editorial Board for Pediatric
Transplantation and International Journal of Artificial Organs. Dr Alexander has received research funds, grants, or contracts from Amgen,
AstraZeneca Inc., Genentech Inc., National Institutes of Health, Southwest Pediatric Nephrology
Study Group (SPNSG), and Watson Pharmaceuticals.
Michel Fischbach, MD, is Chief of the Pediatric Department at the University Hospital of
Strasbourg and Professor of Pediatrics at the
University Louis Pasteur of Strasbourg, France.
Dr Fischbachs clinical and research focus is end
stage renal disease with a special interest in
hemodialysis and peritoneal dialysis. As a member of the European Pediatric Dialysis Work
Group (EPDWG), he published as a first author
on the European Peritoneal Dialysis Guidelines
(2002) for children. He is also the primary author
in more than 100 international articles on dialysis in children and he serves as an Associate
S166
Editor for Pediatric Nephrology, Dialysis section.

Denis F. Geary, MB, MRCP(UK), FRCP(C),
is a Professor at Department of Pediatrics in
University of Toronto and Chief at Division of
Nephrology, The Hospital for Sick Children. He
is the past-President of the Canadian Association
of Pediatric Nephrologists and his current areas
of interest include nocturnal hemodialysis for
children, antenatally diagnosed renal disease,
growth in children with renal failure, and anemia
in children with chronic renal failure. Dr Geary
has received research funds, grants, or contracts
from Amgen and Hoffman La Roche.
Franz Schaefer, MD, is Professor of Pediatrics and Chief of the Pediatric Nephrology division at Heidelberg University Medical Center.
He established the Mid European Pediatric Peritoneal Dialysis Study Group (MEPPS) and the
European Study Group on Progressive Chronic
Kidney Disease in Children (ESCAPE). He currently serves as Co-Principal Investigator of the
International Pediatric Peritonitis Registry and
he is also a member of the European Pediatric
PD Working Group. He has co-edited the book
Pediatric Dialysis and has published more than
220 articles and book chapters. In addition, he is
a current council member of the European Society for Pediatric Nephrology and serves as pediatric liaison officer at the council of the International Society of Peritoneal Dialysis. Dr Schaefer
also serves as an Assistant Editor for Pediatric
Nephrology and sits in the Editorial Boards of
Peritoneal Dialysis International, Current Pediatric Reviews and Biomed Central Nephrology.
Dr Schaefer has received research funds, grants,

or contracts from AstraZeneca, Baxter Healthcare, Fresenius Medical Care, IBM, Pfizer, and
Roche.
Cornelis H. Schrder, MD, PhD, is Director
of the Pediatric Nephrology, Dialysis, and Transplantation Department at the Wilhelmina Childrens Hospital and Professor of Pediatric Nephrology at the University of Utrecht, The
Netherlands. His main research focuses are hereditary glomerular diseases and kidney replacement therapy, with particular emphasis on peritoneal dialysis. He is a member of the European
Pediatric Dialysis Working Group, and has published several guidelines on behalf of this group.
He is the author of more than 150 articles and
book chapters in the field of pediatric nephrology.
Professor Alan R. Watson, FRCP, is Director of the Children & Young Peoples Kidney
Unit, Nottingham City Hospital and Professor of
Paediatric Nephrology at the University of Nottingham, UK. His research interests have been in
clinical nephrology including nutrition, dialysis,
psychosocial aspects and ethics. He is the group
coordinator of the European Dialysis Working
Group, which has produced 7 published guidelines to date. Prof. Watson has published over
200 articles and book chapters and he is a Council member of the European Society for Paediatric Nephrology since 2003. He is also currently
on the Editorial Boards of the British Journal of
Renal Medicine and Peritoneal Dialysis International.
REFERENCES
1. Cockcroft DW, Gault MH: Prediction of creatinine
clearance from serum creatinine. Nephron 16:31-41, 1976
2. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N,
Roth D: A more accurate method to estimate glomerular
filtration rate from serum creatinine: A new prediction
equation. Modification of Diet in Renal Disease Study
Group. Ann Intern Med 130:461-470, 1999
3. Levey AS, Greene T, Kusek JW, Beck GJ, Group MS:
A simplified equation to predict glomerular filtration rate
from serum creatinine. J Am Soc Nephrol 11:155A, 2000
(abstr)
4. Schwartz GJ, Brion LP, Spitzer A: The use of plasma
creatinine concentration for estimating glomerular filtration
rate in infants, children, and adolescents. Pediatr Clin North
Am 34:571-590, 1987
5. Stevens LA, Levey AS: Measurement of kidney function. Med Clin North Am 89:457-473, 2005
6. Mohler JL, Barton SD, Blouin RA, Cowen DL,
Flanigan RC: The evaluation of creatinine clearance in
spinal cord injury patients. J Urol 136:366-369, 1986
7. Gonwa TA, Jennings L, Mai ML, Stark PC, Levey AS,
Klintmalm GB: Estimation of glomerular filtration rates
before and after orthotopic liver transplantation: Evaluation
of current equations. Liver Transpl 10:301-309, 2004
8. Sherman DS, Fish DN, Teitelbaum I: Assessing renal
function in cirrhotic patients: Problems and pitfalls. Am J
Kidney Dis 41:269-278, 2003
9. Jafar TH, Schmid CH, Levey AS: Serum creatinine as
marker of kidney function in South Asians: A study of
reduced GFR in adults in Pakistan. J Am Soc Nephrol
16:1413-1419, 2005
10. Moss AH: Shared decision-making in dialysis: The new
RPA/ASN guideline on appropriate initiation and withdrawal
of treatment. Am J Kidney Dis 37:1081-1091, 2001
11. Moss AH: Too many patients who are too sick to
benefit start chronic dialysis: Nephrologists need to learn to
just say no. Am J Kidney Dis 41:723-727, 2003
12. Galla JH: Clinical practice guideline on shared decision-making in the appropriate initiation of and withdrawal
from dialysis. The Renal Physicians Association and the
American Society of Nephrology. J Am Soc Nephrol
11:1340-1342, 2000
13. Moss AH, Holley JL, Davison SN, et al: Palliative
care. Am J Kidney Dis 43:172-173, 2004
14. Levin A, Lewis M, Mortiboy P, et al: Multidisciplinary predialysis programs: Quantification and limitations
of their impact on patient outcomes in two Canadian
settings. Am J Kidney Dis 29:533-540, 1997
15. Lopes AA, Bragg J, Young E, et al: Depression as a
predictor of mortality and hospitalization among hemodialysis patients in the United States and Europe. Kidney Int
62:199-207, 2002
16. Arora P, Obrador GT, Ruthazer R, et al: Prevalence,
predictors, and consequences of late nephrology referral at a
tertiary care center. J Am Soc Nephrol 10:1281-1286, 1999
17. Astor BC, Eustace JA, Powe NR, et al: Timing of
nephrologist referral and arteriovenous access use: The
CHOICE Study. Am J Kidney Dis 38:494-501, 2001
18. Avorn J, Bohn RL, Levy E, et al: Nephrologist care

and mortality in patients with chronic renal insufficiency.
Arch Intern Med 162:2002-2006, 2002
19. Avorn J, Winkelmayer WC, Bohn RL, et al: Delayed
nephrologist referral and inadequate vascular access in patients
with advanced chronic kidney failure. J Clin Epidemiol 55:711716, 2002
20. Levey AS, Coresh J, Balk E, et al: National Kidney
Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, classification, and stratification. Ann Intern
Med 139:137-147, 2003
21. Keshaviah PR, Emerson PF, Nolph KD: Timely
initiation of dialysis: A urea kinetic approach. Am J Kidney
Dis 33:344-348, 1999
22. Nolph KD: Rationale for early incremental dialysis
with continuous ambulatory peritoneal dialysis. Nephrol
23. Tattersall J, Greenwood R, Farrington K: Urea kinetics and when to commence dialysis. Am J Nephrol 15:283289, 1995
MD, 2004
25. Ellis PA, Reddy V, Bari N, Cairns HS: Late referral of
end-stage renal failure. QJM 91:727-732, 1998
26. Ifudu O, Dawood M, Homel P, Friedman EA: Timing
of initiation of uremia therapy and survival in patients with
progressive renal disease. Am J Nephrol 18:193-198, 1998
27. Roubicek C, Brunet P, Huiart L, et al: Timing of
nephrology referral: Influence on mortality and morbidity.
28. Sesso R, Belasco AG: Late diagnosis of chronic renal
failure and mortality on maintenance dialysis. Nephrol Dial
Transplant 11:2417-2420, 1996
29. Fink JC, Burdick RA, Kurth SJ, et al: Significance of
serum creatinine values in new end-stage renal disease
30. Korevaar JC, Jansen MA, Dekker FW, et al: When to
initiate dialysis: Effect of proposed US guidelines on survival.
Lancet 358:1046-1050, 2001
31. Traynor JP, Simpson K, Geddes CC, Deighan CJ, Fox
JG: Early initiation of dialysis fails to prolong survival in
patients with end-stage renal failure. J Am Soc Nephrol
13:2125-2132, 2002
31A. The Renal Association UK Registry. The Sixth
Annual Report, December 2003. This report was prepared
by Dr David Ansell, Professor Terry Feest, Dr Catherine
Byrne, and Dr Azhar Ahmad. Available at: www.renalreg.com/Report%202003/Cover3_Frames.htm. Accessed July
31, 2005
MD, 2003
33. Curtis BM, Barret BJ, Jindal K, et al: Canadian
survey of clinical status at dialysis initiation 1998-1999: A
multicenter prospective survey. Clin Nephrol 58:282-288,
2002
S167
S168
34. Cooper BA, Branley P, Bulfone L, et al: The Initiating

Dialysis Early and Late (IDEAL) Study: Study rationale and
design. Perit Dial Int 24:176-181, 2004
35. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure. Am J
36. Churchill DN, Thorpe KE, Nolph KD, Keshaviah PR,
Oreopoulos DG, Page D: Increased peritoneal membrane
transport is associated with decreased patient and technique
survival for continuous peritoneal dialysis patients. The
Canada-USA (CANUSA) Peritoneal Dialysis Study Group.
J Am Soc Nephrol 9:1285-1292, 1998
37. Bargman JM, Thorpe KE, Churchill DN: Relative
contribution of residual renal function and peritoneal clearance to adequacy of dialysis: A reanalysis of the CANUSA
38. Paniagua R, Amato D, Vonesh E, et al: Effects of
increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol 13:1307-1320, 2002
39. Lo WK, Ho YW, Li CS, et al: Effect of Kt/V on
survival and clinical outcome in CAPD patients in a
randomized prospective study. Kidney Int 64:649-656, 2003
40. Paniagua R, Amato D, Vonesh E, Guo A, Mujais S:
Health-related quality of life predicts outcomes but is not
affected by peritoneal clearance: The ADEMEX trial. Kidney Int 67:1093-1104, 2005
41. Szeto CC, Wong TY, Leung CB, et al: Importance of
dialysis adequacy in mortality and morbidity of Chinese
CAPD patients. Kidney Int 58:400-407, 2000
42. Diaz-Buxo JA, Lowrie EG, Lew NL, Zhang SM, Zhu
X, Lazarus JM: Associates of mortality among peritoneal
dialysis patients with special reference to peritoneal transport rates and solute clearance. Am J Kidney Dis 33:523534, 1999
43. Rocco MV, Frankenfield DL, Prowant B, Frederick P,
Flanigan MJ: Risk factors for early mortality in U.S.
peritoneal dialysis patients: Impact of residual renal function. Perit Dial Int 22:371-379, 2002
44. Termorshuizen F, Korevaar JC, Dekker FW, van
Manen JG, Boeschoten EW, Krediet RT: The relative
importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: An
analysis of the Netherlands Cooperative Study on the
Adequacy of Dialysis (NECOSAD)-2. Am J Kidney Dis
41:1293-1302, 2003
45. Chung SH, Heimburger O, Stenvinkel P, Qureshi AR,
Lindholm B: Association between residual renal function,
inflammation and patient survival in new peritoneal dialysis
46. Jager KJ, Merkus MP, Dekker FW, et al: Mortality
and technique failure in patients starting chronic peritoneal
dialysis: Results of The Netherlands Cooperative Study on
the Adequacy of Dialysis. NECOSAD Study roup. Kidney
Int 55:1476-1485, 1999
47. Merkus MP, Jager KJ, Dekker FW, de Haan RJ,
Boeschoten EW, Krediet RT: Predictors of poor outcome in
chronic dialysis patients: The Netherlands Cooperative
Study on the Adequacy of Dialysis. The NECOSAD Study
Group. Am J Kidney Dis 35:69-79, 2000
48. Ates K, Nergizoglu G, Keven K, et al: Effect of fluid

and sodium removal on mortality in peritoneal dialysis
49. Wang AY, Wang M, Woo J, et al: Inflammation,
residual kidney function, and cardiac hypertrophy are interrelated and combine adversely to enhance mortality and
cardiovascular death risk of peritoneal dialysis patients.
J Am Soc Nephrol 15:2186-2194, 2004
50. Goldfarb-Rumyantzev AS, Baird BC, Leypoldt JK,
Cheung AK: The association between BP and mortality in
patients on chronic peritoneal dialysis. Nephrol Dial Transplant 20:1693-1701, 2005
51. Utas C: Patient and technique survival on CAPD in
Turkey. Perit Dial Int 21:602-606, 2001
52. Wang AY, Sanderson J, Sea MM, et al: Important
factors other than dialysis adequacy associated with inadequate dietary protein and energy intakes in patients receiving maintenance peritoneal dialysis. Am J Clin Nutr 77:834841, 2003
53. Szeto CC, Wong TY, Chow KM, Leung CB, Li PK:
Oral sodium bicarbonate for the treatment of metabolic
acidosis in peritoneal dialysis patients: A randomized placebocontrol trial. J Am Soc Nephrol 14:2119-2126, 2003
54. Eustace JA, Coresh J, Kutchey C, et al: Randomized
double-blind trial of oral essential amino acids for dialysisassociated hypoalbuminemia. Kidney Int 57:2527-2538, 2000
55. Gonzalez-Espinoza L, Gutierrez-Chavez J, del Campo
FM, et al: Randomized, open label, controlled clinical trial
of oral administration of an egg albumin-based protein
supplement to patients on continuous ambulatory peritoneal
dialysis. Perit Dial Int 25:173-180, 2005
56. Teixido-Planas J, Ortiz A, Coronel F, et al: Oral
protein-energy supplements in peritoneal dialysis: A multicenter study. Perit Dial Int 25:163-172, 2005
57. Jones CH, Wells L, Stoves J, Farquhar F, Woodrow
G: Can a reduction in extracellular fluid volume result in
increased serum albumin in peritoneal dialysis patients?
Am J Kidney Dis 39:872-875, 2002
58. Szeto CC, Wong TY, Chow KM, Leung CB, Law
MC, Li PK: Independent effects of renal and peritoneal
clearances on the mortality of peritoneal dialysis patients.
Perit Dial Int 24:58-64, 2004
59. Bernardini J, Piraino B: Measuring compliance with
prescribed exchanges in CAPD and CCPD patients. Perit
Dial Int 17:338-342, 1997
60. Sevick MA, Levine DW, Burkart JM, Rocco MV,
Keith J, Cohen SJ: Measurement of continuous ambulatory
peritoneal dialysis prescription adherence using a novel
approach. Perit Dial Int 19:23-30, 1999
61. Blake PG, Korbet SM, Blake R, et al: A multicenter
study of noncompliance with continuous ambulatory peritoneal dialysis exchanges in US and Canadian patients. Am J
Kidney Dis 35:506-514, 2000
62. Wazny LD, Stojimirovic BB, Heidenheim P, Blake
PG: Factors influencing erythropoietin compliance in peritoneal dialysis patients. Am J Kidney Dis 40:623-628, 2002
63. Bernardini J, Piraino B: Compliance in CAPD and
CCPD patients as measured by supply inventories during
home visits. Am J Kidney Dis 31:101-107, 1998
64. Kutner NG, Zhang R, McClellan WM, Cole SA:
Psychosocial predictors of non-compliance in haemodialysis
REFERENCES
and peritoneal dialysis patients. Nephrol Dial Transplant

17:93-99, 2002
65. Canada-USA (CANUSA) Peritoneal Dialysis Study
Group:Adequacy of dialysis and nutrition in continuous peritoneal
dialysis: Association with clinical outcomes. J Am Soc Nephrol
7:198-207, 1996
66. Lutes R, Perlmutter J, Holley JL, Bernardini J,
Piraino B: Loss of residual renal function in patients on
peritoneal dialysis. Adv Perit Dial 9:165-168, 1993
67. Szeto CC, Wong TY, Chow KM, et al: Impact of
dialysis adequacy on the mortality and morbidity of anuric
Chinese patients receiving continuous ambulatory peritoneal
dialysis. J Am Soc Nephrol 12:355-360, 2001
68. Szeto CC, Lai KN, Wong TY, et al: Independent
effects of residual renal function and dialysis adequacy on
nutritional status and patient outcome in continuous ambulatory peritoneal dialysis. Am J Kidney Dis 34:1056-1064,
1999
69. Szeto CC, Wong TY, Chow KM, Leung CB, Li PK:
Are peritoneal dialysis patients with and without residual
renal function equivalent for survival study? Insight from a
retrospective review of the cause of death. Nephrol Dial
Transplant 18:977-982, 2003
70. Lo WK, Lui SL, Chan TM, et al: Minimal and
optimal peritoneal Kt/V targets: Results of an anuric peritoneal dialysis patients survival analysis. Kidney Int 67:20322038, 2005
71. Brown EA, Davies SJ, Rutherford P, et al: Survival of
functionally anuric patients on automated peritoneal dialysis: The European APD Outcome Study. J Am Soc Nephrol
14:2948-2957, 2003
72. Jansen MA, Termorshuizen F, Korevaar JC, Dekker
FW, Boeschoten E, Krediet RT: Predictors of survival in
anuric peritoneal dialysis patients. Kidney Int 68:1199-1205,
2005
73. Bhaskaran S, Schaubel DE, Jassal SV, et al: The
effect of small solute clearances on survival of anuric
peritoneal dialysis patients. Perit Dial Int 20:181-187, 2000
74. Szeto CC, Wong TY, Chow KM, et al: The impact of
increasing the daytime dialysis exchange frequency on
peritoneal dialysis adequacy and nutritional status of Chinese anuric patients. Perit Dial Int 22:197-203, 2002
75. Lye WC, Chan PS, Leong SO, van der Straaten JC:
Psychosocial and psychiatric morbidity in patients on CAPD.
Adv Perit Dial 13:134-136, 1997
76. Wuerth D, Finkelstein SH, Ciarcia J, Peterson R,
Kliger AS, Finkelstein FO: Identification and treatment of
depression in a cohort of patients maintained on chronic
peritoneal dialysis. Am J Kidney Dis 37:1011-1017, 2001
77. Bargman JM, Bick J, Cartier P, et al: Guidelines for
adequacy and nutrition in peritoneal dialysis. Canadian
Society of Nephrology. J Am Soc Nephrol 10:S311-S321,
1999 (suppl 13)
77A. CARI (Caring for Australasians with Renal Impairment) PD Guidelines. Available at: www.cari.org.au. Updated January 11, 2006. Copyright 2004, CARI
77B. The Renal Association Treatment of Adults and
Children with Renal Failure Standards and Audit Measures,
3rd edition. Prepared by the Standards and Audit Subcommittee of the Renal Association on behalf of the Renal
Association and the Royal College of Physicians of London
S169
in collaboration with the British Transplantation Society, the

Intensive Care Society and the British Association of
Paediatric Nephrologists.
78. Dombros N, Dratwa M, Feriani M, et al: European
best practice guidelines for peritoneal dialysis. 7: Adequacy
of peritoneal dialysis. Nephrol Dial Transplant 20:ix24-ix27,
2005 (suppl 9)
79. Rocco M, Soucie JM, Pastan S, McClellan WM:
Peritoneal dialysis adequacy and risk of death. Kidney Int
58:446-457, 2000
80. Lo WK, Tong KL, Li CS, et al: Relationship between
adequacy of dialysis and nutritional status, and their impact
on patient survival on CAPD in Hong Kong. Perit Dial Int
21:441-447, 2001
81. Davies SJ, Phillips L, Russell GI: Peritoneal solute
transport predicts survival on CAPD independently of residual
renal function. Nephrol Dial Transplant 13:962-968, 1998
82. Perez RA, Blake PG, Spanner E, et al: High creatinine excretion ratio predicts a good outcome in peritoneal
dialysis patients. Am J Kidney Dis 36:362-367, 2000
83. Park HC, Kang SW, Choi KH, Ha SK, Han DS, Lee
HY: Clinical outcome in continuous ambulatory peritoneal
dialysis patients is not influenced by high peritoneal transport status. Perit Dial Int 21:S80-S85, 2001 (suppl 3)
84. Aslam N, Bernardini J, Fried L, Piraino B: Peritoneal
dialysis clearance can replace residual renal function. Perit
Dial Int 21:263-268, 2001
85. Tonbul Z, Altintepe L, Sozlu C, Yeksan M, Yildiz A,
Turk S: The association of peritoneal transport properties
with 24-hour blood pressure levels in CAPD patients. Perit
Dial Int 23:46-52, 2003
86. Woodrow G, Oldroyd B, Stables G, Gibson J, Turney
JH, Brownjohn AM: Effects of icodextrin in automated
peritoneal dialysis on blood pressure and bioelectrical
impedance analysis. Nephrol Dial Transplant 15:862-866,
2000
87. Menon MK, Naimark DM, Bargman JM, Vas SI,
Oreopoulos DG: Long-term blood pressure control in a
cohort of peritoneal dialysis patients and its association with
residual renal function. Nephrol Dial Transplant 16:22072213, 2001
88. Wang AY, Wang M, Woo J, et al: A novel association
between residual renal function and left ventricular hypertrophy in peritoneal dialysis patients. Kidney Int 62:639-647,
2002
89. Singhal MK, Bhaskaran S, Vidgen E, Bargman JM,
Vas SI, Oreopoulos DG: Rate of decline of residual renal
function in patients on continuous peritoneal dialysis and
factors affecting it. Perit Dial Int 20:429-438, 2000
90. Sarnak MJ, Levey AS, Schoolwerth AC, et al: Kidney
disease as a risk factor for development of cardiovascular
disease: A statement from the American Heart Association
Councils on Kidney in Cardiovascular Disease, High Blood
Pressure Research, Clinical Cardiology, and Epidemiology
and Prevention. Circulation 108:2154-2169, 2003
91. Eknoyan G, Beck GJ, Cheung AK, et al: Effect of
dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 347:2010-2019, 2002
92. Foley RN, Parfrey PS: Cardiovascular disease and
mortality in ESRD. J Nephrol 11:239-245, 1998
S170
93. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia): Randomised placebo-controlled
trial of effect of ramipril on decline in glomerular filtration
rate and risk of terminal renal failure in proteinuric, nondiabetic nephropathy. Lancet 349:1857-1863, 1997
94. Brenner BM, Cooper ME, de Zeeuw D, et al: Effects
of losartan on renal and cardiovascular outcomes in patients
with type 2 diabetes and nephropathy. N Engl J Med
345:861-869, 2001
95. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD: The
effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl
J Med 329:1456-1462, 1993
96. Lewis EJ, Hunsicker LG, Clarke WR, et al: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.
N Engl J Med 345:851-860, 2001
97. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P: The effect of irbesartan on the
development of diabetic nephropathy in patients with type 2
diabetes. N Engl J Med 345:870-878, 2001
98. Moist LM, Port FK, Orzol SM, et al: Predictors of
loss of residual renal function among new dialysis patients.
J Am Soc Nephrol 11:556-564, 2000
99. Li PK, Chow KM, Wong TY, Leung CB, Szeto CC:
Effects of an angiotensin-converting enzyme inhibitor on
residual renal function in patients receiving peritoneal
dialysis. A randomized, controlled study. Ann Intern Med
139:105-112, 2003
100. Suzuki H, Kanno Y, Sugahara S, Okada H, Nakamoto H: Effects of an angiotensin II receptor blocker,
valsartan, on residual renal function in patients on CAPD.
Am J Kidney Dis 43:1056-1064, 2004
101. Shin SK, Noh H, Kang SW, et al: Risk factors
influencing the decline of residual renal function in continuous ambulatory peritoneal dialysis patients. Perit Dial Int
19:138-142, 1999
102. Shemin D, Maaz D, St Pierre D, Kahn SI, Chazan
JA: Effect of aminoglycoside use on residual renal function
in peritoneal dialysis patients. Am J Kidney Dis 34:14-20,
1999
103. Baker RJ, Senior H, Clemenger M, Brown EA:
Empirical aminoglycosides for peritonitis do not affect
residual renal function. Am J Kidney Dis 41:670-675, 2003
104. Kshirsagar AV, Poole C, Mottl A, et al: NAcetylcysteine for the prevention of radiocontrast induced
nephropathy: A meta-analysis of prospective controlled
trials. J Am Soc Nephrol 15:761-769, 2004
105. Tepel M, van der Giet M, Schwarzfeld C, Laufer U,
Liermann D, Zidek W: Prevention of radiographic-contrastagent-induced reductions in renal function by acetylcysteine. N Engl J Med 343:180-184, 2000
106. Gunal AI, Duman S, Ozkahya M, et al: Strict
volume control normalizes hypertension in peritoneal dialysis patients. Am J Kidney Dis 37:588-593, 2001
107. Jansen MA, Hart AA, Korevaar JC, Dekker FW,
Boeschoten EW, Krediet RT: Predictors of the rate of decline
of residual renal function in incident dialysis patients.
Kidney Int 62:1046-1053, 2002
108. Jassal SV, Lok CE, Walele A, Bargman JM: Continued transplant immunosuppression may prolong survival
after return to peritoneal dialysis: Results of a decision

analysis. Am J Kidney Dis 40:178-183, 2002
109. Bhatla B, Moore HL, Nolph KD: Modification of
creatinine clearance by estimation of residual urinary creatinine and urea clearance in CAPD patients. Adv Perit Dial
11:101-105, 1995
110. Rodby RA, Firanek CA, Cheng YG, Korbet SM:
Reproducibility of studies of peritoneal dialysis adequacy.
Kidney Int 50:267-271, 1996
111. Johnson DW, Mudge DW, Sturtevant JM, et al:
Predictors of decline of residual renal function in new
peritoneal dialysis patients. Perit Dial Int 23:276-283, 2003
112. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular disease in chronic renal disease.
113. Multiple Risk Factor Intervention Trial Research
Group: Multiple Risk Factor Intervention Trial. Risk factor
changes and mortality results. JAMA 248:1465-1477, 1982
114. Konings CJ, Kooman JP, Schonck M, et al: Fluid
status, blood pressure, and cardiovascular abnormalities in
patients on peritoneal dialysis. Perit Dial Int 22:477-487,
2002
115. Sharma AP, Blake PG: Should fluid removal be
used as an adequacy target in peritoneal dialysis? Perit Dial
Int 23:107-108, 2003
116. Harnett JD, Foley RN, Kent GM, Barre PE, Murray
D, Parfrey PS: Congestive heart failure in dialysis patients:
Prevalence, incidence, prognosis and risk factors. Kidney Int
47:884-890, 1995
117. Foley RN, Parfrey PS, Harnett JD, Kent GM,
Murray DC, Barre PE: Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease.
Kidney Int 49:1379-1385, 1996
118. Mahon A, Fan SL: Accuracy of ultrafiltration volume measurements for patients on peritoneal dialysis. Perit
Dial Int 25:92-93, 2005
119. Medcalf JF, Harris KP, Walls J: Role of diuretics in
the preservation of residual renal function in patients on
continuous ambulatory peritoneal dialysis. Kidney Int 59:
1128-1133, 2001
120. Davies SJ, Brown EA, Frandsen NE, et al: Longitudinal membrane function in functionally anuric patients
treated with APD: Data from EAPOS on the effects of
glucose and icodextrin prescription. Kidney Int 67:16091615, 2005
121. Davies SJ, Phillips L, Naish PF, Russell GI: Peritoneal glucose exposure and changes in membrane solute
transport with time on peritoneal dialysis. J Am Soc Nephrol
12:1046-1051, 2001
122. Davies SJ, Woodrow G, Donovan K, et al: Icodextrin improves the fluid status of peritoneal dialysis patients:
Results of a double-blind randomized controlled trial. J Am
Soc Nephrol 14:2338-2344, 2003
123. Konings CJ, Kooman JP, Schonck M, et al: Effect of
icodextrin on volume status, blood pressure and echocardiographic parameters: A randomized study. Kidney Int 63:15561563, 2003
124. Rodriguez-Carmona A, Fontan MP: Sodium removal in patients undergoing CAPD and automated peritoneal dialysis. Perit Dial Int 22:705-713, 2002
REFERENCES
125. Rodriguez-Carmona A, Perez-Fontan M, GarcaNaveiro R, Villaverde P, Peteiro J: Compared time profiles

of ultrafiltration, sodium removal, and renal function in
incident CAPD and automated peritoneal dialysis patients.
Am J Kidney Dis 44:132-145, 2004
126. de Fijter CW, Oe LP, Nauta JJ, et al: Clinical
efficacy and morbidity associated with continuous cyclic
compared with continuous ambulatory peritoneal dialysis.
Ann Intern Med 120:264-271, 1994
127. Finkelstein FO, Sorkin M, Cramton CW, Nolph K:
Initiatives in peritoneal dialysis: Where do we go from here?
Perit Dial Int 11:274-278, 1991
128. Schaubel DE, Blake PG, Fenton SS: Trends in
CAPD technique failure: Canada, 1981-1997. Perit Dial Int
21:365-371, 2001
129. Woodrow G, Turney JH, Brownjohn AM: Technique
failure in peritoneal dialysis and its impact on patient
survival. Perit Dial Int 17:360-364, 1997
130. Krishnan M, Thodis E, Ikonomopoulos D, et al:
Predictors of outcome following bacterial peritonitis in
peritoneal dialysis. Perit Dial Int 22:573-581, 2002
131. Piraino B, Bailie GR, Bernardini J, et al: Peritoneal
dialysis-related infections recommendations: 2005 Update.
Perit Dial Int 25:107-131, 2005
132. Troidle L, Gorban-Brennan N, Kliger A, Finkelstein
FO: Continuous peritoneal dialysis-associated peritonitis: A
review and current concepts. Semin Dial 16:428-437, 2003
133. Flanigan M, Gokal R: Peritoneal catheters and
exit-site practices toward optimum peritoneal access: A
review of current developments. Perit Dial Int 25:132-139,
2005
134. Gokal R, Alexander S, Ash S, et al: Peritoneal
catheters and exit-site practices toward optimum peritoneal
access: 1998 Update. (Official report from the International
Society for Peritoneal Dialysis). Perit Dial Int 18:11-33,
1998
135. Thodis E, Passadakis P, Ossareh S, Panagoutsos S,
Vargemezis V, Oreopoulos DG: Peritoneal catheter exit-site
infections: Predisposing factors, prevention and treatment.
Int J Artif Organs 26:698-714, 2003
136. Strippoli GF, Tong A, Johnson D, Schena FP, Craig
JC: Catheter-related interventions to prevent peritonitis in
peritoneal dialysis: A systematic review of randomized,
controlled trials. J Am Soc Nephrol 15:2735-2746, 2004
137. Einwohner R, Bernardini J, Fried L, Piraino B: The
effect of depressive symptoms on survival in peritoneal
dialysis patients. Perit Dial Int 24:256-263, 2004
138. Kimmel PL, Peterson RA, Weihs KL, et al: Multiple
measurements of depression predict mortality in a longitudinal study of chronic hemodialysis outpatients. Kidney Int
57:2093-2098, 2000
139. Lopes AA, Albert JM, Young EW, et al: Screening
for depression in hemodialysis patients: Associations with
diagnosis, treatment, and outcomes in the DOPPS. Kidney
Int 66:2047-2053, 2004
140. Mapes DL, Lopes AA, Satayathum S, et al: Healthrelated quality of life as a predictor of mortality and
hospitalization: The Dialysis Outcomes and Practice Patterns Study (DOPPS). Kidney Int 64:339-349, 2003
141. Troidle L, Watnick S, Wuerth DB, Gorban-Brennan
N, Kliger AS, Finkelstein FO: Depression and its association
S171
with peritonitis in long-term peritoneal dialysis patients.

Am J Kidney Dis 42:350-354, 2003
142. Lew SQ, Piraino B: Quality of life and psychological issues in peritoneal dialysis patients. Semin Dial 18:119123, 2005
143. Wuerth D, Finkelstein SH, Finkelstein FO: The
identification and treatment of depression in patients maintained on dialysis. Semin Dial 18:142-146, 2005
144. Rubin HR, Fink NE, Plantinga LC, Sadler JH,
Kliger AS, Powe NR: Patient ratings of dialysis care with
peritoneal dialysis vs hemodialysis. JAMA 291:697-703,
2004
145. Wuerth DB, Finkelstein SH, Schwetz O, Carey H,
Kliger AS, Finkelstein FO: Patients descriptions of specific
factors leading to modality selection of chronic peritoneal
dialysis or hemodialysis. Perit Dial Int 22:184-190, 2002
146. Schaefer F, Langenbeck D, Heckert KH, Scharer K,
Mehls O: Evaluation of peritoneal solute transfer by the
peritoneal equilibration test in children. Adv Perit Dial
8:410-415, 1992
147. Warady BA, Alexander SR, Hossli S, et al: Peritoneal membrane transport function in children receiving
long-term dialysis. J Am Soc Nephrol 7:2385-2391, 1996
148. Morgenstern BZ, Wuhl E, Nair KS, Warady BA,
Schaefer F: Anthropometric prediction of total body water in
children who are on pediatric peritoneal dialysis. J Am Soc
Nephrol 17:285-293, 2006
149. Verrina E, Brendolan A, Gusmano R, Ronco C:
Chronic renal replacement therapy in children: Which index
is best for adequacy? Kidney Int 54:1690-1696, 1998
150. de Boer AW, van Schaijk TC, Willems HL, Reddingius RE, Monnens LA, Schroder CH: The necessity of
adjusting dialysate volume to body surface area in pediatric
peritoneal equilibration tests. Perit Dial Int 17:199-202,
1997
151. Schaefer F, Haraldsson B, Haas S, Simkova E, Feber
J, Mehls O: Estimation of peritoneal mass transport by
three-pore model in children. Kidney Int 54:1372-1379,
1998
152. Warady BA, Alexander S, Hossli S, Vonesh E,
Geary D, Kohaut E: The relationship between intraperitoneal volume and solute transport in pediatric patients.
Pediatric Peritoneal Dialysis Study Consortium. J Am Soc
Nephrol 5:1935-1939, 1995
153. Morgenstern BZ: Peritoneal equilibration in children. Perit Dial Int 16:S532-S539, 1996 (suppl 1)
154. Warady BA, Fivush B, Andreoli SP, et al: Longitudinal evaluation of transport kinetics in children receiving
peritoneal dialysis. Pediatr Nephrol 13:571-576, 1999
155. Warady BA, Morgenstern B, Alexander SR: Peritoneal dialysis, in Pediatric Nephrology. Philadelphia, PA,
Lippincott Williams & Wilkins, 2004, pp 1375-1394
156. Warady BA, Watkins SL, Fivush BA, et al: Validation of PD Adequest 2.0 for pediatric dialysis patients.
Pediatr Nephrol 16:205-211, 2001
157. The Fourth Report on the Diagnosis, Evaluation,
and Treatment of High Blood Pressure in Children and
Adolescents. Pediatrics 114:S555-S576, 2004 (suppl 2)
158. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis
Patients. Am J Kidney Dis 45:S1-S153, 2005 (suppl 3)
S172
159. Mitsnefes M, Stablein D: Hypertension in pediatric

patients on long-term dialysis: A report of the North
American Pediatric Renal Transplant Cooperative Study
(NAPRTCS). Am J Kidney Dis 45:309-315, 2005
160. Mitsnefes MM, Daniels SR, Schwartz SM, Meyer
RA, Khoury P, Strife CF: Severe left ventricular hypertrophy
in pediatric dialysis: Prevalence and predictors. Pediatr
Nephrol 14:898-902, 2000
161. Robinson RF, Nahata MC, Sparks E, et al: Abnormal left ventricular mass and aortic distensibility in pediatric
dialysis patients. Pediatr Nephrol 20:64-68, 2005
162. Holtta T, Happonen JM, Ronnholm K, Fyhrquist F,
Holmberg C: Hypertension, cardiac state, and the role of
volume overload during peritoneal dialysis. Pediatr Nephrol
16:324-331, 2001
163. de Boer AW, Schroder CH, van Vliet R, Willems JL,
Monnens LA: Clinical experience with icodextrin in children: Ultrafiltration profiles and metabolism. Pediatr Nephrol 15:21-24, 2000
164. Rusthoven E, Krediet RT, Willems HL, Monnens
LA, Schroder CH: Peritoneal transport characteristics with
glucose polymer-based dialysis fluid in children. J Am Soc
Nephrol 15:2940-2947, 2004
165. Dart A, Feber J, Wong H, Filler G: Icodextrin
re-absorption varies with age in children on automated
peritoneal dialysis. Pediatr Nephrol 20:683-685, 2005
166. National Kidney Foundation: K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents
in Chronic Kidney Disease. Am J Kidney Dis 43:S1-S290,
2004 (suppl 1)
167. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 2005 Annual Report. Boston, MA,
NAPRTCS Administrative Office, 2005
168. Furth SL, Hwang W, Yang C, Neu AM, Fivush BA,
Powe NR: Growth failure, risk of hospitalization and death
for children with end-stage renal disease. Pediatr Nephrol
17:450-455, 2002
168A. Mahan JD, Warady BA, on behalf of the Growth in
Children with CKD Consensus Committee: Assessment and
treatment of short stature in pediatric patients with chronic
kidney disease: A consensus statement. Pediatr Nephrol
2006 (in press)
169. Proceedings of the IPNA Seventh Symposium on
Growth and Development in Children with Chronic Kidney
Disease: The Molecular Basis of Skeletal Growth. April 1-3,
2004. Heidelberg, Germany. Pediatr Nephrol 20:249-440,
C247-C211, 2005
170. Greenbaum LA, Del Rio M, Bamgbola F, Kaskel F:
Rationale for growth hormone therapy in children with
chronic kidney disease. Adv Chronic Kidney Dis 11:377386, 2004
171. Kaskel F: Chronic renal disease: A growing problem. Kidney Int 64:1141-1151, 2003
172. Warady BA, Alexander SR, Watkins S, Kohaut E,
Harmon WE: Optimal care of the pediatric end-stage renal
disease patient on dialysis. Am J Kidney Dis 33:567-583,
1999
173. Neu AM, Ho PL, McDonald RA, Warady BA:
Chronic dialysis in children and adolescents. The 2001
NAPRTCS Annual Report. Pediatr Nephrol 17:656-663,
2002
174. Davies SJ, Russell L, Bryan J, Phillips L, Russell GI:

Comorbidity, urea kinetics, and appetite in continuous ambulatory peritoneal dialysis patients: Their interrelationship and
prediction of survival. Am J Kidney Dis 26:353-361, 1995
175. Mak SK, Wong PN, Lo KY, Tong GM, Fung LH,
Wong AK: Randomized prospective study of the effect of
increased dialytic dose on nutritional and clinical outcome in
continuous ambulatory peritoneal dialysis patients. Am J
Kidney Dis 36:105-114, 2000
176. Uribarri J, Dimaano F, London RD, Dowling J,
Marcus RG: Increase in Kt/V increased serum albumin but
not nPCR in a group of patients on continuous peritoneal
177. Harty J, Boulton H, Faragher B, Venning M, Gokal
R: The influence of small solute clearance on dietary protein
intake in continuous ambulatory peritoneal dialysis patients:
A methodologic analysis based on cross-sectional and
prospective studies. Am J Kidney Dis 28:553-560, 1996
178. Cheng LT, Tang W, Wang T: Strong association
between volume status and nutritional status in peritoneal
dialysis patients. Am J Kidney Dis 45:891-902, 2005
179. Herzig KA, Purdie DM, Chang W, et al: Is Creactive protein a useful predictor of outcome in peritoneal
dialysis patients? J Am Soc Nephrol 12:814-821, 2001
180. Arkouche W, Fouque D, Pachiaudi C, et al: Total
body water and body composition in chronic peritoneal
dialysis patients. J Am Soc Nephrol 8:1906-1914, 1997
181. Woodrow G, Oldroyd B, Turney JH, Davies PS, Day
JM, Smith MA: Measurement of total body water and urea
kinetic modelling in peritoneal dialysis. Clin Nephrol 47:5257, 1997
182. Dahl NV, Foote EF, Kapoian T, Steward CA,
Sherman RA: Measuring total body water in peritoneal
dialysis patients using an ethanol dilution technique. Kidney
Int 56:2297-2303, 1999
183. Johansson AC, Samuelsson O, Attman PO, Bosaeus
I, Haraldsson B: Limitations in anthropometric calculations
of total body water in patients on peritoneal dialysis. J Am
Soc Nephrol 12:568-573, 2001
184. Jones MR: Etiology of severe malnutrition: Results
of an international cross-sectional study in continuous
ambulatory peritoneal dialysis patients. Am J Kidney Dis
23:412-420, 1994
185. Tzamaloukas AH, Murata GH: Estimating urea
volume in amputees on peritoneal dialysis by modified
anthropometric formulas. Adv Perit Dial 12:143-146, 1996
186. Wong KC, Xiong DW, Kerr PG, et al: Kt/V in
CAPD by different estimations of V. Kidney Int 48:563-569,
1995
187. Tzamaloukas AH, Murata GH, Piraino B, et al: The
relation between body size and normalized small solute
clearances in continuous ambulatory peritoneal dialysis.
J Am Soc Nephrol 10:1575-1581, 1999
188. Keshaviah PR, Nolph KD, Moore HL, et al: Lean
body mass estimation by creatinine kinetics. J Am Soc
Nephrol 4:1475-1485, 1994
189. Lo WK, Prowant BF, Moore HL, et al: Comparison
of different measurements of lean body mass in normal
individuals and in chronic peritoneal dialysis patients. Am J
Kidney Dis 23:74-85, 1994
REFERENCES
190. Gilbert R, Gokal RK: The gastrointestinal system, in

Eknoyan G, Knochel JP (eds): The Systemic Consequences
of Renal Failure. New York, NY, Grune & Stratton, 1984, p
133
191. Ikizler TA, Wingard RL, Hakim RM: Malnutrition
in peritoneal dialysis patients: Etiologic factors and treatment options. Perit Dial Int 15:S63-S66, 1995 (suppl 5)
192. Hylander B, Barkeling B, Rossner S: What contributes to poor appetite in CAPD patients? Perit Dial Int
11:S117, 1991 (suppl 1; abstr)
193. Hylander B, Barkeling B, Rossner S: Appetite and
eating behaviorA comparison between CAPD patients,
HD patients, and healthy controls. Perit Dial Int 12:S137A,
1992 (suppl 1; abstr)
194. Lindholm B, Bergstrom J: Nutritional management
of patients undergoing peritoneal dialysis, in Nolph KD (ed):
Peritoneal Dialysis (ed 3). Boston, MA, Kluwer, 1989, pp
230-260
195. Bannister DK, Acchiardo SR, Moore LW, Kraus AP
Jr: Nutritional effects of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. J Am Diet Assoc
87:53-56, 1987
196. Acchiardo SR, Moore LW, Latour PA: Malnutrition
as the main factor in morbidity and mortality of hemodialysis patients. Kidney Int Suppl 16:S199-S203, 1983
197. Degoulet P, Legrain M, Reach I, et al: Mortality risk
factors in patients treated by chronic hemodialysis. Report
of the Diaphane collaborative study. Nephron 31:103-110,
1982
198. Lowrie EG, Lew NL: Death risk in hemodialysis
patients: The predictive value of commonly measured
variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458-482, 1990
199. Held PJ, Port FK, Agadoa LYC: Survival Probabilities and Causes of Death. Bethesda, MD, National Institutes
of Health, NIDDKD, 1991, pp 31-40
200. Enia G, Sicuso C, Alati G, Zoccali C: Subjective
global assessment of nutrition in dialysis patients. Nephrol
201. Kopple JD, Jones MR, Keshaviah PR, et al: A
proposed glossary for dialysis kinetics. Am J Kidney Dis
26:963-981, 1995
202. Harty JC, Boulton H, Curwell J, et al: The normalized protein catabolic rate is a flawed marker of nutrition in
CAPD patients. Kidney Int 45:103-109, 1994
203. Health Care Financing Administration: 2000 Annual
Report, End-Stage Renal Disease Clinical Performance
Measures Project. Baltimore, MD, Department of Health
and Human Services, Health Care Financing Administration, Office of Clinical Standards and Quality, 2000
204. Blumenkrantz MJ, Kopple JD, Moran JK, Coburn
JW: Metabolic balance studies and dietary protein requirements in patients undergoing continuous ambulatory peritoneal dialysis. Kidney Int 21:849-861, 1982
205. Diamond SM, Henrich WL: Nutrition and peritoneal dialysis, in Mitch WE, Klahr S (eds): Nutrition and the
Kidney. Boston, MA, Little, Brown, 1988, pp 198-223
206. Bergstrom J, Lindholm B: Nutrition and adequacy
of dialysis. How do hemodialysis and CAPD compare?
Kidney Int Suppl 40:S39-S50, 1993
S173
207. Nolph KD: Whats new in peritoneal dialysisAn

overview. Kidney Int Suppl 38:S148-S152, 1992
208. Lim VS, Flanigan MJ: Protein intake in patients
with renal failure: Comments on the current NKF-DOQI
guidelines for nutrition in chronic renal failure. Semin Dial
14:150-152, 2001
209. Uribarri J, Levin NW, Delmez J, et al: Association
of acidosis and nutritional parameters in hemodialysis
210. Juergensen PH, Gorban-Brennan N, Finkelstein FO:
Compliance with the dialysis regimen in chronic peritoneal
dialysis patients: Utility of the pro card and impact of patient
education. Adv Perit Dial 20:90-92, 2004
211. Twardowski ZJ, Nolph KD, Khanna R, et al: Peritoneal equilibration test. Perit Dial Bull 7:138-147, 1987
212. Blake P, Burkart JM, Churchill DN, et al: Recommended clinical practices for maximizing peritoneal dialysis
clearances. Perit Dial Int 16:448-456, 1996
213. Burkart JM, Schreiber M, Korbet SM, et al: Solute
clearance approach to adequacy of peritoneal dialysis. Perit
Dial Int 16:457-470, 1996
214. Davies SJ: Monitoring of long-term peritoneal membrane function. Perit Dial Int 21:225-230, 2001
215. Pannekeet MM, Imholz AL, Struijk DG, et al: The
standard peritoneal permeability analysis: A tool for the assessment of peritoneal permeability characteristics in CAPD patients. Kidney Int 48:866-875, 1995
216. Ho-dac-Pannekeet MM, Atasever B, Struijk DG,
Krediet RT: Analysis of ultrafiltration failure in peritoneal
dialysis patients by means of standard peritoneal permeability analysis. Perit Dial Int 17:144-150, 1997
217. Haraldsson B: Assessing the peritoneal dialysis
capacities of individual patients. Kidney Int 47:1187-1198,
1995
218. Mujais S, Nolph K, Gokal R, et al: Evaluation and
management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc
Committee on Ultrafiltration Management in Peritoneal
Dialysis. Perit Dial Int 20:S5-S21, 2000 (suppl 4)
219. Rocco MV, Jordan JR, Burkart JM: Changes in
peritoneal transport during the first month of peritoneal
220. Johnson DW, Mudge DW, Blizzard S, et al: A
comparison of peritoneal equilibration tests performed 1 and
4 weeks after PD commencement. Perit Dial Int 24:460-465,
2004
221. Davies SJ, Phillips L, Griffiths AM, Russell LH,
Naish PF, Russell GI: What really happens to people on
long-term peritoneal dialysis? Kidney Int 54:2207-2217,
1998
222. Heimburger O, Waniewski J, Werynski A, Tranaeus
A, Lindholm B: Peritoneal transport in CAPD patients with
permanent loss of ultrafiltration capacity. Kidney Int 38:495506, 1990
223. Krediet RT: The physiology of peritoneal solute
transport and ultrafiltration, in Gokal R, Khanna R, Krediet
RT, Nolph K (eds): Textbook of Peritoneal Dialysis. Dordrecht, The Netherlands, Kluwer, 2000, pp 135-172
224. Virga G, Amici G, da Rin G, et al: Comparison of
fast peritoneal equilibration tests with 1.36 and 3.86%
dialysis solutions. Blood Purif 12:113-120, 1994
S174
225. Pride ET, Gustafson J, Graham A, et al: Comparison

of a 2.5% and a 4.25% dextrose peritoneal equilibration test.
Perit Dial Int 22:365-370, 2002
226. Smit W, van Dijk P, Langedijk MJ, et al: Peritoneal
function and assessment of reference values using a 3.86%
glucose solution. Perit Dial Int 23:440-449, 2003
227. Rubin J, Ray R, Barnes T, Bower J: Peritoneal
abnormalities during infectious episodes of continuous ambulatory peritoneal dialysis. Nephron 29:124-127, 1981
228. Krediet RT, Zuyderhoudt FM, Boeschoten EW,
Arisz L: Alterations in the peritoneal transport of water and
solutes during peritonitis in continuous ambulatory peritoneal dialysis patients. Eur J Clin Invest 17:43-52, 1987
229. Panasiuk E, Pietrzak P, Klos M, Wankowicz Z:
Characteristics of peritoneum after peritonitis in CAPD
patients. Adv Perit Dial 4:42-45, 1988
230. Brophy DF, Sowinski KM, Kraus MA, Moe SM,
Klaunig JE, Mueller BA: Small and middle molecular
weight solute clearance in nocturnal intermittent peritoneal
231. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease,
2000. Am J Kidney Dis 37:S182-S238, 2001 (suppl 1)
232. American Academy of Pediatrics: National Cholesterol Education Program: Report of the Expert Panel on
Blood Cholesterol Levels in Children and Adolescents.
Pediatrics 89:525-584, 1992
233. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Management of Dyslipidemias in Patients With Kidney Disease. Am J Kidney Dis 41:S1-S91,
2003 (suppl 3)
234. Morton KA, Pisani DE, Whiting JH Jr, Cheung AK,
Arias JM, Valdivia S: Determination of glomerular filtration
rate using technetium-99m-DTPA with differing degrees of
renal function. J Nucl Med Technol 25:110-114, 1997
235. Perrone RD, Steinman TI, Beck GJ, et al: Utility of
radioisotopic filtration markers in chronic renal insufficiency: Simultaneous comparison of 125I-iothalamate,
169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification
of Diet in Renal Disease Study. Am J Kidney Dis 16:224235, 1990
236. Greenbaum LA, Schaefer F: The decision to initiate
dialysis in children and adolescents, in Warady BA, Schaefer
F, Fine RN, Alexander S (eds): Pediatric Dialysis. Dordrecht, The Netherlands, Kluwer, 2004, pp 177-195
237. Shemesh O, Golbetz H, Kriss JP, Myers BD:
Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 28:830-838, 1985
238. Lubowitz H, Slatopolsky E, Shankel S, Rieselbach
RE, Bricker NS: Glomerular filtration rate. Determination in
patients with chronic renal disease. JAMA 199:252-256,
1967
239. van Olden RW, Krediet RT, Struijk DG, Arisz L:
Measurement of residual renal function in patients treated
with continuous ambulatory peritoneal dialysis. J Am Soc
Nephrol 7:745-750, 1996
240. Hellerstein S, Berenbom M, Alon US, Warady BA:
Creatinine clearance following cimetidine for estimation of
glomerular filtration rate. Pediatr Nephrol 12:49-54, 1998
241. Hellerstein S, Erwin P, Warady BA: The cimetidine
protocol: A convenient, accurate, and inexpensive way to
measure glomerular filtration rate. Pediatr Nephrol 18:7172, 2003

242. Schwartz GJ, Haycock GB, Edelmann CM Jr,
Spitzer A: A simple estimate of glomerular filtration rate in
children derived from body length and plasma creatinine.
Pediatrics 58:259-263, 1976
243. Seikaly MG, Loleh S, Rosenblum A, Browne R:
Validation of the Center for Medicare and Medicaid Services
algorithm for eligibility for dialysis. Pediatr Nephrol 19:893897, 2004
244. Alexander SR, Warady BA: The demographics of
dialysis in children, in Warady BA, Schaefer F, Fine RN,
Alexander S (eds): Pediatric Dialysis. Dordrecht, The Netherlands, Kluwer, 2004, pp 35-45
245. Fine RN, Ho M: The role of APD in the management of pediatric patients: A report of the North American
Pediatric Renal Transplant Cooperative Study. Semin Dial
15:427-429, 2002
246. Warady BA, Schaefer F, Alexander SR, Firanek C,
Mujais S: Care of the pediatric patient on peritoneal dialysis:
Clinical process for optimal outcomes. Deerfield, IL, Baxter
Healthcare, 2004
246A. Goldstein SL, Graham N, Burwinkle T, Warady B,
Farrah R, Varni JW: Health-related quality of life in pediatric
patients with ESRD. Pediatr Nephrol 2006 (in press)
247. Watson AR, Gartland C: Avoiding and coping with
patient and family burnout, in Fine RN, Alexander SR,
Warady BA (eds): CAPD/CCPD in Children. Boston, MA,
Kluwer, 1998, pp 491-506
248. Oreopoulos DG: Beyond Kt/V: Redefining adequacy of dialysis in the 21st century. Int Urol Nephrol
34:393-403, 2002
249. Wong CS, Hingorani S, Gillen DL, et al: Hypoalbuminemia and risk of death in pediatric patients with endstage renal disease. Kidney Int 61:630-637, 2002
250. Chadha V, Blowey DL, Warady BA: Is growth a
valid outcome measure of dialysis clearance in children
undergoing peritoneal dialysis? Perit Dial Int 21:S179-S184,
2001 (suppl 3)
251. Holtta T, Ronnholm K, Jalanko H, Holmberg C:
Clinical outcome of pediatric patients on peritoneal dialysis
under adequacy control. Pediatr Nephrol 14:889-897, 2000
252. Chen HH, Shetty A, Afthentopoulos IE, Oreopoulos
DG: Discrepancy between weekly KT/V and weekly creatinine clearance in patients on CAPD. Adv Perit Dial 11:8387, 1995
253. Twardowski ZJ: Relationship between creatinine
clearance and Kt/V in peritoneal dialysis: A response to the
defense of the DOQI document. Perit Dial Int 19:199-203,
1999
254. Mellits ED, Cheek DB: The assessment of body
water and fatness from infancy to adulthood. Monogr Soc
Res Child Dev 35:12-26, 1970
255. Mendley SR, Majkowski NL, Schoeller DA: Validation of estimates of total body water in pediatric dialysis
patients by deuterium dilution. Kidney Int 67:2056-2062,
2005
256. Morgenstern B, Nair KS, Lerner G, Neu A, Quan A,
Warady BA: Impact of total body water errors on Kt/V
estimates in children on peritoneal dialysis. Adv Perit Dial
17:260-263, 2001
REFERENCES
257. Morgenstern BZ, Mahoney DW, Warady BA: Estimating total body water in children on the basis of height
and weight: A reevaluation of the formulas of Mellits and
Cheek. J Am Soc Nephrol 13:1884-1888, 2002
258. DuBois D, DuBois EF: A formula to estimate the
approximate surface area if height and weight be known.
Arch Intern Med 17:863-871, 1916
259. Gehan EA, George SL: Estimation of human body
surface area from height and weight. Cancer Chemother Rep
54:225-235, 1970
260. Fischbach M, Terzic J, Menouer S, et al: Effects of
automated peritoneal dialysis on residual daily urinary
volume in children. Adv Perit Dial 17:269-273, 2001
261. Wuhl E, Mehls O, Schaefer F: Antihypertensive and
antiproteinuric efficacy of ramipril in children with chronic
renal failure. Kidney Int 66:768-776, 2004
262. Phakdeekitcharoen B, Leelasa-nguan P: Effects of
an ACE inhibitor or angiotensin receptor blocker on potassium in CAPD patients. Am J Kidney Dis 44:738-746, 2004
264. Gerson A, Hwang W, Fiorenza J, et al: Anemia and
health-related quality of life in adolescents with chronic
kidney disease. Am J Kidney Dis 44:1017-1023, 2004
265. Gerson AC, Riley A, Fivush BA, et al: Assessing
health status and health care utilization in adolescents with
chronic kidney disease. J Am Soc Nephrol 16:1427-1432, 2005
S175
266. Fischbach M, Terzic J, Laugel V, Escande B,

Dangelser C, Helmstetter A: Measurement of hydrostatic
intraperitoneal pressure: A useful tool for the improvement
of dialysis dose prescription. Pediatr Nephrol 18:976-980,
2003
267. Parekh RS, Flynn JT, Smoyer WE, et al: Improved
growth in young children with severe chronic renal insufficiency who use specified nutritional therapy. J Am Soc
Nephrol 12:2418-2426, 2001
268. Montini G, Amici G, Milan S, et al: Middle molecule and small protein removal in children on peritoneal
dialysis. Kidney Int 61:1153-1159, 2002
269. Fischbach M, Stefanidis CJ, Watson AR: Guidelines
by an ad hoc European committee on adequacy of the
paediatric peritoneal dialysis prescription. Nephrol Dial
Transplant 17:380-385, 2002
270. Szeto CC, Chow KM, Kwan BC, et al: Hypokalemia
in Chinese peritoneal dialysis patients: Prevalence and
prognostic implication. Am J Kidney Dis 46:128-135, 2005
271. Chung SH, Heimburger O, Lindholm B, Lee HB:
Peritoneal dialysis patient survival: A comparison between a
Swedish and a Korean centre. Nephrol Dial Transplant
20:1207-1213, 2005
272. del Peso G, Fernandez-Reyes MJ, Hevia C, et al:
Factors influencing peritoneal transport parameters during
the first year on peritoneal dialysis: Peritonitis is the main
factor. Nephrol Dial Transplant 20:1201-1206, 2005
Vascular Access 2006

Anatole Besarab, MD
Henry Ford Hospital
Detroit, MI
Jack Work, MD
Emory University School of Medicine
Atlanta, GA
Work Group
Deborah Brouwer, RN, CNN

McMurray, PA
Timothy E. Bunchman, MD
DeVos Childrens Hospital
Grand Rapids, MI
Lesley C. Dinwiddie, MSN, RN, FNP, CNN
American Nephrology Nurses Association
Cary, NC
Stuart L. Goldstein, MD
Texas Childrens Hospital
Houston, TX
Klaus Konner, MD
Medical Univerity of Cologne
Cologne General Hospital Merheim Medical Center
Cologne, Germany
Alan Lumsden, MD, FACS
Baylor College of Medicine
Houston, TX
Thomas M. Vesely, MD
Mallinckrodt Institute of Radiology
St Louis, MO
Mitchell L. Henry, MD
Ohio State University
Dublin, OH
National Kidney Foundation Center for Guideline Development and Implementation
at Tufts-New England Medical Center, Boston, MA
Amy Earley, BS
Rebecca Persson, BA
Gowri Raman, MD
Priscilla Chew, MPH

Stanley Ip, MD
Mei Chung, MPH

Tables
Table 1.
Table 2.
Table 3.
Table 4.
Table 5.
Table 6.
Table 7.
Table 8.
Table 9.
Table 10.
Table 11.
Table 12.
Table 13.
Table 14.
Table 15.
Table 16.
Table 17.
Table 18.
Table 19.
Table 20.
Table 21.
Table 22.
Table 23.
Table 24.
Table 25.
Patient Evaluation Prior to Access Placement ................................................................. S190

Skin Preparation Technique for Subcutaneous AV Accesses ........................................... S202
Technique for Mature AVF Cannulation.......................................................................... S202
Technique for AVG Cannulation...................................................................................... S203
Access Physical Examination .......................................................................................... S204
Considerations for Accessing Catheters and Cleansing Catheter Exit Sites .................... S207
Flow Methods in Dialysis Access .................................................................................... S211
Static Intra-Access Pressure (IAP) Surveillance ............................................................. S212
Criteria for Intervention................................................................................................... S212
Access Flow Protocol Surveillance ................................................................................. S217
Diagnostic Accuracy of Tests Used for Access Surveillance in the HD Population:
Angiogram for Stenosis versus Other Test ...................................................................... S223
Comparison of Diagnostic Tests for Access Surveillance and Monitoring in the HD
Population: Duplex Doppler Ultrasound as Reference.................................................... S224
Comparison of Diagnostic Tests to Predict Thrombosis in Chronic HD Patients ........... S224
Comparison of Newer Tests to Established Tests for Stenosis Detection........................ S225
Patient Education Basics ................................................................................................. S228
Access Surveillance Studies With PTA Intervention ....................................................... S231
Summary of Physical Examination ................................................................................. S238
Signs of CVC Dysfunction: Assessment Phase ............................................................... S249
Prophylaxis of TCC-Related Thrombosis ....................................................................... S250
Causes of Early Catheter Dysfunction............................................................................. S251
Available Thrombolytics ................................................................................................. S252
Effect of Lytics in Occluded Hemodialysis Catheters ..................................................... S253
Treatments of TCC Fibrin Sheath Occlusion................................................................... S253
Prophylaxis for Dual-Lumen TCC-Related Infections.................................................... S256
Semipermanent HD Catheter and Patient Size Guideline ............................................... S276
Figures
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Figure 8.
Figure 9.
Figure 10.
Figure 11.
Starting a Buttonhole ..................................................................................................... S208

Cannulating a Buttonhole............................................................................................... S208
Pressure Profiles in Grafts (top) and Fistulae (bottom).................................................. S213
IAPs Within Normal Grafts and Fistulae ....................................................................... S214
Effect of Venous Outlet Stenosis on Pressure Profile..................................................... S215
Effect of Graft Venous Outlet Stenosis .......................................................................... S215
Relationship of IAP Ratio to Access Flow ..................................................................... S219
Treatment of Stenosis..................................................................................................... S238
Assessing Dysfunction of Catheters .............................................................................. S251
Fibrin Sheath (A) Prior to Therapy and (B) After Treatment With PTA ........................ S273
Pediatric Progress From CKD Stages 1 to 5 and KRT/Access Algorithm ..................... S275
S177

aOR
AMI
AUC
AV
AVF
AVG
BFR
BP
BTM
CDC
CHF
CI
CKD
CLS
CMS
CPG
CPM
CPR
CQI
CRB
CrCl
CVC
CVD
DD
DDU
DOPPS
DOQI
DRIL
DSA
DU
DVP
FDA
FFBI
GFR
GPT
Hct
HD
HDM
HTN
IAP
IgG
INR
IV
IVC
IVUS
KDOQI
KLS
KRT
LVH
MAP
MRA
S178
Adjusted odds ratio

Acute myocardial infarction
Area under the curve
Arteriovenous
Arteriovenous fistula
Arteriovenous graft
Blood flow rate
Blood pressure
Body Thermal Monitor
Centers for Disease Control and Prevention
Confidence interval
Catheter lock solution
Centers for Medicare & Medicaid Services
Clinical performance measure
Catheter-related bacteremia
Central venous catheter
In line dialysance
Duplex Doppler ultrasound
Dialysis Outcomes and Practice Patterns Study
Distal revascularizationinterval ligation
Digital subtraction angiography
Doppler ultrasound
Dynamic venous pressures
Food and Drug Administration
Fistula First Breakthrough Initiative
Glucose pump infusion technique
Hematocrit
Hemodialysis
Hemodynamic monitoring
Hypertension
Intra-access pressure
Immunoglobulin G
International normalized ratio
Intravenous
Inferior vena cava
Intravascular ultrasound
Mean arterial (blood) pressure
Magnetic resonance angiography
N
NCC
nd
NKF
NS
NVAII
OABF
ORX
P
PAVA
PD
PE
PFSS
PIA
PICC
PSV
PTA
PTFE
PU
PVD
QA
QA/CQI
QB
QBP
Qf
QIP
QOL
RCT
ROC
RR
rTPA
SGA
SVC
SVR
TCC
TD
tPA
TQA
UDT
UK
UOP
UreaD
UrCl
URR
US
USRDS
VAT
VDP
VFDU
Number of subjects
Noncuffed catheter
No data reported
Not significant
National Vascular Access Improvement Initiative
Optodilution by ultrafiltration
Optodilutional recirculation measurement technique
Pressure gradient
Proximal arteriovenous anastomosis
Peritoneal dialysis
Pulmonary embolism
Percutaneous fibrin sheath stripping
Intra-access pressure
Peripherally inserted central catheter
Peak systolic velocity
Percutaneous angioplasty
Polytetrafluoroethylene
Polyurethane
Peripheral vascular disease
Access blood flow
Quality assurance/continuous quality improvement
Blood pump flow delivered to the dialyzer
Blood pump flow
Ultrafiltration rate
Quality improvement project
Quality of life
Receiver operating characteristic
Relative risk
Recombinant tissue plasminogen activator
Superior vena cava
Systolic velocity ratio
Tunneled cuffed catheter
Thermal dilution
Tissue plasminogen activator
Transcutaneous optodilution flow method
Ultrasound dilution technique
Urokinase
Urine output
Urea dialysance
Urea clearance
Urea reduction ratio
Ultrasonography
Vascular access team
Venous drip chamber pressure
Variable flow Doppler ultrasound
S179
Glossary
Anastomosis: An opening created by surgical, traumatic, or pathological means between 2 normally
separate spaces or organs.
Aneurysm: An abnormal blood-filled dilation of a blood vessel wall (most commonly in arteries)
resulting from disease of the vessel wall.
Pseudoaneurysm: A vascular abnormality that resembles an aneurysm, but the outpouching is not
limited by a true vessel wall, rather by external fibrous tissue.
Angioplasty: The repair of a blood vessel abnormality.
Percutaneous transluminal angioplasty: The repair of a lesion using an endoluminal approach, usually
with a balloon that can be inflated to pressures up to 30 atmospheres.
Antibiotic lock: Instillation of an antibiotic solution into the lumen of a dialysis catheter for the entire
interdialytic period; antibiotics tested include vancomycin, aminoglycosides, and minocycline.
Antimicrobial lock: Instillation of an antimicrobial solution into the lumen of a dialysis catheter for
the entire interdialytic period; antimicrobial solutions include high-concentration citrate, highconcentration EDTA, and taurolidine.
Antimicrobial: Any agent capable of destroying or inhibiting the growth of microorganisms.
Antiseptic: Any agent capable of preventing infection by inhibiting the growth of microorganisms.
Cannulation: The insertion of cannulae (by definition, a needle with a lumen) or angiocaths into a
vascular vessel.
Buttonhole technique or constant-site technique: The repeated cannulation into the exact same puncture
site so that a scar tissue tunnel track develops. The scar tissue tunnel track allows the needle to pass
through to the outflow vessel of the fistula following the same path with each cannulation time. Only
used in fistulae. Should not be used for accessing grafts.
Catheter: A device providing access to the central veins or right atrium, permitting high-volume flow
rates.
Exit site: The location on the skin that the catheter exits through the skin surface.
Insertion site: Location at which the catheter enters the vein, for example, the right internal jugular vein
is the preferred insertion site.
Long-term catheter: Also known as tunneled cuffed catheter (TCC); a device intended for use for longer
than 1 week that typically is tunneled and has a cuff to promote fibrous ingrowth to prevent catheter
migration and accidental withdrawal.
Port catheter system: Subcutaneous device for hemodialysis access that is cannulated with needles; the
device contains a ball-valve system that is connected to 1 or more central venous catheters (CVCs).
Short-term catheter: A device intended for short-term use (1 week) that typically is not tunneled.
Intended for use in hospitalized patients; not for outpatient maintenance dialysis.
Diagnostic testing: Specialized testing that is prompted by some abnormality or other medical
indication and that is undertaken to diagnose the cause of the vascular access dysfunction.
Dialysance: The number of milliliters of blood completely cleared of any substance by an artificial
kidney or by peritoneal dialysis in a unit of time, usually a minute, with a specified concentration
gradient.
Distal revascularizationinterval ligation (DRIL): A surgical procedure to reduce ischemia to the
hand caused by steal syndrome.
Elastic recoil: The recurrence of stenosis following angioplasty.
Fistula (plural, fistulae): Autogenous autologous arteriovenous fistula, also referred to as native.
Brescia-Cimino (radiocephalic) fistula: An autologous fistula constructed between the radial artery and
the cephalic vein at the wrist.
S180
GLOSSARY
S181
Gracz fistula: An autologous fistula constructed between the brachial artery and a branch of the medial
antecubital vein, the perforating vein, below the elbow.
Snuff-box fistula: An autologous fistula constructed between a branch of the radial artery and an adjacent
vein in the anatomic snuff box of the hand.
Fistula maturation: The process by which a fistula becomes suitable for cannulation.
Rule of 6s: A fistula in general must be a minimum of 6 mm in diameter with discernable margins when a
tourniquet is in place, less than 6 mm deep, have a blood flow greater than 600 mL/min, and should
be evaluated for nonmaturation if, after 6 weeks from surgical creation, it does not meet these
criteria.
Flow: The amount of blood flowing through a system.
QA: Access blood flow.
Qf: Ultrafiltration rate.
QB: Blood pump flow delivered to the dialyzer.
Flow measurement methods:
Crit line: Using changes in hematocrit (Hct) induced by ultrafiltration.
GPT: Glucose pump (infusion) technique.
HDM: Hemodialysis monitor using magnetic detection of differential conductivity.
Ionic dialysance: A method that uses a change in dialysis fluid sodium concentration to calculate flow.
ORX: Optodilutional recirculation measurement technique.
TD: Thermal dilution method.
TQA: Direct transcutaneous optodilutional flow method.
UDT: Ultrasound dilution technique.
VFDU: Variable flow Doppler ultrasound.
Graft: A conduit of synthetic or biological material connecting artery to vein.
Synthetic: Made of plastic polymers, such as polytetrafluoroethylene (PTFE), polyurethane (PU).
Biological: Made of biological materials, such as bovine carotid artery, cryopreserved human femoral
veins, etc.
Tapered: Grafts for which internal diameter varies from the arterial to the venous end.
Untapered: Grafts with a uniform diameter, usually 6 mm.
Kt/V: A dimensionless quantity that assesses the amount of dialysis delivered.
Monitoring: The evaluation of the vascular access by means of physical examination to detect
physical signs that suggest the presence of dysfunction.
Magnetic resonance angiography (MRA): A technique to visualize the arterial and venous systems
using gadolinium as the imaging agent.
Neointimal hyperplasia: The myoendothelial proliferation of cells and matrix that produces stenosis,
primarily in grafts.
Online: The conductance of a test during a hemodialysis procedure.
Physical examination (of the access): Inspection, palpation, and auscultation of the access.
Pressure: Force applied uniformly over a surface, measured as force per unit of area; stress or force
acting in any direction against resistance.
Mean arterial pressure (MAP): Usually recorded in the arm opposite the vascular access.
PIA: Pressure in the access when there is no external blood flow for dialysis, also referred to as the static
pressure.
Venous drip chamber pressure (VDP): Also referred as dynamic venous pressure (DVP). Measured in
the venous tubing and equal to the pressure required to infuse blood back into the vascular access at
the blood pump flow set.
S182
GLOSSARY
Recirculation: The return of dialyzed blood to the systemic circulation without full equilibration.
Cardiopulmonary recirculation: Resulting from the return of dialyzed blood without full equilibration
with all systemic venous return.
Access recirculation: Resulting from the admixture of dialyzed blood with arterial access blood without
equilibration with the systemic arterial circulation. Occurs under conditions in which blood pump
flow is greater than access flow.
Receiver operating characteristic (ROC) curve: A technique to evaluate the sensitivity and specificity
of a diagnostic test to detect/predict the presence of a disease state.
Steal syndrome: Signs and symptoms (pain, coldness, cyanosis, necrosis) produced by an access as a
result of the diversion of arterial blood flow into the fistula.
Acronecrosis: Gangrene occurring in the distal part of the extremities, usually fingertips and toes.
Stenosis: A constriction or narrowing of a duct or passage; a stricture.
Cephalic arch stenosis: A common site for stenosis of the cephalic vein at an anatomic site where there
is a narrowing of the cephalic vein as it arches over the shoulder in the region of the deltopectoral
groove before the vein junction with the axillary vein.
Surveillance: The periodic evaluation of the vascular access by means of tests, which may involve
special instrumentation and for which an abnormal test result suggests the presence of dysfunction.
Tissue plasminogen activator (tPA): A natural lytic used to dissolve fibrin or nonorganized thrombus.
Transposition: The movement of a vein from its normal position either by elevation to bring the vein
closer to the skin or laterally to permit easier cannulation.
Ultrasound: The use of ultrasonic waves for diagnostic or therapeutic purposes, specifically to image
an internal body structure.
Doppler ultrasound (DU): Ultrasound that uses the Doppler effect to measure movement or flow in the
body and especially blood flow; also referred to as Doppler ultrasonography.
Duplex Doppler ultrasound (DDU): Combines Doppler and B-mode (grayscale) imaging to provide
diagnostic ultrasound used for quantitative color velocity imaging, also referred to as Doppler
sonography.
Systolic velocity ratio (SVR): The ratio of velocity in an abnormal vessel relative to a normal vessel.
Urokinase: A natural lytic used to dissolve fibrin or nonorganized thrombus.
Vascular access team (VAT): Patient and group of professionals involved in management of vascular
access (includes caregivers who construct, cannulate, monitor, detect problems in, and repair vascular
accesses). Caregivers include nephrologist, nephrology nurse, patient care technician, nurse practitioner, physician assistant, interventionalist, surgeons, and vascular access coordinator.
Foreword
he publication of the second update of the

Clinical Practice Guidelines (CPGs) and
Clinical Practice Recommendations (CPRs) for
Vascular Access represents the second update of
guidelines established the importance of placing
fistulae in long-term hemodialysis patients. Several of these guidelines have been selected as
clinical performance measures by regulatory
agencies to drive the process of quality improvement in long-term dialysis patients, and an initiative in the United States called Fistula First
recently was started in an effort to increase the
percentage of patients who have an arteriovenous fistula placed for long-term hemodialysis
therapy.
Several major changes have occurred since the
publication of the first set of guidelines. First, a
number of clinical trials have been performed to
determine the efficacy of different methods of
identifying an access that is beginning to fail.
Thus, this update of the guideline includes a
substantial revision of accepted methods for access dysfunction detection. Second, cannulation
techniques have been updated to include the
importance of training staff in cannulation techniques and the appropriate uses of the buttonhole
technique for arteriovenous fistulae. Finally,
urokinase was removed from the market and
other thrombolytic agents have been developed
to assist with reestablishing patency in dialysis
catheters. The use of these newer agents is addressed in this update.
practice recommendations, or CPRs. These
CPRs are opinion based and are based on the
expert consensus of the Work Group members. It
is the intention of the Work Group that the
guideline statements in Section I can be considered for clinical performance measures because
of the evidence that supports them. Conversely,
because the CPRs are opinion based, and not
evidence based, they should not be considered to
have sufficient evidence to support the develop-
ment of clinical performance measures. The third

to combine all the research recommendations for
the guidelines into 1 major section and also have
in how the research recommendations are presented is to provide a guidepost for funding
agencies and investigators to target research efforts in areas that will provide important information to benefit patient outcomes.
This final version of the Clinical Practice Guidelines and Recommendations for Vascular Access
has undergone extensive revision in response to
comments during the public review. While considerable effort has gone into their preparation
during the past 2 years and every attention has
been paid to their detail and scientific rigor, no
set of guidelines and clinical practice recommendations, no matter how well developed, achieves
its purpose unless it is implemented and translated into clinical practice. Implementation is an
integral component of the Kidney Disease Outcomes Quality Initiative (KDOQI) process and
accounts for the success of its past guidelines.
The Kidney Learning System (KLS) component
of the National Kidney Foundation is developing
implementation tools that will be essential to the
success of these guidelines.
In a voluntary and multidisciplinary undertaking of this magnitude, many individuals make
contributions to the final product now in your
hands. It is impossible to acknowledge them
individually here, but to each and every one of
them, we extend our sincerest appreciation. This
limitation notwithstanding, a special debt of gratitude is due to the members of the Work Group
and their co-chairs, Anatole Besarab of Henry
Ford Hospital and Jack Work of Emory University. It is their commitment and dedication to the
KDOQI process that has made this document
possible.

KDOQI Chair
KDOQI Vice-Chair
S183
Introduction
ore than 300,000 individuals in the

United States rely on a vascular access
to receive hemodialysis (HD) treatment.1 Vascular access continues to be a leading cause for
hospitalization and morbidity in patients with
chronic kidney disease (CKD) stage 5.2 Appropriate care of HD patients with CKD stage 5
requires constant attention to the maintenance
of vascular access patency and function. An
ideal access delivers a flow rate to the dialyzer
adequate for the dialysis prescription, has a
long use-life, and has a low rate of complications (eg, infection, stenosis, thrombosis, aneurysm, and limb ischemia). Of available accesses, the surgically created fistula comes
closest to fulfilling these criteria. Studies over
several decades consistently demonstrate that
native fistula accesses have the best 4- to
5-year patency rates and require the fewest
interventions compared with other access
types.3-5 However, in the United States between 1985 and 1995, the growth of the CKD
Stage 5 HD program was accompanied by
decreased use of native fistulae and increased
use of grafts and cuffed central catheters for
permanent HD access.5,6 In 1995, the United
States Renal Data System (USRDS) reported,
for the 1990 incident cohort of patients, that
insertion of polytetrafluoroethylene (PTFE)
grafts occurred almost twice as often as construction of native accesses.6 Significant geographic variation in the ratio of native fistula
construction to graft placement also was noted.
The substitution of grafts for fistulae increased patient care costs, in part because of
the increased number of procedures needed to
maintain patency of grafts compared with native fistulae.7 A review of Medicare billing
showed that the first-year total yearly costs for
patients initiating HD therapy using a fistula
were lowest ($68,002) compared with grafts
($75,611) and catheters ($86,927).8 Although
the second-year total yearly costs were lower
for all groups, catheters still resulted in the
highest costs at $57,178 compared with $54,555
for grafts and $46,689 for fistulae. Similarly, in
a single-center Canadian study, the cost of
vascular accessrelated care was lower by more
than 5-fold for patients who began the study
S184
period with a functioning fistula compared

with those treated with a long-term catheter or
graft.9
Before the first dissemination of the Dialysis
Outcomes Quality Initiative (DOQI) recommendations on vascular access in 1997, many
studies showed that practice patterns were contributing to patient morbidity and mortality, as
well as costs. The failure of access was noted
to be a major cause of morbidity for patients
on HD therapy, with a number of reports
indicating that a high percentage of hospitalizations for patients with CKD stage 5 were
caused by vascular access complications.6,7,10-12 The USRDS reported that HD
access failure was the most frequent cause of
hospitalization for patients with CKD stage 5,6
and, in some centers, it accounted for the
largest number of hospital days.13 Reports also
indicated a decreasing interval between placement of a vascular access and a surgical procedure needed to restore patency,7,12 with significant costs to restore patency.6,13 Since then, a
study using data from the USRDS Morbidity
and Mortality Study Wave 1 showed that patients receiving catheters and grafts have greater
mortality risk than patients dialyzed with fistulae.14 In patients with and without diabetes
mellitus, cause-specific analyses found higher
infection-related deaths for cuffed central catheters. In patients without diabetes, relative
risks (RRs) were 1.83 (P 0.04) with catheters and 1.27 (P 0.33) with arteriovenous
(AV) grafts (AVGs). In patients with diabetes,
the RR was even higher than in those without
diabetes: RR of 2.30 (P 0.06) for catheters
and RR of 2.47 (P 0.02) for grafts compared
with fistulae. Cardiac cause of death was highest in patients with central venous catheters
(CVCs). A number of subsequent epidemiological studies, both in the United States15,16 and
abroad,17 reaffirmed that greater use of fistulae
was associated with reduced mortality and
morbidity.
It was shown that an aggressive policy for
monitoring hemodynamics within an AVG or
AV fistula (AVF) to detect access dysfunction
may reduce the rate of thrombosis (see Clinical
Practice Guideline [CPG] 4). Thus, much ac-
INTRODUCTION
cess-related morbidity and associated costs

might be avoided. The number of interventions
required to maintain access patency may be
decreased further by the use of fistulae rather
than AVGs. Studies showed that the number of
access events is 3- to 7-fold greater in prosthetic bridge grafts than in fistulae,3,18 thereby
contributing to the increased cost of grafts.
Whether utilization of such interventions to
reduce thrombosis rates ultimately prolongs
the useable life of the access are unknown and
should not be the sole outcome measure.
Thrombosis is associated with additional risks
to the patient that are not present with simple
percutaneous angioplasty (PTA).19
The National Kidney Foundation (NKF) issued the Kidney Disease Outcomes Quality Initiative (KDOQI) CPGs for Vascular Access in an
effort to improve patient survival and quality of
life (QOL), reduce morbidity, and increase efficiency of care. Vascular access patency and adequate HD are essential to the optimal management of HD patients with CKD stage 5. The first
is a necessary prerequisite for the second. To
improve QOL and overall outcomes for HD
patients, 2 primary goals were originally put
forth in the vascular access guidelines20:
Increase the placement of native fistulae

Detect access dysfunction before access
thrombosis.
We believe these goals still apply, with the

emphasis on placement of the functioning fistula.
The Centers for Medicare & Medicaid Services
(CMS) has actively collected data on 3 Clinical
Performance Measures (CPMs) derived from
the original and revised KDOQI Guidelines for
Vascular Access. The failure to adequately
increase the number of fistulae among either
incident or prevalent HD patients during the past
6 years2 or to reduce the use of catheters led to a
CMS mandate that the ESRD networks develop
Quality Improvement Projects (QIPs) on Vascular Access. These have been distilled into 3 key
points: avoid central catheterization, thus avoiding loss of central patency; maintain existing
access by detecting impending failure, followed
by prompt intervention; and maximize creation
of fistulae as the best long-term access. Out of
these concepts has grown the National Vascular
Access Improvement Initiative (NVAII), empha-
S185
sizing a fistula-first approach. Recently, the target for fistula creation was set as 65% by 2009
(www.cms.hhs.gov/ESRDQualityImproveInit/
04_FistulaFirstBreakthrough.asp). The Work
Group acknowledges the importance of increasing the number of fistulae in use, but believes
that the emphasis should be shifted from the
fistula construction rate to the rate of usable fistula
accesses. This shift in emphasis is important to
minimize wasted time and effort and reduce the
primary failure rate and salvage procedures.
A number of barriers need to be overcome to
achieve the goals set for vascular fistula construction; chief among these is the late referral
of patients for permanent access placement,
reflected in patient hospitalizations. In some
regions, up to 73% of patients are hospitalized
for initiation of HD therapy, almost invariably
for dialysis catheter access placement.21 Unexpectedly, the modest increases in fistula use
rates have been accompanied by increases in
the use of catheters.2 Early referral of patients
with CKD stage 5 to a nephrologist is absolutely essential to allow for access planning
and thus increase the probability of fistula
construction and maturation, thereby decreasing the need for catheter placement.
To achieve these objectives, the current Work
Group has developed and revised the vascular
access practice guidelines and strategies for
implementation and has made a concerted effort to differentiate guidelines from recommendations. At the core of these guidelines is the
goal of early identification of patients with
progressive kidney disease and the identification and protection of potential fistula construction sitesparticularly sites using the cephalic
veinby members of the health care team and
patients.
After access has been constructed, dialysis
centers need to use a multifaceted continuous
quality improvement (CQI) program to detect
vascular accesses at risk, track access complication rates, and implement procedures that
maximize access longevity. Vascular access
databases that are available to all members of
the vascular access team (VAT) are crucial.
The Work Group has developed explicit guidelines regarding which tests to use to evaluate a
given access type and when and how to intervene to reduce thrombosis and underdialysis.
S186
The Work Group believes that the guidelines

are reasonable, appropriate, and achievable.
Attainment of these goals will require the
concerted efforts of not only practicing nephrologists, but also nephrology nurses, access
surgeons, vascular interventionalists, patients,
and other members of the health care team.
VASCULAR ACCESS
In this update of the Vascular Access Guidelines,

the Work Group did not perform a comprehensive
review of all the guidelines. Seven topics underwent systematic review, and these are identified.
The other guidelines were unified and consolidated. More recent references, including reviews,
were included when appropriate.
I. CLINICAL PRACTICE GUIDELINES FOR

VASCULAR ACCESS
GUIDELINE 1. PATIENT PREPARATION FOR PERMANENT

HEMODIALYSIS ACCESS
Appropriate planning allows for the initiation of dialysis therapy at the appropriate
time with a permanent access in place at the
start of dialysis therapy.
1.1 Patients with a glomerular filtration rate
(GFR) less than 30 mL/min/1.73 m2 (CKD
stage 4) should be educated on all modalities of kidney replacement therapy (KRT)
options, including transplantation, so that
timely referral can be made for the appropriate modality and placement of a permanent dialysis access, if necessary. (A)
1.2 In patients with CKD stage 4 or 5, forearm and upper-arm veins suitable for
placement of vascular access should not
be used for venipuncture or for the placement of intravenous (IV) catheters, subclavian catheters, or peripherally inserted
central catheter lines (PICCs). (B)
1.3 Patients should have a functional permanent access at the initiation of dialysis
therapy.
1.3.1 A fistula should be placed at least 6
months before the anticipated start
of HD treatments. This timing allows for access evaluation and additional time for revision to ensure a
working fistula is available at initiation of dialysis therapy. (B)
1.3.2 A graft should, in most cases, be placed
at least 3 to 6 weeks before the anticipated start of HD therapy. Some newer
graft materials may be cannulated
immediately after placement. (B)
1.3.3 A peritoneal dialysis (PD) catheter
ideally should be placed at least 2
weeks before the anticipated start of
dialysis treatments. A backup HD
access does not need to be placed in
most patients. A PD catheter may be
used as a bridge for a fistula in
appropriate patients. (B)
1.4 Evaluations that should be performed
before placement of a permanent HD
access include (Table 1):
1.4.1 History and physical examination, (B)
S188
1.4.2 Duplex ultrasound of the upper-extremity arteries and veins, (B)

1.4.3 Central vein evaluation in the appropriate patient known to have a previous catheter or pacemaker. (A)
BACKGROUND
Since implementation of the NKF KDOQI
Vascular Access Guidelines in 1997, which encouraged increased placement of fistulae, CMS
has embraced this recommendation with the
implementation of the Fistula First Breakthrough
Initiative (FFBI). This initiative endorses the
goals recommended by the NKF KDOQI: fistula
rates of 50% or greater for incidentand at least
40% for prevalentpatients undergoing HD. The
FFBI promotes the placement of fistulae in all
suitable HD patients. Working through the ESRD
Networks, the FFBI promotes the placement of
fistulae using 11 Change Concepts that encourage the development of specific strategies; these
11 Change Concepts have been identified to help
the kidney community improve the rate of fistula
placement. Five of these strategies emphasize
the same goals as CPG 1 and Clinical Practice
Recommendation (CPR) 1: education of patients
regarding fistulae, protection of vessels, vessel
mapping, and sufficient lead-time for fistula maturation (NVAII; www.fistulafirst.org). The breakthrough initiative has reset the goal for fistula
creation to 65% by 2009.
RATIONALE
Characteristics of a patients arterial, venous,
and cardiopulmonary systems will influence
which access type and location are most desirable for each patient.22-27 The patients life expectancy and planned duration of CKD stage 5
therapy also can influence the type and location
of the access. All patients should be evaluated as
in Table 1.
Venipuncture complications may render veins
potentially available for vascular access unsuitable for construction of a primary fistula. Patients and health care professionals should be
educated about the need to preserve veins to
avoid loss of potential access sites in the arms
and maximize chances for successful fistula place-
PATIENT PREPARATION FOR PERMANENT HEMODIALYSIS ACCESS
ment and maturation. Subclavian vein catheterization is associated with central venous stenosis.28-30 Significant subclavian vein stenosis
generally will preclude the use of the entire
ipsilateral arm for vascular access. Thus, subclavian vein catheterization should be avoided for
temporary access in patients with kidney disease.31 The incidence of central vein stenosis and
occlusion after upper-extremity placement of peripherally inserted long-term catheters (PICCs)
and venous ports was 7% in 1 retrospective study
of 150 patients.32 PICCs also are associated with
a high incidence of upper-extremity thrombosis.
The incidence of upper-extremity venous thrombosis varies between 11% and 85%, which leads
to loss of potential upper-extremity fistulae.33-35
Because of the substantial risk for loss of useable
upper-extremity veins and central venous stenosis with PICCs, the Work Group recommends
strongly that PICCs not be used in patients with
CKD.
Ideally, patients should have a functional permanent access at the time of dialysis therapy
initiation. Function implies that the access not
only delivers adequate blood flow for dialysis,
but may be cannulated easily. In general, such an
access has a flow of approximately 600 mL/min,
is less than 0.6 cm below the surface of the skin,
and has a minimal diameter of 0.6 cm (Rule of
6s) Both the size and anatomic qualities of venous and arterial components of primary fistulae
can influence fistula maturation time. An aggressive policy of primary fistula creation may result
in failures in patients with marginal anatomy.
However, timely attempts to create a primary
fistula before the anticipated need for dialysis
therapy will allow adequate time for the fistula to
mature and will allow sufficient time to perform
another vascular access procedure if the first
attempt fails, thus avoiding the need for temporary access. Early referral of a patient with CKD
to a nephrologist is needed to facilitate CKD
therapy with medications and diets that preserve
kidney function. In addition, counseling patients
about CKD stage 5 treatment options is essential
to plan for ideal access (ie, PD and HD access)
(see CPG 2) (Table 1).
The Work Groups consensus is that maturation of an AVG access sitedefined as reduction
of surgically induced swelling and the grafts
adherence to its tunnel tissueusually requires
S189
about 3 weeks. Thus, ideally, AVGs should be

placed 3 to 6 weeks before use.
Long-term catheters are the method of choice
for temporary access of longer than 1 week
duration. Catheters are suitable for immediate
use. To maximize their use-life, they should not
be inserted until needed. However, the Work
Group recommends that a catheter be used for
dialysis access for as brief a period as necessary
(see CPG 2).
A vein must be mature, both physically and
functionally, before use for vascular access. The
time required for fistula maturation varies among
patients. The Work Group does not advise use of
the fistula within the first month after construction because premature cannulation of a fistula
may result in a greater incidence of infiltration,
with associated compression of the vessel by
hematoma and permanent loss of the fistula. In
general, allowing the fistula to mature for 6 to 8
weeks before investigating the reason for failure
to mature is appropriate (see CPG 2). For a
fistula to be considered successful, it must be
usable. In general, a working fistula must have
all the following characteristics: blood flow adequate to support dialysis, which usually equates
to a blood flow greater than 600 mL/min; a
diameter greater than 0.6 cm, with location accessible for cannulation and discernible margins to
allow for repetitive cannulation; and a depth of
approximately 0.6 cm (ideally, between 0.5 to
1.0 cm from the skin surface). This combination
of characteristics can be remembered easily as
the Rule of 6s.
Although there are no definitive data in the
literature, any intervention that increases blood
flow to the extremity may improve the chances
of successful fistula development. Therefore,
regular hand-arm exercises, with or without a
lightly applied tourniquet, are recommended until the fistula matures. Failure of a fistula to
mature occasionally is caused by venous side
branches that drain critical flow from the primary
vessel. Ligating these side branches may result in
successful maturation (see CPG 6).
Studies relating to preoperative venous imaging/mapping for AVF construction underwent
systematic review. Duplex ultrasound is the preferred method for preoperative vascular mapping. Vascular mapping in preparation for the
creation of a vascular access refers to the evalua-
S190
tion of vessels, both arterial and venous, of

patients with CKD who have selected HD therapy,
and it should be performed in all patients before
placement of an access. Preoperative vascular
mapping was shown to substantially increase the
total proportion of patients dialyzing with fistulae.36-39 Several studies support the 2.0- to
2.5-mm vein diameter threshold for successful
creation of a fistula.39,40 Radiocephalic fistulae
constructed in veins less than 2.0 mm in diameter
had only a 16% primary patency at 3 months
compared with 76% for those with veins greater
than 2.0 mm.40 In a pivotal study,39 a threshold
GUIDELINES FOR VASCULAR ACCESS
of 2.5-mm vein diameter, assessed by using

duplex ultrasound, was used; this resulted in an
increase in fistula creation to 63% compared
with a retrospective 14% rate in the absence of
vascular mapping.22 A similar study using the
same duplex ultrasound criteria showed a fistula
increase from 34% in historical controls to 64%.
Importantly, in this study, duplex ultrasound altered the surgical plan based entirely on the
surgeons clinical evaluation, resulting in increased placement of fistulae.41
There is no generally accepted standard for
what constitutes vascular mapping. The arterial
PATIENT PREPARATION FOR PERMANENT HEMODIALYSIS ACCESS
evaluation should include pulse examination, differential blood pressure measurement, assessment of the palmar arch for patency, arterial
diameter assessed by using duplex ultrasound,
and the presence of arterial calcification. A preoperative arterial diameter less than 1.6 mm has
been associated with a high failure rate in radiocephalic fistulae.42,43 Other studies suggested
that a minimum diameter of 2.0 mm is required
for successful fistula creation.39 Venous evaluation should include a luminal diameter of 2.5 mm
or greater, continuity with the proximal central
veins, and absence of obstruction.39 The central
veins may be assessed indirectly by using duplex
ultrasound.44 Compared with invasive venography, duplex ultrasound had a specificity of 97%
and sensitivity of 81% for detecting central vein
occlusion.45 Alternatively, venography or magnetic resonance angiography (MRA) may be
S191
used to evaluate central veins.46 (See CPR 1.4

for suitable imaging studies for central veins).
LIMITATIONS
There has been no study comparing vascular
access surgery based only on the clinical evaluation to preoperative vascular mapping outcomes.
Such a study would be the equivalent of requiring a randomized prospective study comparing
the efficacy of pulmonary clinical evaluation
(tactile fremitus and auscultation, ie, physical
examination only) with a chest radiograph (imaging) in identifying lung pathological states. Such
a study is unlikely, based on current data showing that vascular mapping increases fistula creation. Although the level of evidence of a prospective randomized trial is not available, the Work
Group consensus based on many studies supports vascular mapping as a guideline.
GUIDELINE 2. SELECTION AND PLACEMENT OF

HEMODIALYSIS ACCESS
A structured approach to the type and location of long-term HD accesses should help
optimize access survival and minimize complications.
The access should be placed distally and
in the upper extremities whenever possible.
Options for fistula placement should be considered first, followed by prosthetic grafts if
fistula placement is not possible. Catheters
should be avoided for HD and used only
when other options listed are not available.
2.1 The order of preference for placement of
fistulae in patients with kidney failure
who choose HD as their initial mode of
KRT should be (in descending order of
preference):
2.1.1 Preferred: Fistulae. (B)
2.1.1.1 A wrist (radiocephalic) primary fistula. (A)
2.1.1.2 An elbow (brachiocephalic)
primary fistula. (A)
2.1.1.3 A transposed brachial basilic vein fistula: (B)
2.1.2 Acceptable: AVG of synthetic or biological material, such as: (B)
2.1.2.1 A forearm loop graft, preferable to a straight configuration.
2.1.2.2 Upper-arm graft.
2.1.2.3 Chest wall or necklace
prosthetic graft or lowerextremity fistula or graft; all
upper-arm sites should be
exhausted.
2.1.3 Avoid if possible: Long-term catheters. (B)
2.1.3.1 Short-term catheters should
be used for acute dialysis and
for a limited duration in hospitalized patients. Noncuffed
femoral catheters should be
used in bed-bound patients
only. (B)
2.1.3.2 Long-term catheters or dialysis port catheter systems
should be used in conjunction with a plan for permaS192
nent access. Catheters capable of rapid flow rates are

preferred. Catheter choice
should be based on local experience, goals for use, and
cost. (B)
2.1.3.3 Long-term catheters should
not be placed on the same
side as a maturing AV access, if possible. (B)
Special attention should be
paid to consideration of avoiding femoral catheter access
in HD patients who are current or future kidney transplant candidates. MRA imaging of both arteries and veins
is the diagnostic procedure of
choice for evaluating central
vessels for possible chest wall
construction.
2.1.4 Patients should be considered for
construction of a primary fistula after failure of every dialysis AV access. (B)
2.1.5 While this order of access preference is similar for pediatric patients, special considerations exist
that should guide the choice of
access for children receiving HD.
Please refer to CPG 9 for specific
recommendations.
2.1.6 In the patient receiving PD who is
manifesting signs of modality failure, the decision to create a backup
fistula should be individualized by
periodically reassessing need. In individuals at high risk for failure (see
the PD Adequacy Guidelines), evaluation and construction should follow the procedures in CPG 1 for
patients with CKD stage 4.
2.2 Fistulae:
2.2.1 Enhanced maturation of fistulae
can be accomplished by selective
obliteration of major venous side
branches in the absence of a downstream stenosis. (B)
SELECTION AND PLACEMENT OF HEMODIALYSIS ACCESS
2.3 Dialysis AVGs:

2.3.1 The choice of synthetic or biological material should be based on the
surgeons experience and preference. The choice of synthetic or
biological conduits should consider
local experience, technical details,
and cost. (B)
2.3.2 There is no convincing evidence to
support tapered versus uniform tubes,
externally supported versus unsupported grafts, thick- versus thinwalled configurations, or elastic versus nonelastic material. (A)
2.3.3 While the majority of past experience
with prosthetic grafts has been with
the use of PTFE, other prosthetics
(eg, polyurethane [PU]) and biological conduits (bovine) have been used
recently with similar outcomes. (B)
2.3.4 Patients with swelling that does not
respond to arm elevation or that
persists beyond 2 weeks after dialysis AV access placement should receive an imaging study or other
noncontrast study to evaluate central venous outflow (see CPG 1). (B)
2.4 Catheters and port catheter systems:
2.4.1 The preferred insertion site for tunneled cuffed venous dialysis catheters or port catheter systems is the
right internal jugular vein. Other
options include the right external
jugular vein, left internal and external jugular veins, subclavian veins,
femoral veins, and translumbar and
transhepatic access to the IVC. Subclavian access should be used only
when no other upper-extremity or
chest-wall options are available. (A)
2.4.2 Ultrasound should be used in the
placement of catheters. (B)
2.4.3 The position of the tip of any central
catheter should be verified radiologically. (B)
RATIONALE
Order of Placement (CPG 2.1)
There are no randomized controlled trials
(RCTs) comparing the recommended anatomic
S193
order of distal-to-proximal access construction.

However, good surgical practice makes it obvious that when planning permanent access placement, one should always consider the most distal
site possible to permit the maximum number of
future possibilities for access.23 In general, a
peripheral-to-central sequence of fistulae construction should be envisioned in the ideal case,
beginning with the snuff box fistula at the base
of the thumb, followed by the standard BresciaCimino wrist fistula, followed by a forearm cephalic fistula at dorsal branch and finally a midforearm cephalic fistula. If a forearm fistula is
not feasible, an antecubital fistula,47 cephalic fistula at elbow, and, finally, a transposed basilic
fistula should be considered. In cases in which a
fistula is not constructed initially, a graft can be
used as a planned bridge to a fistula. Failing
forearm grafts can be converted to upper-arm
fistulae, and lower-level fistulae can be converted to higher-level fistulae. If a graft is constructed, preference is given to the following
sequence: forearm loop; upper-arm, straight or
curved; upper-arm loop. All upper-extremity options should be considered before using the thigh.
At times, exotic grafts can be constructed on
the anterior chest wall or to the internal jugular
vein. Even in these situations, a systematic radiological evaluation of the venous systems should
be conducted before placement.
Maintaining long-term functioning access can
be difficult and frustrating for physicians and
patients; starting distally and moving proximally
provides for the possibility of preserving as many
potential sites as possible for future access creation. It is a tragedy for patients and caretakers
alike to exhaust anatomic sites prematurely by
initially bypassing more distal sites. The decision
to use a more proximal site initially should be
documented by preoperative imaging studies or
the likelihood for the development of arterial
steal.23,48 (See CPGs 1, 5, and 6.) However, if
upper-extremity options have been exhausted,
the anatomic locations left for permanent access
are the thigh (where grafts49,50 and, less commonly, fistulae51 can be constructed) and upper
chest, where a variety of graft accesses can be
constructed.52 The possibilities in the chest usually are defined by preoperative evaluation of the
central venous system and, at times, angiography53 or MRA is required.54 Because vascular
S194
access infection is intrinsically more likely in the

thigh, access construction in this site usually is
deferred to one of last resort. Graft patency in the
thigh is minimally better than in the upper arm,55
and the greater risk for infection mandates against
its initial use. In extreme cases, the forgotten
Thomas shunt can be constructed.56
The preference of fistulae over all other forms
of access arises from their functional advantages
because of a lower rate of complications.
Fistulae have the lowest rate of thrombosis57
and require the fewest interventions,57,58 providing longer survival of the access.3,4,57,58
The number of access events is 3- to 7-fold
greater in prosthetic bridge grafts than in
native fistulae.4,57,58
As a result, costs of implantation and access
maintenance are the lowest.4,6,8
Fistulae have lower rates of infection than
grafts, which, in turn, are less prone to infection than percutaneous catheters and subcutaneous port catheter systems.59 Vascular access
infections in HD patients are common, can be
severe, and contribute to infection as the second
leading cause of death in patients with CKD
stage 5.60
Fistulae are associated with increased survival
and lower hospitalization.
Patients receiving catheters (RR 2.3) and
grafts (RR 1.47) have a greater mortality
risk than patients dialyzed with fistulae.14
Epidemiological evidence also indicates
that greater use of fistulae reduces mortality
and morbidity.14-17
Wrist (radiocephalic)61 and elbow (brachiocephalic)62 primary fistulae are the preferred types
of access because of the following characteristics:
Superior patency to other accesses after they

are established and matured.3,4,23,24,57,58,63-69
Lower complication rates compared with other
access options,3,23,24,63-69 including lower incidence of conduit stenosis, infection, and vascular steal phenomenon.
In most cases, flow increases early (first week),
with little additional increase as the fistula
matures (see CPG 5).70-72 Failure of fistula
flow to increase is a sign of access dysfunction
(see CPG 4).
The Work Group concluded that the 3 advantages of wrist and elbow primary fistulae, as
listed, outweigh the following 4 potential disadvantages:
The vein may fail to enlarge and/or increase

blood flow to satisfactory levels (ie, fail to
mature).23,24,73
Comparatively long maturation times (1 to 4
months) must elapse after creation of these
fistulae before they can be used. Thus, the
access must be created several months in
advance of the anticipated need for dialysis or
an alternative temporary method of vascular
access must be used while the fistula matures
(see CPG 1).
In some individuals, the vein may be more
difficult to cannulate than an AVG. However,
this can be addressed by mobilizing the vein
superficially.74
The enlarged vein may be visible in the forearm
and be perceived as cosmetically unattractive
by some individuals.
The wrist fistula is the first choice of access
type because of the following advantages:
It is relatively simple to create.61,75
It preserves more proximal vessels for future
access placement.23,24,73
It has few complications. Specifically, the
incidence of vascular steal is low, and in
mature fistulae, thrombosis and infection rates
are low.3,4,24,57,58,65,66
The only major disadvantage of the wrist

(radiocephalic) fistula is a lower blood flow rate
(BFR) compared with other fistula types. If adequate flow to support the HD prescription is not
achieved with a radiocephalic fistula within 4
months after appropriate evaluation for correctable or modifiable factors (see CPG 4), another
type of access should be established (see CPG 1).
The major drawback of a radiocephalic fistula is
the relatively high primary failure rate (15%) and
only moderate secondary patency rate at 1 year
(62%).76
The elbow (brachiocephalic) primary fistula
is the second choice for initial placement of an
access. Its advantages include the following:62,63,68,77-79
It has a higher blood flow compared with the

wrist fistula.
The cephalic vein in the upper arm usually is
comparatively easier to cannulate and is easily
covered, providing a potential cosmetic benefit.
The disadvantages of the elbow (brachiocephalic) primary fistula include the following:26,66,77-80
It is slightly more difficult to create surgically

than a radiocephalic fistula.
It may result in more arm swelling than a
radiocephalic fistula.
It is associated with an increased incidence of
steal compared with a radiocephalic fistula.
It is associated with a greater incidence of
cephalic arch stenosis than a forearm radiocephalic fistula.
If a wrist radiocephalic or elbow brachiocephalic fistula cannot be created, the patient
should be considered for a transposed basilic
vein fistula. In some cases, a forearm graft can
be a viable alternative to mature the venous
system for an elbow fistula as a secondary access. Transposed brachiobasilic fistulae have several disadvantages compared with other fistulae:62,66,79,81-83
The transposition procedure may create significant arm swelling and patient pain.
They have a greater incidence of steal and arm
swelling than other fistula types.
They are more technically challenging, especially in obese individuals.
The NVAII, now recognized as the FFBI, is a
CMS-mandated 3-year CKD Stage 5 Network
improvement project emphasizing a fistula-first
approach.84-88 The Work Group agrees with the
mission statement to increase the likelihood
that every eligible patient will receive the most
optimal form of vascular access for him/her, in
the majority of cases an arterial venous fistula.
For FFBI to optimally succeed, all its recommendations must be followed (NVAII, www.
fistulafirst.org; last accessed 2/20/2006). However, the Work Group recognizes that in some
cases, the fistula first at all costs approach may
not be the most cost-effective or optimal for each
individual. A functional fistula is the goal, not
the insertion of a fistula with a poor chance at
S195
maturing. A graft can be used as a planned

bridge to a fistula, and failing forearm grafts can
be converted to upper-arm fistulae. Similarly,
fistulae at a lower level can be converted to more
proximal fistulae.
AVGs have the following advantages:
A large surface area and vessel available for

cannulation initially.64,89-91
They are technically easy to cannulate.64
The lag-time from insertion to maturation is
short. For PTFE-derived grafts, it is recommended that not less than 14 days should elapse
before cannulation to allow healing and incorporation of the graft into local tissues,25,64,92
although ideally, 3 to 6 weeks are recommended.
Multiple insertion sites are available.26,64,67,90-94
A variety of shapes and configurations is available to facilitate placement.64,67,89-92,94
It is easy for the surgeon to handle, implant, and construct the vascular anastomosis.25,26,64,91,92,94-104
The graft is comparatively easy to repair
either surgically 65,94,101,105-107 or endovascularly.108-112
The sum of the available data, until recently,

supported PTFE grafts over other biological and
other synthetic materials, based on lower risk for
disintegration with infection, longer patency, better availability, and improved surgical handling.
Biological grafts (bovine heterografts) have
greater reported rates of complications compared
with synthetic grafts.91-93,100
For nearly 2 decades, PTFE has been the
material of choice for bridge grafts. However,
during the past decade, modifications113 and the
use of other materials, such as PU,114,115 cryopreserved femoral vein,116,117 bovine mesenteric
vein, and hybrids118 with self-sealing composite
material, have been developed and used.119 None
of these has shown any survival patency over
plain PTFE, except for the composite/PU graft.
The latter has an advantage because of its selfsealing property to be cannulated within hours, if
needed, for dialysis. As a result, it can be placed
without having to use a catheter for initiation of
dialysis therapy, in some cases. Direct comparisons between PTFE and human umbilical cord
vein grafts and other synthetic polymers have not
been made.
S196
The lure to construct AVGs using larger more

proximal vessels should be resisted. Although
these have higher flow and better initial function
and/or patency, they limit potential sites for future placement.23,25,73 A synthetic dialysis AVG
is expected to last 3 to 5 years.73 Grafts using
smaller more peripheral vessels can experience
more frequent thromboses that require treatment.
However, these grafts have the advantage of
preserving more proximal sites for new access
creation should this become necessary in the
future.4,23-25 The 2 preferred graft site types are
the antecubital loop graft and upper-arm curved
graft. Femoral placement of access has been
associated with proximal venous stenosis, which
may be problematic later in patients receiving
kidney transplantation.
Potential sites for arterial inflow include radial
artery at the wrist, brachial artery in the antecubital fossa, brachial artery in the lower portion of
the arm, brachial artery just below the axilla,
axillary artery, and femoral artery. Potential sites
for venous outflow include median antecubital
vein, proximal and distal cephalic vein, basilic
vein at the level of the elbow, basilic vein at the
level of the upper arm, axillary vein, jugular
vein, and femoral vein.
Fistulae (CPG 2.2)
A 70% AV working fistula access rate can be
achieved, even in patients who have diabetes85-88 and women.84 Results from the Dialysis
Outcomes and Practice Patterns Study (DOPPS)
indicate that the fistula can be cannulated as early
as 1 month after construction.120 Thus, an access
that shows evidence of maturation failure on
physical examination or by using duplex ultrasound72 should undergo investigation. A study
found that combining venous diameter (0.4
cm) and flow volume (500 mL/min) increased
the predictive power of adequate fistula maturation to 95% (19 of 20) versus neither criterion
met (33%; 5 of 15).72 Women were less likely to
have an adequate outcome vein diameter of 0.4
cm or greater: 40% (12 of 30) compared with
69% in men (27 of 39). However, of note, the
accuracy of experienced dialysis nurses in predicting eventual fistula maturity was excellent at
80% (24 of 30).
Many accesses with multiple outflow veins can
be salvaged by ligation of side branches.121,122
As more older patients have fistula constructions, the possibility of the access failing to
mature is likely to increase.123 Failure to mature
should be evaluated by 6 weeks after construction by physical examination and, if needed,
ultrasound.72,124 Prompt correction should be
undertaken.125,126
Exercises to Mature the Fistula (B-)
Isometric exercise has been shown to increase
the diameter of forearm veins,127 and exercise
should be prescribed if there is sufficient lead
time before surgery.
Dialysis AVGs (CPG 2.3)
Graft patency is independent of manufacturer,128-130 unaffected by an external wrap
around the graft,131 and is not affected by wall
thickness.131,132 The provision of a cuff or hood
at the venous outflow to enlarge the outflow and
reduce shear stress has produced only a marginal
increase in graft patency.133-136 To control inflow
or shear stresses, a variety of tapers have been
examined at both arterial and venous anastomoses. There seems to be little effect from using a 6to 8-mm graft compared with the standard straight
6 mm.137 A straight 8 mm also can be used and
gives the highest flows.138 Arterial tapers are
used to restrict inflow and reduce the risk for
steal syndrome. Their effectiveness is questionable, and they may negatively affect patency and
survival.139
As previously discussed in CPG 2.1, a variety
of modifications to the graft or other materials is
available to the surgeon.113-119 Several studies
are available to guide the interested reader.140-142
Predictors for successful placement of AVGs
have been analyzed.143
The neointimal hyperplasia that produces stenosis has been considered to be, in part, a reaction to injury. No improvement in patency was
noted in an RCT that compared staples with
standard sutures at the vascular anastamoses.144
Use of nitinol surgical clips produces less intimal
damage than conventional sutures,145 but RCTs
showing a resulting change in outcome are
lacking.
It should be remembered that a short segment
of graft material can be used to develop a predominant fistula at the elbow.146
Catheters and Port Catheter Systems (CPG 2.4)

Basic Principles
1. Long-term catheter systemstunneled cuffed
catheters (TCCs) and tunneled port catheter
systemsshould have their tips within the
right atrium confirmed by fluoroscopy for
optimal flow.
2. Short-term catheter tips should be in the
superior vena cava (SVC) and confirmed by
using chest radiograph or fluoroscopically at
the time of placement before initiating dialysis therapy.
3. Uncuffed HD catheters should only be used
in hospitalized patients and for less than 1
week. Uncuffed femoral catheters should
only be used in bed-bound patients.
4. There should be a plan to: i) discontinue, or
ii) convert any short-term catheter to a longterm catheter within 1 week.
5. Long-term catheters and port catheter systems, if possible, should not be placed on the
same side as a maturing AV access.
6. Femoral catheters should be a suitable length
to deliver high-volume flow and be positioned to minimize recirculation. One that
does not reach the IVC frequently cannot
deliver 300 mL/min. Longer catheters (24 to
31 cm) are more likely to reach the desired
position, although there is more resistance
from the catheter length.
7. There currently is no proven advantage of 1
long-term catheter design over another, although this area is undergoing a great deal of
study. Catheters capable of a rapid BFR
(350 mL/min at prepump pressures not
more negative than 250 mm Hg) are preferred. Catheter choice should be based on
local experience, goals for use, and cost.
8. Pediatric exception: Some pediatric data
exist suggesting that the twin-catheter system may provide better performance than the
standard dual-lumen catheter configuration.
Please refer to the Pediatric Guidelines.
9. Dialysis port catheter systems may be used in
lieu of long-term catheters for a bridge
access or as a permanent access for patients.
Catheter devices can be defined according to
design, intent, and duration of use. For the entirety of the discussion, catheters will be referred
S197
to as acute short-term noncuffed catheters (NCCs)

or long-term TCCs intended as access for dialysis over weeks to months. The term right arterial
catheter should be avoided. They are either NCCs
and placed predominantly for acute use (3 to 5
dialyses within 1 week) or TCCs and placed
when the need for dialysis therapy is believed to
be longer than 1 week. Long-term catheters usually are tunneled. The catheters themselves usually are dual lumen and can be coaxial (now
unusual) or double D (most common) and are
either stepped (ie, the arterial and venous tips
are staggered by 1 to 2 cm) or split so that the tips
are not next to each other. Newer designs incorporate a spiral separator allowing either lumen
to be used as the arterial port catheter system.
Port catheter systems are a distinct kind of
catheter-based device system in which the catheter tubing is connected to a subcutaneously
placed device. In the only port device currently
in use for HD, access to the catheter lumen occurs
percutaneously by using a buttonhole technique.
These port catheter systems have a pinch valve
mechanism that requires special cannulation
needles to open the valves accessing the circulation.
Tunneled Cuffed Venous Catheters
Tunneled cuffed venous catheters have been
shown to have the following advantages, relative
to other access types:
1. They are universally applicable.
2. They can be inserted into multiple sites
relatively easily.
3. No maturation time is needed, ie, they can be
used immediately.
4. Skin puncture not required for repeated vascular access for HD.
5. They do not have short-term hemodynamic
consequences, eg, changes in cardiac output
or myocardial load.
6. They have lower initial costs and replacement costs.
7. They possess the ability to provide access
during a period of months, permitting fistula
maturation in patients who require immediate HD.73,147-155
8. They facilitate correcting thrombotic complications.147,156-158
S198
Tunneled cuffed venous catheters possess the

following disadvantages relative to other access
types:
1. High morbidity caused by:
Thrombosis148,156-158 and
Infection.30,148,159
2. Risk for permanent central venous stenosis

or occlusion.30,148,160,161
3. Discomfort and cosmetic disadvantage of an
external appliance.
4. Shorter expected use-life than other access
types.64,69,156,162
5. Overall lower BFRs, requiring longer dialysis times.163
Tunneled cuffed venous catheters should be
placed in an area where ultrasound guidance and
fluoroscopy are available. The preferred site is
the right internal jugular vein because this site
offers a more direct route to the right atrium than
the left-sided great veins. Catheter insertion and
maintenance in the right internal jugular vein are
associated with a lower risk for complications
compared with other potential catheter insertion
sites.164-166 Catheter placement in the left internal jugular vein potentially puts the left arms
vasculature in jeopardy for a permanent access
on the ipsilateral side. Catheter placement in the
left internal jugular vein may be associated with
poorer BFRs and greater rates of stenosis and
thrombosis.150,166 Femoral and translumbar vein
placement are associated with the greatest infection rates compared with other sites.167 Catheters
should not be placed in the subclavian vessels on
either side because of the risk for stenosis,30,168
which can permanently exclude the possibility of
upper-extremity permanent fistula or graft. Catheters should not be placed on the same side as a
slowly maturing permanent access. Catheterinduced central vein stenosis is related to the site
of insertion,169,170 number and duration of catheter uses, and occurrence of infection.170,171
Ultrasound insertion has been shown to limit
insertion complications.172-174 Evidence is sufficient to recommend that ultrasound guidance be
used for all insertions because it minimizes inadvertent arterial cannulation.175,176 Fluoroscopy
allows ideal catheter tip placement177,178 to maximize blood flow.179 At the time of placement, the
tip(s) of the catheter should be in the midatrium,

with the arterial lumen facing the mediastinum.
Use of catheters presents a conundrum because of the need for immediate vascular access
versus the risk for complications from prolonged
catheter use.180 Blood flow for dialysis obtained
from catheters typically is less than that obtained
from fistulae or grafts.2 Catheter length becomes
crucial when TCCs are placed in the femoral area
or through the translumbar or transhepatic
routes.181 Correlations between arterial prepump
or venous return pressures and dialyzer blood
flows are not linear.182,183 It is possible to develop an optimal relationship between catheter
length and diameter to achieve standardized (average, low, and high) blood flows regardless of
the lengths of the catheters by incorporating the
pressure-flow relationships, as well as Poiseuilles equation.183
Use of catheters as first choice for long-term
vascular access is discouraged because of infection, susceptibility to thrombosis, and inconsistent delivery of blood flow. In patients with
documented inadequate vascular access anatomy, use of catheters is feasible with both doublelumen184-188and twin-catheter systems.189-191
However, exceptions may occur in children.
In the United States, the demand for greater
blood flows to reduce treatment times has resulted in catheters with larger lumens being
placed. A variety of catheters can consistently
deliver a flow greater than 350 mL/min to the
dialyzer at prepump pressure of 200 to 250
mm Hg. The decision to use a step or a split
design should be decided by local preferences. In
general, all catheters will develop recirculation
at some point,182,192 particularly if the arterial
and venous blood tubing are reversed for any
reason.193 This is minimized by using a split-tip
catheter,194,195 but other designs are likely to
produce the same effect.
The decision to use the femoral vein for longterm access (catheter or graft) as reported by
some196,197 should be undertaken with great care.
Any patient who has the option of undergoing a
kidney transplantation should not have a femoral
catheter placed to avoid stenosis of the iliac vein,
to which the transplanted kidneys vein is anastomosed. The Work Group recommends the concept of shared governance in this type of decision,198 with both dialysis staff and transplant
team planning long-term access for such patients. There are no data on the effect of catheter
length from the femoral vein site. Although length
increases resistance, it also reaches anatomic
sites with greater IVC flow. If dialysis blood flow
is less than 300 mL/min from a properly placed
femoral catheter, guidewire exchange to a longer
catheter should be considered.
Noncuffed Double-Lumen Catheters
These catheters are suitable for percutaneous
bedside insertion and provide acceptable BFRs
(300 mL/min) for temporary HD.64,147,161,199,200
These catheters are suitable for immediate use,
but have a finite use-life and therefore should not
be inserted until they are needed.64,147,161 The
rate of infection for internal jugular catheters
suggests they should be used for no more than 1
week.60,64,147,161,201,202 Infection and dislodgment rates for femoral catheters require that
they be left in place for no more than 5 days
and only in bed-bound patients with good
exit-site care. To minimize recirculation, femoral catheters should be at least 19 cm long to
reach the IVC.203 The Work Group believes
that TCCs are preferred for longer durations of
HD therapy over NCCs because they are associated with lower infection rates and greater
BFRs.60,64,147,149,151-153,155,161,184,201-204 Shortterm catheters may be used for up to 1 week.
Beyond 1 week, the infection rate increases exponentially. Actuarial analysis of 272 catheters (37
TCCs versus 235 NCCs) showed a difference in
infection rates by 2 weeks.205 Infection rates per
1,000 days at risk for NCCs were more than 5
times as great as with internal jugular TCCs and
almost 7 times greater with femoral NCCs.205
Ultrasound-directed cannulation of NCCs
minimizes insertion complications, as it does
with TCCs, and should be used when available.206,207 Because most NCCs are placed at the
bedside, the need for a postinsertion chest radiograph after internal jugular or subclavian insertion is mandatory to confirm the position of
the catheter tip in the SVC and exclude such
complications as pneumothorax and hemothorax.28,64,147,151,208-212 Although there are no studies reporting on the safety of patients with NCCs
going home while awaiting placement at a dialysis center, the Work Group believes that the risk
for infection, inadvertent removal, hemorrhage,
S199
air embolism, and patient comfort mandates that

patient safety come first. Therefore, a patient
with an NCC should not be discharged. A shortterm catheter can be converted to a TCC if there
is no evidence of active infection.213
Port Catheter Systems
In an effort to surmount many of the infection
problems associated with long-term catheters, totally
implantable access systems have been designed.214,215
Clinical data support the use of subcutaneous HD
access systems as a bridge device216-218 in patient
populations at greater risk for fistula maturation
failure or needing longer periods to mature fistulae
(1 operation or multiple attempts need to be
made). Studies also documented the utility of subcutaneous HD access systems in catheter-dependent patients who have exhausted other access
options219 and in children.220 The most significant
limitation of these devices has been infection, particularly of the implantation pocket. Although these
can be treated successfully,221 prevention is key.
Recommended procedures for accessing and maintaining these devices are mandatory to achieve
optimal device performance.
Complications of catheter access are detailed
more fully in CPG 7, and accessing the patients
circulation is discussed in CPG 3.
LIMITATIONS
The recommendations made in this section are
based on the best currently available information
and basic principles of surgery. No RCTs will ever
be performed comparing the 3 access types available, nor should they be in view of the known risks
of catheters. However, developments in the future
of synthetic materials or the prevention of neointimal hyperplasia may permit such trials.
SUMMARY
Management of the patient who requires HD
access for KRT demands continuous attention
from the VAT. With the increase in incidence of
HD-dependent patients with CKD within our
population, the multidisciplinary KDOQI CPGs
and CPRs presented provide a pathway and strategy for HD access insertion and/or creation. The
most appropriate initial access depends on immediate need for HD, history and physical examination findings, and suitability of available veins in
the extremity. Percutaneous catheter-based ac-
S200
cess affords the luxury of immediate access and

absence of requirement for cannulation; however, these devices are plagued by their propensity for infection, thrombosis, inadequate blood
flow, andmost importantlydamage to large
central veins, leading to stenosis and jeopardizing
long-term permanent access. The fistula access,
while at times less successful in the immediate
short term, is always the preferred long-term
access type because of its greater longevity,
fewer interventions for maintenance, and lower
infection rates. The surgeon should focus on sites
distally on the extremity, reserving proximal sites
for potential future access insertions should the

initial access site fail. In the absence of a
suitable vein for a fistula, prosthetic access can
be considered. When all sites in the upper extremities have been exhausted, the lower extremity or chest should be considered for access
creation. Long-term catheters and port catheter
systems should be reserved for last except in
those with severe comorbidities, such as congestive heart failure (CHF) and severe peripheral
vascular disease (PVD), the very elderly, those
with inadequate vascular anatomy, or those with
limited life expectancy.
GUIDELINE 3. CANNULATION OF FISTULAE AND GRAFTS

AND ACCESSION OF HEMODIALYSIS CATHETERS AND PORT
CATHETER SYSTEMS
The use of aseptic technique and appropriate cannulation methods, the timing of fistula
and graft cannulation, and early evaluation of
immature fistulae are all factors that may
prevent morbidity and may prolong the survival of permanent dialysis accesses.
3.1 Aseptic techniques:
3.1.1 For all vascular accesses, aseptic
technique should be used for all
cannulation and catheter accession
procedures. (See Table 2.) (A)
3.2 Maturation and cannulation of fistulae:
3.2.1 A primary fistula should be mature,
ready for cannulation with minimal
risk for infiltration, and able to
deliver the prescribed blood flow
throughout the dialysis procedure.
(See Table 3.) (B)
3.2.2 Fistulae are more likely to be useable when they meet the Rule of 6s
characteristics: flow greater than
600 mL/min, diameter at least 0.6
cm, no more than 0.6 cm deep, and
discernible margins. (B)
3.2.3 Fistula hand-arm exercise should be
performed. (B)
3.2.4 If a fistula fails to mature by 6
weeks, a fistulogram or other imaging study should be obtained to determine the cause of the problem. (B)
3.3 Cannulation of AVGs:
Grafts generally should not be cannulated
for at least 2 weeks after placement and
not until swelling has subsided so that
palpation of the course of the graft can be
performed. The composite PU graft should
not be cannulated for at least 24 hours
after placement and not until swelling has
subsided so that palpation of the course of
the graft can be performed. Rotation of
cannulation sites is needed to avoid pseudoaneurysm formation. (See Table 4.) (B)
3.4 Dialysis catheters and port catheter systems:
Infection-control measures that should be

used for all HD catheters and port catheter systems include the following:
3.4.1 The catheter exit site or port cannulation site should be examined for
proper position of the catheter/port
catheter system and absence of infection by experienced personnel at
each HD session before opening and
accessing the catheter/port catheter
system. (B)
3.4.2 Changing the catheter exit-site
dressing at each HD treatment, using either a transparent dressing or
gauze and tape. (A)
3.4.3 Using aseptic technique to prevent
contamination of the catheter or
port catheter system, including the
use of a surgical mask for staff and
patient and clean gloves for all catheter or port catheter system connect, disconnect, and dressing procedures. (A)
RATIONALE
There is considerable evidence that the use of
maximal sterile precautions, as opposed to clean
aseptic technique, for cannulation of AV accesses
and catheter accession is both impractical and
unnecessary.222-225 However, the importance of
strict dialysis precautions226 and aseptic technique222 cannot be overemphasized in the prevention and minimization of all access infection.227
Despite the general acceptance of the importance
of standard precautions for hand washing and
glove changes, these simple acts to minimize
transmission of disease frequently are skipped.
An audit in a selection of Spanish HD units
examined opportunities to wear gloves and wash
hands per the standard preventive guidelines
(high-risk activities of connection, disconnection, and contact between patients during dialysis). Gloves were worn by only 19% and hands
were washed after patient contact on only 32% of
all occasions.228 Mandatory hand washing before patient contact occurred only 3% of the
time. A decade later, wearing of gloves improved
S201
S202
to 92%, but the practice of hand washing before

or after these patient-oriented procedures remained low at 36% after and 14% before such
activities.229 Greater adherence was found in
acute than in long-term HD units. A greater
patient-nurse ratio independently influenced
hand-washing rates. With the increasing microbial resistance to mainstream antibiotics,230 infection prevention must be considered the first rule
of vascular access maintenance.231 Data from
prospective studies in both Canada and the United
States clearly show that great variability exists

between centers in infection rates, indicating the
need to have not only a national registry, but also
a local (ie, in-center) infection surveillance program.232-234 Increased awareness at the individual center level is key to stemming access
infection and its extreme consequences, such as
endocarditis and metastatic infections (eg, spinal
abscesses), conditions that are disabling at best,
sometimes fatal, and prohibitively costly to
treat.235,236
CANNULATION OF FISTULAE AND GRAFTS AND ACCESSION OF DIALYSIS CATHETERS AND PORTS
In the effort to prevent infection, it is not only

staff that must be vigilant to potential breaks in
technique and the need for the appropriate use of
masks. Patients also must be taught that lapses in
their use of masks and poor personal hygiene are
known to increase their risk for infection. Patients with type 2 diabetes are at increased risk
for nasal staphylococcal carriage and catheterrelated bacteremia (CRB) as a result.237,238
Maturation and Cannulation of Fistulae
(CPG 3.2)
If the fistula is created with both adequate
inflow artery and outflow vein, the increased
flow in the vein should be immediately apparent
postoperatively, evidenced by larger appearance
and the presence of a continuous audible and
palpable thrill along the vein, as well as actual
flow measurements.126 Experienced staff should
examine the fistula and the outflow vein each
time the patient comes to dialysis to monitor the
maturation progress. Aspects of the physical examination are summarized in Table 5. The ability
of trained, experienced dialysis nurses to accurately predict eventual fistula maturity is excellent.72 This is even more reason to have a protocol for regular clinical examination in place in
dialysis centers to teach the skills of physical
examination (see CPG 4 and CPG 5) to all staff
members and assess the developing fistula and
not focus on the access in current use only. The
S203
optimal time to do this examination is before

fluid removal because hypotension can confound
the findings. Patients who are not yet on dialysis
therapy should be taught how to perform selfexamination and be given appropriate contact
information for questions and concerns. Poor
prognostic signs, such as significant decrease in
the thrill, should be referred immediately back to
the surgeon or the interventionalist for prompt
evaluation and intervention. At a minimum, all
newly created fistulae must be physically examined by using a thorough systematic approach by
a knowledgeable professional 4 to 6 weeks postoperatively to ensure appropriate maturation for
cannulation.239 The steps for cannulation are
summarized in Table 3.
Protocol for Initial Cannulation of AVFs
If the physical assessment has shown that the
fistula is adequately matured, ideally, the next
step is to perform a trial cannulation. In general,
the earliest that this situation occurs is when the
vein diameter is greater than 0.4 cm, has a flow
greater than 500 mL/min,59 and at least 1 month
has elapsed since fistula creation60 (Table 3). If
possible, the trial cannulation of the fistula should
be done on a nondialysis day. This serves to
eliminate any potential complications associated
with the administration of heparin.
If a trial cannulation is not possible, it is best
to perform the initial cannulation of the new
S204
access at the patients midweek HD treatment.

Performing the initial cannulation midweek helps
avoid such complications as fluid overload and
elevated chemistry test results associated with
the weekends.
To ensure that the needle is placed properly,
needle placement should be confirmed with a
normal saline flush before connecting the needles
to the blood pump and starting the pump. Blood
return alone is not enough to show good needle
placement. One option to easily check for proper
needle placement is the use of wet needles.
The needle is purged of air and the saline in the
attached syringe is used to flush the needle. If an
infiltration has occurred, the normal saline is less
harmful to the surrounding AVF tissue. The wet
needle also prevents the risk for a blood spray or
spill if dry needles are used for cannulation and
the caps are opened to bleed out the needle
from the air. The opening of the needle is a risk
for blood exposure to the dialysis team member,
patient, and nearby patients. For these reasons,
use of a wet needle is a safer technique for the

AVF, patient, and dialysis team members, especially for the initial AVF cannulation. This option
should be considered as part of the dialysis units
cannulation policy and procedures. The recommended procedure is described next.
1. Attach a 10-mL syringe filled with 8 mL of
normal saline solution to the AVF needle, but
do not prime the needle until immediately
before the cannulation.
2. Grasp the fistula needle by the butterfly wings
and prime the needle with normal saline
until all the air is purged. Clamp the needle
closed. Remove the protective cap and immediately proceed with the cannulation technique.
3. When the needle has advanced into the vessel,
blood flashback will be visible (the needle
may need to be unclamped to see the blood
flashback) and, if visible, aspirate back 1 to 5
mL with the 10-mL syringe. Flush the needle
with the normal saline solution and clamp.

The syringe must aspirate and flush with
ease. Monitor for signs or symptoms of
infiltration. Patients usually experience immediate sharp pain upon infiltration of saline or
blood into the tissues.
Needle selection for the initial cannulation
is critical. One method used to select the
appropriate needle size is a visual and tactile
examination. This examination allows the cannulator to determine which needle gauge would
be most appropriate, based on the size of the
vessels in the fistula. Alternately, place 17 G
and 16 G needles with the protective cap in
place (prevents a needle stick) over the cannulation site. Compare the vein size with the
needle size with and without the tourniquet
applied. If the needle is larger than the vein
with the tourniquet, it is too large and may
infiltrate with cannulation. Use the needle size
that is equal to or smaller than the vein (without the tourniquet) for the cannulation.
The smallest needle available, usually a 17
G, typically is used for initial cannulation
attempts. It is important to keep in mind that
blood flow delivered by a 17 G needle is
limited. Prepump arterial monitoring is recommended to ensure that blood pump speed does
not exceed that which the needle can provide.
Prepump arterial pressure should not exceed
250 mm Hg. Based on performance of the
fistula using a 17 G needle, the decision to
increase the needle size for subsequent cannulation can be made.
A needle with a back eye should always be
used for the arterial needle to maximize the flow
from the access and reduce the need for flipping
the needle.
1. Apply a tourniquet to the access arm.
2. After disinfecting the access site per unit
protocol, carefully cannulate the fistula, using a 25 insertion angle.
3. When blood flash is observed, flatten the
angle of the needle, parallel to the skin, and
advance slowly. When the needle is in the
vessel, remove the tourniquet and tape the
needle securely per unit protocol.
4. Assess for adequate blood flow by alternately aspirating and flushing the needle with
a syringe.
S205
5. Assess carefully for signs of infiltration, ie,

pain, swelling, or discoloration.
6. Repeat steps 1 to 5 for the second needle.
Cannulation Tips
1. A fistula that only works with a tourniquet in
place is still underdeveloped, usually because of inflow stenosis, and needs more
time or reevaluation by the VAT before use.
2. The combined use of the new fistula and
bridge vascular access (ie, TCC as a return
for blood) may be necessary until the fistula
is well developed.
3. Cannulation performed at a nonturnover time
may provide more time for the cannulation
procedure.
Infiltrations, Problems, and Tips
1. Infiltrations with the cannulation can occur
before dialysis, during dialysis with the blood
pump running, or after dialysis with the needle
removal.
2. Monitor closely for signs and symptoms of
infiltration. A quick response to a needle
infiltration can help minimize damage to the
access.
3. If the infiltration occurs after the administration of heparin, care must be taken to properly clot the needle tract and not the fistula.
In some cases, the decision to leave the
needle in place and cannulate another site
may be appropriate. The immediate application of ice can help decrease the pain and size
of the infiltration and may decrease bleeding
time.
4. Use caution when taping needles. Avoid
lifting up on the needle after it is in the vein.
An improper needle flip or taping procedure
can cause an infiltration.
5. If the fistula is infiltrated, it is best to rest
the fistula for at least 1 treatment. If this is
not possible, the next cannulation should be
above the site of the infiltration. If the patient
still has a catheter in place, restart use of the
fistula with 1 needle and advance to 2 needles,
larger needle size, and greater BFRs as the
access allows.
6. Proper needle removal prevents postdialysis
infiltrations. Apply the gauze dressing over
the needle site, but do not apply pressure.
S206
Carefully remove the needle at approximately the same angle as it was inserted. This
prevents dragging the needle across the patients skin. Using too steep of an angle
during needle removal may cause the needles cutting edge to puncture the vein wall.
7. Do not apply pressure to the puncture site
until the needle has been completely removed.
Fistula Hand-Arm Exercise (CPG 3.2.3)
Strengthening the forearm by using isometric
exercises to increase handgrip strength (eg,
squeezing a rubber ball with or without a lightly
applied tourniquet) may increase blood flow,
thereby enhancing vein maturation,240 and has
been shown to significantly increase forearm
vessel size,127,241 thereby potentially increasing
flow through a fistula created using these vessels.
The resulting muscle mass increase also may
enhance vein prominence. Exercise also may
decrease superficial fat. Correction of anemia
also could increase cardiac output and decrease
peripheral resistance, potentially resulting in increased flow through the fistula.
Access Flow for Dialysis in Fistulae (CPG 3.3)
After appropriate physical examination, a fistulogram is the gold standard for evaluating poor
maturation of the fistula if the patient is already
on dialysis therapy. Use of a non-nephrotoxic
contrast material, carbon dioxide, or ultrasound
should be used for patients not yet on dialysis
therapy. Although a fistula can maintain patency
at lower blood flows than grafts, thrombosis still
occurs and, if not treated promptly, can lead to
permanent loss of the access. Thrombosis rates
can be reduced by prospective correction of
problems.242 Delivery of dialysis is flow dependent: access flow less than 350 mL/min is likely
to produce recirculation and inadequate delivery
of dialysis. (See the HD Adequacy Guidelines.)
Some centers have used diluted contrast (25%),
and there are now published data that suggest
this diluted contrast does not adversely impact
residual kidney function.639 The images are of
acceptable quality. The appropriate intervention
for poor maturation is based on the cause of the
dysfunction and may involve PTA of stenotic
lesions, ligation or occlusion of vein branches (if
the problem is simply 1 major outflow
vein),122,243 and/or surgical intervention, including revision of the anastomosis.75,125,126

Cannulation of AVGs (CPG 3.4)
Manufacturers guidelines are based on the
time needed for tissue-to-graft incorporation,
thereby preventing the possibility of a hematoma
dissecting along the perigraft space. However,
most patients experience significant tissue swelling as a result of the tunneling, and palpation of
the graft is difficult for the cannulator and painful
for the patient.
Placement of a graft that allows for early
cannulation may be advantageous in the patient
who needs to begin dialysis therapy, has no other
access, and does not have veins suitable for a
fistula. Such an access would preclude the necessity to place a catheter while a conventional graft
matures. This type of graft confers no additional
benefit beyond early cannulation.114,119,128
Biografts are more likely to become aneurysmal than PTFE grafts,116 and cannulation techniques should be a hybrid of the techniques for a
graft regarding depth of the access and the texture of an autogenous vein. Rotation of cannulation sites should be observed in these grafts;
however, constant cannulation (buttonhole) has
not been studied.244
Dialysis Catheters and Port Catheter Systems
(CPG 3.5)
A dislodged (cuff exposed) or potentially infected catheter or exit site requires further assessment and possibly an intervention before being
deemed safe to access for dialysis.
The Centers for Disease Control and Prevention (CDC) has no preference between transparent dressing and gauze, except in the case in
which the exit site is oozing, which requires
gauze.222 Standard practice is to clean the exit
site and redress at each dialysis treatment (see
Table 6).
Airborne contaminants from both patients and
staff are prevented best by the use of surgical
masks when the catheter lumens or exit site are
exposed. Wearing clean gloves and avoiding
touching exposed surfaces further decreases the
risk for infection. Aseptic technique includes
minimizing the time that the catheter lumens or
exit site are exposed.222,226 Manufacturers directions should be adhered to for the types of
disinfectants recommended for safe cleaning of

the skin and device. If not contraindicated, the
CDC recommends use of 2% chlorhexidine,222
shown to be superior to povidone-iodine.245,246
Careful attention to hub care can decrease the
CRB rate almost 4-fold to a rate approaching 1
episode/1,000 days.247
LIMITATIONS
Many of the guidelines are based on good
standards of clinical practice. Those relating to
the use of aseptic technique follow the recommendations of the CDC. It is unlikely that
randomized trials will ever be done in this
area.
S207
4. Disinfect the cannulation sites per facility

protocol.
5. Using a sharp fistula needle, grasp the needle
wings and remove the tip protector. Align the
needle cannula, with the bevel facing up,
over the cannulation site and pull the skin
taut (Fig 1A).
Cannulate the site at a 25 angle; self-cannulators may require a steeper angle (Fig 1B). It is
important to cannulate the developing constantsite access in exactly the same place, using the
same insertion angle and depth of penetration
each time.* This requires that a single cannulator perform all cannulations until the sites are
well established.
AUXILLARY MATERIALS
Establishing Constant-sites in Native Fistulae
by Using Standard Sharp Fistula Needles
1. Perform a complete physical assessment of
the fistula and document the findings.
2. Select the cannulation sites carefully. Consider straight areas, needle orientation, and
ability of the patient to self-cannulate. Sites
should be selected in an area without aneurysms and with a minimum of 2 inches
between the tips of the needles.
3. Remove any scabs over the cannulation sites.
* Note: It takes approximately 6-10 cannulations using a

sharp needle to create a scar tissue tunnel track. Arterial and
venous sites may not develop at the same rate. Once a scar
tissue tunnel track is well formed, the antistick dull bevel
needles should be used. If standard sharp needles are used
beyond the creation of the buttonhole sites, the scar tissue
tunnel can be cut. More pressure and more needle manipulation will be required to advance the antistick needle down
the tunnel track. This can lead to bleeding or oozing from the
needle site during use on HD. The sharp needle can also
puncture the vessel at a new site or cause an infiltration. The
quick transition to the antistick needle will preserve the
integrity of the buttonhole site and prevent complications.
S208
Fig 1.
Fig 2.
Starting a buttonhole. Reproduced with permission from Medisystems Inc.
Cannulating a buttonhole. Reproduced with permission from Medisystems Inc.
A flashback of blood indicates the needle is

in the access. Lower the angle of insertion.
Continue to advance the needle into the fistula
until it is appropriately positioned within the
vessel (Fig 1C).
Securely tape the fistula needle (Fig 1D) and
proceed with dialysis treatment per facility
protocol.
Cannulating Mature Constant Sites in Native

Fistulae Using an Antistick Dull Bevel
1. Perform a complete physical assessment of
the fistula and document the findings.
2. Remove any scabs over the cannulation sites.
3. Disinfect the cannulation sites per facility
protocol.
4. Using an antistick dull bevel, grasp the
needle wings and remove the tip protector.
Align the needle cannula, with the bevel
S209
facing up, over the cannulation site and

pull the skin taut (Fig 2A).*
Carefully insert the needle into the established

cannulation site (Fig 2B). Advance the needle
along the scar tissue tunnel track. If mild to
moderate resistance is met while attempting to
insert the needle, rotate the needle as you
advance it, using gentle pressure (Fig 2C).
A flashback of blood indicates when the
needle is in the access. Lower the angle of
insertion. Continue to advance the needle into
the fistula until it is appropriately positioned
within the vessel.
Securely tape the needle set (Fig 2D) and proceed
with the dialysis treatment per facility protocol.
* Note: Ensure that the same needle insertion angle and

depth of penetration are used consistently for each cannulation of a constant site.
GUIDELINE 4. DETECTION OF ACCESS DYSFUNCTION:

MONITORING, SURVEILLANCE, AND DIAGNOSTIC TESTING
Prospective surveillance of fistulae and
grafts for hemodynamically significant stenosis, when combined with correction of the
anatomic stenosis, may improve patency
rates and may decrease the incidence of
thrombosis.
The Work Group recommends an organized monitoring/surveillance approach with
regular assessment of clinical parameters of
the AV access and HD adequacy. Data from
the clinical assessment and HD adequacy
measurements should be collected and maintained for each patients access and made
available to all staff. The data should be
tabulated and tracked within each HD center as part of a Quality Assurance (QA)/CQI
program.
4.1 Physical examination (monitoring):
Physical examination should be used to
detect dysfunction in fistulae and grafts
at least monthly by a qualified individual. (B)
4.2 Surveillance of grafts:
Techniques, not mutually exclusive, that
may be used in surveillance for stenosis in
grafts include:
4.2.1 Preferred:
4.2.1.1 Intra-access flow by using
1 of several methods that
are outlined in Table 7 using sequential measurements with trend analysis.
(A)
4.2.1.2 Directly measured or derived static venous dialysis
pressure by 1 of several
methods. (A) (Protocol provided in Table 8 for using
transducers on HD machines
to measure directly; criteria
in Table 9 for derived methods.)
4.2.1.3 Duplex ultrasound. (A)
4.2.2 Acceptable:
4.2.2.1 Physical findings of persistent swelling of the arm,
presence of collateral veins,
S210
prolonged bleeding after

needle withdrawal, or altered characteristics of
pulse or thrill in a graft.
(B)
4.2.3 Unacceptable:
4.2.3.1 Unstandardized dynamic venous pressures (DVPs) should
not be used. (A)
4.3 Surveillance in fistulae:
Techniques, not mutually exclusive, that
may be used in surveillance for stenosis in
AVFs include:
4.3.1 Preferred:
4.3.1.1 Direct flow measurements. (A)
4.3.1.2 Physical findings of persistent
swelling of the arm, presence
of collateral veins, prolonged
bleeding after needle withdrawal, or altered characteristics of pulse or thrill in the
outflow vein. (B)
4.3.1.3 Duplex ultrasound. (A)
4.3.2 Acceptable:
4.3.2.1 Recirculation using a non
urea-based dilutional method.
(B)
4.3.2.2 Static pressures (B), direct
or derived. (B)
4.4 When to refer for evaluation (diagnosis)
and treatment:
4.4.1 One should not respond to a single
isolated abnormal value. With all
techniques, prospective trend analysis of the test parameter has greater
power to detect dysfunction than
isolated values alone. (A)
4.4.2 Persistent abnormalities in any of
the monitoring or surveillance parameters should prompt referral for
access imaging. (A)
4.4.3 An access flow rate less than 600
mL/min in grafts and less than 400
to 500 mL/min in fistulae. (A)
4.4.4 A venous segment static pressure
(mean pressures) ratio greater than
0.5 in grafts or fistulae. (A)
DETECTION OF ACCESS DYSFUNCTION: MONITORING, SURVEILLANCE, AND DIAGNOSTIC TESTING
4.4.5 An arterial segment static pressure ratio greater than 0.75 in

grafts. (A)
RATIONALE
Definitions
The following terms will apply to HD vascular
access
Monitoringthe examination and evaluation of
the vascular access by means of physical
examination to detect physical signs that
suggest the presence of dysfunction.
Surveillancethe periodic evaluation of the vascular access by using tests that may involve
special instrumentation and for which an
abnormal test result suggests the presence of
dysfunction.
Diagnostic testingspecialized testing that is
prompted by some abnormality or other medical indication and that is undertaken to diagnose the cause of the vascular access
dysfunction.
Purpose of Access Surveillance
Vascular access function and patency are essential for optimal management of HD patients.
Low BFRs and loss of patency limit HD delivery, extend treatment times, and, in too many
cases, result in underdialysis that leads to increased morbidity and mortality.248 Between 1991
and 2001, the incidence of vascular access events
in patients undergoing HD increased by 22%.249
In long-term AV accesses, especially grafts,
thrombosis is the leading cause of loss of vascular access patency. Thrombosis increases health
care spending7,250 and adversely affects
QOL,162,250-253 and vascular accessrelated complications account for 15% to 20% of hospitaliza-
S211
tions among patients with CKD stage 5 undergoing HD.7,12,252 Prevention of access dysfunction
by maintaining adequate flow and preventing
thrombosis translates into a policy of Dialysis
Dose Protection. (See the KDOQI HD Adequacy Guidelines.) It is not feasible for any one
individual to manage all aspects of access care.
Multidisciplinary teams should be formed at each
HD center,254-256 with a VAT coordinator, if
possible. Whatever the teams size and composition, its most important function is to work
proactively to ensure the patient is receiving an
adequate dialysis dose by maintaining access
function and patency.
The basic tenet for vascular access monitoring
and surveillance is that stenoses develop over
variable intervals in the great majority of vascular accesses and, if detected and corrected, underdialysis can be minimized or avoided (dialysis
dose protection) and the rate of thrombosis can
be reduced. Whether prospective monitoring and
surveillance can prolong access survival currently is unproven. However, it fosters the ability
to salvage vascular access sites through planning, coordination of effort, and elective corrective intervention, rather than urgent procedures
or replacement.257 A number of monitoring and
surveillance methods are available: sequential
access flow, sequential dynamic or static pressures, recirculation measurements, and physical
examination.
Failure to detect access dysfunction has consequences on morbidity and mortality.248,249 In a
recent study of 721 randomly selected patients
from all 22 long-term HD units in northeast
Ohio, barriers found to significantly (P 0.001)
and independently relate to inadequate dialysis
dose delivery were patient noncompliance, low
S212
dialysis prescription, catheter use, and access

thrombosis.253 Every 0.1 decrease in Kt/V was
independently and significantly (P 0.05) associated with 11% more hospitalizations, 12% more
hospital days, and a $940 increase in Medicare
inpatient expenditures. Vascular accessrelated
complications accounted for 24% of all hospital
admissions.258 The reader is referred to the
KDOQI HD Adequacy Guidelines for additional
information on the importance of achieving the

prescribed dialysis dose with regard to mortality.
Asymptomatic, but hemodynamically significant, stenoses usually are detected through a
systematic monitoring and surveillance program.
Detection of such stenoses is important to prevent progression to a functionally significant
stenosis, currently defined as a decrease of greater
than 50% of normal vessel diameter, accompa-
S213
Fig 3. Pressure profiles in grafts (top) and fistulae (bottom). Symbols: P, pressure; P, change in pressure; R,
resistance; QAC, access flow; A, arterial; V, venous. Figure adapted from Sullivan K, Besarab A: Strategies for
maintaining dialysis access patency. Chapter 11. In Cope C (ed): Current Techniques in Interventional Radiology
(ed 2). Philadelphia, PA, Current Medicine, 1995, pp 125-131.
nied by hemodynamic or clinical abnormality,

such as abnormal recirculation values, elevated
venous pressures, decreased blood flow, swollen
extremity, unexplained reduction in Kt/V, or elevated negative arterial prepump pressures, that
prevent increasing to acceptable blood flow.259
This definition evolves from an analysis of hemodynamics and clinical correlation.
Normal Hemodynamics
Access flow and pressure are related in a
permanent AV access through the relationship:
QA = P/R
The driving force for access flow, QA, is the

pressure gradient, P, between the artery and
central veins. This driving force tends to be the
same for both fistulae and grafts. Within the
constraints imposed by the arterial anastomotic
site, the ultimate access flow in mature accesses
tends to be similar in fistulae and grafts.260,261
What differs is the rate of maturation. Grafts
reach their maximum flow rate in a matter of

days to weeks, as opposed to fistulae, which may
require weeks to months to mature.71,138,262-264
This difference in achieving maximum flow may
explain the difference in the incidence of immediate steal between the 2 access types, with the
fistulae permitting more time for adaptation to
occur.
The pressure profile differs in the 2 access
types. As shown in Fig 3, the pressure decrease
profile in a graft progressively decreases along
the length of the graft. At both anastomoses,
there are pressure gradients, even in the absence
of stenosis (illustrated as the luminal incursions).
Within the body of the graft, there is a 20- to
30-mm P that is the effective driving force.265-267
Conversely, in a fistula, the preponderance of
the arterial pressure is dissipated within the first
few centimeters of the access; pressures in the
arterial segment are only approximately 20%
of those in the feeding artery.265-267 Fig 4 shows
the difference in profiles.
S214
1.0
0.9
0.8
Graft
0.7
Arterial
Cannulation
Sections
Intra Access 0.6

Pressure 0.5
Ratio
Venous
Cannulation
Sections
0.4
0.3
0.2
0.1
Native Fistula
0
Artery
Art. Limb
Ven. Limb
Location
The IAP ratio refers to the actual pressure at

the site of measurement divided by the mean
arterial blood pressure (MAP). The effective P
in the fistula generally is only 8 to 10 mm Hg,
frequently 25%, and seldom more than half those
noted in grafts. Despite these differences in pressure profiles, access flow in grafts and fistulae
are approximately equal at 6 months267 because
the overall P is the same. However, fistulae
unlike graftshave an intact endothelial lining
that allows them to actively dilate and remodel
over extended periods. As a result, progressive
flow increases are limited only by cardiac factors. Fistulae also differ from grafts in having
side branches that reduce resistance to flow (parallel circuits). However, multiple accessory veins
can limit the development of the major superficial
vein needed for cannulation (see CPGs 1 and 2).
Ligation of accessories or spontaneous occlusion
of side branches within a fistula results in an
access that hemodynamically mimics the profile
of a graft.
It is immediately apparent that 2 anatomic
factors determine access function: (1) quality
and (2) physical dimensions of the artery and
vein. The major determinant of QA in a given
patient will be determined by the capacity of the
artery to dilate and its general health. In general, arteries at more distal sites have less capacity to deliver flow than more proximal sites, ie,
radial brachial axillary femoral. Arteries
that are calcified or affected by atherosclerosis
will result in lower flow accesses whether supplying a fistula or a graft. If the artery is healthy,
Central Vein
Fig 4. IAPs within normal

grafts and fistulae. Reprinted
with permission: Besarab A, Frinak S, Aslam M: Pressure measurements in the surveillance of
vascular accesses. In Gray R
(ed): A Multidisciplinary Approach for Hemodialysis Access. Philadelphia, PA, Lippincott Williams & Wilkins, 2002,
Chapter 21, pp 137-150.
flow capacity will be determined by the characteristics of the vein used in access construction. Too
small a vein will limit the flow in both a fistula
and graft. Unfortunately, arterial disease is not
uncommon; access inflow stenosis occurs in one
third of the patients referred to interventional
facilities with clinical evidence of venous stenosis or thrombosis.268 This is much greater than
has been traditionally reported.10,24,105,108,269
Thus, it is very important to assess the access by
using physical examination early after its construction. Because flow and pressure measurements are not performed routinely until the access is cannulated, initial assessment of the access
depends on the physical examination, which can
detect many problems in a fistula.
Effect of Stenosis on Hemodynamics: Access
Flow, IAP, Access Recirculation, and
Physical Examination
In grafts, the majority of stenoses develop
in the venous outflow, frequently right at or
within several centimeters of the venous anastomosis.10,24,105,108 Lesions within the graft also
occur, and most accesses have more than 1 lesion
at any 1 time.10,266,267,269 The pathophysiological state of graft failure arises from neointimal
hyperplasia. In a fistula, there may be ischemic
effects, as well as injury resulting from recurrent
cannulation and subsequent fibrosis. Stenoses in
a fistula tend to occur at the surgical swing sites
(including the arterial anastomosis) or the puncture zone of the vein. The outcome is the same in
both fistulae and grafts: a reduction in access
S215
Fig 5. Effect of venous outlet stenosis on pressure profile. Reproduced with permission from Medisystems Inc.
flow rate. However, the effect on IAP differs

according to access type and site of stenosis. As
illustrated in Fig 5, an outlet stenosis in a graft
will increase the pressure at all locations upstream from the stenosis. Conversely, an inflow
lesion will decrease all pressures downstream of
the stenosis. An intragraft stenosis between the
needles will decrease flow while increasing pressure upstream and decreasing pressure downstream of the lesion.
In a fistula, pressure profiles depend on the
location of the lesion and the presence or absence
of collateral or accessory veins. Arterial inflow
lesions that develop after acceptable maturation
1.0
are detected more easily by using QA, the inability

to deliver blood flow to the dialyzer, reductions in
adequacy, and recirculation measurements270,271
than by IAP measurements. Intra-access pressure
(PIA) with inflow lesions tends to remain unchanged or decrease as QA decreases over time.272
An outflow lesion will produce a pressure profile
similar to that seen in grafts; the magnitude of
the pressure elevation is dictated by the number
of venous tributaries. Not uncommonly, in upperarm fistulae, there is spontaneous or deliberate
occlusion of side branches (as with transposition); an outflow lesion then produces a pressure
profile very similar to that of grafts.
Access Recirculation
Region
0.9
Graft Thrombosis
Region
0.8
ARTERIAL
0.7
Intra Access
Pressure
Ratio
Pressure
Thresholds
0.6
0.5
VENOUS
0.4
0.3
0.2
Region of Good
Function
0.1
0.0
0
500
1000
1500
2000
2500
Intra Access Flow (mL/min)
3000
3500
Fig 6. Effect of graft venous

outlet stenosis. Reprinted with
permission: Besarab A: Blood
Purif
2006;24:77-89
(DOI:
10.1159/000089442). S. Karger
AG, Basel.
S216
For a given graft access, the access flow pressure profile resulting from venous outflow stenosis is illustrated in Fig 6.
An initially well-functioning graft with an
access flow approaching 2 L/min (usually in the
upper arm) will manifest decreasing flow as both
the arterial and venous pressure slowly increase
with the development of outflow tract stenosis.
Hemodynamic simulations indicate that flow decreases by less than 20% until the stenosis process produces a 40% to 50% decrease in luminal
diameter. Thereafter, flow decreases rapidly as
the degree of stenosis increases to 80%.273 Because the intimal hyperplasia process progresses
with time, its detection requires sequential measurements of flow or pressure or both to detect a
threshold at which action should be taken. Note
that the graft thrombosis region by flow shown in
the hatched area is reached long before a graft
would show recirculation and therefore affect the
delivered dose of dialysis. Access recirculation
in grafts is a late manifestation of stenosis and a
poor predictor of imminent thrombosis; it occurs
in less than 20% of cases.271 For this reason, the
Work Group no longer recommends recirculation measurements in grafts. Conversely, because fistulae typically can maintain patency at
much lower flows than grafts, recirculation occurs much more frequently; 1 study reported that
about one third of fistulae had a significant recirculation fraction by using an ultrasound dilution
technique.271 When recirculation was measured
by using the Fresenius Body Thermal Monitor
(BTM), the device was able to detect fistulae
requiring revision with a sensitivity of 81.8%
and specificity of 98.6%, although the BTM
method does not differentiate between access
and cardiopulmonary recirculation.274
The main issue for most HD clinics is which
surveillance test best meets their needs. The
following discussion summarizes the methods
available and the reason for the ordering of the
test by the Work Group in CPGs 4.2 and 4.3.
Physical Examination (Look, Touch, Listen)
Physical examination can be used as a monitoring tool to exclude low flows associated with
impending graft failures.275,276 There are 3 components to the access examination: inspection
(look), palpation (touch), and auscultation (listen).276 The Work Group is convinced that the
basic skills have been largely abandoned in favor

of technology and need to be taught to all individuals who perform HD procedures.277 Simple
inspection can reveal the presence of aneurysms.
A fistula that does not at least partially collapse
with arm elevation is likely to have an outflow
stenosis. This logic applies to the case in which a
tourniquet does not appear necessary for optimal
cannulation. Strictures can be palpated and the
intensity and character of the bruits can suggest
the location of stenosis. Downstream stenosis
also produces an overall dilation of the vein,
giving it aneurysmal proportions.
In grafts, one can determine the direction of
flow in a loop configuration and avoid inadvertent recirculation by erroneous needle insertion.
In a patent graft in which blood flow is less than
the blood pump flow setting, the presence of
recirculation can be detected easily by occluding
the graft between the needles and looking at the
arterial and venous pressures. A strong pulse too
often is misinterpreted as being evidence of good
flow, rather than the opposite. A pulse suggests
lower flows.278 In a newly thrombosed graft, the
arterial pulse often is transmitted into the proximal end of the graft, leading to erroneous cannulation, which could be avoided easily by simply
using a stethoscope to confirm absence of flow. A
bruit over an access system and its draining veins
that is only systolic is always abnormal; it should
be continuous. An intensification of bruit suggests a stricture or stenosis.278 Palpable thrill at
the arterial, middle, and venous segments of the
graft predicts flows greater than 450 mL/min.278
A palpable thrill in the axilla correlates with a
flow of at least 500 mL/min.279 The character of
pulse and thrill correlates with postintervention
outcome for stenosis.280 The interested reader is
referred to additional literature for further enjoyment and enlightenment.271
Of note, a preliminary study has shown that
sounds acquired by using electronic stethoscopes
that were then digitized and analyzed on a personal computer could be used to characterize
stenoses.281 Stenotic vessel changes were found
to be associated with changes in acoustic amplitude and/or spectral energy distribution. Acoustic parameters correlated well (r 0.98; P
0.0001) with change in degree of stenosis, suggesting that stenosis severity may be predicted
from these parameters. Furthermore, acoustic
parameters appeared to be sensitive to modest

diameter changes of 20%. These results suggest
that, in the future, readily available computerized
analysis of vascular sounds may be useful in
vessel patency surveillance.
Access Flow
Access flow can be measured by using a number
of techniques, as summarized in Table 7. Doppler
ultrasound (DU)282-287 and MRA46,54,288-290 are
direct techniques for assessing flow in vascular
accesses. Duplex Doppler ultrasound (DDU) requires an accurate measurement of the crosssectional diameter of the access. The method is
operator dependent and subject to error caused by
variation in cross-sectional area and the angle of
insonation.291,292 Because turbulence in the access
can limit the accuracy of the measurements, flow
measurements can be made in the feeding artery
(usually the brachial) or distal part of the access.272
The difference between the flow in the artery and
the access usually is less than 10%. Despite these
operator-related and equipment-related limitations, sequential measurements have been used
extensively to detect and refer patients for interventions or predict the risk for thrombosis. In
addition to flow measurements, both DDU and
MRA provide anatomic assessment and direct
evidence for the presence, location, and severity
of access stenosis. However, the current cost of
these methods, as well as the inability to make
measurements during HD, limits their use. Research and development are needed to simplify
procedures and reduce costs.
Indirect methods use an indicator dilution technique; the major techniques include ultrasound
dilution (UDT),272,293 a timed ultrafiltration
method294; transcutaneous access flow rate
S217
(TQA), a method that can be performed during

or independently of HD295,296; glucose infusion297,298; differential conductivity299,300; and,
finally, ionic dialysance.301,302 All the methods
described, except for TQA, variable flow DU,
and glucose infusion, require measurements with
the blood tubing initially in the normal position
and then reversed to induce access recirculation.
With UDT, access flow is measured from the
induced recirculation when the needles are reversed. The software calculates the area under
the curves (AUC) as a measure of recirculation.
Q A = Q BP (1/R 1)
where QBP is blood pump flow and R is degree of

recirculation induced. The UDT method is the
only one that independently measures actual flow
in the tubings, rather than accepting the readings
on the HD system for the roller pump.
Pitfalls in measurement have been identified
and recently reviewed.303 Accurate calibration of
the blood pump is essential with most methods,
but frequently is not performed regularly. The
indicator injection also must not affect flow in
the access itself. The technique must separate
access recirculation from cardiopulmonary recirculation that is unavailable with high-efficiency
dialysis. Finally, access flow is a function of the
ratio of systemic to access resistance, and measurements should be conducted within the first
90 minutes of dialysis to minimize effects of
hypotension. Table 10 summarizes the recommendations for access flow surveillance. All
methods require some modification/interruption of the dialysis treatment, except perhaps
ionic dialysance.
Table 10. Access Flow Protocol Surveillance

Access flow measured by ultrasound dilution, conductance dilution, thermal dilution, Doppler
or other technique should be performed monthly. The assessment of flow should be
performed during the first 1.5 hr of the treatment to eliminate error caused by decreases in
cardiac output or blood pressure related to ultrafiltration/hypotension. The mean value of 2
separate determinations (within 10% of each other) performed at a single treatment should
be considered the access flow.
Graft
If access flow is <600 mL/min in a graft, the patient should be referred for fistulogram.
If access flow 1,000 mL/min that has decreased by more than 25% over 4 mo, the patient
should be referred for fistulogram.
S218
With ionic dialysance, alteration of the proportioning ratio of dialysate to water alters the dialysis
sodium concentration, as well as blood sodium
level. The resulting change in blood sodium level,
as well as the change in dialysate conductivity,
serves as the indicator for calculating QA.
QA = [(D Dr)/(D Dr)] [1/(blood water fraction)]
where D is the dialysance in the normal blood

tubing position and Dr is the value with the tubing
reversed. As with UDT, ultrafiltration should be
minimized and recirculation must be absent in the
normal blood tubing configuration. At flow rates
less than 1,000 mL/min, the method consistently
underestimates access flow compared with
UDT.301,302
With the timed ultrafiltration method, a difference in hematocrit (Hct) is the indicator
QA = Qf.H0(Hr Hn)
where Qf is ultrafiltration rate, H0 is initial Hct,

and H is change in Hct induced by ultrafiltration with the tubing in reversed (r) and normal
(n) positions. The method correlates well with
UDT.
The TQA method has not been extensively
used.
The variable-flow DU method304-306 measures
velocity between the 2 dialysis needles at varying dialyzer blood flows. Using a conservation of
volume approach, a computer algorithm solves
for access flow without the need to measure the
cross-sectional diameter of the access.306 The
methods accuracy is best at flows less than
1,000 mL/min.
The easy availability of urea as a marker has
led some to use it as an indicator substance to
calculate recirculation and therefore derive flow.
Such measurements underestimate flow compared with conductivity.307 Although QA can be
estimated by using the urea method, the sensitivity and specificity of a low value is a poor
predictor of access outcome and may lead to
cost-ineffective investigations.307
Variation in access flow during dialysis308 can
result from changes with cardiac output,309-311
MAP,309,310 and changes in blood volume.311
Access flow can increase by up to 11% or decrease by up to 30% from initial values by the
end of dialysis, potentially impairing the ability
of QA to predict impending vascular access failure.312 Access resistance remains stable during
treatments and could be a more useful measure
of vascular access performance as part of an
access surveillance program. For all these reasons, it is recommended that measurements be
made early in the HD treatment.
Access Pressure
Measurements of pressure from the HD circuit
were not originally designed to assess access
(dys)function, either directly or indirectly. Rather,
they were used to calculate the mean transmembrane pressure so that the appropriate ultrafiltration rate could be achieved. Volumetric control
systems made these measurements unnecessary.
Pressure measurements were retained to provide
safety. During HD, blood is drawn out of the
vascular access through the arterial needle by the
blood pump on the HD machine.
Prepump pressures are now used to determine
whether the prescribed dialyzer blood flow can
be delivered without generating excessive negative pressures. At high negative pressures, the
collapse of the pump segment reduces the true
flow and true flow may differ from displayed
flow by up to 15%.313,314 The degree of collapse
is affected, in turn, by differences among manufacturer tubing sets.315 These considerations are
important in evaluating the relationship of flow
to access pressure. Excessively negative pressures can result in hemolysis.316 Differences in
blood tubing performance are of obvious importance to manufacturers, leading to improvements. The newer generations available may
show little differences with the improved blood
flow delivered during dialysis, benefiting all
patients.
When blood passes through the dialyzer, the
blood traverses the venous drip chamber and
returns to the patients vascular access though
the venous needle. The pressure required to infuse blood back into the access is recorded as the
venous drip chamber pressure (VDP) or DVP.
The original purpose of VDP was to detect infiltration or malpositioning of the needle because
partial occlusion of the needle orifice or infiltration would quickly increase and sound an alarm.
There still is no alarm for detecting accidental
withdrawal of the needle outside the body; exsanguinations have occurred.
One of the components of the VDP is the

actual IAP (PIA). As shown in Fig 4, the IAP
(PIA) in a graft is usually less than 50% of MAP.
Most of this pressure decrease occurs at the
arterial anastomosis, unless there is intragraft
stenosis. When outflow stenosis develops (eg,
because of neointimal hyperplasia at or downstream from the graft-vein anastomosis), PIA
increases and flow decreases. When PIA increases to greater than 50% of MAP (PIA/MAP
greater than 0.50), graft flow commonly has
decreased into the thrombosis-prone range of
600 to 800 mL/min (Fig 6), and the presence of
stenosis is likely. If a stenosis develops in the
body of a graft between the areas used for arterial
and venous limb cannulation, PIA at the venous
needle remains normal or can even decrease
despite increasing stenosis.270,271 Stenosis at the
arterial anastomosis of both grafts and fistulae
causes PIA to decrease. Conversely, a high basal
PIA can be observed with a healthy artery in the
absence of stenosis when the flow delivered is in
excess of the venous systems initial capacity.
Because of these pressure confounders, there is
little correlation between a single measurement
of flow and PIA/MAP.317 Serial measurements of
pressure in each patient are more valuable than
isolated measurements of either PIA or PIA/MAP
ratio. This is illustrated in Fig 7. Note that the
arterial pressure ratio is approximately 0.2 units
higher than the venous ratio and the baseline
initial value for both ratios is lower than usual
because of the use of a 4- to 6-cm taper at the
arterial anastomosis that limits inflow to prevent
steal.
S219
In fistulae, blood entering the venous system

returns through multiple collateral veins. As a
consequence, PIA/MAP in a fistula is, on average, less than in a graft and may not increase
with outlet stenosis. The test, therefore, theoretically is less valuable as a surveillance tool for
stenosis in fistulae. However, most elbow-level
fistulae do not have or lose collaterals and often
behave hemodynamically like grafts. In both
fistula types, elevation of PIA/MAP indicates the
development of a stenosis in the venous outflow
from the access and is associated with an increased
probability of access failure or need for revision to
provide adequate blood flow for HD.10,265,266,317
Like access flow, measurement of PIA has
evolved.
Direct measurement of static pressure. Pressures in the access can be measured directly at
the site of cannulation in the arterial and venous segments of the graft or fistula by using a
pressure-measuring device. Although one can
use a sophisticated electronic method (separate
transducers placed in line with the dialysis tubing)265-267 as originally reported, a much simpler
technique uses a device consisting of a hydrophobic Luer-Lok connector that connects a standard
dialysis needle to an aneroid manometer.318
IAPs also can be measured by using the pressure transducers of the dialysis machine. Under
conditions of no blood flow and no ultrafiltration,
the only difference between the pressure measured by an independent transducer and the machine transducer is that resulting from the height
differential between the location of the machine
transducers and the access. The two pressures
New Access in 73 y/o Diabetic Male
1
0.8
Angioplasty
Fig 7. Relationship of IAP ratio

to access flow. Reprinted with permission: Besarab A: Blood Purif
2006;24:77-89
(DOI:
10.1159/
000089442). S. Karger AG, Basel.
800
0.75
Access
Pressure 0.6
Ratio 0.5
1000
ml/min
Arterial
Venous
600
0.4
400
0.2
200
0 1
Flow
9 10 11 12 13 14
Time (weeks)
S220
can be equated by either moving the access to the

level of the venous drip chamber or moving the
drip chamber to the level of the access. Alternatively, the height difference, h, can be measured and the additional pressure (0.76 h) can
be added to the machine transducer reading.319
Table 8 provides the sequence of steps for
measuring static pressure. It is important that the
pressure transducers be calibrated accurately.
Interpretation. Venous outlet stenosis can
be detected with venous PIA alone. Trend analysis is more useful than any single measurement.
The greater the degree of stenosis at the outlet,
the greater the venous pressure ratio. Strictures
between the area of arterial and needle cannulation cannot be detected by measuring venous
(PIA) pressure alone.271 Detection of these lesions requires simultaneous measurement of pressures from both the arterial and venous needles.
Central stenoses that have collateral circulation
may have normal pressures, but these usually
present with significant ipsilateral edema. Accesses can be classified into the categories listed
in Table 9. Using the equivalent PIA ratios from
the arterial or venous needles, the criteria must
be met on each of 2 consecutive weeks to have a
high likelihood of a 50% diameter lesion.
Patients who develop a progressive and reproducible increase in venous or arterial segment
greater than 0.25 units more than their previous
baseline, irrespective of access type, also are
likely to have a hemodynamically significant
lesion. Intra-access strictures usually are characterized by the development of a difference between the arterial and venous pressure ratios
greater than 0.5 in grafts or greater than 0.3 in
native fistulae. Because fistulae can remain patent
at much lower flows than grafts, sequential measurement of conductance (ie, a blood pump/
absolute value of prepump pressure), particularly
at maximum prepump pressure permitted by the
system, can detect fistula dysfunction and stenosis.320,321
Although measuring static pressure as described in Table 8 is straightforward, it is tedious,
time consuming, and not user friendly. Staff
frequently bypass crucial steps, leading to poorquality data being collected and recorded. This
has led to a reevaluation of statistical methods to
use the information within the dynamic pressure.
VDP or DVP and extraction of equivalent

PIA. DVP (also referred to as VDP under conditions of blood flow) is measured routinely during
HD in the presence of extracorporeal blood flow.
These pressures can be read off the dialysis
machine or stored electronically with the blood
pump running. One of the components of DVP is
the actual IAP (PIA) because the pressure needed
to return blood into the access is the sum of that
needed to overcome the needle resistance and
IAP. DVP/VDP has been used to detect venous
outlet problems,322 but measurements are meaningful only if obtained at the beginning of dialysis and usually with low BFRs (50 to 225 mL/
min) because at high BFRs, much of the resistance
to flow is from the needle, and not the vascular
access.
Measurement of DVP is less sensitive and
specific than direct measurements of access flow
rates or static pressure measurements. The reason for poorer performance results from many
factors, including the lack of consistency about
which flow should be the standard, varying in
studies from 50 to 425 mL/min322-325; differences in needle design (wall thickness, actual
length); and effects of viscosity affected chiefly
by Hct. In addition, use of DVP as a method also
requires that studies be performed to standardize
the critical value as a function of needle gauge,
length, and inner diameter (wall thickness). Consistency requires that a uniform flow value to test
at be determined.
Indirect methods for determining PIA. Most
HD systems can store the blood pump values
associated with DVP. A computerized algorithm
has been developed that uses an empirical formula to calculate an equivalent PIA from the
DVP made during treatment. During a given
treatment, many measurements at different flows
can be made along with the simultaneous MAP,
and an average equivalent PIA/MAP can be calculated. The average values can be trended with
each treatment and examined for an upward
trend. When the ratio exceeds 0.55, the access
has a greater risk for clotting.326 This technique
has been commercialized, providing monthly reports and trend analysis. Its ability to predict
thrombosis is equal to that of direct measurement
of PIA. In the evolution of the IAP ratio to detect
stenosis, the discriminator value has progressively increased from 0.4 using the ratio of
systolic pressures, 0.45 using the ratio of mean

pressures measured directly, 0.5 using transducers on the machine, and finally 0.55 when deriving PIA from the dynamic pressure.
Recirculation: Method, Limits, Evaluation,
and Follow-Up
Recirculation is the return of dialyzed blood to
the dialyzer without equilibration with the systemic arterial circulation. The technique is not
recommended as a surveillance tests in grafts.
However, up to one third of dysfunctional fistulae will show an increase in recirculation that
may be manifested as a decrease in urea reduction ratio (URR) or Kt/V, but this occurs late.
Access recirculation in a properly cannulated
access is a sign of low access blood flow192 and a
marker for the presence of vascular access stenosis, particularly in fistulae. Such stenoses can be
corrected, preventing underdialysis and decreasing the risk for access thrombosis.327 Access
recirculation can be measured accurately by using UDT328 or conductivity.299 A K-dilution
method is more reliable than the 2-needle ureabased method and compared with UDT, has
100% sensitivity, 95% specificity, 91% positive
predictive value, and 100% negative predictive
value.329 In analogy to access flow measurement, glucose infusion also has been used to
measure recirculation.330
The amount of recirculation occurring with
reversed needles usually is substantial (20%),
as confirmed when the tubings are deliberately
reversed for access flow measurements. However, even with ideal sample timing and proper
cannulation, laboratory variability in urea-based
measurement methods will produce variability in
calculated recirculation.331 Therefore, individual
recirculation values less than 10% by using ureabased methods may be clinically unimportant.
The Work Group believes that they do not prompt
further evaluation. Values greater than 10% by
using urea-based recirculation measurement
methods require investigation.
New loop grafts are at particular risk for
reversed needle placement because of a lack of
familiarity with the access anatomy. When possible, an access diagram that depicts the arterial
and venous limbs should be obtained from the
surgeon who constructed the access to aid in
proper cannulation. If not available, the anatomy
S221
can be deduced by temporarily occluding the

graft at its midportion. The portion retaining a
pulse is the arterial limb.
Comparison of Surveillance Methods
Accuracy and Reproducibility
Only 1 study has directly compared many of
the available flow techniques with regard to
reproducibility.332 Reproducibility is assessed by
using duplicate measurement at unchanged conditions, whereas accuracy is determined under
controlled change in a relevant measurement
condition (2 different blood flows for ultrasound,
changed sensor position in TQA). An accurate
method produces the same result. In most studies
using some form of dilution or concentration of
an indicator, UDT is taken as the reference
method for comparison because it most accurately separates cardiopulmonary from access
recirculation and independently measures blood
flow to the dialyzer. Ultrasonic flow is approximately 10% to 15% less than indicated by the
blood roller pump, the magnitude correlating
inversely with negative arterial blood tubing pressure.333 It shows very high reproducibility, for
measurement at the same extra corporeal blood
flow, QB (correlation coefficient of duplicate
measurement, r 0.97; n 58) and measurement at 2 different QB (r 0.97; n 24),
justifying its current status of a reference method
in QA evaluation.334 The coefficient of variation
usually is less than 8%.327 Slightly lower reproducibility is found with thermal dilution (TD) or Fresenius BTM at the same QB (r 0.92; n 40) and 2
different QB (r 0.851; n 168); this inaccuracy
can be overcome by increasing the number of
measurements with averaging. Use of the simple
Krivitski formula, QA QBP (1/R 1) in TD
(which measures total recirculation, ie, sum of
access recirculation and cardiopulmonary recirculation) brings about underestimation of QA,
which progressively increases from QA of about
600 mL/min upward. High correlation of TD
versus UDT (r 0.95; n 54) makes TD a
viable clinical alternative in QA evaluation. Consistently different QA values obtained at 2 different QBs should prompt closer investigation of
anatomic conditions of the access. Good correlation (r 0.87; n 27) also is found between QA
measured by using DDU and UDT.332,335
S222
The direct TQA method showed very high

reproducibility (r 0.97; n 85); however,
only for unchanged sensor position. Correlation
of QA measured at 2 different sensor positions
was much worse (r 0.73; n 22). Correspondence of TQA with UDT was satisfactory (r
0.81; n 36). Skilled and experienced operators
are a must with this method. Similar results were
found by others who reported, for triplicate measurements, coefficients of variation of 7.5% for
differential conductivity by hemodynamic monitoring (HDM), 9.1% for UDT, and 17.4% for
optodilution by ultrafiltration (OABF).336 Repeatability data (variation among temporally separated measurements) showed values of 10.6%
for HDM, 13.0% for UDT, and 25.2% for OABF.
Fewer comparisons have been made with the
other methods. Glucose pump test (GPT) flow
measurements correlate well with UDT measurements and have acceptable replicability.298
Ionic dialysance or conductivity dialysance, as
it frequently is referred to, is being used increasingly by clinicians to measure access flow in
both the United States and Europe, particularly
with Fresenius dialysis delivery systems, in which
the methodology is built into the machines as
on-line clearance. Major refinements have been
made to increase the replicability and accuracy
of this method at lower BFRs, but preliminary
reports comparing the measurements with UDT
have not yet been formally published.
Detection of Stenosis or Predicting Thrombosis
As important as accuracy of a method is, the
goal of any surveillance method is to detect
access stenosis in a timely way so that appropriate correction can be undertaken before thrombosis. A hemodynamically significant stenosis is
the substrate for thrombosis by reducing flow,
increasing turbulence, and increasing platelet activation and residence time against the vessel
wall.
Table 11 summarizes the available studies in
which the presence and degree of stenosis was
confirmed by using angiography. As reflected by
data in the table, DDU is most accurate because
it can directly visualize the degree of stenosis.
When DDU is used to measure flow, rather than
identify anatomic stenosis, sensitivity and specificity decrease. A quick survey of the table clearly
shows that none of the tests consistently achieves a

sensitivity of 90% and specificity greater than 80%.
Because of the accuracy of DDU in detecting
the presence of a 50% (by diameter) stenosis,337
it has been used in some studies as the reference
method, rather than angiography, to avoid invasive procedures. As shown in Table 12, UDT has
good accuracy, whereas physical examination
has high specificity, but poor sensitivity.
Table 13 shows that DDU and UDT are equivalent in predicting thrombosis.
Data are still limited for some of the newer
surveillance tests. Table 14 summarizes the observations. There is excellent correlation between
flow measurements by means of GPT and UDT
(r 0.9).298 GPT also has been validated recently as a surveillance technique in grafts. Using DDU to assess for the presence of stenosis,
GPT picked up severe stenosis in 14 of 112 grafts
(100% sensitivity) and performed better than
UDT (86% sensitivity).297 Specificity was less
than 60% for both tests. Diagnostic efficiency
(percentage of grafts with agreement between
test result and factual situation) was 90% and
80% (P 0.056) for GPT and UDT, respectively. MRA also can provide anatomic338 and
QA measurements, but it is prohibitively expensive. Intravascular ultrasounds (IVUSs) can be
used to evaluate abnormalities in fistulae297 and
may find abnormalities not seen with angiography. However, it is too expensive for routine use,
but may be a valuable adjunct in evaluating the
efficacy or completeness of the intervention on
the access.
An important issue in fistulae is the assessment of such abnormalities as aneurysms and
extreme tortuosity in well-functioning fistulae.
DU is a very valuable technique, particularly in
fistulae; in addition to measuring flow and identifying stenosis directly, it can detect other abnormalities in presumably well-functioning accesses.345 Pseudoaneurysms do not decrease
access flow; QA is significantly greater than the
mean (1,204 mL/min) in fistulae with aneurysms, calcifications, and tortuous vessels and,
of course, less in those with stenosis. No correlation is noted between QA or the presence of
stenosis with fistula age. Some degree of stenosis
was detected in 64% of fistulae, with 57% of
stenoses located in the anastomotic region; 22%,
in the vein junction; 19%, at 1 or both ends of the
S223
S224
S225
S226
aneurysm; and 2%, in the remaining region of

the efferent vein.345 Chronic venous occlusion
with collateral veins was detected in 6% of
fistulae.345 Aneurysms were observed in 54% of
fistulae with a mean diameter of 12.4 mm, with
96% of them located at puncture sites. Ten patients had a small thrombus in an aneurysm and
at puncture sites. Thus, although a high level of
abnormalities is present in well-functioning mature fistulae, the abnormalities are not sufficient
to affect the functioning of the HD fistula and, in
most cases, need only observation. More advanced lesions require therapy (see CPG 5).
DDU is a particularly useful modality to determine reasons for maturation failure of fistulae 4
to 12 weeks after construction,346 even if preoperative vein mapping had shown adequate vein
size (3 mm) and outflow. Using the criteria of
peak systolic velocity ratio (SVR) of 2:1 or
greater to detect a 50% or greater stenosis involving arterial inflow, and venous outflow and an
SVR of 3:1 or greater to detect a 50% or greater
anastomotic stenosis, DDU of 54 native fistulae
(23 brachiocephalic, 14 radiocephalic, and 17
basilic vein transpositions) found that 20% were
occluded and 26% were normal. The remainder
showed a variety of lesions: 16 fistulae (42%),
venous outflow; 13 fistulae (34%), anastomotic;
and 2 fistulae (5%), inflow stenoses. In 7 fistulae
(18%), branch steal with reduced flow was found.
Sensitivity, specificity, and accuracy of DDU in
detecting stenoses of 50% or greater were 93%,
94%, and 97% compared with fistulography,
respectively. Because many of these fistulae cannot be studied by using other surveillance techniques, routine DDU surveillance of primary
fistulae should be considered to identify and
refer for correction of flow-limiting stenoses that
may compromise the long-term patency and use
of the fistula.
Inflow stenosis is more common than previously believed (ie, 5% of cases). An inflow
stenosis is defined as stenosis within the arterial
system, artery-graft anastomosis (graft cases),
artery-vein anastomosis (fistula cases), or juxtaanastomotic region (the first 2 cm downstream
from the arterial anastomosis) with a 50% or
greater reduction in luminal diameter judged by
comparison with either the adjacent vessel or
graft. Such stenosis was found in nearly a third
of 223 cases referred to an interventional facility
serving several centers.268 All referred accesses

had a coexisting stenosis on the venous side. The
frequency of inflow stenosis was less in grafts
(29% of cases) than fistulae (40 of 101; 40%). Of
these, 22 (54%) had a coexisting lesion on the
venous side. Access inflow stenosis thus is much
greater than traditionally reported in cases referred to interventional facilities with clinical
evidence of venous stenosis or thrombosis.
Attempts to combine the various surveillance
techniques have been performed. One study found
no difference in the ability to detect stenoses in
grafts from using QA by UDT compared with
static venous pressure ratios.340 However, DVPs
were of little use. Use of a PIA compared with QA
also was examined in 125 grafts followed up for
80.5 patient-years.347 Standardized monitoring
of either PIA, QA, or the combination of both,
followed by subsequent corrective intervention,
decreased the thrombosis rate in grafts compared
with a historical control rate.348 Rates in 2 separate parts of the study for thrombosis not preceded by a positive test result were 0.24 and 0.32
episodes/patient-year at risk compared wth a
historical rate greater than 0.7, respectively. The
surveillance strategies were equally effective in
decreasing thrombosis rates, and access survival
curves were not significantly different between
subgroups.347 Again, DVP alone was not useful
because either QA or PIA turned positive before
the dynamic pressure limit (150 mm Hg at 200
mL/min) was reached. Unlike these 2 studies
showing limited to no utility of DVP alone,
another study was able to find some utility for
DVP measurements for grafts.349 Stenosis greater
than 50% by diameter on fistulography or a
thrombotic event was defined as a vascular
access impairment episode, whereas stenosis
less than 50% or the absence of a thrombotic
event was defined as no vascular access impairment episode. By combined dynamic pressure
readings and flow surveillance (DVP 120 mm
Hg; QA 500 mL/min in fistulae and 650
mL/min in grafts or a decrease in QA 25%
compared with the highest previously measured
value were considered positive), improved sensitivity over flow alone for fistulae, but not grafts,
was observed.268 Sensitivity and specificity of
the combined surveillance protocol for fistulae
were 73.3% and 91%; in grafts, they were 68.8%
and 87.5%, respectively. The rate of thrombotic
events was less in patients with fistulae who

underwent early repair, but in grafts, the addition
of DVP did not decrease the thrombosis rate any
further than surveillance based on QA alone.
Finally, when UDT, DDU flow, DVP, and prepump pressure were examined as predictors of
thrombosis in 172 grafts, DVP used alone was
not predictive.285
In summary, available data suggest that the
utility of DVP at flows of 150 to 225 mL/min to
predict stenosis or thrombosis is limited or absent in grafts. Studies are needed to determine
whether the method retains any utility in fistulae.
Conversely, flow measurements, DDU assessment for stenosis, and static pressure measurements (direct or indirect by using computers) can
detect hemodynamically significant stenosis in
grafts and fistulae. Although the location of stenosis in fistulae (inflow) favors QA over PIA, no
direct comparisons have been made by using
DDU anatomic imaging or contrast angiography
to determine the accuracy of the techniques in
this access type. If the prescribed Kt/V is not
delivered in a patient who is using a fistula,
measurement of access flow should be performed
by using a recommended method (Table 7).
The Work Group believes there is insufficient
evidence to suggest 1 surveillance technique
from those listed in the guidelines as preferred
or acceptable because the choice at a particular
site is affected by many variables; chief among
these are access type, technology, effect of operator, and cost (usually labor). Although DDU
studies are predictive of access stenosis and the
likelihood for failure,350 frequency of measurement is limited by expense. In addition, interobserver variability in measurement of DDU flow
in some instances can reduce the reliability of
DDU flow measurement.351 Variation in the internal software used for calculating DDU flow
measurements by different manufacturers also is
a factor preventing standardization. Magnetic
resonance flow is accurate, but expensive. Both
DDU flow and magnetic resonance are difficult
to perform during HD sessions.
Conversely, flow measurements performed by
using UDT and other techniques can be done
on-line during HD, thereby providing rapid feedback. The same applies for PIA. Both access flow
and IAP techniques have been validated in prospective observational studies.10,322,347,349,352,353 Mea-
S227
suring static venous pressures is the least expensive method of surveillance for stenosis.322,354
Because of efficiency or cost, these methods are
listed as preferred. In-line access flow measurements (DDU) are available and have been improved in terms of accuracy and replicability.
However, there are no data yet on efficacy in
detecting stenosis or effect on thrombosis rate.
The Work Group believes that recirculation is
a relatively late predictor of access dysfunction
and, if used, has a minor role in fistulae only.
Nonurea-based recirculation measurements are
very accurate, but require specialized devices.
Unexplained decreases in delivered dialysis
dose, measured by using Kt/V or URR, frequently are associated with venous outflow stenoses.355 However, many other factors influence
Kt/V and URR, making them less sensitive and
less specific for detecting access dysfunction.
Inadequate delivery of dialysis dose is more
likely to occur with a fistula than a graft.
In primary fistulae, inadequate flow through
the access is the main functional defect predictive of thrombosis and access failure (defined as
thrombosis or failure to provide adequate dialysis dose). Indirect measures of flow, such as
dynamic and static venous dialysis pressure, may
be less predictive of thrombosis and access failure in fistulae compared with grafts. However,
measurement of recirculation becomes a more
useful screening tool in fistulae compared with
grafts because flow in fistulae, unlike grafts, can
decrease to a level less than the prescribed blood
pump flow (ie, 300 to 500 mL/min) while still
maintaining access patency.192,270,271 DDU may
be useful in fistulae.346 Comparative studies using HDM (QA, PIA) and DDU need to be performed before firm recommendations can be
made by the Work Group.
Regular assessment of physical findings (monitoring) may supplement and enhance an organized surveillance program to detect access dysfunction. Specific findings predictive of venous
stenoses include edema of the access extremity,
prolonged postvenipuncture bleeding (in the absence of excessive anticoagulation), failure of
the vein to collapse with arm elevation, and
changes in physical characteristics of the pulse
or thrill in the graft.108,354 Physical examination
is a useful screening tool to exclude low flow
(450 mL/min) in grafts with impending fail-
S228
Table 15. Patient Education Basics

All patients should be taught how to:
a.
Compress a bleeding access;
b.
Wash skin over access with soap and water daily and before HD;
c.
Recognize signs and symptoms of infection;
d.
Select proper methods for exercising fistula arm with some resistance to
venous flow;
e.
Palpate for thrill/pulse daily and after any episodes of hypotension,
dizziness, or lightheadedness;
f.
Listen for bruit with ear opposite access if they cannot palpate for any
reason.
All patients should know to:
a.
Avoid carrying heavy items draped over the access arm or wearing
occlusive clothing;
b.
Avoid sleeping on the access arm;
c.
Insist that staff rotate cannulation sites each treatment;
d.
Ensure that staff are using proper techniques in preparing skin prior to
cannulation and wearing masks for all access connections;
e.
Report any signs and symptoms of infection or absence of bruit/thrill to
dialysis personnel immediately.
ure.275,277,278 In the context of proper needle

position, an elevated negative arterial prepump
pressure that prevents increasing the BFR to the
prescribed level also is predictive of arterial
inflow stenoses.
When a test indicates the likely presence of a
stenosis, angiography should be used to definitively establish the presence and degree of stenosis. Currently, the Work Group is in agreement
with the Society for Interventional Radiology,
which recommends angioplasty if the stenosis is
greater than 50% by diameter. Angioplasty by its
very nature is a disruptive force on the vessel
and can injure endothelium and underlying
smooth muscle; each angioplasty can produce
benefit or harm. However, there have been no
large-scale trials to determine whether correction
of only hemodynamically significant lesions
(those associated with low access flows or
high pressures or a change in access flow or
pressure) is superior to correction of all stenosis
greater than 50%. At the time of intervention,
hemodynamic evaluation of each stenosis generally is not carried out.
Until such studies are conducted, the Work
Group believes that the value of routine use of
any technique for detecting anatomic stenosis
alonewithout concomitant measurement of access flow, venous pressure, recirculation, or other
physiological parametershas not been estab-
lished. Stenotic lesions should not be repaired

merely because they are present. If such correction is performed, then intraprocedural studies of
QA or PIA before and after PTA should be conducted to show a functional improvement with a
successful PTA.
The Patient as His or Her Own Surveyor
and Protector
The Work Group strongly advocates that all
patients should be taught the basics of how to
take care of their vascular access, including
steps in personal hygiene, cleanliness, avoidance
of scab picking, and so on, as discussed in Table 15.
In addition, patients should be taught where and
how to detect a pulse, where and how to feel
for a thrill, how to recognize infection, and
most importantlywhen to notify a member of
the dialysis staff of physician when the pulse or
thrill is absent. Delay in recognizing loss of
patency may influence the likelihood of restoring
patency.
The patient must be taught the reason for
avoiding 1-site-itis. Topical anesthetics should
be used judiciously if they help the patient comply with the policy of rotation of needle sites. To
avoid aneurysm formation, the patient should
insist on site rotation unless a buttonhole method
is being used in a native fistula. With the large
staff turnover ratios prevalent in HD units in the
United States, the patient must be diligent that

staff uses the proper aseptic techniques whenever the access is palpated, inspected, or cannulated.
Surveillance and Thrombosis
Nonrandomized Trials
In dialysis AVGs, thrombotic events result primarily, but not solely, from progressive venous
outflow stenosis.10,24,105,300,354,356-358 Thrombotic
events that cannot be resolved (ie, patency restored) are the leading cause of access loss. These
stenoses are caused by intimal and fibromuscular
hyperplasia in the venous outflow tract, typically
at the graft venous anastomosis,359-362 but can
occur in the body of the graft, as well. The details
of pathophysiology are beyond the limits of this
discourse except to state that, to date, promising
therapies in animal models have not yielded
success in humans. Possible future therapeutic
approaches have been summarized.363
As stenoses increase in severity, they produce
a resistance to flow, increasing PIA with an accompanying decrease in blood flow.266,318 Crosssectional studies using DDU or UDT showed a
progressive increase in risk for access thrombosis during a follow-up interval of 1 to 6 months.
The absolute value of the critical or threshold
QA depends on the method used. Average access
flow rates obtained by DDU are less (600 to 900
mL/min)252,335,364 than those measured by using
magnetic inductance (mean, 1,100 mL/min) or
UDT (mean range, 900 to 1,200 mL/min).336
Studies also showed that when access flow is
measured repeatedly, trends of decreasing flow
add predictive power for the detection of access
stenosis or thrombosis.284-286,300,311,318,349,364-371
Grafts with access blood flows less than 600 to 800
mL/min have a greater rate of access thrombosis
than grafts with flow rates greater than 800 mL/
min.268,284,286,300,311,318,372 In addition to this absolute value, a decrease of 25% in access flow from a
previous stable baseline greater than 1,000 mL/
min has been suggested as a criterion for further
diagnostic evaluation of grafts to detect the presence of at least one 50% (by diameter) stenosis
within the access.285,364,369-371 In general, the
interval that is present to correct the lesion in
grafts before the access thromboses varies inversely with the access flow, being less than 8
S229
weeks at a flow less than 450 mL/min371 and 3

months at flow rates of 600 to 800 mL/min.285
Although many centers refer patients directly
for angiographic study without intermediate studies when a critical value is obtained, there may
be a role for DDU anatomic scanning.282 Because fistulae maintain patency at lower flows
than grafts, criteria for intervention in fistulae are
not as well established. Values of 400 to 650
mL/min have been proposed. Higher values increase sensitivity, but lose specificity. Some fistulae can maintain patency for years at flows less
than 400 mL/min, but with high-efficiency/
high-flux dialysis, the treatment time requires
extension. Conversely, intervention with PTA
almost invariably triggers a process of repeated
need for PTA because the frequency of at least 1
abnormality in an access is so high. Optimal care
of a particular patient requires individualization,
and not rigid application of protocols.
Because the development and severity of stenosis evolve to varying degrees among patients
over time, the likelihood of detecting a hemodynamically significant stenosis increases if the
surveillance test is repeated frequently. Therefore, surveillance should be performed at intervals of 1 month or lessdepending on the complexity and costto detect access dysfunction
early and permit sufficient lead time for intervention. The Work Group concluded that trend analysis could be as important as any individual
value for any monitoring technique. Because
access pressure measurements do not require
complex technology, their frequency should be
greater than that for access flow measurements.
For direct measurement of access pressure, a
frequency of twice a month appears sufficient.
With methods more likely to produce variation
under real-world clinical practice conditions (such
as those from the HD system transducers), measurements once every 1 to 2 weeks are needed to
detect a trend. The Work Group believes that
measurement of static pressures every 2 weeks is
the minimum frequency that is compatible with
current HD staffing patterns. Derived static pressures need analysis from all available treatments
for the month. Dynamic pressures should not be
performed in grafts.
Measurement of access flow also was shown
to be a valuable tool in determining the success
of a therapeutic intervention. Failure to increase
S230
access flow by at least 20% after an intervention

reflects failure of the intervention to correct the
underlying problem.282,369 In 1 study, values
before PTA and QA correlated with the subsequent decrease in QA (P 0.005).282 It was
observed that QA increased after PTA (from 371
mL/min to 670 mL/min in a total of 65 grafts and
33 fistulae), but in a substantial percentage of
cases, not to levels greater than 600 mL/min. QA
values before PTA and the increase in QA values
correlated with long-term outcomes, whereas angiographic results did not. Unfortunately, in many
of the studies, the literature has admixed results
for flow and outcome for both fistula and graft,
making it impossible to sort out effects in grafts
as opposed to fistulae. The Work Group believes
there may be important differences in the response of fistulae (compared with grafts) to PTA,
and surgical approaches also may influence outcomes. Research is needed in this area.
A large number of studies that used historical
control data showed that prospective surveillance/
monitoring to detect stenosis reduces the rate of
thrombosis, although at the expense of increased
procedures.10,322,343,373,374 A seminal study
showed that a prospective program of dynamic
pressure surveillance could detect stenotic lesions, reduce thrombosis rates, and reduce access
replacement rates.322 In that study, fistulae and
grafts were not differentiated with respect to
efficiency of the test. Unfortunately, criteria developed with needles designed for low-efficiency dialysis (16 G; pressure 150 mm Hg at
a flow of 200 mL/min) were not adapted for
larger bore needles (15 G and 14 G), and other
investigators did not independently standardize
their pressure criteria for the flow actually used
(150 to 225 mL/min). Accordingly, results of this
study generally were not duplicated.340 Until
such standardization is performed, DVP alone is
not recommended. Additional studies using static
pressure,10 physical examination alone,352,353
DVP combined with access recirculation plus physical finding,373 DDU,284,374 and QA341,366,369,375 all
showed a 41% to 67% reduction in thrombosis rate
in grafts. A review suggested that the effect may be
smaller in fistulae.374
Receiver operating characteristic (ROC) curve
analyses have been performed to assess the overall performance of access flow and pressure in
predicting thrombosis. Although in some studies,
a good AUC of 0.84 to 0.9 was achieved for

access flow, overall AUC for 10 studies was only
0.7.376 Addition of a change in flow increased
AUC slightly to 0.82, but not to the value of 0.9
that an excellent test would produce (90% sensitive and 80% specific).377 The sum of QA and
QA did not perform any better than PIA/MAP.
Unfortunately, the high baseline rate of thrombosis in grafts precludes a sensitive test that can
unequivocally predict the likelihood of thrombosis or not over a specified time. During a 3-month
observation period, grafts can clot in the absence of
any stenosis and do so at flows equal to those that
remain patent, 1,209 versus 1,121 mL/min.270 In
these cases, PIA remains unchanged. Grafts that
required intervention or that thrombosed because
of an anatomic lesion had much lower access
flows, 656 mL/min and 609 mL/min, respectively. At flows greater than the threshold, the
incidence of thrombosis may be as high as 20%
per 6-month period.375 Even with flows in the
highest quartile, greater than 1,395 mL/min, another study found a thrombosis rate of 9% during
a period of 3 months (annualized risk, 36%).285
Until more studies are performed that examine
the frequency of thrombosis in the absence of
stenosis and the frequency of patency in the
presence of arterial or venous stenosis, the debate will go on.378-381
At the present time, the development of a
surveillance abnormality should be correlated
with other findings on physical examination and
adequacy of HD. Any abnormality (QA, PIA)
must be confirmed before further referral for
either DDU (stenosis characterization) or angiography.
Randomized Trials of Preemptive PTA in
Response to Surveillance
To date, only a small number of studies have
been performed prospectively to assess the impact of surveillance on outcome. These are summarized in Table 16.
The concept that prophylactic or preemptive
PTA would decrease graft thrombosis initially
was refuted.382 In a study of 64 patients identified to have a 50% stenosis by using DDU and
confirmed by using angiography, preemptive PTA
produced no change in 6-month or 12-month
patency. Because of confounding issues, a subanalysis was performed on 21 virgin grafts that
S231
S232
had not previously clotted or required intervention.383 Preemptive PTA from the time of diagnosis of stenosis reduced the thrombosis rate from
0.44 to 0.10 episodes/patient-year at risk. Both
rates were much less than the rate of 0.91 in
patients without virgin grafts. However, sample
size was small (n 19). It should be noted that
in this study, only anatomic assessment was
obtained; no hemodynamic assessment was
performed.
The small number of patients in this and all
other prospective studies has limited assessment
of efficacy. One prospective study using PIA was
performed.384 Although the study itself was well
designed, it was flawed by the surveillance technique. A preliminary study was performed in
which monthly static venous pressure measurements were made during 2 consecutive HD sessions in all patients with a functioning upperextremity graft in 2 HD units during a 16-month
period. The method for deriving PIA ratio differed significantly from that originally described10
in that the ratio of systolic PIA pressure to MAP
was calculated instead of the ratio of systolic PIA
pressure/systolic blood pressure.385 The net effect of this error is that the ratio would have been
falsely elevated and the threshold value of 0.4
would not apply. In addition, measurements were
performed less frequently than recommended.
Not surprisingly, ROC analysis yielded curves
with areas less than 0.64.383 Subsequently, 64
patients with elevated static venous pressure
measured in an upper-extremity graft were randomized to intervention (underwent angiography
and repair of identified stenoses) or observation
(underwent stenosis repair only in the event of
access thrombosis or clinical evidence of access
dysfunction), with the primary end point being
access abandonment. Information on the fraction
in the interventional group who had a stenosis is
not provided. There was no difference in access
abandonment (14 patients in each group) during
the 3.5-year study period or in time to access
abandonment. However, the proportion of patients with a thrombotic event was greater in the
observation group (72%) than the intervention
group (44%; P 0.04), but overall thrombosis
rates were similar in the groups (ie, there was a
difference in mean number of thrombosis per
graft in the intervention group in grafts that did
thrombose). Not detailed was the number of
PTAs that had to be performed in both groups

during the entire study period.
Two randomized studies examined the role of
access surveillance by using QA. In the first, it
was found that stenotic lesions are detected more
commonly by using QA (QA 650 mL/min or
20% decrease in QA) than routine surveillance
(physical examination plus DVP 150 mm Hg)
in a total of 112 patients, but elective PTA for
lesions greater than 50% did not alter thrombosis
rate.386 Rates of graft loss, times to graft loss,
and overall thrombosis rates did not differ between the 2 groups. However, interventions increased by 30% in the intervention group. In the
second study, 101 patients were randomized to 3
groups: control, low surveillance QA (Transonics) monthly, or stenosis detection by using DDU
quarterly.387 Referral for angiogram was based
on clinical characteristics in all, less than 600
mL/min in QA, and greater than 50% diameter in
the DDU stenosis groups. QA was measured in
all 3 groups, but only used for referral in the flow
surveillance group. Baseline thrombosis rates
were 0.7 and 0.9/patient-year in the control and
QA groups, respectively. Results showed that QA
increased PTA rate marginally (from 0.22 to
0.33/patient-year) and had no effect on thrombosis rate. Stenosis surveillance increased PTA to
0.65/patient-year and reduced thrombosis rates
to 0.5/patient-year, but did not affect 2-year
survival rate. QA less than 600 mL/min was
found in 4 of 18, 4 of 31, and 3 of 11 in the
control, QA, and stenosis groups in grafts that
clotted (overall, 11 of 60). However, 26 of 35 in
the stenosis group underwent PTA for stenosis.
In both studies, 20% to 25% of accesses clotted
without a surveillance abnormality, ie, in a totally unexpected manner.
However, the overriding conclusion of the
studies that surveillance using QA and PTA in
response to a threshold value of QA did not alter
graft survival has to be tempered by the small
sample size of the studies, the comparator used,
and the efficacy of the intervention. Graft survival studies require a sample size of approximately 700 patients to detect an increase in graft
survival of 1 year or a 33% difference in survival
by 3 years (H. Feldman, personal communication). None of the studies had 20% of this number. It also is important to assess the skill level of
the staff. If the staff can reach a positive predic-
tive value of 80% (when stenosis is present and

needs intervention) through use of physical examination and clinical characteristics (monitoring), use of a surveillance method that has a
sensitivity of only 80% will produce no benefit
over good monitoring. Determining which lesions should undergo correction has already been
addressed. Elastic recoil needs to be assessed.
In contrast to grafts, the role of QA surveillance appears to be more established in fistulae.
In 1 study, the positive predictive value, negative
predictive value, sensitivity, and specificity of
ultrafiltration method for vascular access stenosis (OABF CritLine III) were 84.2%, 93.5%,
84.2%, and 93.5%, respectively. Vascular access
thrombosis rates in 50 QA surveillance patients
were less (2 of 50 patients; 4%) than in 94
patients not followed up with flow measurements
(16 of 94 patients; 17%; P 0.024).242
In a second study, a 5-year RCT of blood flow
surveillance and preemptive repair of subclinical
stenoses (1 or both of angioplasty and open
surgery) with standard monitoring and intervention based upon clinical criteria alone was carried out in Italy.388 Surveillance with blood pump
flow (QB) monitoring during HD sessions and
quarterly QA or recirculation measurements identified 79 fistulae with angiographically proven
significant (50% diameter) stenosis that were
then randomized to either a control group (intervention done in response to a decrease in delivered dialysis dose or thrombosis; n 36) or
preemptive treatment group (n 43). KaplanMeier analysis showed that preemptive treatment decreased the failure rate (P 0.003) and
the Cox hazards model identified treatment (P
0.009) and greater baseline QA (P 0.001) as
the only variables associated with favorable outcome. Access survival was significantly greater
in preemptively treated than control fistulae (P
0.050), with greater postintervention QA as the
only variable associated with improved access
longevity (P 0.044). This study provides evi-
S233
dence that active blood flow surveillance and

preemptive repair of subclinical stenosis reduce
the thrombosis rate and prolong the functional
life of mature forearm fistulae and that QA greater
than 350 mL/min before intervention portends
a superior outcome with preemptive action in
fistulae.
Finally, in a third study, a prospective controlled open trial to evaluate whether prophylactic PTA of stenosis not associated with access
dysfunction improves survival in native virgin
radiocephalic forearm fistulae, 62 stenotic functioning fistulae (ie, able to provide adequate dose
of dialysis) were enrolled: 30 were allocated to
control, and 32, to PTA.389 Kaplan-Meier analysis showed that PTA improved fistula functional
failure-free survival rates (P 0.012) with a
4-fold increase in median survival and a 2.87fold decrease in risk for failure. A Cox proportional hazards model identified PTA as the only
variable associated with outcome (P 0.012). It
was found that PTA increased QA by 323 mL/
min (P 0.001), suggesting that improved fistula survival is the result of increased access
flow. PTA also was associated with a significant
decrease in access-related morbidity, halving the
risk for hospitalization, central venous catheterization, and thrombectomy (P 0.05). Because
prophylactic PTA of stenosis in functioning forearm fistulae improves access survival and decreases access-related morbidity, it supports the
use of a surveillance program for the early detection of these stenoses.
LIMITATIONS
At present, a vascular surveillance program to
identify patients who may benefit from angiography and PTA appears to offer the most likelihood
of benefit and may reduce thrombosis rates.
However, we need additional studies to examine
the characteristics of stenoses that produce incomplete responses to PTA so that patients are adequately treated at the time of their interventions.
GUIDELINE 5. TREATMENT OF FISTULA COMPLICATIONS

Appropriate interventions for access dysfunction may result in an increased duration
of survival of the AVF.
5.1 Problems developing in the early period
after AVF construction (first 6 months)
should be promptly addressed.
5.1.1 Persistent swelling of the hand or
arm should be expeditiously evaluated and the underlying pathology
should be corrected. (B)
5.1.2 A program should be in place to
detect early access dysfunction, particularly delays in maturation. The
patient should be evaluated no later
than 6 weeks after access placement. (B)
5.2 Intervention:
Intervention on a fistula should be performed for the presence of:
5.2.1 Inadequate flow to support the
prescribed dialysis blood flow. (B)
5.2.2 Hemodynamically significant venous stenosis. (B)
5.2.3 Aneurysm formation in a primary
fistula. Postaneurysmal stenosis that
drives aneurysm also should be corrected. The aneurysmal segment
should not be cannulated. (B)
5.2.4 Ischemia in the access arm (B).
5.3 Indications for preemptive PTA:
A fistula with a greater than 50% stenosis
in either the venous outflow or arterial
inflow, in conjunction with clinical or
physiological abnormalities, should be
treated with PTA or surgical revision. (B)
5.3.1 Abnormalities include reduction in
flow, increase in static pressures,
access recirculation preempting adequate delivery of dialysis, or abnormal physical findings. (B)
5.4 Stenosis, as well as the clinical parameters used to detect it, should return to
within acceptable limits following intervention. (B)
5.5 Thrombectomy of a fistula should be attempted as early as possible after thrombosis is detected, but can be successful even
after several days. (B)
S234
5.6 Access evaluation for ischemia:

5.6.1 Patients with an AVF should be
assessed on a regular basis for
possible ischemia. (B)
5.6.2 Patients with new findings of ischemia should be referred to a vascular access surgeon emergently. (B)
5.7 Infection:
Infections of primary AVFs are rare and
should be treated as subacute bacterial
endocarditis with 6 weeks of antibiotic
therapy. Fistula surgical excision should be
performed in cases of septic emboli. (B)
RATIONALE
Initial Problems (CPG 5.1)
Minor swelling normally is found postoperatively after placement of an AVF regardless of
location and type of anastomosis. This physiological swelling disappears within the first week.
Swelling of the hand or area of the fistula should
be treated with hand elevation and patient reassurance. Because prevention is always preferable to
therapy, a major aspect of preventing postoperative swelling is to rest the arm. Persistent swelling requires further attention to exclude major
outflow obstruction. Hematoma, infection, and
venous hypertension also should be excluded by
clinical examination277,391,392; noninvasive ultrasound examination helps confirm extravasations
and hematomas or purulent infiltrations, as well
as strictures/stenoses of the venous outflow
tract.45,124,393 Although angiography (fistulography) can show a venous stenosis causing venous
hypertension, DDU is the preferred diagnostic
method because it avoids any diagnostic cannulation of the newly created AVF and thereby avoids
iatrogenic damage of the thin wall of the freshly
arterialized vein. If a stenosis is found, it should
be treated with a balloon angioplasty.
Persistent hand edema usually follows a sideto-side anastomosis for creating the fistula and
invariably results from downstream stenosis forcing the flow through venous collaterals. This
process can produce classic chronic venostasis
with skin ulceration. The lesion should be treated
early by ligation of the tributaries. If delayed
healing of the wound is noted in patients, the
surgical technique should be examined closely.
TREATMENT OF FISTULA COMPLICATIONS
The surgical technique to close the skin preferably should use degradable suture material in an
exclusively subcutaneous position supported by
externally applied sterile adhesive strips to minimize the thickness of the scar.
Risk for bleeding and hematoma formation is
greatest in the early stages of use of a fistula and
greater in brachiobasilic fistulae than other types
of fistulae at the wrist or elbow.77 Manifestations
of an infiltration or hematoma aside from the
obvious discoloration and swelling include the
presence of high-frequency bruit on auscultation
and a difference in intravascular pressure on
palpation.277,391,392 Because hematoma may lead
to access loss,77 hematomas should be treated
surgically if they are compromising the lumen of
the arterialized vein (producing stenosis).388 In
the absence of luminal compromise by physical
examination or DDU, the access should be rested
until the margins of the fistula are again well
demarcated.
Proficiency in cannulating fistulae is suboptimal in the United States despite considerable
efforts to remedy the situation.120,394-396 One can
improve needle design to minimize trauma397
and develop methods to increase the efficiency
of buttonhole development,398 but it is for naught
if the fistula cannot be cannulated consistently
without infiltrations. Because an inability to be
sure of the location of the 2 lateral borders of
the fistula contributes to miscannulation (particularly in those who are obese or have deep fistulae) and is manifested by so-called clot aspiration and because DDU is very precise in depicting
the borders of vessels (see CPG 1),344,399,400
patients should be referred for access mapping
and photography. A useful procedure is for the
ultrasonographer to draw a map on the surface of
the skin with a washable marker directly over the
center of the lumen (or the 2 lateral borders),
make a digital photo map of the fistula based on
ultrasound, and send the photograph of the usable portion of the fistula access to the dialysis
center. Alternatively, the access can be marked
with indelible ink that permits the establishment
of a series of subsequent successful puncture
sites to demarcate the center of the vessels if the
rotating-site system of cannulation is used (see
CPG 3). These techniques both educate the staff
and develop expertise and confidence. In addition,
they should foster greater expertise in assessing
S235
fistulae during the first postoperative weeks for

delayed maturation. Prospective studies are needed
to demonstrate this opinion-based strategy.
The majority of fistula creations can be performed on an outpatient basis. A crucial element
is the postoperative examination and surveillance follow-up that is scheduled by either the
surgeon or a vascular access coordinator representing the interdisciplinary VAT. The primary
purpose is to detect problems of maturation (see
CPG 2). Although a variety of factors can produce maturation failure,86,123,125 a greater than
70% successful fistula access rate can be
achieved, even among patients who have diabetes86,87,401,402 and women.84 In a multiple logistic regression analysis of 148 grafts (60% forearm, 40% elbow), predictive factors of early
failure were distal location (adjusted odds ratio
[aOR], 8.21; 95% confidence interval [CI], 2.63
to 25.63; P 0.001), female sex (aOR, 4.04;
95% CI, 1.44 to 11.30; P 0.008), level of
surgical expertise (aOR, 3.97; 95% CI, 1.39 to
11.32; P 0.010), and diabetes mellitus (aOR,
3.19; 95% CI, 1.17 to 8.71; P 0.024).403 Much
of the prevention of delayed fistula maturation
must occur preoperatively (see CPG 1) through
appropriate selection of arterial and venous vessels, as well as procedures most suitable for the
individual patient. Although it is the vein that
must dilate and accept higher flows, the artery
must be healthy too. The resistive index of the
artery used to construct the fistula is a strong
predictor of early primary HD fistula failure.404
However, despite selection of the best available
artery and vein, maturation failure can still occur.
By combining venous diameter (0.4 cm) and
flow volume (500 mL/min) during DDU evaluation within the first 4 months after access construction, one can predict the likelihood of maturing a fistula,72 ie, one that can be cannulated and
provides sufficient blood flow for dialysis, with
95% certainty (19 of 20 fistulae). Women were
less likely to have an adequate fistula diameter of
0.4 cm or greater: 40% (12 of 30) compared with
69% for men (27 of 39). However, of note, the
accuracy of experienced dialysis nurses in predicting eventual fistula maturity was excellent at
80% (24 of 30).72 This is more reason to have a
protocol for regular clinical examination in place
in dialysis centers to teach the skills of physical
examination (see CPG 4) to all staff members
S236
and assess the developing fistula and not focus

on only the access in current use. A new fistula
should be monitored regularly during the postoperative 4 to 6 weeks for swelling, hematoma,
infiltration, wound healing, and failure to mature.
Intervention (CPG 5.2)
Inadequate Flow
A primary fistula should be revised when it is
unable to sustain adequate HD blood flow, manifested by the inability to achieve the prescribed
Kt/V within a reasonable HD duration. Low
access blood flow has a major effect on the
delivery of dialysis: inadequate blood flow may
result in inadequate dialysis, thereby increasing
patient mortality and morbidity.405,406 Impaired
flow in fistulae is caused by impaired arterial
inflow related to the site of cannulation. Location
of the anatomic reason varies between arterial
and venous lesions, as well as lesions within the
anastomotic area.
Arterioatherosclerotic narrowing of the feeding artery with reduced flow and stenosis of the
artery are found in an increasing portion of the
elderly, patients with hypertension, and patients
with diabetes. Therefore, careful preoperative
evaluation should document data on anatomic
and functional status of the arterial vasculature,
including flow in the brachial artery (see CPG 1).
As stated, peripheral location of first fistula,
female sex, diabetes mellitus, and, finally, surgical expertise are the main predictive factors of
early fistula failure.72 Because it is known that
arterial calcification in patients with diabetes is
more pronounced in the wrist than elbow region,407 selection of a more proximally located
site for creation of the AV anastomosis, eg, the
proximal radial or beginning brachial artery in
the proximal forearm, may be the better alternative. Inadequate flow in the area of the AV
anastomosis is produced primarily by surgical
factors. Two studies403,408 emphatically stressed
that the early failure rate of fistula may be 3-fold
greater when constructed by occasionally working access surgeons compared with experienced
surgeons.
However, an initially adequate artery may
become inadequate in time. Four of 40 patients
had brachial artery lesions contributing to access
dysfunction.409 In a larger series, 41 of 101
fistulae had arterial inflow lesions at the time of

therapeutic intervention for dysfunction.268
In case of reduced flow caused by arterial
inflow, 2 therapeutic options exist: stenosis of the
feeding artery may require interventional angioplasty or surgical revision, or inadequate quality
of the feeding artery (caused, eg, by calcification) may require a more proximally located new
AV anastomosis. Although chronic arterial lesions
in upper limbs bearing vascular access devices
for HD most often manifest themselves as insufficient flow for HD treatment, the process may be
severe enough to produce thrombosis and ischemia. For correcting stenoses, PTA is a safe and
effective technique with a low rate of reintervention.268
Juxta-anastomotic venous stenosis is a commonly observed lesion. It occurs from the change
in hemodynamic flow character from the artery
into the vein and from devascularization of the
venous wall during exposure, even after excellent surgery. Placement of the arterial needle
downstream of this stenosis obviously supports
the phenomenon of impaired flow. At times, it
may be impossible to traverse the AV anastomosis by using the retrograde approach, and antegrade puncture of the brachial artery will be
needed.410 Although interventional procedures
are successful with this type of lesion,411 construction of a new AV anastomosis (revision) at a
more proximal location is the preferred procedure.112 However, the therapeutic strategy depends on the type of lesion and variability of
local expertise.
Hemodynamically Significant Venous Stenosis
The commonly used parameter to characterize
the hemodynamic relevance of a stenosis is a
reduction in vessel diameter exceeding 50% based
on angiographic and/or ultrasonographic findings. In contrast to an exact diagnosis in a synthetic AVG with a known standard diameter, it
may be difficult to describe reliably the percentage of narrowing in a native vein, particularly
because this vein may present a prestenotic and/or
poststenotic aneurysmic enlargement. The hemodynamic relevance of a 50% stenosis in a
native AVF therefore should be supported by
clinical symptoms, abnormal physical findings, and flow measurements (see CPG 4). The
diagnosis of hemodynamically relevant ve-
nous stenosis based on a combination of clinical and technical findings should initiate a
corrective procedure, either percutaneous or
surgical intervention.
In AVFs, significant stenoses may not elevate
dynamic or static pressures, although such lesions can result in decreased access flow and
elevated recirculation (see CPG 4) that are associated with increased risk for thrombosis.369
Treatment of hemodynamically significant venous stenosis prolongs the use-life of the
AVF.322,356,358,369,412 A study of 32 patients and
30 controls showed a beneficial effect on AVF
survival of prophylactic angioplasty of stenoses.390 Subsequent Kaplan-Meier analysis of a
larger cohort of patients over 5 years showed that
preemptive treatment decreased the failure rate
(P 0.003), and the Cox hazards model identified treatment (P 0.009) and greater baseline
access flow (P 0.001) as the only variables
associated with favorable outcome.389 A significant increase in access blood flow rate was
observed, as well as a significant decrease in
access-related morbidity by approximately halving the risk for hospitalization, central venous
catheterization, and thrombectomy. This group
showed, in a population of 120 patients with
AVFs, that UDT measurements were reproducible and highly accurate in detecting stenosis and
predicting thrombosis in forearm AVFs. Neither
QA/MAP nor QA improved the diagnostic performance of QA alone, although its combination
with QA increased the tests sensitivity for
stenosis.339 These data support the value of monitoring and surveillance in AVFs (see CPG 4). In
AVFs, 75% of stenoses producing low flow are at
or near the AV anastomosis and 25% are in the
outflow track.
Aneurysm Formation in a Primary Fistula
Progressive enlargement of an aneurysm eventually can compromise the skin above the fistula,
leading to possible rupture. This can result in
hemorrhage, exsanguination, and death. In the
Work Groups opinion, large aneurysms can prevent access to the adjacent fistula for needle
placement, thereby limiting potential cannulation areas.
Aneurysm formation in a primary fistula can
be observed in the following situations:
S237
1. Within the first postanastomotic venous segment in the presence of a hemodynamically

relevant stenosis in the juxta-anastomotic
position. The therapy of choice is a new AV
anastomosis using a healthy venous segment located a few centimeters more proximally, but as close to the former anastomosis
as possible, to preserve the maximum area
for cannulation. Here, surgery may provide
better results than angioplasty. Secondary
patency rates may be very similar, although
repeated angioplasty is far more expensive,
with increased morbidity, risk for catheter
placement, and inadequate HD sessions.
2. Within cannulation areas. This type of aneurysm is caused mainly by the so-called
1-site-itis cannulation413 and should lead
to abandonment of the area for cannulation
(see CPG 3) and strict enforcement of the
rope-ladder cannulation method if a buttonhole does not seem practical. The latter is by
far the best available method for prevention.
For hemodynamic reasons, aneurysms of this
type are combined at times with a preaneurysm stenosis, but more commonly with a
postaneurysm stenosis.
Therapeutic options for managing the aneurysms include the following:
1. Cannulation should not be continued along
any type of venous aneurysm, particularly in
patients for whom the skin layer within the
aneurysm is thin and prone to infectiona
sign of impending perforation.
2. In cases of progression of aneurysm and
stenosis, a series of surgical procedures are
available, including: i) partial resection of
the wall of the aneurysm and insertion of the
resected material as patch along the stenosis,
forming a patch from a segment of a venous
branch; ii) mobilizing an adjacent venous
branch for local repair by a swing-bytechnique; and iii) other options. In all cases
in which surgery can provide a (nearly)
perfect inner diameter while preserving cannulation sites, angioplasty should be the
second choice. Currently, stent insertion
should be avoided along cannulation sites in
fistulae.
3. Aneurysms along the venous outflow tract
where cannulations are not performed rou-
S238
Fig 8.
Treatment of stenosis. (Courtesy of Dr Thomas Vesely)
tinely are found for anatomic reasons (eg, in

junctions of veins, areas of venous valves
with a rigid basic ring, and cases of old
venous lesions caused by former venotomy,
catheter insertion, and so on) as nucleus for a
stenosis followed by a prestenotic aneurysm.
Sometimes these lesions are caused by 1site-itis, in which the same area is cannulated repeatedly without any attempt at buttonhole development. It is particularly prone
to develop when intra-AVF pressures are
high, as in arm AVFs with cephalic arch
stenosis, or in high-flow AVFs. The therapy
of choice for these stenoses is angioplasty;
when elastic recoil occurs, PTA should be
combined with stent insertion in these more
central outflow veins. Recurrent stenoses
should undergo surgery.
Indications for Preemptive PTA (CPG 5.3)
Preemptive PTA may be indicated in certain
cases of abnormal physical findings (see Fig 8).
These findings are more important than other
criteria. See also the rationale for CPG 5.2.

However, certain facets should be kept in mind.
This may be particularly important in underserved areas where the dialysis staff has no
choice other than to rely on abnormal physical
findings.
Tools for physical examination have been described in CPG 4. However, Table 17 provides a
quick summary.
To detect the early beginning of an abnormality requires continuous meticulous education and
daily practice. When a high level of expertise is
achieved, a definitive diagnosis can be achieved
in approximately 60% to 80% of cases through
the presence of abnormal physical findings that
lead to an intervention. These findings should be
documented and preserved in the chart andif
possibleelectronically to continue the observation of the very earliest abnormality. In the remaining 20% to 40% of patients without a definitive diagnosis after physical examination, further
diagnostic steps should be undertaken using (pref-
Table 17. Summary of Physical Examination

Inspection
Palpation
Auscultation
Examine for erythema, swelling, gangrene, change of size of aneurysms over time.
Feel for intravascular pressure along the veins; examine for segmental differences
in quality.
Feel for elevated/low skin temperature; check the quality of pulsation along arteries
and veins.
Check for pain caused by finger pressure.
Check for the presence of typical low-frequency bruit with systolic and diastolic
components.
Examine for abnormal high-frequency bruit produced by turbulence due to a stenosis.
erably first) ultrasound followed by, if necessary,

angiographic techniques, including the option of
angioplasty during the same session; however, this
is dependent on local availability and expertise.
Previous Thrombosis in the Access
It was shown repeatedly that thrombosis of
AVFs is caused by anastomotic disorders, predominantly stenosis. Episodes of hypotension
during HD may be contributory in some cases.
No data exist to determine whether hypotension
alone, even if for a few hours, can produce
thrombosis in the absence of an underlying stenosis limiting flow into the access. Irrespective of
type of treatment given for the previous episode(s) of access thrombosis, these patients
should be considered at risk because anastomotic
residuals or recurrent development of stenosis at
the same site are common. Therefore, special
attention should be taken to prevent recurrence
of clinical signs. This strategy requires repeated
continuous physical examinationa quick chairside procedure in the hands of experienced personnel preceding any cannulation procedure.
Persistent Abnormal Surveillance Test
(see CPG 4.2)
Because surveillance test results at times are
observer dependent, an abnormal isolated finding in any case should be supported by abnormal
physical symptoms. Persistence of abnormal
physical findings and surveillance test results
(elevated pressures, low flows, abnormal recirculation) require that further diagnostic steps be
initiated to establish an exact diagnosis and lead
to timely treatment (see CPG 4).
Stenosis (CPG 5.4)
In the absence of method errors, repeated
failure to deliver the prescribed dialysis dose by
using an AVF should result in immediate evaluation of the vascular access when other reasons
can be excluded, eg, technical errors, timing
errors, and so on. (See the Guidelines for HD
Adequacy and also the rationales for CPG 5.1
and CPG 5.2.)
The degree of stenosis is graded by the percentage of narrowing of the access, the reference
being the diameter of the immediately upstream
or downstream normal vessel. The reference
diameter can be difficult to determine when the
S239
AVF is irregular or aneurysmal or at the confluence of 2 vessels. Grading of severity also can be
done on the basis of the drop-off in systolic or
mean pressure across the stenosis.414,415 The
degree of residual effacement tolerated varies
among interventionalists. Some demand no residual at all unless it is the first PTA ever done.
Swelling, local or generalized in the arm, caused
by central venous stenosis may take additional
time to resolve.
Dilation often is painful locally and local
anesthesia may be needed at times. Venous stenosis in the outflow may be rock hard and require
high-pressure balloons (bursting pressures of 25
to 30 atmospheres), as well as more prolonged
inflation periods. Resistant stenoses are less common, usually less than 1% in forearm and 5% of
upper-arm fistulae.112 There is no convincing
proof that such lesions respond better to cutting
ballons416 because studies have been small and
not prospective. The Work Group recommends
that high-pressure balloons be used first because
cutting devices have not been studied adequately.
Thrombectomy (CPG 5.5)
In most patients, thrombosis is the final complication after a period of AVF dysfunction.
Treatment of thrombosis should start as early as
possible. The risk of delay is progressive growth
of the thrombus that makes interventional/
surgical procedures more difficult and risky with
regard to long-term success. The vascular access
should be reopened as soon as possible to resume
regular dialysis treatment and avoid resorting to
a short-term catheter. In addition, delay produces
a longer period of contact between the surface of
the thrombus and the vessel wall, thereby increasing the risk that extraction of thrombus may
further damage the endoluminal layer. This could
favor future thrombotic events. Early intervention increases the likelihood that the same AVF
can be used to provide future dialyses.
Although thrombectomy procedures are more
challenging in fistulae than grafts, results are
more rewarding.417 Better long-term patency has
been achieved in the largest series to date as long
as the underlying stenoses are sufficiently dilated: 1-year primary patency rates of 50% and
secondary patency rates of 80% have been reported.418 Results reported in the upper arm are
not as good. The unmasking of stenoses in close
S240
to 100% of cases warrants stenosis-detection

programs similar to those for grafts.419
After thrombosis is established, resolution depends on local expertise. Interventional thrombectomy and PTA of the underlying stenosis have
gained wide acceptance. Nevertheless, there are
no results from a larger series of surgical treatment of AVF thromboses available. This leads to
the astonishing fact that there are no comparable
data available in this important field of access
care.
Thrombosed fistulae can be declotted by using
purely mechanical methods (dilation and aspiration),419 a thrombolytic,420 or a combination of
both.421 Success rates are greater than 90% for
the techniques. If a central vein stenosis is found,
interventionalists frequently resort to the use of
stents. Long-term results after dilation in the
largest series are better in forearm native fistulae
compared with grafts. Initial success rates for
declotting are better in grafts compared with
forearm fistulae, but early rethrombosis is frequent in grafts; thus, primary patency rates can
be better for native fistulae after the first months
follow-up.419 Although AVF function may be
reestablished successfully as long as a week after
thrombosis occurs, most should be treated as
soon as possible.422
A variety of devices are available for mechanical thromboaspiration. With all, there are the
issues of residual clots and cost-effectiveness of
the devices over the simple procedure of catheterdirected aspiration. A meta-analysis should be
performed.
Surgical thrombectomy is performed by using
a Fogarty thrombectomy catheter, supported by
retrograde digital expression of the thrombotic
material and followed by correction of the stenosis by using a couple of techniques according to
the individually varying condition. However,
there are only scattered reports with initial success rates of only 65%423 compared with 90% or
better for endovascular techniques. In a small
study of 29 patients, a primary patency rate of
50% at 4 months was reported.424 Surgery seems
to be the preferred technique to treat thrombosis
in forearm AVFs with juxta-anastomotic stenoses, mainly by placement of a new anastomosis.424 With more proximally/centrally located
thromboses, preference should be given to interventional endoluminal techniques. Early recur-
rence of stenosis/thrombosis can be decreased by

insertion of a stent. On occasion, when both the
artery and vein are thrombosed, conversion from
a side-to-side to end-to-side anastomosis can be
attempted, with the goal of using the newly
created fistula immediately. This procedure was
successful in 57% of 72 patients, particularly
those with thrombosis of the AVF to the first side
branch only, with the remaining fistula maintaining patency through collateral flow.425
Access Evaluation for Ischemia (CPG 5.6.1)
This evaluation should be a part of regular
monitoring conducted routinely in all dialysis
facilities. Particularly elder and hypertensive patients with a history of peripheral arterial occlusive disease and/or vascular surgery, as well as
patients with diabetes, are prone to develop
access-induced steal phenomenon and steal syndrome. In any case, clinical examination is mandatory, followed by ultrasound or radiological
evaluation, as necessary. The patient must be
referred to a vascular surgeon to decide on additional procedures. Delay can lead to catastrophic
gangrene and hand amputation. The importance
of this type of monitoring will increase in the
future because of demographic changes in the
dialysis population.
An AVF normally produces an alteration in
blood flow patterns, a physiological steal phenomenon,426 that is seen in forearm AVFs and in
a greater incidence in elbow/upper-arm AVFs.427
Physiological steal occurs in 73% of AVFs and
91% of AVGs.428 With the aging of the HD
population and the increase in arterial changes
caused by diabetes and hypertensive remodeling,
the incidence of symptomatic peripheral ischemia to the hand/arm (pain, necrosis of 1
fingertips) is increasing, but fortunately is still
uncommon (1% to 4%).48 Milder symptoms of
coldness and some pain during dialysis may
occur in up to 10% of cases and fortunately
improve over weeks to months.429 It also is more
common with prosthetic bridge grafts; less than
2% versus 4%.48,430 A decrease in distal perfusion pressures is found regularly and is more
pronounced in patients with advanced arteriomedial sclerosis. In this type of patient, occurrence
of a steal syndrome seems less dependent on
access flow volume than on degree of the peripheral arterial obstructive disease.
Recently, staging according to lower-limb ischemia was proposed48:

1. Stage I, pale/blue and/or cold hand without
pain;
2. Stage II, pain during exercise and/or HD;
3. Stage III, pain at rest;
4. Stage IV, ulcers/necrosis/gangrene.
It is important to differentiate the findings of
hand ischemia from those of carpal tunnel compression syndrome, tissue acidosis, and edema
from venous hypertension. Noninvasive evaluation should be performed, including digital blood
pressure measurement, DDU, andif available
transcutaneous oxygen measurement.48
Corrective results may be good at an early
point in the process, but in any of these patients,
one should be aware that the process of arterial
damage could be progressive. Particularly in
older patients with diabetes with an elbow/upperarm AVF, monomelic ischemic neuropathy can
be observed; an acute neuropathy with global
muscle pain, weakness, and a warm hand with
palpable pulses starting within the first hours
after creation of the AVF.431 Diagnosis of
monomelic ischemic neuropathy is a clinical
diagnosis, and immediate closure of the AVF is
mandatory.
Emergent Referral to a Vascular Access
Surgeon (CPG 5.6.2)
Although most ischemic manifestations occur
early after surgery, in about a quarter of all
patients, they can develop months to years after
arterial constrictions. Fingertip necroses are an
alarming symptom with an initially slow progression in most patients over weeks and a rapid final
deterioration leading to necrosis and gangrene,
indicating that one should aim for early intervention. If ischemic manifestations threaten the viability of the limb, the outflow of the fistula
should be ligated.
Therapeutic options depend on the cause of
steal syndrome. Arterial stenoses proximal to
the anastomosis obstructing the arterial inflow
may be dilated by angioplasty,411 but not in the
case of advanced general arterial calcification.
High-flowinduced steal syndrome requires a
decrease in AVF flow volume. Banding procedures of the postanastomotic vein segment using
different techniques as practiced in the past were
S241
not as successful as expected.432 It is more beneficial to decrease the diameter of the anastomosis or create a new AV anastomosis distally.
The success of the procedure after surgery
should be evaluated by using access flow
measurements.
In cases in which a physiological steal phenomenon becomes clinically symptomatic, ligation
of the peripheral limb of the radial artery may be
successful. Clinically symptomatic steal syndromes with normal or low BFRs represent the
majority of cases with access-related peripheral
ischemia. Since the new technique of the distal
revascularizationinterval ligation (DRIL) operation was published in 1988,429 several groups
have confirmed the good results.48,433 In patients
with a venous anastomosis to the brachial artery,
with the DRIL procedure, the anastomosis is
bridged by a venous bypass, after which the
artery is ligated closely peripherally to the anastomosis. BFR into the AVF does not change
substantially. Most patients do significantly better, presumably because of an increase in peripheral arterial perfusion.
In patients with low BFRs and signs of peripheral ischemia, the proximal AV anastomosis technique provides satisfactory results.434 The idea is
to ligate the preexisting anastomosis to the brachial artery in the region of the elbow or distal
upper arm and place a new arterial anastomosis
in the proximal upper arm, somewhere near the
beginning of the subclavian artery. Blood volume is brought down to the vein through an
interposed vein graft or small-diameter PTFE
graft. Thus, a sufficient BFR into the vein is
provided and peripheral perfusion pressure is
reestablished; cannulation for HD can be continued immediately.
Infection (CPG 5.7)
Although infections of fistulae are rare, any
episode of infection potentially is lethal in face
of the impaired immunologic status of long-term
dialysis patients.
Very rare access infections at the AV anastomosis require immediate surgery with resection of
the infected tissue. Should an arterial segment be
resected, an interposition graft using a vein can
be attempted or a more proximal new AV anastomosis may be created with exclusive use of
degradable suture material.
S242
More often, infections in AVFs occur at cannulation sites. Cannulation at that site must cease,
and the arm should be rested.
In all cases of AVF infection, antibiotic therapy
is a must, initiated with broad-spectrum vancomycin plus an aminoglycoside. Based on results of
culture and sensitivities, conversion to the appropriate antibiotic is indicated. Infections of primary AVFs should be treated for a total of 6
weeks, analogous to subacute bacterial endocarditis.435 A serious complication of any access-
related bacteremia is represented by metastatic

complications, as described.159
LIMITATIONS
Considerably fewer data have been published
regarding management of complications in fistulae compared with grafts. Some aspects are accepted as the standard of care because they are
described in standard surgical textbooks and surgeons/interventionalists accept them.
GUIDELINE 6. TREATMENT OF ARTERIOVENOUS

GRAFT COMPLICATIONS
Appropriate management and treatment of
AVG complications may improve the function
and longevity of the vascular access.
6.1 Extremity edema:
Patients with extremity edema that persists beyond 2 weeks after graft placement should undergo an imaging study
(including dilute iodinated contrast) to
evaluate patency of the central veins. The
preferred treatment for central vein stenosis is PTA. Stent placement should be
considered in the following situations:
6.1.1 Acute elastic recoil of the vein (>50%
stenosis) after angioplasty. (B)
6.1.2 The stenosis recurs within a
3-month period. (B)
6.2 Indicators of risk for graft rupture:
Any of the following changes in the integrity of the overlying skin should be evaluated urgently:
6.2.1 Poor eschar formation. (B)
6.2.2 Evidence of spontaneous bleeding. (B)
6.2.3 Rapid expansion in the size of a
pseudoaneurysm. (B)
6.2.4 Severe degenerative changes in the
graft material. (B)
6.3 Indications for revision/repair:
6.3.1 AVGs with severe degenerative
changes or pseudoaneurysm formation should be repaired in the
following situations:
6.3.1.1 The number of cannulation sites are limited by
the presence of a large
(or multiple) pseudoaneurysm(s). (B)
6.3.1.2 The
pseudoaneurysm
threatens the viability of
the overlying skin. (B)
6.3.1.3 The pseudoaneurysm is
symptomatic (pain, throbbing). (B)
6.3.1.4 There is evidence of infection. (B)
6.3.2 Cannulation of the access through a
pseudoaneurysm must be avoided if
at all possible and particularly so
if the pseudoaneurysm is increasing in size. (B)

6.4 Treatment of stenosis without thrombosis:
Stenoses that are associated with AVGs
should be treated with angioplasty or
surgical revision if the lesion causes a
greater than 50% decrease in the luminal
diameter and is associated with the following clinical/physiological abnormalities:
6.4.1 Abnormal physical findings. (B)
6.4.2 Decreasing intragraft blood flow
(<600 mL/min). (B)
6.4.3 Elevated static pressure within the
graft. (B)
6.5 Outcomes after treatment of stenosis without thrombosis:
After angioplasty or surgical revision of a
stenosis, each institution should monitor
the primary patency of the AVG. Reasonable goals are as follow:
6.5.1 Angioplasty:
6.5.1.1 The treated lesion should have
less than 30% residual stenosis
and the clinical/physiological
parameters used to detect the
stenosis should return to acceptable limits after the intervention. (B)
6.5.1.2 A primary patency of 50% at 6
months. (B)
6.5.2 Surgical revision:
6.5.2.1 The clinical/physiological parameters used to detect the
stenosis should return to acceptable limits after the intervention. (B)
6.5.2.2 A primary patency of 50% at 1
year. (B)
6.6 If angioplasty of the same lesion is required more than 2 times within a
3-month period, the patient should be
considered for surgical revision if the
patient is a good surgical candidate.
6.6.1 If angioplasty fails, stents may be
useful in the following situations:
6.6.1.1 Surgically inaccessible lesion. (B)
S243
S244
6.6.1.2 Contraindication to surgery. (B)

6.6.1.3 Angioplasty-induced vascular rupture. (B)
6.7 Treatment of thrombosis and associated
stenosis:
Each institution should determine which
procedure, percutaneous thrombectomy
with angioplasty or surgical thrombectomy
with AVG revision, is preferable based
upon expediency and physician expertise
at that center.
6.7.1 Treatment of AVG thrombosis
should be performed urgently to
minimize the need for a temporary
HD catheter. (B)
6.7.2 Treatment of AVG thrombosis can
be performed by using either percutaneous or surgical techniques.
Local or regional anesthesia should
be used for the majority of patients. (B)
6.7.3 The thrombectomy procedure can
be performed in either an outpatient or inpatient environment. (B)
6.7.4 Ideally, the AVG and native veins
should be evaluated by using intraprocedural imaging. (B)
6.7.5 Stenoses should be corrected by
using angioplasty or surgical revision. (B)
6.7.6 Methods for monitoring or surveillance of AVG abnormalities that
are used to screen for venous stenosis should return to normal after
intervention. (B)
6.8 Outcomes after treatment of AVG thrombosis:
After percutaneous or surgical thrombectomy, each institution should monitor the
outcome of treatment on the basis of
AVG patency. Reasonable goals are as
follows:
6.8.1 A clinical success rate of 85%;
clinical success is defined as the
ability to use the AVG for at least 1
HD treatment. (B)
6.8.2 After percutaneous thrombectomy,
primary patency should be 40% at
3 months. (B)
6.8.3 After surgical thrombectomy, primary patency should be 50% at 6

months and 40% at 1 year. (B)
6.9 Treatment of AVG infection:
Superficial infection of an AVG should be
treated as follows:
6.9.1 Initial antibiotic treatment should
cover both gram-negative and grampositive microorganisms. (B)
6.9.1.1 Subsequent antibiotic therapy should be based upon
culture results.
6.9.1.2 Incision and drainage may
be beneficial.
6.9.2 Extensive infection of anAVG should
be treated with appropriate antibiotic therapy and resection of the
infected graft material. (B)
BACKGROUND
In this update of the KDOQI Guidelines, the
Work Group did not perform a comprehensive
literature and data review of recent studies of
AVG complications. The primary change from
previous versions of the KDOQI Vascular Access Guidelines is consolidation of related material on AVGs into a single unified guideline.
However, the fundamental tenets are unchanged
from previous editions. Newer references, including reviews, are included when appropriate.
RATIONALE
Extremity Edema and Stenosis (CPG 6.1)
The AVG, although decreasing in frequency of
use, remains a major type of vascular access for
HD in the United States.2 The natural history of
an AVG is the progressive development of neointimal hyperplastic stenoses in the outflow track.
Although these stenotic lesions most commonly
occur at the venous anastomosis, they also can
occur at the arterial anastomosis and within the
native veins that provide outflow from the AVG.
This resulting increase in venous pressure leads
to edema proximally and, in extreme circumstances, evidence of venous collateral flow. The
presence of a hemodynamically significant stenosis can decrease the ability of the access to
deliver adequate flow and increase the risk for
AVG thrombosis. Early detection and treatment
of hemodynamically significant stenoses is con-
TREATMENT OF ARTERIOVENOUS GRAFT COMPLICATIONS
sidered a primary tenet of a vascular access

management program.
Extremity edema persisting beyond 2 weeks
(immediate postoperative period) after placement of an AVG may indicate inadequate venous
drainage or central venous obstruction.30,436 In
many cases, the stenosis results from the prior
placement of a subclavian catheter; risk for stenosis is increased by previous catheter infection.170
PTA of the stenotic or obstructed venous segment
can lead to resolution of the edema. However, acute
elastic recoil may occur after angioplasty of large
central veins.437 Studies have shown that the use of
stents may improve long-term patency of the
central vein in certain circumstances.438-442 Surgical treatment of central venous stenosis is
associated with substantial morbidity and should
be reserved for extraordinary circumstances.443
Graft Degeneration and Pseudoaneurysm
Formation (CPG 6.2, CPG 6.3)
Repeated cannulation of an AVG may cause
degeneration of the graft material that can
progress to involve the subcutaneous tissues overlying the vascular access.444,445 These degenerative changes may eventually compromise the
circulation to the skin. Degeneration of the AVG
and necrosis of the overlying subcutaneous tissue may lead to a progression of clinical problems, including difficulty achieving hemostasis
upon needle withdrawal, spontaneous bleeding
from cannulation sites, severe hemorrhage, and
ultimatelyacute graft rupture. The degeneration of AVGs combined with a venous outflow
stenosis fosters formation of a pseudoaneurysm.
Progressive enlargement of a pseudoaneurysm
produces thinning of the overlying skin, thereby
accelerating skin necrosis that increases the risk
for acute graft rupture. A large pseudoaneurysm
can limit the availability of needle cannulation
sites. Dialysis needles must not be inserted into a
pseudoaneurysm. A severely degenerated graft
or enlarging pseudoaneurysm should be repaired
to decrease the risk for acute rupture and restore
additional surface area for cannulation.
A pseudoaneurysm is treated most effectively
by resection and segment interposition.106,446
Pseudoaneurysms that are not resected may expand and rupture, resulting in significant blood
loss. Pseudoaneurysms that exceed twice the
diameter of the graft or those that are increasing
S245
in size should be surgically corrected because of

their increased risk for rupture. At times, an
endovascular covered stent option may exist.447
Pseudoaneurysm expansion that threatens the
viability of the skin places the patient at risk for
graft infection. In these cases, surgical correction
is indicated.
Treatment of Stenoses (CPG 6.4-6.8)
Venous stenosis is the most common lesion in
AVGs, although in many cases, more than 1
lesion is present within the graft or at the anastomoses. Although previous studies suggested that
arterial inflow lesions were uncommon (5% of
all lesions),108,266 more recent experience suggests
the arterial or arterial anastomotic lesion affecting
blood flow into the AVG may be up to 20% to 25%
of all lesions identified by angiography.
A hemodynamically significant outflow stenosis decreases intragraft blood flow and increases
intragraft pressure.10 The lower blood flow, in
turn, may reduce the efficiency of HD treatment327,355 and increase the risk for vascular
access thrombosis.285,287,322,340,347,364,376,448,449
Conversely, inflow lesions and intragraft lesions
may be associated with low pressure in the body
of the graft and venous outflow. A hemodynamically significant stenosis is defined as a 50% or
greater reduction in normal vessel diameter accompanied by a hemodynamic, functional, or
clinical abnormality (see CPG 4).449,450 By means
of angiography, about 90% of thrombosed grafts
are associated with stenosis, predominantly in
the outflow, at the venous anastomosis, and more
centrally.109,110,451,452
PTA or surgical repair of a hemodynamically
significant stenosis associated with a nonthrombosed AVG can maintain functionality and delay
thrombosis of the vascular access.269,453,454 Many
nonrandomized trials have shown that preemptive treatment of stenoses reduces the rate of
thrombosis10,322,374,455 and perhaps prolongs the
useful life span of the AVG.10,322,374 A number of
observational, but not randomized, studies show
that a greater fraction of grafts remain free of
interventions or thrombosis if the AVG is patent
at the time of intervention.111,112,269,354,456 The
fraction of AVGs free of further intervention or
thrombosis ranged from 71% to 85% among 4
studies if PTA was performed preemptively com-
S246
pared with only 33% to 63% if PTA was performed

after thrombectomy of the graft.10,322,374,455
Although these results would suggest that elective correction of stenoses before thrombosis might
increase the long-term survival of the AVG, recent
studies suggested that prophylactic treatment of
stenoses, although reducing thrombosis events, does
not extend the useful life span of AVG rates.384,386
Thus, the major reason for surveillance is the prevention of thrombosis (see CPG 4).
No convincing evidence exists showing that
repair of an asymptomatic anatomic stenosis
(50% diameter reduction) improves function
or delays thrombosis of the vascular access.
Therefore, prophylactic treatment of a stenosis that
fulfills the anatomic criteria (50% diameter reduction), but is not associated with a hemodynamic,
functional, or clinical abnormality, is not warranted
and should not be performed.10,322,354
Arterial stenosis associated with diminished
access inflow and frequently suspected by the
presence of excessively negative dialysis circuit
prepump pressures (arterial tubing to pump)
should be evaluated and corrected when found.
After PTA, anatomic success is defined as
residual stenosis less than 30%.20,457 Published
series have consistently reported a 6-month primary (unassisted) patency rate of 40% to 50%
after PTA of stenoses associated with nonthrombosed AVGs.108,111,112,269,354,456 The expected
primary patency rate after surgical repair of stenoses associated with nonthrombosed grafts is
less well established.458 Previous Vascular Access Work Groups have determined that a 1-year
primary patency rate of 50% after surgical revision should be the goal.
Individual patients may have a rapid recurrence of stenoses that requires repeated PTA.108,453
In these patients, repeated angioplasty may not be
cost-effective, and surgical revision may be beneficial. Previous Vascular Access Work Groups
have defined rapid recurrence of a stenosis as the
need for more than 2 angioplasty procedures
within a 3-month interval.
Previous studies reported that the use of endovascular stents as the primary treatment for venous stenosis provides long-term results that are
similar to those obtained with angioplasty
alone.382,459-461 Stents should be reserved for
patients with contraindications to surgical revi-
sion and for treatment of angioplasty-induced

venous rupture.462-464
Several studies have directly compared percutaneous thrombectomy with surgical thrombectomy with revision for treatment of AVG thrombosis.465-470 A review of comparative and
noncomparative studies reveals conflicting results and does not yield a definitive preference.24,106,356,467-479 In the opinion of the Work
Group, percutaneous thrombectomy or surgical
thrombectomy with revision are both effective
techniques for the treatment of AVG thrombosis
and associated stenosis. The thrombectomy procedure should be performed expeditiously to
avoid the need for a short-term catheter. Hospitalization and general anesthesia increase the cost
and risk of the thrombectomy procedure and
should be avoided when possible.
An underlying stenosis frequently (85%) is
the cause of AVG thrombosis.108,480,481 Intraprocedural imaging should be used to evaluate the
outflow veins for improved detection of significant stenoses.382,470 Identification and treatment
of all significant stenoses are essential to optimize long-term patency of the thrombectomy
procedure. PTA of stenoses associated with AVG
thrombosis correlates with poorer outcomes compared with nonthrombosed AVGs.269 After percutaneous thrombectomy, the majority of reported
3-month primary (unassisted) patency rates range
from 30% to 40%.471,473,476,478,480,481 The Work
Group believes that percutaneous thrombectomy
should achieve a 3-month primary patency rate
of 40%. After surgical thrombectomy, the achievable goals are a 6-month primary patency rate of
50% and a 1-year primary patency rate of 40%.
Surgical procedures are held to a higher standard
because the AVG usually is extended farther up
the extremity when a surgical revision of a stenosis is performed, using up venous capital.
Infection (CPG 6.9)
While cardiac causes account for almost half
the deaths in adult patients with CKD stage 5, the
second leading cause of death is infection, much
of it related to the type of vascular access in
use.60 AVGs have a greater rate of infection than
autologous fistulae, and, unfortunately, antibiotics alone frequently are inadequate and surgical
procedures are needed.482 Management of an AVG
infection is a balance between achieving resolution
TREATMENT OF ARTERIOVENOUS GRAFT COMPLICATIONS
of the infection while preserving the vascular access.59,483 Superficial infections should be treated
initially with broad-spectrum antibiotic therapy.
Subsequent antibiotic therapy should be based upon
the identification of the causative bacterial organism.201,484 A more extensive AVG infection can
lead to bacteremia, sepsis, and death. Surgical
exploration and removal of infected graft material, combined with antibiotic therapy, often is
necessary for complete resolution.484
Subclinical infection can develop in AVGs,
typically resulting from retained graft material.
Diagnosis may require performance of indiumlabeled white blood cell or gallium scans. Such
infection frequently is manifested as resistance
to epoetin therapy, along with evidence of a
systemic inflammatory response; frequently, it
S247
occurs in abandoned and nonfunctioning grafts.

Epoetin responsiveness is restored only after
removal of the graft.
LIMITATIONS AND COMPARISON TO
OTHER GUIDELINES
These updated CPGs are essentially unchanged
in content from those of previous editions of the
KDOQI Vascular Access Guidelines. More evidence now is available for the guidelines than in
previous editions. However, there is still a paucity
of RCTs to better define the effect of interventions
on clinically important outcomes. These guidelines also are comparable to those recommended
by the Society of Interventional Radiology,457
American College of Radiology,485 and a joint
committee of several surgical societies.458
GUIDELINE 7. PREVENTION AND TREATMENT OF

CATHETER AND PORT COMPLICATIONS
Catheters and ports are essential tools for
providing urgent and, in some cases, longterm vascular access. Prevention and early
treatment of complications should greatly reduce associated morbidity and mortality.
7.1 Catheters and ports should be evaluated
when they become dysfunctional. Dysfunction is defined as failure to attain and
maintain an extracorporeal blood flow of
300 mL/min or greater at a prepump
arterial pressure more negative than 250
mm Hg. (B)
7.2 The exception is pediatric or smaller
adult catheters that are not designed to
have flows in excess of 300 mL/min. (B)
7.3 Methods that should be used to treat a
dysfunctional or nonfunctional catheter
or port include:
7.3.1 Repositioning of a malpositioned
catheter. (B)
7.3.2 Thrombolytics, using either an
intraluminal lytic, intradialytic
lock protocol, or an intracatheter
thrombolytic infusion or interdialytic lock. (B)
7.3.3 Catheter exchange with sheath disruption, when appropriate. (B)
7.4 Treatment of an infected HD catheter or
port should be based on the type and
extent of infection.
7.4.1 All catheter-related infections, except for catheter exit-site infections, should be addressed by initiating parenteral treatment with an
antibiotic(s) appropriate for the
organism(s) suspected. (A)
7.4.2 Definitive antibiotic therapy should
be based on the organism(s) isolated. (A)
7.4.3 Catheters should be exchanged as
soon as possible and within 72 hours
of initiating antibiotic therapy in
most instances, and such exchange
does not require a negative blood
culture result before the exchange.
(B) Follow-up cultures are needed
1 week after cessation of antibiotic
therapy (standard practice).
S248
7.4.4 Port pocket infections should be

treated with systemic antibiotics
and irrigation, in conjunction with
the manufacturers recommendations. (B)
RATIONALE
Evaluation of Dysfunction (CPG 7.1)
Catheter dysfunction can be attributed to many
causes, and progression of dysfunction to nonfunction varies accordingly.182 The most common complications are thrombosis and infection.486,487 Even with care, fewer than half the
catheters placed as long-term access are in use
a year after their placement,488 and about a third
are removed because they fail to deliver adequate blood flow. The definition of adequate
blood flow varies inversely with the efficiency
of HD. High-efficiency dialysis as practiced in
the United States requires dialyzer-delivered
BFRs greater than 300 mL/min to achieve the
target single-pool Kt/V of 1.2 (see the KDOQI
HD Adequacy Guidelines). Conversely, in Europe, BFRs less than 300 mL/min frequently are
used because dialysis treatment durations are
longer.203 Adequacy of dialysis is influenced
additionally by the site of placement and degree
of recirculation.489,490 Recirculation in femoral
catheters is significantly greater than that in
internal jugular catheters (13.1% versus 0.4%;
P 0.001).193 In addition, femoral catheters
shorter than 20 cm have significantly greater
recirculation (26.3%) than those longer than 20
cm (8.3%; P 0.007). This length dependency
may result from the ultimate tip position of
longer catheters in the IVC as opposed to the
common iliac vein with shorter catheters. The
greater blood flow available to the catheter at
the IVC site reduces recirculation. When dialysis
dose delivery is a priority, placing the short-term
catheter in the internal jugular vein is an advantage. Recirculation may increase when the lines
are reversed (inversion of inlet and outlet lumens), even in well functioning nonsplit catheters (from 2% to 3% to 10%).491 Although
reversal of tubings may increase urea clearance
by increasing blood flow temporarily,184 it usually is at a BFR less than 300 mL/min and should
PREVENTION AND TREATMENT OF CATHETER AND PORT COMPLICATIONS
S249
Table 18. Signs of CVC Dysfunction: Assessment Phase

Blood pump flow rates <300 mL/min
Arterial pressure (< 250 mm Hg)
Venous pressure (>250 mm Hg)
Conductance (<1.2) : the ratio of blood pump flow to the absolute value of prepump pressure
URR progressively <65% (or Kt/V <1.2)
Unable to aspirate blood freely (late manifestation)
Frequent pressure alarmsnot responsive to patient repositioning or catheter flushing
Trend analysis of changes in access flow is the best predictor of access patency and risk
for thrombosis.
never be used except temporarily until the problem is definitively corrected.

A dysfunctional catheter usually is easier to
salvage than a nonfunctional catheter, thereby
preventing complications of a new placement.249
Early treatment also reduces the likelihood and
minimizes the extent of inadequacy of dialysis
caused by catheter dysfunction. Delivery of adequate dialysis dose is dependent upon blood
flow and treatment duration. For any given dialyzer, low BFRs during HD extend treatment
times and all too often still result in underdialysis
(caused by unrecognized recirculation). A BFR
less than 300 mL/min was noted in 15% of
treatments with catheters.249 Catheter dysfunction leads to 17% to 33% of untimely catheter
removals,487,488 and thrombosis of the catheter
occurs in access loss in 30% to 40% of patients.
It is to be noted that the criterion for determining access dysfunction, ie, blood flow greater
than 300 mL/min, is qualified by the prepump
arterial pressure182 factored for the length and
lumen diameter of the catheter.183,490 Prepump
arterial pressure monitoring is essential to ensure
valid blood flows, and adequacy is determined
largely by the amount of blood pumped to and
through the dialyzer.189,191,200 Consequences of
catheter dysfunction are many, including increases in morbidity and mortality,20,248,258
increase in economic expenditures,250 and a
real concern to patients, 60% of whom report
fear of thrombosis second only to pain in decreasing their QOL.252
In CVCs, the most likely cause for low BFRs
is thrombotic occlusion. In the likely event that
low BFR or occlusion will occur at some time
during the useful life of a catheter, prospective
monitoring is essential to detect dysfunction.
Regular assessment of dialysis performance is
strongly recommended to ensure dialysis adequacy.189 Catheter performance parameters to
consider are shown in Table 18 and include

maximal consistently achievable BFR, resistance to blood flow indicated by arterial and
venous pressures during HD, and blood recirculation rate.492,493 Of these, the one favored by the
Work Group is the ratio of dialyzer BFR achieved,
factored by the prepump arterial limb pressure in
absolute units.
Early detection of access dysfunction is most
likely if all members of the VAT are involved.198
The use of CQI in catheter access necessitates
collaboration among team members, with specific tasks assigned to certain individuals, who
then provide input and/or feedback.
The minimally accepted dialyzer BFR of 300
mL/min is easily achieved by using newer catheters that are capable of achieving rates of 400
mL/min or greater when properly placed.494
Therefore, 300 mL/min is a conservative value in
current adult practice and waiting until blood
flow decreases to 300 mL/min may be too late to
avoid loss of the catheter and unnecessary loss of
the access site.
Prevention of catheter and access thrombosis
by using antiplatelet agents and anticoagulation
has not been successful (see Table 19).
Use of an antiplatelet agent is not recommended because it was not effective in grafts and
was associated with more bleeding.497 A similar
conclusion was reached in a prospective nonrandomized comparison of warfarin to aspirin.498
Use of a low fixed dose (1 mg) of warfarin also
was found to be ineffective.495 Further studies in
this area with a higher target international normalized ratio (INR) are warranted.
The first step in assessing dysfunction is shown
in Fig 9, which begins with a determination of
the age of the catheter.
In catheters recently placed, inadequate blood
flow usually is the result of mechanical obstruction, improper tip location affected by patient
S250
position, or a problem of catheter integrity, as

shown in Table 20.492
The need to use a Trendelenberg position to
achieve adequate blood flow from a catheter
placed in great veins leading to the right atrium
always implies that the catheter is improperly
placed. If the problem is not obvious and not
easily correctable, the patient should be referred
to an interventional center for study to diagnose
the cause. Although mechanical problems can
develop acutely in catheters previously giving
good performance, access dysfunction occurring
after 2 weeks more likely is the result of progressive occlusion of the catheter tip by fibrin or
thrombus. The location of obstruction may reside
in the following areas:
1. Intraluminal thrombuswithin lumen of
catheter, partial or complete occlusion.
2. Catheter tipin catheters with side holes at
tip of arterial limb, thrombus may occlude or
act like ball valve.
3. Fibrin sheath (fibrin sleeve)fibrin adheres
to external surface of catheter, thrombus
trapped between sheath and catheter tip.
4. Fibrin tail (fibrin flap)fibrin adheres to
CVC end, ball valve effect.
Methods That Should be Used to Treat a
Dysfunctional or Nonfunctional Catheter or
Port (CPG 7.3)
A catheter that has migrated out of the midright atrium should be repositioned. Catheters of
inadequate length should be exchanged over a
guide wire to the appropriate position or replaced.499
All catheters are locked with some anticoagulant. The purpose of the lock is to prevent
thrombosis. Loss of anticoagulant by diffusive
transport would be expected. However, it has
been known for several years that some fraction
of the anticoagulant will leak into the systemic
circulation500,501 by nondiffusive processes and
increase the partial thromboplastin time, thus
possibly contributing to minor or even major
bleeding. In vitro simulations suggest an early
leak within 30 seconds, followed by a slower
loss of locking solution during the next 30 minutes.502 The specific gravity of the locking solution likely also influences the rate of leak.503
Locking solution lost is replaced by blood. It
S251
Fig 9. Assessing dysfunction of catheters. Symbols: IR, imaging for correct position. Abbreviation: tPA, tissue
plasminogen activator; IR, intervention. (Courtesy of Drs Asif and Anatole Besarab).
therefore is not surprising that thrombosis is so

common in catheters because blood is likely to
be in the lumen of the catheter for prolonged
times interdialytically. The loss of anticoagulant
permits the entry of clotting factors into the
catheter lumen. The presence of these processes
is manifested by a change in flow long before
there is occlusion.
After assessment precludes mechanical dysfunction (see Fig 9), such as a kink or dislodgement, thrombotic occlusionpartial (poor flow
on aspiration) or total (unable to aspirate or
push)is the most common cause of catheter
dysfunction and/or occlusion.151,504-506 Pharmacological intervention for catheter-occlusive dysfunction involves treatment with thrombolytics
Table 20. Causes of Early Catheter Dysfunction

Mechanical
Kinks (angulation in tunnel)
Misplaced sutures
Catheter migration
Drug precipitation (some antibody locks or IV IgG)
Patient position
Catheter integrity
Holes
Cracks
S252
that convert plasminogen to plasmin. Thrombolytics are noninvasive, confer no additional

trauma to the patient, have a high level of safety
and efficacy, and are cost-effective.507 A thrombolytic can be administered in the dialysis setting. Because of such advantages and the less
practical alternative treatment options, thrombolytic therapy directed at salvaging the catheter
should be considered before access replacement
because it is the least invasive and least costly of
all catheter salvage techniques.
A variety of thrombolytics have been used
(Table 21), although at the present time, only
tissue plasminogen activator (tPA) is approved
by the Food and Drug Administration (FDA).
Urokinase (UK) is still available (but is no longer
manufactured), as is reteplase, but neither of
these lytics currently is available in convenient
dosages and must be aliquoted and frozen for
use. Teneplase, another lytic, has not been used
for access thrombosis. Formulations of some
lytics have been tried in studies and are used off
label at various institutions.
Thrombolytics have proved highly effective in
opening partially and fully occluded lumens.496,508-525 (See also: Abbott Laboratories,
prescribing information for abbokinase [urokinase] Chicago, IL, 2003; Boehringer Mannheim
GmbH, prescribing information for Reteplase
[reteplase], 2000; Genentech, prescribing information for Cathflo Activase [alteplase],
2001.525A-C) The most common use of lytics
occurs late in the dysfunction process, when
prescribed blood flows are not attained and there
is difficulty even in initiating a dialysis treat-
ment. Currently, the package insert only describes the use of the agent for catheters in a
timed dwell, based on clinical trials in nondialysis catheters.526,527 The recent Cathflo Activase
Pediatric Study has led the FDA to approve tPA
as a thrombolytic in all age groups for the same
indications as in the package insert.
In situations in which the obstructive process
has progressed to a more severe state, dialysis is
urgent, and the catheter is extremely dysfunctional (ie, unable to provide a BFR of 200 mL/
min), tPA reconstituted appropriately and instilled at a lumen fill volume permits resumption
of dialysis in 50% to 90% of instances (see
Table 22), although a second dwell may be
required. Per the package insert, this lytic should
be allowed to dwell for 1 hour or longer. Table 23
summarizes the major studies with tPA in totally
occluded catheters.
In general, efficacy increases with longer dwell
times with tPA as the lytic. Fewer studies are
available with the other agents, but results are
similar.514,517 A recent study showed that a lower
dose of 1 mg/lumen of tPA also is effective,
restoring catheter patency in 72% with 1 dose,
increasing to 83% with a second dose,513 values
only slightly lower than with the standard dose
of 2 mg/lumen.
The Work Group believes that the use of lytics
late in the thrombosis process without adequate
prior diagnostic evaluation is in itself dysfunctional and recommends that the procedures described in Fig 9 be used to evaluate a catheter
access on a recurrent basis. Tracking the relationship of prepump pressure, VDP, and flow (see
S253
S254
Fig 9) can alert the clinician to the development

of catheter dysfunction before late manifestations set in. The emphasis for managing catheter
dysfunction should shift to intervention at an
earlier stage of dysfunction.
Although endoluminal brushes have been used
to clear thrombi from dialysis catheters,528 there
are no convincing data about efficacy and they
are expensive. The Work Group does not currently advocate their routine use. Such brushes
were originally developed to obtain biofilm specimens from catheters.
The management of fibrin sheaths is discussed
further in CPR 7. Currently, the Work Group
recommends change of catheter with disruption
of the sheath by using a balloon. Fibrin sheath
stripping rarely is used because of cost and
increased patient morbidity.
Treatment of an Infected HD Catheter or
Port (CPG 7.4)
Definitions
Exit-site infection. Inflammation confined to
the area surrounding the catheter exit site, not
extending superiorly beyond the cuff if the catheter is tunneled, with exudate culture confirmed
to be positive.
Tunnel infection. The catheter tunnel superior to the cuff is inflamed, painful, and may have
drainage through the exit site that is culture
positive.
Catheter-related bacteremia. Blood cultures are positive for the presence of bacteria
with or without the accompanying symptom of
fever.
The Work Group recommends the following
CDC definitions for catheter-related infections.
Definite bloodstream infection: the same organism from a semiquantitative culture of the catheter tip (15 colony-forming units per catheter
segment) and from a peripheral or catheter blood
sample in a symptomatic patient with no other
apparent source of infection.
Probable bloodstream infection: defervescence of symptoms after antibiotic therapy with
or without removal of catheter, in the setting in
which blood cultures confirm infection, but catheter tip does not (or catheter tip does, but blood
cultures do not) in a symptomatic patient with no
other apparent source of infection.
Possible bloodstream infection: defervescence

of symptoms after antibiotic treatment or after
removal of catheter in the absence of laboratory
confirmation of bloodstream infection in a symptomatic patient with no other apparent source of
infection.
Although thrombotic occlusions leading to
flow delivery problems are more common than
infection, catheter-related infection has emerged
as the primary barrier to long-term catheter use.
The greater infection rate in catheters compared
with grafts and fistulae is its major limitation.
Infection is the leading cause of catheter removal
and morbidity in dialysis patients.148,156,201,532,533
The most recent USRDS data indicate that the
rate of septicemia in HD patients continues to
increase, and hospital admissions for vascular
access infection doubled in the last decade.235
The use of long-term HD catheters instead of
short-term catheters has not yet translated into a
significant reduction in the incidence of CRB
and resultant infective endocarditis in our
population.234,534-539
Accurate and early diagnosis is essential. A
meta-analysis of 8 different methods comparing
those that do and do not require catheter removal
showed that paired quantitative blood cultures
from the peripheral blood and the catheter are the
most accurate,540 but are not routinely performed. However, routine culture methods have
negative predictive power (99%), whereas the
positive predictive value increases with the pretest probability for infection. Dialysis programs
should monitor vascular access and especially
catheter-related infections with attention to incidence, bacteriology, and outcomes.
Significant risk factors (P 0.05) for bacteremic episodes include the presence of diabetes,
peripheral atherosclerosis, a previous history of
bacteremia, nasal carriage of Staphylococcus aureus, longer catheter use duration, more frequent
UK catheter infusion, and local infection.532,537
One report identified elderly women as being
more at risk.541
Infection monitoring should be in place to
identify outbreaks that can result from manufacturing defects.542 A doubling of the rate is cause
for concern.542 One study provides a means to
standardize the reporting of vascular access infection rates.543 Analyzing nearly 40,000 dialysis
sessions, infection rates were greatest among
short-term catheters (recommended for in-hospital use only) and least among permanent native
AVFs or synthetic grafts. Another analysis in
Canada of 184 bloodstream infections in 133,158
dialysis procedures confirmed these findings.232
AVFs were associated with the lowest risk for
bloodstream infection (0.2/1,000 dialysis procedures; RR increased 2.5-fold with AVGs, 15.5fold with TCC access, and 22.5-fold with uncuffed CVC access; all P 0.001). Significant
variation in infection rates was observed among
centers, even when controlling for types of access used, suggesting that access-specific infection rates within and among centers could be
used to develop quality improvement. Experience with femoral TCCs has been mixed. Some
reports indicated no increase in infection
rate,544,545 but that has not been the experience
of members of the Work Group. Even if there is
no decrease in infection-free survival,545 use of
femoral catheters is associated with ipsilateral
vein thrombosis in about 26% of patients that
necessates use of anticoagulants with uncertain
effects on the upstream iliac vein (see CPG 2).
All indwelling vascular catheters are colonized by microorganisms within 24 hours after
insertion.546 The formation of biofilm on the
external and internal surface of vascular catheters is thought to have an important role in the
colonization process. The biofilm is produced by
a combination of host factors (eg, fibrinogen,
fibrin, fibronectin, and extracellular polysaccharides) and microbial products (eg, glycocalyx or
slime) and has a critical role in bacterial antimicrobial resistance and recalcitrant infections.547
Prevention of infection is the key first step, and
the reader should consult the recommendations
of the CDC.222 Although documented by a variety of methods, the relationship of thrombin
sheath to infection has not been evaluated clinically. Proteins in the fibrin sheath provide adhesions for organism binding, particularly by S
aureus. Whether more aggressive prevention of
fibrin sheaths could reduce the infection rate is
unknown. Sporadic reports suggested that concomitant use of a lytic with antibiotics could
salvage more catheters.
In general, uncuffed catheters have a greater
rate of infection, 3.8 to 6.6 episodes/1,000 days,
compared with TCCs, with 1.6 to 5.5 episodes/
1,000 days.534,542,544,548 This wide range obvi-
S255
ously reflects differences in practice.544 Rates as

low as 1/1,000 days at risk have been achieved
with detailed catheter protocols.247 Programs with
greater rates of infection in long-term catheters
should institute CQI analysis techniques. Catheter infection usually requires replacement of the
catheter in half the episodes despite antibiotic
therapy.532 Systemic antibiotics used to treat
bacteremia do not penetrate into the biofilm and
therefore do not eradicate it,549 leading to potential treatment failures and eventual sacrifice of
the catheter. Among uncuffed short-term catheters, femoral catheters have the highest infection rate, averaging 7.6 episodes/1,000 days,
with more than 10% being infected by 1 week.199
Catheter exit-site infections alone usually can
be salvaged with topical and oral antibiotics without the need for catheter replacement.148,149,151,550
CRB is the major reason for catheter loss156 and
has been associated with substantial morbidity,
including metastatic infection.159 It is a lifethreatening condition requiring initial hospitalization and parenteral antibiotic therapy if the patient is clinically septic. The observation in a
large trial of patients with CRB that systemic
antibiotics alone were able to salvage less than
25% of catheters533 led to the commonly used
salvage of site rather than salvage of catheter
approach.551,552 Attempts to salvage the catheter
in situ were associated with recurrence of infections soon after the antibiotics were discontinued.533 Conversely, studies using catheter guide
wire exchange in stable patients without tunnel
involvement under the cover of antibiotics alone
salvaged 80% to 88% of sites without apparent
ill effects.158,551,552 There is no advantage in
delaying replacement of the catheter by several
days.553 A decision-tree hypothetical analysis
showed that TCC exchange over a guide wire
reduced net charges by approximately $5,200
and $750 (US dollars in year 2000) compared
with TCC salvage and immediate TCC removal,
respectively.554 Expected 3-month patient survival for TCC guide wire exchange and immediate TCC removal were similar (93%), whereas
survival for TCC salvage was worse.554 A negative culture result is not required before catheter
exchange.551
An alternative to this management of dialysis CRB (systemic antibiotics with catheter
exchange, as well as removal of the infected
S256
catheter) is catheter salvage by combining systemic antibiotics in conjunction with antibiotic

locks.555-559 The former is burdensome at times
and expensive and creates short-term problems
for dialysis access if the infectious disease
consultant demands that a 24- to 48-hour catheter-free period is needed before the catheter
can be placed. As stated previously, bacterial
biofilms form routinely in the catheter lumen
and act as the nidus for bacteremic episodes.
Instillation of a concentrated antibiotic-anticoagulant solution into the catheter lumen (antibiotic lock) at concentrations orders of magnitude higher than those achievable in the blood
may permit successful eradication of the infection while salvaging the patients catheter. A
number of studies now confirm the validity of
this approach,556-559 with salvage of the catheter and without recurrence of infection in
about 65% to 70% of cases, comparing favorably with the catheter-exchange approach. With
the latter method, catheter replacement is necessary in patients with persistent fever or positive surveillance blood culture results. A direct
head-to-head RCT of the 2 methods is needed
(see Research Recommendations).
Bacteremia with tunnel-tract involvement
should prompt catheter removal. Unstable patients require removal of the catheter for rapid
response to therapy. The Work Group believes
that a minimum of 3 weeks of systemic antibiotic
therapy is needed to treat CRB and that new
permanent access should not be placed until
culture results have been negative for at least 48
hours after cessation of antibiotic therapy.
Prevention of CRB can be difficult despite the
use of rigorous infection-control techniques. As
shown in Table 24, silver impregnation of the
catheter was ineffective,560 whereas a gentamycin/citrate solution561 and a taurolidine solution
used as interdialytic antibiotic locks were effective.562,563 Minocycline/rifampin coating has not
been tested in dialysis catheters.
The subject of antibiotic locking has been
discussed extensively.564 Other pharmacological
measures that may be useful for prophylaxis
against CRB include application of an antimicrobial ointment (mupirocin or polysporin) to the
catheter exit site.565,566 Subcutaneous port catheter devices do not reduce the frequency of CRB
unless an antimicrobial solution is used with the
device.567 A preliminary study showed that a

topically applied Medihoney was as effective
as mupirocin in reducing catheter infection.568
The former has a lower likelihood for selecting
out resistant organisms. It unfortunately is forgotten that good practice and attention to hub care
can significantly reduce CRB by 4-fold.247
However, with all preventive strategies other
than good catheter care (see CPG 3), there are
few long-term data on the development of antimicrobial resistance, and future studies are re-
S257
quired. Until such data are available, it is unlikely that the use of such locks and ointments
will receive official approval from the FDA.
LIMITATIONS
Considerable uncertainty exists about the most
effective regimen for preventing catheter dysfunction by using lytics because there are no sufficiently powered studies to compare the efficacy
and economics of different protocols. The same
applies to prevention of CRB.
GUIDELINE 8. CLINICAL OUTCOME GOALS

8.1 Goals of access placement:
8.1.1 Each center should establish a database and CQI process to track
the types of accesses created and
complication rates for these accesses.
8.1.2 The goals for permanent HD access placement should include:
8.1.2.1 Prevalent functional AVF
placement rate of greater
than 65% of patients.
(B)
8.1.2.2 Cuffed catheter for permanent dialysis access (eg, not
as a bridge) in less than
10% of patients. Long-term
catheter access is defined as
the use of a dialysis catheter for more than 3 months
in the absence of a maturing permanent access
graft or fistula. (B)
8.2 The primary access failure rates of HD
accesses in the following locations and
configurations should not be more than
the following:
8.2.1 Forearm straight grafts: 15%. (B)
8.2.2 Forearm loop grafts: 10%. (B)
8.2.3 Upper-arm grafts: 5%. (B)
8.2.4 Tunneled catheters with blood flow
less than 300 mL/min: 5%. (B)
8.3 Access complications and performance:
8.3.1 Fistula complications/performance
should be as follows:
8.3.1.1 Fistula thrombosis: fewer
than 0.25 episodes/patientyear at risk. (B)
8.3.1.2 Fistula infection: less than
1% during the use-life of
the access. (B)
8.3.1.3 Fistula patency greater
than 3.0 years (by life-table
analysis). (B)
8.3.2 Graft complications/performance
should be as follows:
8.3.2.1 Graft thrombosis: fewer
than 0.5 thrombotic episodes/
patient-year at risk. (B)
S258
8.3.2.2 Graft infection: less than

10% during the use-life of
the access. (B)
8.3.2.3 Graft patency greater than
2 years (by life-table analysis). (B)
8.3.2.4 Graft patency after PTA:
longer than 4 months. (B)
8.3.3 Catheter complications/performance should be as follows:
8.3.3.1 Tunneled catheter-related
infection less than 10% at
3 months and less than
50% at 1 year. (B)
8.3.3.2 The cumulative incidence
of the following insertion
complications should not
exceed 1% of all catheter
placements: (B)
Pneumothorax requiring a chest tube
Symptomatic air embolism
Hemothorax
Hemomediastinum
Hematoma requiring
evacuation.
8.3.4 Cumulative patency rate of TCCs:
Not specified. (B)
8.4 Efficacy of corrective intervention:
The rate of certain milestones after correction of thrombosis or stenosis should
be as follows:
8.4.1 AVF patency after PTA: greater
than 50% unassisted patency at 6
months (and <30% residual stenosis postprocedure or lack of resolution of physical findings postprocedure);
AVF patency following surgery:
greater than 50% unassisted patency at 1 year. (B)
8.4.2 AVG patency after PTA: please refer to CPG 6.5.1;
AVG patency after surgery: please
refer to CPG 6.5.2;
AVG after either PTA or surgery:
greater than 90% with postprocedure restoration of blood flow and
CLINICAL OUTCOME GOALS
greater than 85% postprocedure

ability to complete 1 dialysis treatment. Please refer to 6.8. (B)
8.4.3 Surgical correction is set to a higher
standard because of the use of venous capital. (B)
BACKGROUND
HD access failure is a major cause of morbidity and mortality for patients on HD
therapy.7,8,14-17 Expenditures for reconstituting
patency are substantial and increasing.2,8,9,12
Throughout this document, methods and recommendations have been proposed to improve vascular access results. These include:
1. Establishment of QA programs that track
access complication rates and outcomes:
a. Formation of VATs
2. Improvement of the skill set of staff:
a. Physical examination of the accesses
b. Cannulation techniques among staff
c. Aseptic techniques
3. Increasing the percentage of patients with
native or primary AVFs by implementing the
FFBI. Key portions of the program include
the following:
a. Early identification and referral of patients with progressive kidney disease to
nephrologists, allowing access construction well in advance of the need for HD
b. Protection of veins
c. Adequate artery and vein evaluation by
using DDU and/or angiography
d. Reevaluation for a native AVF after every access failure
4. Periodic monitoring of accesses to detect
hemodynamically significant stenoses before
thrombosis:
a. Expeditious referral of patients for appropriate angioplasty or surgical revision
after the detection and characterization of
stenoses
b. Documentation of functional improvement in access function after corrective
intervention
5. Improved catheter care.
The following Clinical Outcome goals are
target suggestions for measuring improvement in
performance.
S259
RATIONALE
Goals of Access Placement (CPG 8.1)
Data should be updated periodically and
methods should be identified to increase the
rate of AVF placement. Flow charts should be
developed and root-cause analysis should be
carried out to identify barriers to fistula placement, causes for excessive thrombosis rates,
and reasons for excessive catheter-related infection.
These goals are greater than those previously recommended in the KDOQI Vascular
Access Guidelines.20,348 They represent the
goals expected by CMS, which has set the
target for fistula prevalence of 65% by 2009.
Although there has been slow improvement in
fistula rates since implementation of the FFBI,
rateshaveincreasedonlyslowly(NVAII,www.fistulafirst.
org; last accessed 2/20/2006). The Work Group
believes that with the reimbursement of DDU procedures and early referral of patients by nephrologists for access evaluation and constructions, rates
will improve. In some cases, this will require the
use of brachial artery level constructions. An increase in percentage of native AVFs is accomplished best by early determination of the patients
preferred dialysis modality while dialysis therapy
initiation is still months away (see CPG 1) because
primary AVFs ideally need an extended period of 1
to 6 months to mature. However, those entering the
CKD stage 5 program with inadequate or no prior
medical care for CKD will continue to blunt the
impact of such efforts.
These goals are achievable.37,38,88,569 A primary AVF using the cephalic vein confers the
best permanent access with the fewest complications (see CPG 2). Native accesses have the
best 4- to 5-year patency rates and require
fewer interventions compared with other access types. In many patients, a previous native
or synthetic access produces dilation of arm
veins, permitting construction of a new primary AV access at a site not previously available.
Catheter usage presents a conundrum. On
one hand, catheters provide access that is immediately available; on the other hand, complications are high.180,359 Blood flow frequently
is inadequate, thrombolytics frequently are required, and the infection rate is an order of
S260
magnitude higher than with grafts or fistulae.

Cuffed catheters are associated with lower
BFRs compared with grafts and fistulae. As a
result, long-term catheter use without appropriate adjustments in treatment duration can compromise dialysis adequacy. Compromise of dialysis adequacy is associated with increased
morbidity and mortality. Systemic and local
infections occur more frequently with cuffed
catheters and account for some of the excess
mortality associated with this access type. Finally, long-term catheter access is associated
with a risk for central venous stenosis development, which can preclude the establishment of
a permanent vascular access for HD (see CPG
2). The initial success, ease of use, and painless
access to the patients blood offered with a
dialysis catheter may foster reluctance in some
patients to accept more permanent access options
with a fistula or graft despite the greater risk for
infection and inadequate dialysis associated with
long-term permanent catheter use. Patients should
be educated on these issues and strongly encouraged to allow creation of a fistula for permanent
access whenever possible.
When a catheter must be used either initially
or to bridge the patient to the next permanent
access, time-urgency for initiating/continuing HD therapy with a permanent access does
not justify substitution of a graft for a fistula
because cuffed catheters are an effective means
of bridging the longer time necessary for primary AVF maturation.148,178,184,200 Although
catheters can be used for long-term dialysis,187,189 they should be reserved for patients
with comorbid conditions limiting life expectancy, those with systolic hypotension in whom
attempts to create/maintain a permanent access
have met with failure, and those in whom all
available sites for fistula or graft (including
chest-wall loop grafts) have been exhausted or
are not feasible.
The Primary Access Failure Rates (CPG 8.2)
Primary failure is defined as the inability to
use the graft at 30 days or obtain sufficient
blood flow from the catheter within the first
week after insertion. By proposing these goals
for 30-day primary failure rates for various
graft configurations, the Work Group does not
wish to imply that upper-arm grafts should be
elected over forearm grafts solely on the basis

of these recommended primary failure rates.
The Work Group encourages the creation and
maintenance of access sites as distally as possible to preserve more proximal veins for future access options. For example, a forearm
straight or a brachial loop graft may be used to
develop a vein for fistula construction. The
Work Group realizes that in some instances, a
dialyzer BFR of 300 mL/min might be excessive and produce disequilibrium during the
first or second treatment of a very uremic
patient. However, by the third treatment, this
should not be an issue, and a limit of 1 week is
set to determine that the catheter can deliver
adequate blood flow.
Primary access failure is considered failure
of patency within the first 30 days after placement. Primary failure of dialysis AVGs is
caused by technical problems or selection of
inappropriate vessels (artery or vein). Neointimal hyperplasia is unlikely to be so virulent as
to cause access graft failure within 30 days of
construction. It is the Work Groups opinion
that the primary failure rate reflects a center
effect that is influenced by surgical access
construction, patient demographics, adequacy
of workup (see CPG 1 and CPG 5), comorbidities, and graft loss caused by premature cannulation and hematoma formation. Primary failure rates of dialysis AVGs at the same anatomic
sites vary depending on whether the grafts are
the primary, secondary, or tertiary access. The
rates provided are derived from the published
literature for first graft accesses constructed in
a general HD population.24-26,65,67,92,423,570
Failure of a graft before use reflects surgical
construction problems. Prosthetic bridge graft
survival is decreased in patients with diabetes,
even at 30 days, and may be affected adversely
by increasing age in patients without diabetes.571
Patient demographics, characteristics, and comorbidities may differ across centers and explain
some of the center effect. Each center should
monitor its performance, recognizing the influence of some demographic factors, but tracking
its own problems in access construction and use
(see CPG 8.1.1). Marked deviations from the
recommended patency rate should invoke a multidisciplinary evaluation of possible factors and
their modification.
A modern properly placed catheter (see CPG

2.4 and CPG 7.1) can deliver more than 300
mL/min at a prepump pressure of 250 mm Hg
in adults. A catheter that cannot deliver a flow
of 300 mL/min is not being run at a sufficient
negative pressure, is improperly positioned, or
is dysfunctional for some other reason. Because blood flow with time is a major determinant of adequacy of dialysis, the cause must be
determined quickly and corrected. The Work
Group believes that catheter blood flow is an
indicator of quality in a program. Data for performance should be collected and analyzed to improve quality and protect the patient from underdialysis.
Access Complications and Performance
(CPG 8.3)
The Work Group believes that it cannot
provide a reasonable estimate of expected cumulative patency of dialysis catheters. The use
of cuffed catheters as permanent vascular access is discouraged, except in particular patient groups (see CPG 3).
The current national average rate of thrombosis of dialysis AVGs can only be approximated because there is no mandatory reporting. It is likely to be greater than the overall
rate (all permanent accesses) of approximately
0.8 episodes/patient-year at risk10,29 because
these rates include the much lower rate of
thrombosis of fistulae. In grafts, rates varying
from 0.5 to almost 2 episodes/graft-year at risk
have been reported in the absence of surveillance or monitoring programs.10,29,374,572 The
rate of graft thrombosis is determined largely
by the presence of unrecognized hemodynamically significant stenosis.10,266,572 Six published studies showing the value of surveillance reported baseline thrombosis rates
varying from 0.5 to 0.8 episodes/graft-year at
risk, which then decreased by 43% to 67% to
rates of 0.2 to 0.4 episodes/graftyear.10,322,343,352,373,374 Implementation of surveillance techniques should reduce stenosis
and make a rate of 0.5 achievable, even in
programs with greater than average rates of
thrombosis Therefore, dialysis grafts should
be monitored/undergo surveillance to permit
early detection of hemodynamically significant stenosis with the goal of reducing the
S261
thrombosis rate to a maximum of 0.5 thrombosis/y for AVGs.

PTA is performed to dilate a stenotic lesion
within a vascular access or its draining vein.
Adequacy of the procedure is measured best
by the duration of effect: ie, duration of subsequent patency until either another PTA is required for recurrence of stenosis or thrombosis
occurs. A number of observational studies
showed that a greater fraction of grafts remained free of interventions or thrombosis if
the AVG was patent at the time of intervention
(see CPG 6). The fraction of AVGs free of
further intervention or thrombosis ranged from
71% to 85% among 4 studies if PTA was
performed preemptively compared with only
33% to 63% if PTA was performed after thrombectomy of the graft.373,374 After PTA of stenoses associated with nonthrombosed AVGs, published series consistently reported a 6-month
primary (unassisted) patency rate of 40% to
50% (see CPG 6). The duration of effect after
thrombectomy and correction of stenosis is
considerably shorter. The 4-month criteria are
meant to foster 2 processes: (1) preemptive
PTA, and (2) assessment of the adequacy of the
intervention (PTA or surgery) because inadequate correction typically is manifested by
thrombosis or recurrence of the lesion within
weeks.
The rate of fistula thrombosis is much less
than that of grafts. Fistulae have the lowest
rate of thrombosis,57 require the fewest interventions,57,58 and provide longer survival of
the access.3,57,58 For native fistulae, access
events are only 14% to 33% of those observed
in grafts.3,57,58 Therefore, a fistula thrombosis
rate that is half that of grafts should result in at
least a 1-year longer access survival in wellfunctioning dialysis programs.
Infectious complications of accesses are a
leading cause of morbidity and mortality in
dialysis patients. The current national combined infection rates for permanent accesses
for local and bacteremic infections are calculated to be 1% to 4% for primary AVFs and
11% to 20% for AVGs during their expected
periods of use.4,16,232,543,573-577 Significant variance among dialysis centers is noted.232,543,575,577
Rates of 1% and 10% are the lower end of the
published ranges and will demand more attention
S262
to aseptic technique (see CPG 3) by some centers.

The catheter infection rate is highly variable532,578,579 and clearly depends on the duration of use.156,211,533 At 2 weeks of catheterization, the incidence of infection of noncuffed
central catheters generally is less than 8%.580
One study reported a bacteremia rate of less
than 5% in cuffed catheters used less than 3
months and a 50% removal rate for cuffed
catheter infection at 12 months of use.156 Other
factors include being an incident patient, changing from 1 vascular access to another, and poor
patient hygiene.238 The National Nosocomial
Infections Surveillance data show that national
surveillance of health careassociated infections combined with an intervention prevention program can reduce infection rates, reduce
morbidity and mortality, and improve patient
safety.581 Establishment of such health care
associated infection surveillance and prevention systems in countries throughout the world
should be a priority.
The Work Groups recommendations are significantly less than the experiences of some
centers. The Work Group believes infection
rates can be decreased significantly through
meticulous attention to detail and, in the case
of catheters, following the recommendations
in CPG 3 and CPG 7. Catheter infection rates
can be decreased to less than 1.5 episodes/
1,000 days by paying scrupulous attention to
the hub,247 a rate that is significantly less
(5%) than the 10% rate proposed. Infection
rates also can be decreased by paying attention
to skin preparation at the time of placement,582
appropriate use of topical antibiotics,578,583
and use of nonocclusive dressings.584 Programs with high infection rates should consider the importance of nurse and patient training585 (see CPG 3.5).
Complications related to the insertion of
TCCs depend on operator skill. Cuffed catheters can be inserted with reference to anatomic landmarks, with or without ultrasound
guidance,151,579,586-588 but always with the use
of fluoroscopy to verify proper positioning of
the catheter tip (see CPG 2.4). Cuffed catheters
can be placed by nephrologists, surgeons, or
radiologists. Cumulative complication rates less
than 5% are obtained routinely without ultra-
sound guidance.151,579 A recommended complication rate less than 2% is less than values
reported in the literature. However, published
results are based on procedures obtained without benefit of ultrasound guidance. The RR for
complication decreased 5-fold with the use of
ultrasound.587 In the Work Groups opinion,
rates of 1% should be obtainable in almost all
centers and should be the goal.
Double-lumen cuffed catheters are used as
both temporary access while a permanent access is maturing and as permanent access in
patients who have exhausted other options.
This variation in intended use creates significant variation in catheter survival rates. A
study reported a median cumulative catheter
survival rate of 18.5 months; 65% of silicone
dual-lumen catheters survived 1 year.151,587
Conversely, another group reported a 1-year
cumulative patency of 30%.579 Another study
using 2 single-lumen Silastic catheters (with
the majority serving to bridge a period until
permanent access was established) reported an
average catheter survival of 57 days.152 Others
reported a 50% catheter survival rate at 12.7
months156 and median survival period of 289
days.186 Finally, 1 study reported an 80% survival rate at 1 year,589 no doubt in part the
result of an all-cause infection rate less than 2
episdes/1,000 days.
Numerous studies reported 1-year patency
rates of grafts between 63% and 90%.24,25,67,590
One report described an overall average patency rate of 70%.4 Many investigators reported patency rates at 2 and 3 years, as
well.4,24,25,67,73 Outflow obstruction, followed
by thrombosis, accounts for the majority of
AVG failures. The Work Group believes that
prospective surveillance and monitoring (see
CPG 4) may improve this reported experience
despite the aging of the population and increasing percentage of patients with diabetes or
peripheral vascular disease. Thus, cumulative
patency targets for grafts of 70% at 1 year,
50% at 2 years, and 50% at 3 years should be
achievable. Because fistulae have a lower
thrombosis rate, their cumulative survival
should be greater. Despite the current problems with maturation and early failure, the
Work Group believes that rates comparable to
those in Europe can be achieved.3,87,591,592
With respect to grafts, there now has been

sufficient time to assess the effect of the efforts
made since the previous guidelines, at which the
time the Work Group recommended that the
primary failure rate of AVFs not be used as an
indicator of quality. This was done for fear that
during the learning curve of fistulae construction, patients with more complex vascular anatomy (ie, patients at greater risk for failure) might
S263
be discouraged. The Work Group recommended

that primary failure of native AVFs be examined
in dialysis centers as part of their QA/CQI vascular access programs. Since then, many studies
documented the superior patency (with lower
thrombotic rates) of fistulae compared with
grafts.3,37,57,570,593-598 The median patency of 3
years is based on current data and may improve
if we can improve cannulation skills.
II. CLINICAL PRACTICE RECOMMENDATIONS FOR

VASCULAR ACCESS

PATIENT PREPARATION FOR PERMANENT
HEMODIALYSIS ACCESS
Factors that may be helpful in preparing
the patient for placement of a permanent HD
access include the following:
1.1 The veins of the dorsum of the hand
should be the preferred site for IV cannulation.
1.2 Sites for venipuncture should be rotated if
arm veins need to be used.
1.3 Patients with CKD stage 5 should be
educated on the risks and benefits associated with catheters and strongly encouraged to allow the evaluation for and
creation of a fistula for long-term access
when appropriate. Such discussions with
the patient should be initiated months
before the anticipated start of dialysis
therapy.
1.4 Alternative imaging studies for central
veins include DDU and magnetic resonance imaging/MRA.
RATIONALE
Venipuncture complications of veins potentially available for vascular access may render
such vein sites unsuitable for construction of a
primary fistula. Patients and health care professionals should be educated about the need to
preserve veins to avoid loss of potential access
sites in the arms and maximize chances for
successful fistula placement and maturation. Subclavian vein catheterization is associated with
central venous stenosis.28-30 Significant subclavian vein stenosis generally will preclude the use
of the entire ipsilateral arm for vascular access.
Thus, subclavian vein catheterization should be
avoided for temporary access in patients with
kidney disease.31 The incidence of central vein
stenosis and occlusion after upper-extremity
placement of PICCs and venous ports was 7% in
1 retrospective series of 150 patients.32 PICCs
also are associated with a high incidence of
upper-extremity thrombosis. The incidence of
upper-extremity venous thrombosis varies between 11% and 85%, which leads to loss of
potential upper-extremity fistulae. 33-35 Be-
cause of the substantial risk for loss of useable

upper-extremity veins and central venous stenosis with PICCs, the Work Group recommends strongly that PICCs not be used in
patients with CKD.
Ideally, patients should have a functioning
permanent access at the time of dialysis therapy
initiation. Function implies that the access not
only deliver adequate blood flow for dialysis, but
also may be cannulated easily and repetitively.
Timely attempts to create a primary fistula before
the anticipated need for dialysis therapy will
allow adequate time for the fistula to mature and
sufficient time to perform another vascular access procedure if the first attempt fails, thus
avoiding the need for temporary access. Early
referral of a patient with CKD to a nephrologist
is needed to facilitate CKD therapy with medications and diets that preserve kidney function. In
addition, counseling patients on CKD treatment
options is essential to plan for ideal access (ie,
PD and HD access).
Duplex ultrasound is the preferred method for
preoperative vascular mapping. Vascular mapping in preparation for the creation of a vascular
access refers to the evaluation of vessels, both
arterial and venous, of patients with CKD who
selected HD in preparation for the creation of a
vascular access. Vascular mapping should be
performed in all patients before placement of an
access. Preoperative vascular mapping was shown
to substantially increase the total proportion of
patients dialyzing with fistulae.36-39 Several studies support the 2.0- to 2.5-mm vein diameter
threshold for successful creation of a fistula.36,39
Radiocephalic fistulae constructed in veins with
a less than 2.0-mm diameter had only 16%
primary patency at 3 months compared with 76%
for those with veins greater than 2.0 mm.36 In a
pivotal study,39 a threshold of 2.5-mm vein diameter assessed by using duplex ultrasound was
used; this resulted in an increase in fistula creation of 63% compared with a retrospective
14% rate in the absence of vascular mapping.22
A similar study using the same duplex ultrasound criteria showed a fistula increase from
34% in historical controls to 64%. Importantly,
S265
S266
in this study, duplex ultrasound altered the

surgical plan based entirely on the surgeons
clinical evaluation, resulting in increased placement of fistulae.72
Although angiography remains the standard
for evaluating the central veins, the central veins
RECOMMENDATIONS FOR VASCULAR ACCESS
may be assessed indirectly by using duplex ultrasound.44 Compared with invasive venography,
duplex ultrasound had a specificity of 97% and
sensitivity of 81% for detecting central vein
occlusion.45 Alternatively, MRA may be used to
evaluate central veins.46

GUIDELINE 2: SELECTION AND PLACEMENT
OF HEMODIALYSIS ACCESS
Recommendations for fistulae:
2.1 When a new native fistula is infiltrated (ie,
presence of hematoma with associated
induration and edema), it should be rested
until the swelling is resolved.
RATIONALE
There are no studies evaluating the need to rest
a fistula after an infiltration. Common sense
dictates that cannulation should be avoided in the
involved area until landmarks can be seen clearly.
The most common reason for infiltration is poor
cannulation. Successful cannulation and use of
the fistula can be engendered by providing a

digital photo map of the fistula based on ultrasound. This educates the staff and develops expertise. Dialysis units should develop a new AVF
cannulation protocol to prevent trauma to the
newly cannulated AVF, such as progressive evolution of needle gauge used for cannulation (see
CPG 3). The needle gauge and BFR should be
increased slowly to prevent infiltrations and
should be detailed clearly in the fistula breakin cannulation protocol. The role of improving
the cannulation needles requires further investigation.397
S267

CANNULATION OF FISTULAE AND GRAFTS AND ACCESSION
OF DIALYSIS CATHETERS AND PORTS
3.1 Cannulation skill:
Staff should be appropriately trained and
observed for technical mastery before
cannulating any AV access. Only those
with said technical mastery should be
allowed to cannulate a new fistula. A
protocol for minimizing vessel damage
should be used for cannulation failure.
Recannulation should be attempted only
when the cannulation site is healed and
the vessel is assessed to be normal and
appropriate for cannulation. Heparin
management should be reviewed on a
case-by-case basis to minimize postdialysis bleeding.
3.2 Self-cannulation:
Patients who are capable and whose access
is suitably positioned should be encouraged
to self-cannulate. The preferred cannulation
technique is the buttonhole.
3.3 Buttonhole:
Patients with fistula access should be considered for buttonhole (constant-site) cannulation. (See protocol in CPG 3.)
3.4 Elevation of arm for swelling:
The AVG access arm should be elevated
as much as possible until swelling subsides, which may take as long as 3 to 6
weeks. Increase in symptoms requires
urgent evaluation.
S268
RATIONALE
Data from DOPPS599 show that a functional
fistula should have an outflow vein that can be
successfully cannulated 1 month postoperatively.
The previous KDOQI Vascular Access Guidelines recommendation of 3 to 4 months after
access creation was opinion based as a result of
anecdotes of early cannulation failure with resulting tissue infiltrations and vessel damage. Consideration should be given to marking, with the
aid of ultrasound, veins that are difficult to see
and feel, with accompanying measurements of
the vein margins to prevent aspiration of clots
when the needle is placed too close to the vein
wall.
Many centers have higher doses of heparin for
catheter-dependent patients than for patients with
subcutaneous access. New fistulae are more likely
to bleed for a variety of reasons: infiltrations,
patient and staff inexperience with hemostasis,
and lack of clarity regarding when to reduce the
heparin dose if a patient is using both a fistula
and 1 lumen of the catheter.
There is growing evidence that buttonhole
(constant-site) cannulation may be less likely
to infiltrate, may be pain free for the patient,
may help preserve the integrity of the outflow
vein,244 and may be easier for patients to
self-cannulate.

DETECTION OF ACCESS DYSFUNCTION: MONITORING,
SURVEILLANCE, AND DIAGNOSTIC TESTING
4.1 Monitoring the access:
4.1.1 Access patency should be ensured
before each treatment before any
attempts to cannulate the access.
4.1.2 All caregivers, including fellows in
training, should learn and master
the methods for examining a vascular access.
4.1.3 Access characteristics, such as pulsatility and presence of thrill, as
well as flow and pressure, should be
recorded and tracked in a medical
record and be available to all caregivers of the VAT.
4.2 Frequency of measurement is dependent
on the method used:
4.2.1 It is not clear that access flow measurements performed at a monthly
frequency provide sufficient data stability to make decisions. Until additional studies are performed to determine the optimal frequency, more
frequent measurements are recommended.
4.2.2 Static pressure measurements require less technology and should be
made more frequently than flow measurements. Direct measurements of
static pressure ratios should be made
every 2 weeks. Less-direct measurements should be made weekly. Dynamic pressures, if used (see CPG
4.2.3), should be measured with each
dialysis treatment, but derivation
of a static pressure should be attempted, rather than using the raw
numbers.
4.2.3 Measurement of recirculation is not
recommended as a surveillance technique in grafts.
4.3 Frequency of measurement for access
complications:
4.3.1 Thrombosis in fistulae develops more
slowly than in grafts. Flow measurements performed at a monthly frequency appear to be adequate. Until
additional studies are performed to
determine the optimal frequency,

less frequent measurements are not
recommended.
4.3.2 Because static pressure measurements are inherently less accurate
in detecting access stenosis in fistulae, the frequency should not be less
than in grafts. Direct measurements
of static pressure ratios should be
made every 2 weeks. Less-direct measurements should be made weekly.
Dynamic pressures should be measured with each dialysis. Increased
recirculation can indicate reduced
effective blood pump flow, resulting
in inadequate dialysis.
4.4 Diagnostic testing:
4.4.1 Characteristics of access (see CPR
4.1), as well as blood pump flow and
pressure performance, should be recorded and tracked in medical
records.
4.4.2 Data should be analyzed at least
monthly to evaluate access dysfunction.
4.4.3 After intervention, the surveillance
parameter should be restored to normal.
4.4.4 Data should be analyzed to improve
success rates and ensure that interventions are appropriately assessed.
For example, PTA and surgical revision rates, recurrence rates, and
number of procedures per patient
year should be systematically analyzed in a CQI process.
4.4.5 A multidisciplinary team should be
involved.
4.4.6 Preemptive correction of hemodynamically significant stenoses should
remain the standard of care.
RATIONALE
There is considerable debate concerning
whether PTA interventions improve long-term
outcomes. Until sufficiently powered clinical
studies are performed, the rationale for monitor-
S269
S270
ing and surveillance are provided in CPG 4. It is

the belief of the Work Group that physical examination and clinical evaluation are forgotten skills
that, if restored, could be as valuable as any
surveillance method.
The utility of any method develops on sequential assessment and evaluation. This requires col-
lection and storage of observations and/or data.

Because stenoses evolve over time, observations
and data should change over time. Because observers may change, data must be available to all
caretakers.
Quality and outcome improvement cannot be
determined without analyses of data.

5.1 If a new fistula access has vein margins
that are difficult to discern on physical
examination and cannulation frequently is associated with aspiration of
clot, the patient should be referred for
access marking by means of DDU to
define the center of the vessel and depth
of the fistula. A diagram of these findings should be sent to the dialysis unit.
5.1.1 The patient should be taught to
examine his or her access daily,
while at home, for thrombosis.
RATIONALE
Many patients present with an occluded access. In a fistula, successful declotting decreases
with the duration of thrombosis (see CPG 5.4.2).
Thrombus may propagate into side branches or
become organized, increasing resistance to extraction. Most thromboses occur at home, and when
questioned, many patients cannot recall when
they last felt for the access thrill or pulse. The
Work Group believes that this area is ripe for
research on the efficacy of simple teaching on the
early detection of thrombosis and the degree of
early, as well as late, patency achieved by intervention.
S271

7: PREVENTION AND TREATMENT OF CATHETER AND
PORT COMPLICATIONS
7.1 Treatment of catheter dysfunction:
Catheter dysfunction should be treated
when a dialyzer blood flow of 300 mL/min
is not being attained in a catheter previously able to deliver greater than 350
mL/min at a prepump pressure of 250
torr.
7.1.1 A dysfunctional catheter (blood flow
< 300 mL/min) for 2 consecutive
treatments should be treated in the
HD unit by using an intraluminal
interdialytic thrombolytic lock protocol between 2 dialysis treatments
(ie, 35 to 69 hours).
7.2 Radiological evaluation:
Any dysfunction that cannot be managed
in the dialysis unit should be sent for
radiographic study to diagnose dysfunction and document the condition of the
vessel.
7.2.1 Catheter imaging with contrast infusion can identify other correctable
problems (eg, residual lumen thrombus, external fibrin catheter sheath,
malpositioned catheter tip). Appropriate interventions may follow, such
as:
7.2.1.1 Repositioning of the catheter.
7.2.1.2 Angioplasty of a vessel.
7.2.1.3 Replacement of a malpositioned catheter over guide
wire.
7.2.1.4 Higher-dose lytic infusion
for occlusive thrombus (eg,
right atrial) or fibrin sheath.
7.3 Choice of thrombolytic and use of other
modalities:
7.3.1 A special brush is used to remove
thrombus from the lumens of a
conventional catheter by using a
protocol specific to this procedure.
7.4 Treatment of infection:
7.4.1 Catheter exit-site infections, in the
absence of a tunnel infection, should
be treated with topical and/or oral
antibiotics, ensuring proper local
S272
exit-site care. In general, it should

not be necessary to remove the catheter.
7.4.2 If a patient with bacteremia is afebrile within 48 hours and is clinically stable, catheter salvage might
be considered by using an interdialytic antibiotic lock solution and 3
weeks of parenteral antibiotics in
appropriate situations. A follow-up
blood culture 1 week after completion of the course of antibiotics
should be performed. (see Table 24)
7.4.3 Antibiotic lock with antibiotic to
which the organism is sensitive is
indicated when follow-up cultures
indicate reinfection with the same
organism in a patient with limited
catheter sites.
7.4.4 Short-term catheters should be removed when infected. There is no
conclusive evidence to support a
rationale for scheduled replacement
except for those in the femoral area.
RATIONALE
Treatment of Catheter Dysfunction (CPR 7.1)
Locking with tPA maintains the conductance
of a catheter better than locking with heparin.496
Alternatively, intracatheter lytic infusion (eg, UK,
20,000 U/lumen/h for 6 hours,600 or alteplase,
2.5 mg/lumen over 1 to 2 hours) during the
dialysis can restore blood flow.601,602
Several studies evaluated the effect of tPA
infusion in restoring patency to dysfunctional
catheters. In general, infusion of 1 to 4 mg/lumen
over 1 to 4 hours permits restoration of flow
(200 mL/min) sufficient to permit completion
of a dialysis treatment,601-603 permitting control
of serum potassium levels and fluid removal.
Infusion may succeed when a simple timed dwell
fails. The difference in efficacy may result from
the amount of lytic that gets to the fibrin/
thrombus in a limited time. With the dwell technique, only the lytic at the catheter tip is biochemically active; the amount that has not leaked
immediately must slowly diffuse to the fibrin or
S273
Fig 10. Fibrin sheath (A) prior to therapy; (B) after treatment with PTA. Abbreviations: LIJ, Left internal jugular;
RA, Right atrium; SVC, Superior Vena Cava. (Courtesy of Dr A. Asim).
thrombus at the tip or exterior to the catheter.

Conversely, push or infusion techniques more
rapidly deliver the lytic in the lumen to the area
of need. However, there have been no head-tohead comparisons. There should be little fear to
use tPA as a long lock dwell or as infusions of
doses less than 10 mg. The half-life of tPA is on
the order of minutes, and it is only active when
bound to fibrin. At the doses and infusion rates
used, there is virtually no risk for systemic thrombolytic effect.
Very few head-to-head comparisons have been
made among the available lytics.525,604,605 Two
studies showed an advantage of tPA over UK, but
neither was randomized. In 1 of the studies, the
push protocol was used as opposed to the passive dwell.525 The choice of agent to be used is
governed by many factors, including availability,
convenience, cost, and comparative efficacy.
Unfortunately, when the fibrin deposition/
thrombus formation process is allowed to advance to a severe degree, the occlusive process
recurs and repeated doses of lytic must be administered496,516,517,523 at a median intertreatment
interval of only 5 to 7 additional dialysis sessions.516 This is believed to result from the
presence of a fibrin sheath that, at times, is so
extensive as to occlude the SVC.606
Endoluminal brushing, although not used
widely in the United States, can remove clots
effectively and also provides material for culture
to rule out or confirm infection.528
Radiological Evaluation (CPR 7.2)
A fibrin sheath can only be diagnosed by
performing a contrast study and requires partial
pull back of the catheter. A representative example is shown in Fig 10.

A fibrin sheath can be treated in 1 of several
ways: fibrin sheath stripping, guide wire catheter
exchange, and lytic infusion.156,157,579,607-609
Studies have shown the success of tPA infusion,607,608 as well as stripping of the catheter.156,609 No difference in outcome was found
between percutaneous stripping and UK infusion.530 See Table 24 in CPG 7.6 for additional
information.
There have been no comparisons of sheath
disruption with an angioplasty balloon compared
with the other 2 techniques. It is intermediate in
complexity. Until such studies are done, the
Work Groups preferred intervention for a fibrin
sheath is removal of the catheter over a guide
wire, disruption of the sheath with a balloon, and
placement of a new catheter (catheter exchange).531
Catheter Maintenance (CPR 7.3)
Increasing focus should be placed on prevention or control of growth of the fibrin sheath
through periodic high-dose lytic infusion600
triggered by a progressive decrease in achievable BFR. Also, some centers are using weekly
instillation of tPA or UK to maintain flow
characteristics of long-term catheters.496,531
There is sufficient evidence of effectiveness
for the Work Group to recommend these approaches for long-term catheter management
with the proviso that this is an area for future
research to optimize the best regimens that are
cost-effective.
CLINICAL PRACTICE RECOMMENDATION 8: VASCULAR

ACCESS IN PEDIATRIC PATIENTS
8.1 Choice of access type:
8.1.1 Permanent access in the form of a
fistula or graft is the preferred form
of vascular access for most pediatric
patients on maintenance HD therapy.
8.1.2 Circumstances in which a CVC may
be acceptable for pediatric longterm access include lack of local
surgical expertise to place permanent vascular access in small children, patient size too small to support a permanent vascular access,
bridging HD for PD training or PD
catheter removal for peritonitis, and
expectation of expeditious kidney
transplantation.
8.1.3 If surgical expertise to place permanent access does not exist in the patients pediatric setting, efforts should
be made to consult vascular access
expertise among local adult-oriented
surgeons to either supervise or place
permanent vascular access in children.
8.1.4 Programs should evaluate their
patients expected waiting times on
their local deceased-donor kidney
transplant waiting lists. Serious consideration should be given to placing permanent vascular access in
children greater than 20 kg in size
who are expected to wait more than
1 year for a kidney transplant.
8.2 Stenosis surveillance:
An AVG stenosis surveillance protocol
should be established to detect venous
anastomosis stenosis and direct patients
for surgical revision or PTA.
8.3 Catheter sizes, anatomic sites, and configurations:
8.3.1 Catheter sizes should be matched to
patient sizes with the goal of minimizing intraluminal trauma and obstruction to blood flow while allowing sufficient blood flow for adequate HD.
8.3.2 External cuffed access should be
placed in the internal jugular with
the distal tip placed in the right
atrium.
S274
8.3.3 The BFR of an external access should

be minimally 3 to 5 mL/kg/min and
should be adequate to deliver the
prescribed HD dose.
INTRODUCTION
Applicability of Previous KDOQI Vascular
Access Guidelines to Pediatric Patients
Provision of validated evidence-based pediatric vascular guidelines is hampered by a number
of pediatric CKD stage 5related epidemiological issues. Most of the recommendations outlined in the first edition of the KDOQI Vascular
Access Guidelines are pertinent to pediatric patients, although few published data exist to support more than opinion-based recommendations.
Some pediatric HD vascular access descriptive
and comparative clinical research has been conducted since the first edition of the KDOQI
Vascular Access Guidelines, which provide data
to formulate a first set of both evidence- and
opinion-based recommendations for children receiving maintenance HD. Rather than restating
the previous CPGs in their entirety with annotation of the few areas in which the emphasis may be
different for pediatric patients, we have opted to
present separate pediatric Vascular Access Guidelines based on the available pediatric literature. For
specific vascular access areas not addressed in
these pediatric guidelines, the practitioner should
refer to the relevant adult KDOQI Guidelines.
RATIONALE
Choice of Access Type (CPR 8.1)
Kidney transplantation remains the preferred
and predominant therapy for pediatric patients
with CKD stage 5; therefore, many pediatric
patients receive maintenance HD through an
indwelling catheter in light of short deceaseddonor waiting list times or a readily available
living-related donor (see Fig 11).610 Because
fewer than 800 pediatric patients receive maintenance HD therapy in the United States, surgical expertise for placing fistulae or grafts in
small patients may be limited by the infrequent
need and sporadic caseload. Smaller patients,
especially those less than 10 kg, present technical challenges in terms of both surgical and
VASCULAR ACCESS IN PEDIATRIC PATIENTS
S275
Fig 11. Pediatric progress

from CKD stages 1 to 5 and KRT/
access algorithm.
nursing skill; therefore, the majority of smaller

patients receive PD for their maintenance dialysis modality.
Recent data show that AVFs and AVGs typically function longer75,611-613 than catheters614-616
in pediatric patients receiving maintenance HD
therapy. Functional survival rates of AVFs and
AVGs are similar to adult patient standards and
those recommended by KDOQI Vascular Access
Guidelines, with centers recently reporting 4-year
functional survival rates of 40% to 60%. Despite
this, the most recent CMS CPM and North American Pediatric Renal Transplant Cooperative Study
data617 show that 62% to 78% of pediatric maintenance HD patients have catheters as their vascular access. While reports of successful permanent vascular access in children less than 10 kg
in size exist,611,612,618 maturation can take up to
4 to 6 months, making routine permanent access
placement impractical in many pediatric situa-
tions. Since the late 1970s, both AVFs and AVGs

have been placed in children requiring maintenance HD.619 The major complications of pediatric fistulae include a primary nonfunction rate of
20% to 33%, usually because of lack of maturation or clotting. Pediatric fistulae can develop
stenosis anywhere along the fistula, most of
which is amenable to either surgical correction or
PTA.620 Given the relatively long life expectancy for pediatric patients with CKD stage 5
(79% at 10 years and 66% at 20 years),621 all
efforts should be made to use distal sites for
initial fistula creation, ie, the radiocephalic fistula configuration. For patients less than 10 kg in
size with a creatinine clearance between 20 and
25 mL/min/1.73 m2 in whom imminent dialysis
is not required, microsurgical techniques should
be used for fistula creation.611,612 Fistulae in
smaller children may require 4 to 6 months for
adequate maturation.
S276
Table 25. Semipermanent HD Catheter and Patient Size Guideline

Patient Size (kg)
<10 kg
10-20 kg
20-25 kg
20-40 kg
>40 kg
Stenosis Surveillance (CPR 8.2)

AVGs offer the advantage of more flexible
surgical configurations, which include the use of
thigh vessels. Recent data show that AVGs can
function well in pediatric patients receiving maintenance HD, with functional survival rates similar to adult patient standards and KDOQI Vascular Access Guidelines.613 As with AVFs, the
more distal anatomic sites should be used for first
access to preserve more proximal sites for access
in later life. AVG venous outflow stenosis predisposes pediatric patients to AVG thrombosis. Recent pediatric data show that UDTs are very
sensitive to predict venous stenosis.365 A proactive ultrasound dilution venous stenosis assessment protocol directing patients to angioplasty
with a corrected access flow less than 650 mL/
min can lead to a significant decrease in AVG
thrombosis rates.622,623 One pediatric study found
that static venous pressure monitoring did not
help in the diagnosis of venous stenosis.624 No
data exist about the long-term effect of decreased
thrombosis rates on AVG survival in children.
Catheter Sizes, Anatomic Sites, and
Configurations (CPR 8.3)
The choice of catheter size and configuration
depends on the size of the patient. Studies to date
suggested that children as small as 4 to 5 kg can
tolerate dual-lumen 8 Fr catheters, and as the
child becomes larger in size, a larger volume
Catheter Options
Made on a case by case basis
8 French dual lumen
7 French twin catheter
10 French dual lumen
10 French Split catheter
11.5 or 12.5 French dual lumen
access can be placed.625 Table 25 serves as a

guideline for matching catheter size to patient
size. Choices often are limited based on availability, but considerations should include flow characteristic, recirculation risk, and ease of placement. Data suggest that for the appropriately
sized patient, twin single-lumen catheters (the
Tesio System) may provide better performance
than standard dual-lumen catheters.616 Longer
and more narrow catheters result in greater resistance to flow.626
Catheter placement considerations in pediatrics are similar to those in adults, with a preference for internal jugular veins over subclavian
veins. Right atrial placement may prevent inlet
or outlet hole occlusion by blood vessels and
thus allow for the high flow rates needed to
provide adequate dialysis. Data have suggested
that subclavian stenosis occurs in excess of 80%
of patients in pediatrics who have subclavian
catheters (Denis Geary, personal communication). Femoral access can be used when upperanatomy venous access is no longer available.627
Flow rates for vascular access should be sufficient to result in a Kt/V greater than 1.2. Kt/V is
influenced further by the recirculation rate. Because flow rates in pediatrics vary by the size of
catheter, which varies by the size of the patient, a
recommended flow rate of 3 to 5 mL/kg/min is
acceptable in most patients.628
PREAMBLE
RCTs are the optimal study design to answer

intervention questions. A recent review concluded that between 1966 and 2002, the number
of RCTs published in nephrology from 1966 to
2002 (2,779) is fewer than in all other specialties
of internal medicine.629 In addition, the overall
quality of RCT reporting in nephrology is low
and has not improved for 30 years. Issues identified included unclear allocation concealment
(89%), lack of reported blinding of outcome
assessors (92%), and failure to perform intention-to-treat analysis (50%). The challenges of
improving the quality and quantity of trials in
nephrology are substantial. We need to use standard guidelines and checklists for trial reporting,
give greater attention to trial methods, and cease
to focus on results of small underpowered studies. We must involve experts in trial design and
reporting, expect multicenter collaboration, and
do larger, but simpler, trials. Many of the research recommendations made in this section
require multicenter trials to enroll sufficient patients to obtain clear-cut answers. Many will not
receive external support from government or
other grant agencies. However, they can be performed by collaboration between those in academic centers and those in clinical practice. We
should emulate cardiology, for which there has
been a 6-fold growth in clinical research trials,
particularly in the number of patients (usually in
the thousands) enrolled into the studies.
evidence and the need for research to provide
additional evidence for the current CPGs and
CPRs. No attempt was made to rank research
recommendations within each of the 3 research
categories.
Although the Vascular Access Work Group
was restricted by the NKF to a thorough literature review in only 4 areas, the Work Group has
developed research questions for all CPGs. These
questions should not be viewed as comprehensive, but as a stimulus to the nephrology community to begin to ask, hopefully, better questions
regarding vascular access with a goal of better
outcomes for our patients.
S278
CRITICAL RESEARCH
RECOMMENDATIONS
Guideline 1. Patient Preparation for Permanent
HD Access
Studies are required to determine the optimal
vascular mapping criteria based on outcome goals
of working fistulae.
Studies are needed to determine the optimal
stratification of patients for fistula placement. Is
there an age component to sizing of the artery
and vein for fistula creation? Specifically, should
the minimal vein diameter for such higher risk
groups as female, diabetic, and elderly patients
be larger to have acceptable working fistula outcomes?
Randomized studies should be performed comparing 1-stage with 2-stage brachial basilic vein
transposition fistula outcomes.
Studies are needed to determine the optimal
surgical techniques for fistula creation with outcomes to identify factors that minimize the development of surgical swing segment stenosis in
fistulae.
Guideline 2. Selection and Placement of
HD Access
Patients should be considered for construction of a primary fistula after failure of every
HD access. There is a paucity of information
about the success of this strategy. If a forearm
loop AVG is placed as initial access, does this
lead to successful construction of elbow-level
fistulae? How often? Do we need an RCT? In
what patients would a graft before fistula be costand resource effective? None? Some? Would a
PU immediate use type of graft be preferable
to a catheter if one had to do immediate (ie,
within days) dialysis?
How often is primary conversion of dysfunctional grafts to fistulae successful? Is it affected
by the previous history of thrombosis or angioplasty (if applicable)? What are the guidelines
for number of angioplasties/thrombectomies performed before compromising the ability to convert to a fistula? What is the optimal timing for
conversion?
The preference for fistulae is based on
lower morbidity associated with their creation
and maintenance compared with other access
types. Is this still true for the US CKD stage 5
population?
Has this remained true as the population has
grown older and the health care system in the
United States has been stretched? Late referrals,

lower skill sets in the staff delivering dialysis and
cannulating accesses, increased comorbidity in
the United States compared with Europe, Japan,
or Canadado these factors influence the selection of initial access and the progression and
choices among different access types?
Guideline 3. Cannulation of Fistulae and Grafts
and Accession of HD Catheters and Port
Catheter Systems
Can intensive structured cannulation training
lead to better access outcomes?
Can increased remuneration for expert cannulators lead to better access outcomes?
Can self-cannulation lead to better outcomes?
Guideline 4. Detection of Access Dysfunction:
Monitoring, Surveillance, and Diagnostic
Testing
Studies are needed to compare outcomes of
physical examination with high-tech methods
in determining the best timing for intervention.
The role of DDU as an intermediate diagnostic
test should be examined to determine the timing for access intervention with PTA or surgery.
There may be important differences in the
susceptibility of grafts and fistulae to thrombosis
as a function of absolute access flow or change in
access flow over time. The best therapy for the
access also may differ according to type. Future
studies should carefully separate the surveillance
data, type of intervention (PTA or surgical),
response to therapy, and both short-term and
long-term outcomes according to access type,
either graft or fistula. Because more proximal
accesses have greater flow rates, data also should
be categorized to access location, primarily the
feeding artery (radial or ulnar versus low brachial, high brachial, and axillary for the upper
arm and femoral for the thigh).
Studies are needed to establish objective criteria for endovascular intervention.
Guideline 5. Treatment of Fistula Complications
The efficacy of physical examination in detecting abnormalities in accesses difficult to cannulate should be studied.
Comparative trials are required to assess interventional versus surgical modalities to correct
maturation failure with measurement of access
flow longitudinally before and after correction.
S279
Studies should examine the effect of intervention on: recurrent stenosis, elastic recoil, and
juxta-anastomotic stenoses.
Guideline 6. Treatment of AVG Complications
Assessing adequacy of the intervention. Is
PTA an effective intervention for treatment of
vascular accessrelated stenosis? We cannot answer this question. A fundamental problem is our
inability to reliably predict the outcomes of our
percutaneous and surgical interventions. The true
determinants of HD graft patency and longevity
remain unknown. It certainly is a complex and
multifactorial process. The primary determinants
of graft failure likely are regulated by both physiological and genetic factors and therefore are
variable within the patient population. To add to
the confusion, neointimal hyperplastic stenoses
develop simultaneously and sequentially in multiple locations. Our success in treating 1 stenosis
is negated by the rapid development of another
lesion. And there is another important variable:
delayed elastic recoil can cause rapid recurrence
of the stenosis after an apparently successful
angioplasty procedure. This phenomenon can
occur minutes to hours after balloon dilation, and
our anecdotal experience suggests that elastic
recoil of a stenosis may happen after 10% to 15%
of our angioplasty procedures. Our current challenge is to identify the determinants for successful angioplasty and optimize our techniques to
improve our clinical outcomes. In addition, we
need to develop pharmacological means to reduce/prevent the recurrence of neointimal hyperplasia after successful angioplasty.
Criteria for success. An end point is used to
define the successful completion of a procedure.
The definition of a successful procedure can be
viewed from several different perspectives. For
example, the end point for clinical success is
alleviation of the patients symptoms. Hemodynamic success is restoration of normal blood
flow throughout the treated vascular segment.
And for treatment of stenoses, the end point for
anatomic success is less than 30% residual diameter reduction. These clinical, hemodynamic, and
anatomic end points serve as the determinants of
a successful endovascular intervention. Our clinical experience has shown that these commonly
used end points are unreliable for predicting the
long-term patency of an HD graft or fistula.
S280
Although we use end points to define immediate

success, there is no postprocedural end point that
correlates with long-term patency. Our inability
to predict the long-term outcome of our endovascular procedures continues to frustrate both the
physician and patient.
After an endovascular intervention, the standard definition of anatomic success is a residual
stenosis with less than 30% diameter reduction.
Although there are well-recognized physiological concepts that support the use of 50% stenosis
as the definition of a hemodynamically significant lesion, there is no such scientific basis for
the use of less than 30% residual stenosis to
define a successful treatment. A consensus committee reached the value of 30% with representatives from interventional radiology and vascular
surgery. This well-accepted standard end point
(30% residual stenosis) has no hemodynamic
or physiological meaning. In addition, the residual stenosis does not allow for proper remodeling of the vein and may contribute to recurrence of stenosis. Therefore, it is not surprising
that use of this parameter as a determinant of
success is not predictive of the long-term patency of an HD graft or fistula. This poor correlation between degree of residual stenosis and
subsequent patency was substantiated in a study
that reported analysis of 96 interventions performed in native AVFs.630 After angioplasty, 17
lesions had greater than 30% residual stenosis
and, by definition, had failed treatment. How-
VASCULAR ACCESS
ever, there was no difference in the long-term

patency of this group compared with patients
who had lesions with less than 30% residual
stenosis on final fistulography.
Obviously, criteria used for success need to be
examined by well-designed outcome studies.
Multiple lesions and criteria for intervention.
According to the KDOQI guidelines, lesions
with less than 50% stenosis should not be treated.
However, it is not uncommon for a graft or
fistula to have multiple areas of endoluminal
irregularity that, when measured individually,
represent less than 50% stenosis and therefore
should not be treated. However, a hemodynamic
abnormality may still exist. The basic principles
of hemodynamics state that the effects of multiple stenoses are additive, similar to an electrical
circuit with a series of multiple resistors. Therefore, our current concepts that emphasize the
evaluation of individual stenoses using anatomic
criteria are flawed.
New methods54 that provide a more global
assessment of the entire vascular access circuit
suggest that subtle lesions can have substantial
hemodynamic effects. The assessment of intragraft blood flow during angioplasty procedures
may provide additional information regarding
the hemodynamic importance of lesions that are
greater than 30% but less than 50% stenosis.
We need to identify physiological/objective
criteria for successful intervention.
IMPORTANT RESEARCH RECOMMENDATIONS

HD Access
Studies are needed to determine the optimum
timing of access placement.
Studies should be performed to examine the
effect of exercises to mature vessels (arterial and
venous) before and after fistulae are constructed.
The use of diluted contrast to characterize the
venous system peripherally and centrally in patients with CKD and the effect on residual kidney function should be studied.
Additional studies are needed to compare the
accuracy of MRA and DDU in evaluating central
veins.
How can we align incentives for the creation
of fistulae for all stakeholders: patients, nephrologists, surgeons, and dialysis providers?
Guideline 2. Selection and Placement
of HD Access
What is the relative benefit of arm exercises
performed before or after fistula construction and
maturation or both?
We need RCTs to determine the effect of
exercise either before or after access construction, alone or combined, on access maturation,
time to cannulation, primary and secondary patency, ease of cannulation, number of procedures
needed during the life span of the access, and
cost analysis. Is pressure inside the fistula important in the maturation process? Is it flow or
intraconduit pressure or both that allow an access
to tolerate cannulation without infiltration?
Should a nonocclusive tourniquet be used during
exercise? Do we use/measure mere clinical end
points for these studies or does fistula flow need
to be measured as well, or does it not matter what
the flow is? Brachial artery flow can be measured
as a surrogate for access flow.
If intrafistula flow is important, what flow is
needed to mature a fistula?
Catheter Systems
Additional studies are needed of disinfectants,
the role of antibiotic locks, and which patients
may benefit most from CVC salvage. Riskbenefit outcomes, as well as long-term antibiotic
susceptibility studies, should be done to detect

resistance.
Studies are needed to examine the effectiveness of data on rotation of sites, buttonhole,
flow/pressure curves, and so on.
Does the bevel-up cannulation method decrease access complications?
What needle tip-to-tip measurements minimize recirculation or prevent erroneous access
flow measurements?
Can buttonhole (constant-site) cannulation be
used in biografts?
Should an infiltrating needle be removed after
the patient undergoes sytemic anticoagulation
with heparin?
How should the timing of flushing and locking
of heparin in a catheter occur in a patient who is
using 1 needle in the fistula and 1 side of the
catheter for return?
Do transparent dressings, where the exit site is
clearly visualized, need to be changed at each
dialysis treatment?
Monitoring, Surveillance, and
Diagnostic Testing
Further evaluation of the acoustic stethoscope
is needed in detecting hemodynamically significant stenoses.
The relationship of access flow to pressure
varies among individuals, affected chiefly by the
health and capacity of the artery to deliver flow
into the access. Within a population, there may
be no obvious relationship between access flow
and PIA if measurements are made cross-sectionally because the important determinant in an
individual is baseline flow (which may vary from
500 to 3,000 mL/min), the presence of 1 or more
stenoses, their location, and the rate of evolution
of the stenosis or stenoses. Additional studies are
needed to determine the natural course of stenoses in grafts and fistulae. Stable stenoses may
need no intervention if they are not associated
with increased risk for thrombosis. Conversely,
there may be significant risk for thrombosis,
even with access flows exceeding 1,000 mL/min.
Noninterventional trials should be conducted with
the clock starting from the time of construction.
Large-scale trials are required to determine
whether correction only of hemodynamically
S281
S282
significant lesions (those associated with low

access flows or high pressures or a change in
access flow or pressure) is superior to correction
of all stenosis greater than 50%.
Studies are required to compare strategies for
treating aneurysms in fistula: surgery with new
anastomosis versus surgical creation of new anastomosis. Cost and outcome analyses should be
performed.
Studies are needed to examine the efficacy of
endoluminal interventional versus surgical procedures for the management of aneurysms in fistulae.
Comparative trials should be performed to
study the efficacy of surgery compared with
interventional endoluminal procedures in correcting stenoses/thrombosis, with the same methods
used for outcomes.
The role of thrombolytics in reestablishing or
maintaining patency after fistula thrombosis
should be examined. Low doses of thrombolytics
have been used to keep costs controlleddoes it
make a difference in outcomes?
Data from RCTs are needed on the duration of
thrombosis and success in reestablishing/maintaining patency. Is surgery more effective early
or later?
Assessing effectiveness of interventions. It
is well accepted that a stenosis causing greater
than 50% diameter reduction is considered to be
a hemodynamically significant lesion. This value
is based on both experimental modeling of flow
stenosis631 and correlation of thrombosis rates
and degree of stenosis.10 This value is based
upon the physiology of a critical arterial stenosis.450,451 A 50% reduction in luminal diameter
corresponds to a 75% reduction in cross-sectional area, the critical point at which blood flow
begins to dramatically decrease.
Measuring technical success. What determines technical success for endovascular interventions? Should technical success be based upon
anatomic criteria, the measurement of which is
both subjective and fraught with error and usually not assessed in 2 orthogonal views? Or
should it be based upon normalization of a hemodynamic parameter that is less subjective and
more reflective of vascular access performance?
VASCULAR ACCESS
Possibilities include the use of flow measurements,

static pressure, or ultrasound imaging during the
PTA procedure or angioscopy after the procedure.
Continued clinical investigation hopefully will
provide scientific support for the use of hemodynamic end points, not anatomic end points.
Endovascular stents would seem to be an ideal
method to treat angioplasty failures. Stents can
oppose elastic recoil and optimize endoluminal
dimensions, thereby improving intragraft blood
flow and prolonging graft patency. However, the
majority of clinical studies showed that the routine use of stents does not provide an additional
benefit compared with angioplasty alone.460,461
The neointimal hyperplastic tissue continues to
grow unabated through the meshwork of the
metallic stent. For these reasons, use of endovascular stents to treat HD-related stenoses continues to be a controversial subject. A recent study
reported that use of nitinol stents provided superior results compared with stainless steel stents.632
Continued improvements in stent design, the use
of stent grafts, or the use of drug-eluting stents
may provide better long-term results. Covered
stents have been used to salvage AVGs, but
efficacy has not been compared with other
strategies.
Balloon sizing and selection. Balloons are
now available in various sizes, have cutting edges,
and are capable of delivering drugs. The proper
selection and use of these balloons requires additional studies.
Mechanical thrombectomy devices. Comparative studies are needed on efficacy and cost.
A reanalysis of existing data with differing devices should be performed.
Thrombolytics and anticoagulation. Although heparin typically is used during an endoluminal thrombectomy procedure, the proper role
of thrombolytics is unknown. The spectrum has
shifted from pharmacolytic to mechanical thrombectomy. Whether some lytics and their efficacy
are superior to others in terms of outcomes is
unknown. Several small series also suggested
that dialysis within hours of thrombectomy influences patency.
Comparison of intervention methods. Do
percutaneous and surgical techniques provide
similar results or are we using percutaneous
techniques simply because of the unavailability
of surgical manpower for performing large num-
bers of vascular accessrelated procedures in an

expedient manner? From another perspective,
are we sacrificing long-term patency of the AVG
to avoid insertion of an HD catheter?
Several reasonable studies reported that surgical techniques for AVG repair can provide substantially better outcomes compared with percutaneous techniques.467,468,472 By establishing
substantially higher primary patency goals after
surgical repair, the KDOQI guidelines have acknowledged the superiority of surgical techniques. However, because of a variety of factors,
including the unavailability of surgeons, the
growth of interventional nephrology, the trend
toward outpatient vascular access services, and
the profitability of percutaneous procedures, the
superiority of surgical techniques seems to have
been forgotten.
Do surgical techniques for AVG repair provide
more durable results with better long-term patency compared with percutaneous techniques?
Is this a political issue, a manpower issue, or a
financial issue?
Prevention of stenosis. This is a particularly important area. Both basic studies and pharmaceutical interventions are needed.
Guideline 7. Prevention and Treatment of
Catheter and Port Complications
The ideal catheter diameter is not established.
Are there concomitantly increased complications
associated with larger diameter catheters?
Studies are needed to evaluate the risk versus
benefit of higher dose warfarin therapy (INR
1.6) on catheter patency.
A comparison of lytic treatments is needed to
examine:
S283
Dwell versus push versus infusion for catheters unable to deliver BFR of 300 mL/min
Comparison of lytic agents for efficacy, cost,
and long-term performance
A number of studies on anticoagulant locks
should be done in which primary outcome
parameters of maintained access flow, resource use, and cost of care are evaluated.
These include:
1. Comparison of heparin at different concentrations (1,000 U and 5,000 U/mL) for all
3 dialysis sessions per week versus substitution of one of the heparin locks by tPA
lock
2. Use of high dose tPA (2.5-5 mg/lumen)
where the catheter blood flow delivered at
250 mm Hg falls to 300 mL/min or
decreases by 100 mL/min from its best
flow ever
A definitive study should be performed to determine the natural history of catheter/port-related
complications in the central veins, by using central
venograms, that begins with de novo catheter placement, every 6-month follow-up, and with each
catheter complication (CRB, fibrin sheath, and all
other types of catheter dysfunction).
Studies are needed to determine the association between infection and fibrin sheaths in catheters.
The optimal duration of antibiotic therapy for
catheter-related infections should be examined.
Prospective studies are needed to examine antibiotic locks as an adjunct to save catheter versus
site salvage. Outcomes as primary and economics as secondary factors should be considered.
OF INTEREST
by UDT or GPT alone flow by in-line dialysance, DDU).

HD Access
Does patient education on the various risks/
benefits of catheters versus fistulae/grafts alter
success in placement? Is it an ethical study?
What demographic variables influence the likelihood of permanent access construction among
a cohort of patients seen in a CKD clinic?

Comparative trials are needed to examine interventional versus surgical modalities to correct
maturation failure, with measurement of access
flow longitudinally before and after correction.
Guideline 2. Selection and Placement

of HD Access
Studies are needed to determine the optimum
duration of rest of a young (in use for 3
months) fistula after it has been infiltrated (ie,
presence of hematoma with associated induration and edema). What parameters should be
examined and how should such a study be designed?
The effects of catheter tip location on catheter
or port catheter system performance should be
studiedin the SVC/right atrium, common iliac,
low IVC, and high IVC/right atrium. For the
same French and luminal diameter, pressure flow
curves should be performed keeping catheter
design constant (ie, without mixing stepped and
split catheters).
Studies are required to examine the effect of
jets from catheter tips on central veins.
Catheter Systems
What effect does correction of anemia have on
access flow in fistulae? Prospective observational studies are needed.
Monitoring, Surveillance, and Diagnostic Testing
Research is needed on portable ultrasound
devices for assessing flow easily and repetitively
without operator effects.
Studies are needed to determine whether a
properly performed DVP test retains any utility
in detecting stenoses in fistulae.
Comparisons of surveillance techniques (access flow, DVP, PIA) are required in fistulae
using DDU anatomic imaging or contrast angiography to determine sensitivity and specificity.
Low-end techniques (physical examination
derived PIA flow achieved/prepump pressure)
should be compared with high-end methods (QA
S284

Treatment of infection. There are few informative data on the treatment of infected grafts.
Decisions on using antibiotics, removal or not of
the AVG, and duration of antibiotic use usually
are made based on experimental considerations
and recommendations from infectious disease
consultants and CDC publications. Most of these
recommendations are extrapolations and are not
based on specific studies of dialysis patients with
AVGs.
Arterial lesions and steal. In an increasingly
older population with a greater incidence of diabetes, arterial lesions are not uncommon in patients
undergoing vascular access constructions.409 Steal
occurs with high-flow fistulae. Prediction of its
occurrence80,633 and means to prevent its development634 require prospective outcome studies. Once
developed, several methods can be used to correct
the problem,411,431,433,635,636 but without consensus about the best procedure.48,637 When distal
digital ischemic changes or gangrene appear ipsilateral to a functioning graft, we need more
studies to determine whether the problem is
purely ischemic or perhaps embolic.431,638
Prediction of successful AVG function. A
multitude of factors probably influence the longevity of AVG function,143 including the individuals genetic predisposition for neointimal hyperplasia, surgical techniques, cannulation, and so
on. These factors have not been systemically
studied.
Guideline 7. Prevention and Treatment of
Catheter and Port Complications
Studies should examine the value of sequential
measurement of dialyzer flow rates and delivered
and prepump arterial pressures during sequential
dialysis treatments in detecting problems while
they are still amenable to pharmacological or mechanical intervention. With modern catheters, what
is the value of the conductance (BFR/arterial prepump pressure) in predicting catheter dysfunction?
Research is needed to define the optimum value
of flow rate: 300 versus 350 mL/min if the initial
flow is greater than 400 mL/min. Outcome parameters should include effects on adequacy, manpower
utilization, and cost of intervention.
Studies should culture the tips of all catheters
removed for both CRB and fibrin sheath disruption
to determine the frequency of occult silent infection.
S285
Additional studies are required to define the

agents and concentrations of antibiotic locks that
can be used, including studies of systemic levels
during prolonged periods.
Long-term studies are needed on antibiotic and
antimicrobial resistance to antibiotic locks and ointments used to prevent infection.

Anatole Besarab, MD (Co-Chair), received
his medical degree from the University of Pennsylvania, USA, and then carried out his internship and residency in medicine at Pennsylvania
Hospital. Dr Besarab then spent 3 years as renal
Fellow at Harvard Medical School (under Dr
Frank Epstein) in Boston, MA, before moving to
Thomas Jefferson University in Philadelphia,
PA, for 19 years, followed by his first stint at
Henry Ford Hospital, Detroit, MI. For 2 years he
was Section Chief at West Virginia University.
He currently is on the faculty of the Division of
Nephrology and Hypertension at Henry Ford
Hospital, and has his academic appointment at
Wayne State University. In the past decade, Dr
Besarabs work has focused on optimizing the
management of anemia and detecting vascular
access dysfunction before thrombosis. His current research interests include evaluation of diagnostic tests to detect angioaccess dysfunction
and developing algorithms that maximize hematopoietic response to epoetin. He is author of
more than 100 papers, 30 chapters, and several
monographs and has spoken extensively at national meetings and academic centers. He has
served on various committees for the Forum of
ESRD Networks of End-Stage Renal Disease
Networks, the American Society of Nephrology,
ASAIO (American Society for Artificial Internal
Organs), and the National Institutes of Health.
He has served on the editorial board of several
journals, reviews extensively for many journals,
and is a reviewer for UpToDate. He is the current
Chairman of the National Kidney Foundation
Work Group on Vascular Access. Dr Besarab has
received research funds, grants or contracts from
Abbott Laboratories, Advanced Magnetics, Affymaz, American Regent Inc. Amgen, Inc., Baxter, Genentech, Hoffman-La Roche, Rockwell
International, Transonic Systems Inc., VascAlert,
and Watson Pharmaceuticals.
Deborah Brouwer, RN, CNN, is Director of
Therapeutic and Clinical Programs at Renal Solutions, Inc. She is a member of the American
Society of Diagnostic and Interventional Nephrology, the National Kidney Foundation Council of
Nephrology Nurses and Technicians, and the
American Nephrology of Nurses Association.
Ms Brouwer has received research funds, grants
S286
or contracts from CR Bard, Genentech, Transonic Systems Inc., and WL Gore.

Timothy E. Bunchman, MD, is Director for
Pediatric Nephrology and Transplantation at
DeVos Childrens Hospital. His areas of interest
include acute renal failure, vascular access, and
solid-organ transplantation. He has received
grants from Gambro Healthcare, Baxter Healthcare, and Dialysis Solution, Inc. Dr Bunchman
has received research funds, grants or contracts
from Baxter, Dialysis Solutions Inc., Gambro,
Hoffman-La Roche, Johnson & Johnson, and
Novartis.
Lesley C. Dinwiddie, MSN, RN, FNP, CNN,
is a self-employed nephrology nurse consultant.
She is a member of the American Nephrology of
Nurses Association. Her areas of interest include vascular access, palliative care, and restless legs. She has received grants from ANNA,
Genentech (and their medical education associates), Shire (including Cardinal MES and
ProActive), American Regent, Ahrens, Balwit
and Associates, Arrow, and Vasca. Ms Dinwiddie
has also received research funds, grants or contracts from Amgen, Arrow International, Genentech, Roche Canada, and Shire US.
Stuart L. Goldstein, MD, is an Associate
Professor of Pediatrics at the Baylor College of
Medicine in Houston, TX. He is the Medical
Director of the Dialysis Unit at the Texas Childrens Hospital and the Administrative Director
of the Pheresis Service at the Texas Childrens
Hospital, both of Houston. He is a member of the
American Academy of Pediatrics, the American
Society of Nephrology, the International Pediatric Nephrology Association, the American Society of Pediatric Nephrology, the International
Society of Nephrology, and the Society for Pediatric Research. In addition, he is on the Medical
Review Board for the End-Stage Renal Disease
Network of Texas, Clinical Affairs Committee for
the American Society of Pediatric Nephrology, Dialysis Advisory Group for the American Society
of Nephrology, and Training/Certification Committee of the American Society of Pediatric Nephrology and is the Pediatric Nephrologist Representative for the International Society of
Nephrology Commission of Acute Renal Failure.
He has received grants from Gambro Renal Prod-
ucts; Dialysis Solutions, Inc; Baxter Healthcare;

B. Braun, Inc; Amgen Inc; Abbott Laboratories;
and Toray Inc. He also has lectured for Genentech. Dr Goldstein has received research funds,
grants or contracts from the American Academy
of Pediatrics, Baxter Healthcare, Dialysis Solutions, Inc., Gambro Renal Products, Genentech,
Luitopold Pharmaceuticals, NxStage Inc., and
the University of Missouri.
Mitchell L. Henry, MD, is Chief of the Division of Transplantation at Ohio State University.
He is a member of the American Society of
Transplant Surgeons. His areas of interest include transplantation, organ preservation, and
immunosuppression. He has received grants from
Novartis and MedImmune. Dr Henry has received research funds, grants or contracts from
Coalescent/Medtronic, Genzyme, Novartis, Hoffman-La Roche, and Wyeth.
Klaus Konner, MD, is now a retired clinical
nephrologist, dedicated particularly to the problems of vascular access, performing (as a nephrologist) access surgery during a period of 30
years, in addition to also practicing diagnostic
and interventional radiology. He is a member of
the European Dialysis and Transplant Association/
European Renal Association, American Society
of Nephrology, and a founding member of the
Vascular Access Society. Dr Konners special
area of interest during the last decade is vascular
access in elderly, hypertensive, and/or diabetic
hemodialysis patients, aiming at a clear preference of the autologous arteriovenous fistula. He
achieved more than 2,500 consecutive arteriovenous fistulae as a first-access procedure. Dr
Konner has received research funds, grants or
contracts from Gambro Renal Products, Germany.
Alan Lumsden, MD, FACS, is Professor and
Chief of the Division of Vascular Surgery and
Endovascular Therapy at the Baylor College of
Medicine. He is a member of the Society of
Vascular Surgery, the American Association for
Vascular Surgery, the Society of Clinical Vascular Surgery, the International Society of Endovascular Specialists, the Association of Vascular
Access Surgeons, the Peripheral Vascular Surgery Society, the International Society of Endo-
S287
vascular Specialists, the Texas Medical Association, the Michael E. DeBakey International
Surgical Society, the Harris County Medical Society, the San Antonio Vascular Surgical Society,
and a fellow of the American College of Surgeons. Furthermore, he is on the editorial board
of the Journal of Endovascular Therapy and
Vascular Ultrasound Today and is an associate
editor of Vascular Surgery. He has performed
clinical trials for VNUS, Medtronic, Boston Scientific, and WL Gore. Dr Lumsden has received
research funds, grants or contracts from Boston
Scientific, Medtronic, WL Gore, and VNUS.
Thomas M. Vesely, MD, is Associate Professor at the Washington University School of Medicine. He is on the board of directors of the
Association of Vascular Access. His area of interest includes vascular access in all of its applications. He has received grants from CR Bard;
Angiodynamics, Inc; Spire BioMedical; Transonic, Inc; Bayer; Datascope; and Enpath. Dr
Vesely has received research funds, grants or
contracts from Angiodynamics, Bayer, CR Bard,
Datascope, Enpath Medical Inc., Pervasis Therapeutics Inc., Spire Biomedical Inc., Rex Medical, Transonic Inc., and WL Gore.
Jack Work, MD (Co-Chair), is Professor of
Medicine and Director of Interventional Nephrology at Emory University. He is the chairperson
of the End-Stage Renal Disease Clinical Performance Measures QI Vascular Access Committee,
a member of the National Vascular Access Improvement Initiative and Leadership group, and
a member of CMS Dialysis Facility Compare
Vascular Access Quality Expert panel. He currently is president of the American Society of
Diagnostic and Interventional Nephrology and a
board member of the Vascular Access Society of
the Americas. His areas of interest include vascular access management, the biology of neointimal hyperplasia, vascular access surveillance techniques, and continuous flow peritoneal dialysis. Dr
Work has received research funds, grants or contracts from Cleveland Clinic, National Kidney Foundations Clinical Meeting, Novoste Corporation,
the University of Missouri Dialysis Conference,
and Vasca Inc.
REFERENCES
1. Eknoyan G, Levin NW: Impact of the new K/DOQI
guidelines. Blood Purif 20:103-108, 2002
2. Centers for Medicare & Medicaid Services: 2004
Annual Report. End-Stage Renal Disease Clinical Performance Measures Project. Baltimore, MD, Department of
Health and Human Services, Centers for Medicare &
Medicaid Services, Center for Beneficiary Choices, 2004
3. Pisoni RL, Young EW, Dykstra DM, et al: Vascular
access use in Europe and the United States: Results from the
DOPPS. Kidney Int 61:305-316, 2002
4. Mehta S: Statistical summary of clinical results of
vascular access procedures for haemodialysis, in Sommer
BG, Henry ML (eds): Vascular Access for Hemodialysis-II
(ed 2). Chicago, IL, Gore, 1991, pp 145-157
5. Kaufman JL: The decline of the autogenous hemodialysis access site. Semin Dial 8:59-61, 1995
6. The Cost Effectiveness of Alternative Types of
Vascular access and the Economic Cost of ESRD. Bethesda,
MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 1995, pp 139-157
7. Feldman HI, Kobrin S, Wasserstein A: Hemodialysis
vascular access morbidity. J Am Soc Nephrol 7:523-535,
1996
8. Eggers P, Milam R: Trends in vascular access procedures and expenditures in Medicares ESRD program, in
Henry ML (ed): Vascular Access for Hemodialysis-VII.
Chicago, IL, Gore, 2001, pp 133-143
9. Lee H, Manns B, Taub K, et al: Cost analysis of
ongoing care of patients with end-stage renal disease: The
impact of dialysis modality and dialysis access. Am J
Kidney Dis 40:611-622, 2002
10. Besarab A, Sullivan KL, Ross RP, Moritz MJ: Utility
of intra-access pressure monitoring in detecting and correcting venous outlet stenoses prior to thrombosis. Kidney Int
47:1364-1373, 1995
11. Carlson DM, Duncan DA, Naessens JM, Johnson WJ:
Hospitalization in dialysis patients. Mayo Clin Proc 59:769775, 1984
12. Feldman HI, Held PJ, Hutchinson JT, Stoiber E,
Hartigan MF, Berlin JA: Hemodialysis vascular access
morbidity in the United States. Kidney Int 43:1091-1096,
1993
13. Mayers JD, Markell MS, Cohen LS, Hong J, Lundin
P, Friedman EA: Vascular access surgery for maintenance
hemodialysis. Variables in hospital stay. ASAIO J 38:113115, 1992
14. Dhingra RK, Young EW, Hulbert-Shearon TE, Leavey
SF, Port FK: Type of vascular access and mortality in U.S.
hemodialysis patients. Kidney Int 60:1443-1451, 2001
15. Woods JD, Port FK: The impact of vascular access
for haemodialysis on patient morbidity and mortality. Nephrol Dial Transplant 12:657-659, 1997
16. Xue JL, Dahl D, Ebben JP, Collins AJ: The association of initial hemodialysis access type with mortality
outcomes in elderly Medicare ESRD patients. Am J Kidney
Dis 42:1013-1019, 2003
17. Polkinghorne KR, McDonald SP, Atkins RC, Kerr
PG: Vascular access and all-cause mortality: A propensity
score analysis. J Am Soc Nephrol 15:477-486, 2004
S288
18. Sands J, Perry M: Where are all the AV fistulas?

Semin Dial 15:146-148, 2002
19. McCutcheon B, Weatherford D, Maxwell G, Hamann
MS, Stiles A: A preliminary investigation of balloon angioplasty versus surgical treatment of thrombosed dialysis
access grafts. Am Surg 69:663-667; discussion 668, 2003
20. National Kidney Foundation: DOQI Clinical Practice
Guidelines for Vascular Access. Am J Kidney Dis 30:S150S191, 1997 (suppl 3)
21. Hood SA, Schillo B, Beane GE, Rozas V, Sondheimer JH: An analysis of the adequacy of preparation for
end-stage renal disease care in Michigan. Michigan Renal
Plan Task Force. ASAIO J 41:M422-M426, 1995
22. Glanz S, Gordon DH, Lipkowitz GS, Butt KM, Hong
J, Sclafani SJ: Axillary and subclavian vein stenosis: Percutaneous angioplasty. Radiology 168:371-373, 1988
23. Harland RC: Placement of permanent vascular access
devices: Surgical considerations. Adv Ren Replace Ther
1:99-106, 1994
24. Palder SB, Kirkman RL, Whittemore AD, Hakim
RM, Lazarus JM, Tilney NL: Vascular access for hemodialysis. Patency rates and results of revision. Ann Surg 202:235239, 1985
25. Raju S: PTFE grafts for hemodialysis access. Techniques for insertion and management of complications. Ann
Surg 206:666-673, 1987
26. Tordoir JH, Herman JM, Kwan TS, Diderich PM:
Long-term follow-up of the polytetrafluoroethylene (PTFE)
prosthesis as an arteriovenous fistula for haemodialysis. Eur
J Vasc Surg 2:3-7, 1988
27. Trerotola S: Interventional radiology in central venous stenosis and occlusion. Semin Interv Radiol 11:291304, 1994
28. Barrett N, Spencer S, McIvor J, Brown EA: Subclavian stenosis: A major complication of subclavian dialysis
catheters. Nephrol Dial Transplant 3:423-425, 1988
29. Marx AB, Landmann J, Harder FH: Surgery for
vascular access. Curr Probl Surg 27:1-48, 1990
30. Schwab SJ, Quarles LD, Middleton JP, Cohan RH,
Saeed M, Dennis VW: Hemodialysis-associated subclavian
vein stenosis. Kidney Int 33:1156-1159, 1988
31. Spinowitz BS, Galler M, Golden RA, et al: Subclavian vein stenosis as a complication of subclavian catheterization for hemodialysis. Arch Intern Med 147:305-307,
1987
32. Gonsalves CF, Eschelman DJ, Sullivan KL, DuBois
N, Bonn J: Incidence of central vein stenosis and occlusion
following upper extremity PICC and port placement. Cardiovasc Interv Radiol 26:123-127, 2003
33. Abdullah BJ, Mohammad N, Sangkar JV, et al:
Incidence of upper limb venous thrombosis associated with
peripherally inserted central catheters (PICC). Br J Radiol
78:596-600, 2005
34. Allen AW, Megargell JL, Brown DB, et al: Venous
thrombosis associated with the placement of peripherally
inserted central catheters. J Vasc Interv Radiol 11:13091314, 2000
35. Martin C, Viviand X, Saux P, Gouin F: Upperextremity deep vein thrombosis after central venous catheter-
REFERENCES
ization via the axillary vein. Crit Care Med 27:2626-2629,

1999
36. Allon M, Lockhart ME, Lilly RZ, et al: Effect of
preoperative sonographic mapping on vascular access outcomes in hemodialysis patients. Kidney Int 60:2013-2020,
2001
37. Ascher E, Gade P, Hingorani A, et al: Changes in the
practice of angioaccess surgery: Impact of dialysis outcome
and quality initiative recommendations. J Vasc Surg 31:8492, 2000
38. Gibson KD, Caps MT, Kohler TR, et al: Assessment
of a policy to reduce placement of prosthetic hemodialysis
access. Kidney Int 59:2335-2345, 2001
39. Silva MB Jr, Hobson RW II, Pappas PJ, et al: A
strategy for increasing use of autogenous hemodialysis
access procedures: Impact of preoperative noninvasive evaluation. J Vasc Surg 27:302-307; discussion 307-308, 1998
40. Mendes RR, Farber MA, Marston WA, Dinwiddie
LC, Keagy BA, Burnham SJ: Prediction of wrist arteriovenous fistula maturation with preoperative vein mapping
with ultrasonography. J Vasc Surg 36:460-463, 2002
41. Robbin ML, Gallichio MH, Deierhoi MH, Young CJ,
Weber TM, Allon M: US vascular mapping before hemodialysis access placement. Radiology 217:83-88, 2000
42. Malovrh M: Approach to patients with end-stage
renal disease who need an arteriovenous fistula. Nephrol
Dial Transplant 18:Sv50-Sv52, 2003 (suppl 5)
43. Wong V, Ward R, Taylor J, Selvakumar S, How TV,
Bakran A: Factors associated with early failure of arteriovenous fistulae for haemodialysis access. Eur J Vasc Endovasc Surg 12:207-213, 1996
44. Patel MC, Berman LH, Moss HA, McPherson SJ:
Subclavian and internal jugular veins at Doppler US:
Abnormal cardiac pulsatility and respiratory phasicity as a
predictor of complete central occlusion. Radiology 211:579583, 1999
45. Passman MA, Criado E, Farber MA, et al: Efficacy of
color flow duplex imaging for proximal upper extremity
venous outflow obstruction in hemodialysis patients. J Vasc
Surg 28:869-875, 1998
46. Smits JH, Bos C, Elgersma OE, et al: Hemodialysis
access imaging: Comparison of flow-interrupted contrastenhanced MR angiography and digital subtraction angiography. Radiology 225:829-834, 2002
47. Gracz KC, Ing TS, Soung LS, Armbruster KF, Seim
SK, Merkel FK: Proximal forearm fistula for maintenance
48. Tordoir JH, Dammers R, van der Sande FM: Upper
extremity ischemia and hemodialysis vascular access. Eur J
Vasc Endovasc Surg 27:1-5, 2004
49. Cull JD, Cull DL, Taylor SM, et al: Prosthetic thigh
arteriovenous access: Outcome with SVS/AAVS reporting
standards. J Vasc Surg 39:381-386, 2004
50. Flarup S, Hadimeri H: Arteriovenous PTFE dialysis
access in the lower extremity: A new approach. Ann Vasc
Surg 17:581-584, 2003
51. Gradman WS, Cohen W, Haji-Aghaii M: Arteriovenous fistula construction in the thigh with transposed
superficial femoral vein: Our initial experience. J Vasc Surg
33:968-975, 2001
S289
52. Huber TS, Seeger JM: Approach to patients with

complex hemodialysis access problems. Semin Dial 16:2229, 2003
53. Debing E, Van den Brande P: Axillo-axillary arteriovenous fistula as a suitable surgical alternative for chronic
haemodialysis access. Nephrol Dial Transplant 14:12521253, 1999
54. Han KM, Duijm LE, Thelissen GR, et al: Failing
hemodialysis access grafts: Evaluation of complete vascular
tree with 3D contrast-enhanced MR angiography with high
spatial resolution: Initial results in 10 patients. Radiology
227:601-605, 2003
55. Miller CD, Robbin ML, Barker J, Allon M: Comparison of arteriovenous grafts in the thigh and upper extremities
in hemodialysis patients. J Am Soc Nephrol 14:2942-2947,
2003
56. Coronel F, Herrero JA, Mateos P, Illescas ML,
Torrente J, del Valle MJ: Long-term experience with the
Thomas shunt, the forgotten permanent vascular access for
haemodialysis. Nephrol Dial Transplant 16:1845-1849, 2001
57. Perera GB, Mueller MP, Kubaska SM, Wilson SE,
Lawrence PF, Fujitani RM: Superiority of autogenous
arteriovenous hemodialysis access: Maintenance of function
with fewer secondary interventions. Ann Vasc Surg 18:6673, 2004
58. Huber TS, Carter JW, Carter RL, Seeger JM: Patency
of autogenous and polytetrafluoroethylene upper extremity
arteriovenous hemodialysis accesses: A systematic review. J
Vasc Surg 38:1005-1011, 2003
59. Nassar GM, Ayus JC: Infectious complications of the
hemodialysis access. Kidney Int 60:1-13, 2001
60. Gulati S, Sahu KM, Avula S, Sharma RK, Ayyagiri A,
Pandey CM: Role of vascular access as a risk factor for
infections in hemodialysis. Ren Fail 25:967-973, 2003
61. Brescia MJ, Cimino JE, Appel K, Hurwich BJ:
Chronic hemodialysis using venipuncture and a surgically
created arteriovenous fistula. N Engl J Med 275:1089-1092,
1966
62. Cantelmo NL, LoGerfo FW, Menzoian JO: Brachiobasilic and brachiocephalic fistulas as secondary angioaccess routes. Surg Gynecol Obstet 155:545-548, 1982
63. Dunlop MG, Mackinlay JY, Jenkins AM: Vascular
access: Experience with the brachiocephalic fistula. Ann R
Coll Surg Engl 68:203-206, 1986
64. Fan PY, Schwab SJ: Vascular access: Concepts for the
1990s. J Am Soc Nephrol 3:1-11, 1992
65. Kherlakian GM, Roedersheimer LR, Arbaugh JJ,
Newmark KJ, King LR: Comparison of autogenous fistula
versus expanded polytetrafluoroethylene graft fistula for
angioaccess in hemodialysis. Am J Surg 152:238-243, 1986
66. Kinnaert P, Vereerstraeten P, Toussaint C, Van Geertruyden J: Nine years experience with internal arteriovenous fistulas for haemodialysis: A study of some factors
influencing the results. Br J Surg 64:242-246, 1977
67. Munda R, First MR, Alexander JW, Linnemann CC
Jr, Fidler JP, Kittur D: Polytetrafluoroethylene graft survival
in hemodialysis. JAMA 249:219-222, 1983
68. Ryan JJ, Dennis MJ: Radiocephalic fistula in vascular
access. Br J Surg 77:1321-1322, 1990
69. Windus DW: Permanent vascular access: A nephrologists view. Am J Kidney Dis 21:457-471, 1993
S290
70. Begin V, Ethier J, Dumont M, Leblanc M: Prospective evaluation of the intra-access flow of recently created
native arteriovenous fistulae. Am J Kidney Dis 40:12771282, 2002
71. Johnson CP, Zhu YR, Matt C, Pelz C, Roza AM,
Adams MB: Prognostic value of intraoperative blood flow
measurements in vascular access surgery. Surgery 124:729737; discussion 737-738, 1998
72. Robbin ML, Chamberlain NE, Lockhart ME, et al:
Hemodialysis arteriovenous fistula maturity: US evaluation.
Radiology 225:59-64, 2002
73. Albers FJ: Causes of hemodialysis access failure.
Adv Ren Replace Ther 1:107-118, 1994
74. Weyde W, Krajewska M, Letachowicz W, Klinger M:
Superficialization of the wrist native arteriovenous fistula
for effective hemodialysis vascular access construction.
Kidney Int 61:1170-1173, 2002
75. Bagolan P, Spagnoli A, Ciprandi G, et al: A ten-year
experience of Brescia-Cimino arteriovenous fistula in children: Technical evolution and refinements. J Vasc Surg
27:640-644, 1998
76. Rooijens PP, Tordoir JH, Stijnen T, Burgmans JP,
Smet de AA, Yo TI: Radiocephalic wrist arteriovenous
fistula for hemodialysis: Meta-analysis indicates a high
primary failure rate. Eur J Vasc Endovasc Surg 28:583-589,
2004
77. Nazzal MM, Neglen P, Naseem J, Christenson JT,
al-Hassan HK: The brachiocephalic fistula: A successful
secondary vascular access procedure. Vasa 19:326-329,
1990
78. Nghiem DD: Angioaccess by reverse brachiocephalic
fistula. Am J Surg 153:574-575, 1987
79. Stonebridge PA, Edington D, Jenkins AM: Brachial/
basilic vein transposition for vascular access. J R Coll Surg
Edinb 40:219-220, 1995
80. Goff CD, Sato DT, Bloch PH, et al: Steal syndrome
complicating hemodialysis access procedures: Can it be
predicted? Ann Vasc Surg 14:138-144, 2000
81. Hossny A: Brachiobasilic arteriovenous fistula: Different surgical techniques and their effects on fistula patency
and dialysis-related complications. J Vasc Surg 37:821-826,
2003
82. Segal JH, Kayler LK, Henke P, Merion RM, Leavey
S, Campbell DA Jr: Vascular access outcomes using the
transposed basilic vein arteriovenous fistula. Am J Kidney
Dis 42:151-157, 2003
83. Zielinski CM, Mittal SK, Anderson P, et al: Delayed
superficialization of brachiobasilic fistula: Technique and
initial experience. Arch Surg 136:929-932, 2001
84. Caplin N, Sedlacek M, Teodorescu V, Falk A, Uribarri J: Venous access: Women are equal. Am J Kidney Dis
41:429-432, 2003
85. Konner K, Hulbert-Shearon TE, Roys EC, Port FK:
Tailoring the initial vascular access for dialysis patients.
Kidney Int 62:329-338, 2002
86. Murphy GJ, Nicholson ML: Autogeneous elbow
fistulas: The effect of diabetes mellitus on maturation,
patency, and complication rates. Eur J Vasc Endovasc Surg
23:452-457, 2002
VASCULAR ACCESS
87. Nguyen VD, Griffith C, Treat L: A multidisciplinary

team approach to increasing AV fistula creation. Nephrol
News Issues 17:54-56, 58, 60, 2003
88. Salgado OJ: Basic steps for increasing the rate of
autogenic vascular accesses for hemodialysis. Ther Apher
Dial 7:238-243, 2003
89. Didlake R, Curry E, Bower J: Composite dialysis
access grafts. J Am Coll Surg 178:24-28, 1994
90. Humphries AL Jr, Nesbit RR Jr, Caruana RJ, Hutchins
RS, Heimburger RA, Wray CH: Thirty-six recommendations for vascular access operations: Lessons learned from
our first thousand operations. Am Surg 47:145-151, 1981
91. Owens ML, Stabile BE, Gahr JA, Wilson SE: Vascular grafts for hemodialysis: Evaluation of sites and materials.
92. Anderson CB, Sicard GA, Etheredge EE: Bovine
carotid artery and expanded polytetrafluroethylene grafts for
hemodialysis vascular access. J Surg Res 29:184-188, 1980
93. Butler HG III, Baker LD Jr, Johnson JM: Vascular
access for chronic hemodialysis: Polytetrafluoroethylene
(PTFE) versus bovine heterograft. Am J Surg 134:791-793,
1977
94. Tordoir JH, Debeylaan P: The morbidity of secondary
vascular access. A lifetime of intervention. Eur J Vasc
Endovasc Surg 19:559, 2000 (letter)
95. Johansen K, Lyman D, Sauvage L: Biomaterials for
hemodialysis access. Blood Purif 12:73-77, 1994
96. Bone GE, Pomajzl MJ: Prospective comparison of
polytetrafluoroethylene and bovine grafts for dialysis. J Surg
Res 29:223-227, 1980
97. Elliott MP, Gazzaniga AB, Thomas JM, Haiduc NJ,
Rosen SM: Use of expanded polytetrafluoroethylene grafts
for vascular access in hemodialysis: Laboratory and clinical
evaluation. Am Surg 43:455-459, 1977
98. Jenkins AM, Buist TA, Glover SD: Medium-term
follow-up of forty autogenous vein and forty polytetrafluoroethylene (Gore-Tex) grafts for vascular access. Surgery
88:667-672, 1980
99. Kaplan MS, Mirahmadi KS, Winer RL, Gorman JT,
Dabirvaziri N, Rosen SM: Comparison of PTFE and
bovine grafts for blood access in dialysis patients. Trans Am
Soc Artif Intern Organs 22:388-393, 1976
100. Lilly L, Nighiem D, Mendez-Picon G, Lee HM:
Comparison between bovine heterograft and expanded PTFE
grafts for dialysis access. Am Surg 46:694-696, 1980
101. May J, Harris J, Patrick W: Polytetrafluoroethylene
(PTFE) grafts for haemodialysis: Patency and complications
compared with those of saphenous vein grafts. Aust N Z
J Surg 49:639-642, 1979
102. Sabanayagam P, Schwartz AB, Soricelli RR, Lyons
P, Chinitz J: A comparative study of 402 bovine heterografts
and 225 reinforced expanded PTFE grafts as AVF in the
ESRD patient. Trans Am Soc Artif Intern Organs 26:88-92,
1980
103. Tellis VA, Kohlberg WI, Bhat DJ, Driscoll B, Veith
FJ: Expanded polytetrafluoroethylene graft fistula for chronic
hemodialysis. Ann Surg 189:101-105, 1979
104. Rubio PA, Farrell EM: Human umbilical vein graft
angioaccess in chronic hemodialysis: A preliminary report.
REFERENCES
105. Etheredge EE, Haid SD, Maeser MN, Sicard GA,

Anderson CB: Salvage operations for malfunctioning polytetrafluoroethylene hemodialysis access grafts. Surgery 94:
464-470, 1983
106. Rizzuti RP, Hale JC, Burkart TE: Extended patency
of expanded polytetrafluoroethylene grafts for vascular access
using optimal configuration and revisions. Surg Gynecol Obstet
166:23-27, 1988
107. Rubio PA, Farrell EM: Modified human umbilical
vein arteriovenous fistula for maintenance hemodialysis: A 3
1/2-year experience. Arch Surg 117:943-945, 1982
108. Kanterman RY, Vesely TM, Pilgram TK, Guy BW,
Windus DW, Picus D: Dialysis access grafts: Anatomic location of venous stenosis and results of angioplasty. Radiology
195:135-139, 1995
109. Beathard GA: Mechanical versus pharmacomechanical thrombolysis for the treatment of thrombosed dialysis
access grafts. Kidney Int 45:1401-1406, 1994
110. Beathard GA: Thrombolysis versus surgery for the
treatment of thrombosed dialysis access grafts. J Am Soc
Nephrol 6:1619-1624, 1995
111. Beathard GA: Percutaneous transvenous angioplasty in the treatment of vascular access stenosis. Kidney
Int 42:1390-1397, 1992
112. Turmel-Rodrigues L, Pengloan J, Baudin S, et al:
Treatment of stenosis and thrombosis in haemodialysis
fistulas and grafts by interventional radiology. Nephrol Dial
Transplant 15:2029-2036, 2000
113. Coyne DW, Lowell JA, Windus DW, et al: Comparison of survival of an expanded polytetrafluoroethylene graft
designed for early cannulation to standard wall polytetrafluoroethylene grafts. J Am Coll Surg 183:401-405, 1996
114. Matsuda H, Miyazaki M, Oka Y, et al: A polyurethane vascular access graft and a hybrid polytetrafluoroethylene graft as an arteriovenous fistula for hemodialysis:
Comparison with an expanded polytetrafluoroethylene graft.
Artif Organs 27:722-727, 2003
115. Peng CW, Tan SG: Polyurethane grafts: A viable
alternative for dialysis arteriovenous access? Asian Cardiovasc Thorac Ann 11:314-318, 2003
116. Bosman PJ, Blankestijn PJ, van der Graaf Y, Heintjes RJ, Koomans HA, Eikelboom BC: A comparison
between PTFE and denatured homologous vein grafts for
haemodialysis access: A prospective randomised multicentre
trial. The SMASH Study Group. Study of Graft Materials in
Access for Haemodialysis. Eur J Vasc Endovasc Surg
16:126-132, 1998
117. Matsuura JH, Johansen KH, Rosenthal D, Clark
MD, Clarke KA, Kirby LB: Cryopreserved femoral vein
grafts for difficult hemodialysis access. Ann Vasc Surg
14:50-55, 2000
118. Nakao A, Miyazaki M, Oka Y, et al: Creation and
use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access. Acta Med Okayama
54:91-94, 2000
119. Kiyama H, Imazeki T, Kurihara S, Yoneshima H:
Long-term follow-up of polyurethane vascular grafts for
hemoaccess bridge fistulas. Ann Vasc Surg 17:516-521,
2003
120. Rayner HC, Pisoni RL, Gillespie BW, et al: Creation, cannulation and survival of arteriovenous fistulae:
S291
Data from the Dialysis Outcomes and Practice Patterns

Study. Kidney Int 63:323-330, 2003
121. Beathard GA, Settle SM, Shields MW: Salvage of
the nonfunctioning arteriovenous fistula. Am J Kidney Dis
33:910-916, 1999
122. Faiyaz R, Abreo K, Zaman F, Pervez A, Zibari G,
Work J: Salvage of poorly developed arteriovenous fistulae
with percutaneous ligation of accessory veins. Am J Kidney
Dis 39:824-827, 2002
123. Patel ST, Hughes J, Mills JL Sr: Failure of arteriovenous fistula maturation: An unintended consequence of
exceeding Dialysis Outcome Quality Initiative Guidelines
for Hemodialysis Access. J Vasc Surg 38:439-445; discussion 445, 2003
124. Malik J, Slavikova M, Malikova H, Maskova J:
Many clinically silent access stenoses can be identified by
ultrasonography. J Nephrol 15:661-665, 2002
125. Berman SS, Gentile AT: Impact of secondary procedures in autogenous arteriovenous fistula maturation and
maintenance. J Vasc Surg 34:866-871, 2001
126. Tordoir JH, Rooyens P, Dammers R, van der Sande
FM, de Haan M, Yo TI: Prospective evaluation of failure
modes in autogenous radiocephalic wrist access for haemodialysis. Nephrol Dial Transplant 18:378-383, 2003
127. Leaf DA, MacRae HS, Grant E, Kraut J: Isometric
exercise increases the size of forearm veins in patients with
chronic renal failure. Am J Med Sci 325:115-119, 2003
128. Glickman MH, Stokes GK, Ross JR, et al: Multicenter evaluation of a polytetrafluoroethylene vascular access graft as compared with the expanded polytetrafluoroethylene vascular access graft in hemodialysis applications. J
Vasc Surg 34:465-472; discussion 472-463, 2001
129. Hurlbert SN, Mattos MA, Henretta JP, et al: Longterm patency rates, complications and cost-effectiveness of
polytetrafluoroethylene (PTFE) grafts for hemodialysis access: A prospective study that compares Impra versus
Gore-Tex grafts. Cardiovasc Surg 6:652-656, 1998
130. Kaufman JL, Garb JL, Berman JA, Rhee SW, Norris
MA, Friedmann P: A prospective comparison of two expanded polytetrafluoroethylene grafts for linear forearm
hemodialysis access: Does the manufacturer matter? J Am
Coll Surg 185:74-79, 1997
131. Lenz BJ, Veldenz HC, Dennis JW, Khansarinia S,
Atteberry LR: A three-year follow-up on standard versus
thin wall ePTFE grafts for hemodialysis. J Vasc Surg
28:464-470; discussion 470, 1998
132. Kao CL, Chang JP: Fully ringed polytetrafluoroethylene graft for vascular access in hemodialysis. Asian
Cardiovasc Thorac Ann 11:171-173, 2003
133. Almonacid PJ, Pallares EC, Rodriguez AQ, Valdes
JS, Rueda Orgaz JA, Polo JR: Comparative study of use of
Diastat versus standard wall PTFE grafts in upper arm
hemodialysis access. Ann Vasc Surg 14:659-662, 2000
134. Freischlag JA: Regarding the effect of venous
anastomosis Tyrell vein patch collar on the primary patency
of arteriovenous grafts in patients undergoing hemodialysis
and effects of a venous cuff at the venous anastomosis of
polytetrafluoroethylene grafts for hemodialysis vascular
access. J Vasc Surg 32:1235-1236, 2000
135. Lemson MS, Tordoir JH, van Det RJ, et al: Effects
of a venous cuff at the venous anastomosis of polytetrafluo-
S292
roethylene grafts for hemodialysis vascular access. J Vasc

Surg 32:1155-1163, 2000
136. Sorom AJ, Hughes CB, McCarthy JT, et al: Prospective, randomized evaluation of a cuffed expanded polytetrafluoroethylene graft for hemodialysis vascular access. Surgery 132:135-140, 2002
137. Garcia-Pajares R, Polo JR, Flores A, GonzalezTabares E, Solis JV: Upper arm polytetrafluoroethylene
grafts for dialysis access. Analysis of two different graft
sizes: 6 mm and 6-8 mm. Vasc Endovasc Surg 37:335-343,
2003
138. Polo JR, Ligero JM, Diaz-Cartelle J, Garcia-Pajares
R, Cervera T, Reparaz L: Randomized comparison of 6-mm
straight grafts versus 6- to 8-mm tapered grafts for brachialaxillary dialysis access. J Vasc Surg 40:319-324, 2004
139. Dammers R, Planken RN, Pouls KP, et al: Evaluation of 4-mm to 7-mm versus 6-mm prosthetic brachialantecubital forearm loop access for hemodialysis: Results of
a randomized multicenter clinical trial. J Vasc Surg 37:143148, 2003
140. Glickman MH, Lawson JH, Katzman HE, Schild
AF, Fujitani RM: Challenges of hemodialysis access for
high risk patients: Impact of mesenteric vein bioprosthetic
graft. J Vasc Access 4:73-80, 2003
141. Scher LA, Katzman HE: Alternative graft materials
for hemodialysis access. Semin Vasc Surg 17:19-24, 2004
142. Senkaya I, Aytac II, Eercan AK, Aliosman A, Percin
B: The graft selection for haemodialysis. Vasa 32:209-213,
2003
143. Rosas SE, Joffe M, Burns JE, Knauss J, Brayman K,
Feldman HI: Determinants of successful synthetic hemodialysis vascular access graft placement. J Vasc Surg 37:10361042, 2003
144. Cook JW, Schuman ES, Standage BA, Heinl P:
Patency and flow characteristics using stapled vascular
anastomoses in dialysis grafts. Am J Surg 181:24-27, 2001
145. Lin PH, Bush RL, Nelson JC, et al: A prospective
evaluation of interrupted nitinol surgical clips in arteriovenous fistula for hemodialysis. Am J Surg 186:625-630,
2003
146. Polo JR, Vazquez R, Polo J, Sanabia J, Rueda JA,
Lopez-Baena JA: Brachiocephalic jump graft fistula: An
alternative for dialysis use of elbow crease veins. Am J
Kidney Dis 33:904-909, 1999
147. Fan PY: Acute vascular access: New advances. Adv
Ren Replace Ther 1:90-98, 1994
148. Schwab SJ, Buller GL, McCann RL, Bollinger RR,
Stickel DL: Prospective evaluation of a Dacron cuffed
hemodialysis catheter for prolonged use. Am J Kidney Dis
11:166-169, 1988
149. Shusterman NH, Kloss K, Mullen JL: Successful
use of double-lumen, silicone rubber catheters for permanent hemodialysis access. Kidney Int 35:887-890, 1989
150. Moss AH, McLaughlin MM, Lempert KD, Holley
JL: Use of a silicone catheter with a Dacron cuff for dialysis
short-term vascular access. Am J Kidney Dis 12:492-498,
1988
151. Moss AH, Vasilakis C, Holley JL, Foulks CJ, Pillai
K, McDowell DE: Use of a silicone dual-lumen catheter
with a Dacron cuff as a long-term vascular access for
hemodialysis patients. Am J Kidney Dis 16:211-215, 1990
VASCULAR ACCESS
152. Canaud B, Beraud JJ, Joyeux H, Mion C: Internal

jugular vein cannulation with two silicone rubber catheters:
A new and safe temporary vascular access for hemodialysis.
Thirty months experience. Artif Organs 10:397-403, 1986
153. Canaud B, Beraud JJ, Joyeux H, Mion C: Internal
jugular vein cannulation using 2 Silastic catheters. A new,
simple and safe long-term vascular access for extracorporeal
treatment. Nephron 43:133-138, 1986
154. Uldall R, DeBruyne M, Besley M, McMillan J,
Simons M, Francoeur R: A new vascular access catheter for
155. Millner MR, Kerns SR, Hawkins IF Jr, Sabatelli
FW, Ross EA: Tesio twin dialysis catheter system: A new
catheter for hemodialysis. AJR Am J Roentgenol 164:15191520, 1995
156. Suhocki PV, Conlon PJ Jr, Knelson MH, Harland R,
Schwab SJ: Silastic cuffed catheters for hemodialysis vascular access: Thrombolytic and mechanical correction of
malfunction. Am J Kidney Dis 28:379-386, 1996
157. Crain MR, Mewissen MW, Ostrowski GJ, PazFumagalli R, Beres RA, Wertz RA: Fibrin sleeve stripping
for salvage of failing hemodialysis catheters: Technique and
initial results. Radiology 198:41-44, 1996
158. Shaffer D: Catheter-related sepsis complicating longterm, tunnelled central venous dialysis catheters: Management by guidewire exchange. Am J Kidney Dis 25:593-596,
1995
159. Kovalik EC, Raymond JR, Albers FJ, et al: A
clustering of epidural abscesses in chronic hemodialysis
patients: Risks of salvaging access catheters in cases of
infection. J Am Soc Nephrol 7:2264-2267, 1996
160. Caruana RJ, Raja RM, Zeit RM, Goldstein SJ,
Kramer MS: Thrombotic complications of indwelling central catheters used for chronic hemodialysis. Am J Kidney
Dis 9:497-501, 1987
161. Bander SJ, Schwab SJ: Central venous angioaccess
for hemodialysis and its complications. Semin Dial 5:121128, 1992
162. Schwab SJ: Assessing the adequacy of vascular
access and its relationship to patient outcome. Am J Kidney
Dis 24:316-320, 1994
163. Atherikul K, Schwab SJ, Twardowski ZJ, et al:
What is the role of permanent central vein access in
hemodialysis patients? Semin Dial 9:392-403, 1996
164. Cimochowski GE, Worley E, Rutherford WE, Sartain J, Blondin J, Harter H: Superiority of the internal jugular
over the subclavian access for temporary dialysis. Nephron
54:154-161, 1990
165. Schillinger F, Schillinger D, Montagnac R, Milcent
T: Post catheterisation vein stenosis in haemodialysis:
Comparative angiographic study of 50 subclavian and 50
internal jugular accesses. Nephrol Dial Transplant 6:722724, 1991
166. Vanholder R, Ringoir S: Vascular access for hemodialysis. Artif Organs 18:263-265, 1994
167. Lund GB, Trerotola SO, Scheel PJ Jr: Percutaneous
translumbar inferior vena cava cannulation for hemodialysis. Am J Kidney Dis 25:732-737, 1995
168. Kamran T, Zaheer K, Khan AA, Khalid M, Akhtar
MS: Applications and complications of subclavian vein
REFERENCES
catheterization for hemodialysis. J Coll Physicians Surg Pak

13:40-43, 2003
169. MacRae JM, Ahmed A, Johnson N, Levin A, Kiaii
M: Central vein stenosis: A common problem in patients on
hemodialysis. ASAIO J 51:77-81, 2005
170. Hernandez D, Diaz F, Rufino M, et al: Subclavian
vascular access stenosis in dialysis patients: Natural history
and risk factors. J Am Soc Nephrol 9:1507-1510, 1998
171. Hernandez D, Diaz F, Suria S, et al: Subclavian
catheter-related infection is a major risk factor for the late
development of subclavian vein stenosis. Nephrol Dial
Transplant 8:227-230, 1993
172. Conz PA, Dissegna D, Rodighiero MP, La Greca G:
Cannulation of the internal jugular vein: Comparison of the
classic Seldinger technique and an ultrasound guided method.
J Nephrol 10:311-313, 1997
173. Lameris JS, Post PJ, Zonderland HM, Gerritsen PG,
Kappers-Klunne MC, Schutte HE: Percutaneous placement
of Hickman catheters: Comparison of sonographically guided
and blind techniques. AJR Am J Roentgenol 155:1097-1099,
1990
174. Mallory DL, McGee WT, Shawker TH, et al:
Ultrasound guidance improves the success rate of internal
jugular vein cannulation. A prospective, randomized trial.
Chest 98:157-160, 1990
175. Forauer AR, Glockner JF: Importance of US findings in access planning during jugular vein hemodialysis
catheter placements. J Vasc Interv Radiol 11:233-238, 2000
176. Yeum CH, Kim SW, Nah MY, et al: Percutaneous
catheterization of the internal jugular vein for hemodialysis.
Korean J Intern Med 16:242-246, 2001
177. Sotirakopoulos N, Skandalos L, Tsitsios T, Stambolidou M, Karamoschos K, Mavromatidis K: The incorrect
placement of hemodialysis catheters in veins. The necessity
for urgent x-ray evaluation for its position. Ren Fail 23:
127-133, 2001
178. Work J: Chronic catheter placement. Semin Dial
14:436-440, 2001
179. Schnabel KJ, Simons ME, Zevallos GF, et al:
Image-guided insertion of the Uldall tunneled hemodialysis
catheter: Technical success and clinical follow-up. J Vasc
Interv Radiol 8:579-586, 1997
180. Schwab SJ, Beathard G: The hemodialysis catheter
conundrum: Hate living with them, but cant live without
them. Kidney Int 56:1-17, 1999
181. Stavropoulos SW, Pan JJ, Clark TW, et al: Percutaneous transhepatic venous access for hemodialysis. J Vasc
Interv Radiol 14:1187-1190, 2003
182. Depner TA: Catheter performance. Semin Dial 14:
425-431, 2001
183. Twardowski ZJ, Haynie JD: Measurements of hemodialysis catheter blood flow in vivo. Int J Artif Organs 25:
276-280, 2002
184. Atherikul K, Schwab SJ, Conlon PJ: Adequacy of
haemodialysis with cuffed central-vein catheters. Nephrol
185. Baumann M, Witzke O, Dietrich R, et al: Prolonged
catheter survival in intermittent hemodialysis using a less
thrombogenic micropatterned polymer modification. ASAIO
J 49:708-712, 2003
S293
186. Cetinkaya R, Odabas AR, Unlu Y, Selcuk Y, Ates A,

Ceviz M: Using cuffed and tunnelled central venous catheters as permanent vascular access for hemodialysis: A
prospective study. Ren Fail 25:431-438, 2003
187. Di Iorio B, Lopez T, Procida M, et al: Successful use
of central venous catheter as permanent hemodialysis access: 84-Month follow-up in Lucania. Blood Purif 19:39-43,
2001
188. McLaughlin K, Jones B, Mactier R, Porteus C:
Long-term vascular access for hemodialysis using silicon
dual-lumen catheters with guidewire replacement of catheters for technique salvage. Am J Kidney Dis 29:553-559,
1997
189. Canaud B, Leray-Moragues H, Kerkeni N, Bosc JY,
Martin K: Effective flow performances and dialysis doses
delivered with permanent catheters: A 24-month comparative study of permanent catheters versus arterio-venous
vascular accesses. Nephrol Dial Transplant 17:1286-1292,
2002
190. Perini S, LaBerge JM, Pearl JM, et al: Tesio
catheter: Radiologically guided placement, mechanical performance, and adequacy of delivered dialysis. Radiology
215:129-137, 2000
191. Webb A, Abdalla M, Harden PN, Russell GI: Use of
the Tesio catheter for hemodialysis in patients with endstage renal failure: A 2-year prospective study. Clin Nephrol
58:128-133, 2002
192. Besarab A, Sherman R: The relationship of recirculation to access blood flow. Am J Kidney Dis 29:223-229,
1997
193. Level C, Lasseur C, Chauveau P, Bonarek H,
Perrault L, Combe C: Performance of twin central venous
catheters: Influence of the inversion of inlet and outlet on
recirculation. Blood Purif 20:182-188, 2002
194. Gallieni M, Conz PA, Rizzioli E, Butti A, Brancaccio D: Placement, performance and complications of the Ash
Split Cath hemodialysis catheter. Int J Artif Organs 25:11371143, 2002
195. Polaschegg HD, Sodemann K, Feldmer B: Enhancing
patency, safety and cost effectiveness of catheters. EDTNA
ERCA J 28:28-32, 2002
196. Chow KM, Szeto CC, Leung CB, Wong TY, Li PK:
Cuffed-tunneled femoral catheter for long-term hemodialysis. Int J Artif Organs 24:443-446, 2001
197. Tashjian DB, Lipkowitz GS, Madden RL, et al:
Safety and efficacy of femoral-based hemodialysis access
grafts. J Vasc Surg 35:691-693, 2002
198. Gilding C, Goodeve J, Metcalf S, et al: The utilisation
of shared governance to improve vascular access catheter
care. EDTNA ERCA J 25:15-17, 1999
199. Oliver MJ: Acute dialysis catheters. Semin Dial
14:432-435, 2001
200. Weijmer MC, ter Wee PM: Temporary vascular access
for hemodialysis treatment. Current guidelines and future
directions. Contrib Nephrol 137:38-45, 2002
201. Butterly DW, Schwab SJ: Dialysis access infections.
Curr Opin Nephrol Hypertens 9:631-635, 2000
202. Dahlberg PJ, Yutuc WR, Newcomer KL: Subclavian
hemodialysis catheter infections. Am J Kidney Dis 7:421427, 1986
S294
203. Kelber J, Delmez JA, Windus DW: Factors affecting

delivery of high-efficiency dialysis using temporary vascular access. Am J Kidney Dis 22:24-29, 1993
204. Blake PG, Huraib S, Wu G, Uldall PR: The use of
dual lumen jugular venous catheters as definitive long term
access for haemodialysis. Int J Artif Organs 13:26-31, 1990
205. Weijmer MC, Vervloet MG, ter Wee PM: Compared
to tunnelled cuffed haemodialysis catheters, temporary untunnelled catheters are associated with more complications
already within 2 weeks of use. Nephrol Dial Transplant
19:670-677, 2004
206. Jaques PF, Mauro MA, Keefe B: US guidance for
vascular access. Technical note. J Vasc Interv Radiol 3:427430, 1992
207. Troianos CA, Jobes DR, Ellison N: Ultrasoundguided cannulation of the internal jugular vein. A prospective, randomized study. Anesth Analg 72:823-826, 1991
208. Tapson JS, Uldall PR: Fatal hemothorax caused by a
subclavian hemodialysis catheter. Thoughts on prevention.
Arch Intern Med 144:1685-1687, 1984
209. Tapson JS, Uldall R: Avoiding deaths from subclavian cannulation for hemodialysis. Int J Artif Organs 6:227230, 1983
210. Vanherweghem JL, Cabolet P, Dhaene M, et al:
Complications related to subclavian catheters for hemodialysis. Report and review. Am J Nephrol 6:339-345, 1986
211. Vanholder V, Hoenich N, Ringoir S: Morbidity and
mortality of central venous catheter hemodialysis: A review
of 10 years experience. Nephron 47:274-279, 1987
212. Zeien LB, Noguchi TT: Fatal hydrothorax associated with subclavian vein catheterization for hemodialysis.
Am J Forensic Med Pathol 13:326-328, 1992
213. Falk A, Parthasarathy S: Conversion of temporary
hemodialysis catheters to tunneled hemodialysis catheters.
Clin Nephrol 63:209-214, 2005
214. Moran JE, Prosl F: Totally implantable subcutaneous devices for hemodialysis access. Contrib Nephrol 142:
178-192, 2004
215. Sandhu J: Dialysis ports: A new totally implantable
option for hemodialysis access. Tech Vasc Interv Radiol
5:108-113, 2002
216. Canaud B, My H, Morena M, et al: Dialock: A new
vascular access device for extracorporeal renal replacement
therapy. Preliminary clinical results. Nephrol Dial Transplant 14:692-698, 1999
217. Schwab SJ, Weiss MA, Rushton F, et al: Multicenter
clinical trial results with the LifeSite hemodialysis access
system. Kidney Int 62:1026-1033, 2002
218. Sodemann K, Polaschegg HD, Feldmer B: Two
years experience with Dialock and CLS (a new antimicrobial lock solution). Blood Purif 19:251-254, 2001
219. Rayan SS, Terramani TT, Weiss VJ, Chaikof EL:
The LifeSite Hemodialysis Access System in patients with
limited access. J Vasc Surg 38:714-718, 2003
220. Nosher JL, Bodner LJ, Ettinger LJ, et al: Radiologic
placement of a low profile implantable venous access port in
a pediatric population. Cardiovasc Intervent Radiol 24:395399, 2001
221. Ross JR: Successful treatment of a LifeSite Hemodialysis Access System pocket infection with large-volume
VASCULAR ACCESS
kanamycin solution irrigation. Adv Ren Replace Ther 10:248253, 2003

222. OGrady NP, Alexander M, Dellinger EP, et al:
Guidelines for the Prevention of Intravascular CatheterRelated Infections. Atlanta, GA, Centers for Disease Control
and Prevention, 2002, pp 1-29
223. Pearce BA, Miller LH, Martin MA, Roush DL:
Efficacy of clean v sterile surgical prep kits. AORN J
66:464-470, 1997
224. Perelman VS, Francis GJ, Rutledge T, Foote J,
Martino F, Dranitsaris G: Sterile versus nonsterile gloves for
repair of uncomplicated lacerations in the emergency department: A randomized controlled trial. Ann Emerg Med
43:362-370, 2004
225. Stotts NA, Barbour S, Griggs K, et al: Sterile versus
clean technique in postoperative wound care of patients with
open surgical wounds: A pilot study. J Wound Ostomy
Continence Nurs 24:10-18, 1997
226. Alter MJ, Lyerla RL, Tokars JI, Miller ER: Recommendations for Preventing Transmission of Infections Among
Chronic Hemodialysis Patients. Atlanta, GA, Centers for
Disease Control and Prevention, 2001, pp 1-43
227. Tokars JI, Arduino MJ, Alter MJ: Infection control
in hemodialysis units. Infect Dis Clin North Am 15:797-812,
viii, 2001
228. Arenas Jimenez MD, Sanchez-Paya J, Gonzales C,
Rivera F, Antolin A: Audit on the degree of application of
universal precautions in a haemodialysis unit. Nephrol Dial
Transplant 14:1001-1003, 1999
229. Arenas MD, Sanchez-Paya J, Barril G, et al: A
multicentric survey of the practice of hand hygiene in
haemodialysis units: Factors affecting compliance. Nephrol
230. Peleman RA, Vogelaers D, Verschraegen G: Changing patterns of antibiotic resistanceUpdate on antibiotic
management of the infected vascular access. Nephrol Dial
Transplant 15:1281-1284, 2000
231. McDonald LC, Hageman JC: Vancomycin intermediate and resistant Staphylococcus aureus. What the nephrologist needs to know. Nephrol News Issues 18:63-64, 66-67,
71-72, 2004
232. Taylor G, Gravel D, Johnston L, Embil J, Holton D,
Paton S: Prospective surveillance for primary bloodstream
infections occurring in Canadian hemodialysis units. Infect
Control Hosp Epidemiol 23:716-720, 2002
233. Tokars JI, Light P, Anderson J, et al: A prospective
study of vascular access infections at seven outpatient
hemodialysis centers. Am J Kidney Dis 37:1232-1240, 2001
234. Tokars JI, Miller ER, Stein G: New national surveillance system for hemodialysis-associated infections: initial
results. Am J Infect Control 30:288-295, 2002
MD, 2004
236. Sexton DJ: Vascular access infections in patients
undergoing dialysis with special emphasis on the role and
treatment of Staphylococcus aureus. Infect Dis Clin North
Am 15:731-742, vii, 2001
237. Saxena AK, Panhotra BR, Venkateshappa CK, et al:
The impact of nasal carriage of methicillin-resistant and
REFERENCES
methicillin-susceptible Staphylococcus aureus (MRSA &

MSSA) on vascular access-related septicemia among patients with type-II diabetes on dialysis. Ren Fail 24:763-777,
2002
238. Taylor G, Gravel D, Johnston L, Embil J, Holton D,
Paton S: Incidence of bloodstream infection in multicenter
inception cohorts of hemodialysis patients. Am J Infect
Control 32:155-160, 2004
239. Beathard GA: An algorithm for the physical examination of early fistula failure. Semin Dial 18:331-335, 2005
240. Oder TF, Teodorescu V, Uribarri J: Effect of exercise
on the diameter of arteriovenous fistulae in hemodialysis
patients. ASAIO J 49:554-555, 2003
241. Rus RR, Ponikvar R, Kenda RB, ButurovicPonikvar J: Effect of local physical training on the forearm
arteries and veins in patients with end-stage renal disease.
Blood Purif 21:389-394, 2003
242. Roca-Tey R, Samon Guasch R, Ibrik O, et al:
[Vascular access surveillance with blood flow monitoring: A
prospective study with 65 patients]. Nefrologia 24:246-252,
2004
243. Beathard GA, Arnold P, Jackson J, Litchfield T:
Aggressive treatment of early fistula failure. Kidney Int
64:1487-1494, 2003
244. Twardowski ZJ: Constant site (buttonhole) method
of needle insertion for hemodialysis. Dial Transplant 24:
559, 1995
245. Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint
S: Chlorhexidine compared with povidone-iodine solution
for vascular catheter-site care: A meta-analysis. Ann Intern
Med 136:792-801, 2002
246. Krau SD: Comment: Chlorhexidine gluconate is
more effective than povidone-iodine for preventing vascular
catheter related bloodstream infection. Evid Based Nurs
6:18, 2003
247. Beathard GA: Catheter management protocol for
catheter-related bacteremia prophylaxis. Semin Dial 16:403405, 2003
248. Hakim RM, Breyer J, Ismail N, Schulman G:
Effects of dose of dialysis on morbidity and mortality. Am J
Kidney Dis 23:661-669, 1994
249. Centers for Medicare & Medicaid Services: 2003
Annual Report. End Stage Renal Disease Clinical Performance Measures Project. Baltimore, MD, Department of
Health and Human Services, Centers for Medicare &
Medicaid Services, Center for Beneficiary Choices, 2003
250. Rocco MV, Bleyer AJ, Burkart JM: Utilization of
inpatient and outpatient resources for the management of
hemodialysis access complications. Am J Kidney Dis 28:250256, 1996
251. Morbidity and mortality of dialysis. NIH Consens
Statement 11:1-33, 1993
252. Bay WH, Van Cleef S, Owens M: The hemodialysis
access: Preferences and concerns of patients, dialysis nurses
and technicians, and physicians. Am J Nephrol 18:379-383,
1998
253. Sehgal AR, Snow RJ, Singer ME, et al: Barriers to
adequate delivery of hemodialysis. Am J Kidney Dis 31:
593-601, 1998
S295
254. Allon M, Bailey R, Ballard R, et al: A multidisciplinary approach to hemodialysis access: Prospective evaluation. Kidney Int 53:473-479, 1998
255. Cull DL, Taylor SM, Russell HE, Langan EM,
Snyder BA, Sullivan TM: The impact of a community-wide
vascular access program on the management of graft thromboses in a dialysis population of 495 patients. Am J Surg
178:113-116, 1999
256. Pfdederer TA, Darras FS, Welsch KW, Knudson J:
How to organize hemodialysis vascular access quality
assurance efforts into a cohesive whole for better patient
outcomes. Contemp Dial Nephrol 21:18-21, 2000
257. Besarab A: Advances in end-stage renal diseases
2000. Access monitoring methods. Blood Purif 18:255-259,
2000
258. Sehgal AR, Dor A, Tsai AC: Morbidity and cost
implications of inadequate hemodialysis. Am J Kidney Dis
37:1223-1231, 2001
259. Aruny JE, Lewis CA, Cardella JF, et al: Quality
improvement guidelines for percutaneous management of
the thrombosed or dysfunctional dialysis access. J Vasc
Interv Radiol 14:S247-S253, 2003 (suppl 2)
260. Besarab A, Lubkowski T, Ahsan M, Lim T, Frinak S:
Access flow (QA) as a predictor of access dysfunction. J Am
Soc Nephrol 11:202A, 1999 (abstr)
261. Besarab A, Ross R, Deane C, Needleman L: Intraaccess flow in vascular accesses. ASAIO J 41:S108A, 1995
(suppl 1; abstr)
262. Chin AI, Chang W, Fitzgerald JT, et al: Intra-access
blood flow in patients with newly created upper-arm arteriovenous native fistulae for hemodialysis access. Am J Kidney
Dis 44:850-858, 2004
263. Kim YO, Yang CW, Yoon SA, et al: Access blood
flow as a predictor of early failures of native arteriovenous
fistulas in hemodialysis patients. Am J Nephrol 21:221-225,
2001
264. Won T, Jang JW, Lee S, Han JJ, Park YS, Ahn JH:
Effects of intraoperative blood flow on the early patency of
radiocephalic fistulas. Ann Vasc Surg 14:468-472, 2000
265. Besarab A, Dorrell S, Moritz M, Michael H, Sullivan K: Determinants of measured dialysis venous pressure
and its relationship to true intra-access venous pressure.
ASAIO Trans 37:M270-M271, 1991
266. Sullivan KL, Besarab A, Bonn J, Shapiro MJ,
Gardiner GA Jr, Moritz MJ: Hemodynamics of failing
dialysis grafts. Radiology 186:867-872, 1993
267. Sullivan KL, Besarab A, Dorrell S, Moritz MJ: The
relationship between dialysis graft pressure and stenosis.
Invest Radiol 27:352-355, 1992
268. Asif A, Gadalean FN, Merrill D, et al: Inflow
stenosis in arteriovenous fistulas and grafts: A multicenter,
prospective study. Kidney Int 67:1986-1992, 2005
269. Lilly RZ, Carlton D, Barker J, et al: Predictors of
arteriovenous graft patency after radiologic intervention in
hemodialysis patients. Am J Kidney Dis 37:945-953, 2001
270. Besarab A, Lubkowski T, Frinak S, Ramanathan S,
Escobar F: Detecting vascular access dysfunction. ASAIO J
43:M539-M543, 1997
271. Besarab A, Lubkowski T, Frinak S, Ramanathan S,
Escobar F: Detection of access strictures and outlet stenoses
S296
in vascular accesses. Which test is best? ASAIO J 43:M543M547, 1997

272. Besarab A, Ross R, Al-Adel F, Deane C, Frinak S,
Zasuwa G: The relation of intra-access pressure to flow.
J Am Soc Nephrol 7:483A, 1995 (abstr)
273. Jones SA, Jin S, Kantak A, Bell DA, Paulson WD:
Mathematical model for pressure losses in the hemodialysis
graft vascular circuit. J Biomech Eng 127:60-66, 2005
274. Wang E, Schneditz D, Ronco C, Levin NW: Surveillance of fistula function by frequent recirculation measurements during high efficiency dialysis. ASAIO J 48:394-397,
2002
275. Beathard GA: The treatment of vascular access graft
dysfunction: A nephrologists view and experience. Adv Ren
Replace Ther 1:131-147, 1994
276. Beathard GA: Physical examination of AV grafts.
Semin Dial 5:74-76, 1996
277. Beathard GA: Physical examination: The forgotten
tool, in Gray RJ, Sands JJ (eds): Dialysis Access: A
Multidisciplinary Approach. Philadelphia, PA, Lippincott
Williams & Wilkins, 2002, pp 111-118
278. Trerotola SO, Scheel PJ Jr, Powe NR, et al: Screening for dialysis access graft malfunction: Comparison of
physical examination with US. J Vasc Interv Radiol 7:
15-20, 1996
279. Agarwal R, McDougal G: Buzz in the axilla: A new
physical sign in hemodialysis forearm graft evaluation. Am J
Kidney Dis 38:853-857, 2001
280. Trerotola SO, Ponce P, Stavropoulos SW, et al:
Physical examination versus normalized pressure ratio for
predicting outcomes of hemodialysis access interventions. J
Vasc Interv Radiol 14:1387-1394, 2003
281. Mansy HA, Hoxie SJ, Patel NH, Sandler RH:
Computerised analysis of auscultatory sounds associated
with vascular patency of haemodialysis access. Med Biol
Eng Comput 43:56-62, 2005
282. Bacchini G, Cappello A, La Milia V, Andrulli S,
Locatelli F: Color Doppler ultrasonography imaging to
guide transluminal angioplasty of venous stenosis. Kidney
Int 58:1810-1813, 2000
283. Basseau F, Grenier N, Trillaud H, et al: Volume flow
measurement in hemodialysis shunts using time-domain
correlation. J Ultrasound Med 18:177-183, 1999
284. Bay WH, Henry ML, Lazarus JM, Lew NL, Ling J,
Lowrie EG: Predicting hemodialysis access failure with
color flow Doppler ultrasound. Am J Nephrol 18:296-304,
1998
285. May RE, Himmelfarb J, Yenicesu M, et al: Predictive measures of vascular access thrombosis: A prospective
study. Kidney Int 52:1656-1662, 1997
286. Shackleton CR, Taylor DC, Buckley AR, Rowley
VA, Cooperberg PL, Fry PD: Predicting failure in polytetrafluoroethylene vascular access grafts for hemodialysis: A
pilot study. Can J Surg 30:442-444, 1987
287. Strauch BS, OConnell RS, Geoly KL, Grundlehner
M, Yakub YN, Tietjen DP: Forecasting thrombosis of
vascular access with Doppler color flow imaging. Am J
Kidney Dis 19:554-557, 1992
288. Laissy JP, Menegazzo D, Debray MP, et al: Failing
arteriovenous hemodialysis fistulas: Assessment with mag-
VASCULAR ACCESS
netic resonance angiography. Invest Radiol 34:218-224,

1999
289. Oudenhoven LF, Pattynama PM, de Roos A, Seeverens HJ, Rebergen SA, Chang PC: Magnetic resonance, a
new method for measuring blood flow in hemodialysis
fistulae. Kidney Int 45:884-889, 1994
290. van Kempen BP, Smits HF, Blankestijn PJ: Haemodialysis access graft with shunting through an iatrogenic
fistulaThe diagnostic role of magnetic resonance flow
measurement. Nephrol Dial Transplant 14:444-446, 1999
291. Stewart SF: Effects of transducer, velocity, Doppler
angle, and instrument settings on the accuracy of color
Doppler ultrasound. Ultrasound Med Biol 27:551-564, 2001
292. Winkler AJ, Wu J: Correction of intrinsic spectral
broadening errors in Doppler peak velocity measurements
made with phased sector and linear array transducers.
Ultrasound Med Biol 21:1029-1035, 1995
293. Krivitski NM: Theory and validation of access flow
measurement by dilution technique during hemodialysis.
Kidney Int 48:244-250, 1995
294. Yarar D, Cheung AK, Sakiewicz P, et al: Ultrafiltration method for measuring vascular access flow rates during
295. Ronco C, Brendolan A, Crepaldi C, DIntini V,
Sergeyeva O, Levin NW: Noninvasive transcutaneous access flow measurement before and after hemodialysis:
Impact of hematocrit and blood pressure. Blood Purif 20:
376-379, 2002
296. Steuer RR, Miller DR, Zhang S, Bell DA, Leypoldt
JK: Noninvasive transcutaneous determination of access
blood flow rate. Kidney Int 60:284-291, 2001
297. Magnasco A, Bacchini G, Cappello A, et al: Clinical
validation of glucose pump test (GPT) compared with
ultrasound dilution technology in arteriovenous graft surveillance. Nephrol Dial Transplant 19:1835-1841, 2004
298. Ram SJ, Magnasco A, Jones SA, et al: In vivo
validation of glucose pump test for measurement of hemodialysis access flow. Am J Kidney Dis 42:752-760, 2003
299. Bosc JY, LeBlanc M, Garred LJ, et al: Direct
determination of blood recirculation rate in hemodialysis by
a conductivity method. ASAIO J 44:68-73, 1998
300. Lindsay RM, Blake PG, Malek P, Posen G, Martin
B, Bradfield E: Hemodialysis access blood flow rates can be
measured by a differential conductivity technique and are
predictive of access clotting. Am J Kidney Dis 30:475-482,
1997
301. Gotch FA, Buyaki R, Panlilio F, Folden T: Measurement of blood access flow rate during hemodialysis from
conductivity dialysance. ASAIO J 45:139-146, 1999
302. Mercadal L, Hamani A, Bene B, Petitclerc T:
Determination of access blood flow from ionic dialysance:
Theory and validation. Kidney Int 56:1560-1565, 1999
303. Depner TA: Analysis of new methods for access
monitoring. Semin Dial 12:376-381, 1999
304. Weitzel WF, Khosla N, Rubin JM: Retrograde
hemodialysis access flow during dialysis as a predictor of
access pathology. Am J Kidney Dis 37:1241-1246, 2001
305. Weitzel WF, Rubin JM, Leavey SF, Swartz RD,
Dhingra RK, Messana JM: Analysis of variable flow Doppler hemodialysis access flow measurements and comparison
with ultrasound dilution. Am J Kidney Dis 38:935-940, 2001
REFERENCES
306. Weitzel WF, Rubin JM, Swartz RD, Woltmann DJ,

Messana JM: Variable flow Doppler for hemodialysis access
evaluation: Theory and clinical feasibility. ASAIO J 46:6569, 2000
307. Lindsay RM, Blake PG, Bradfield E: Estimation of
hemodialysis access blood flow rates by a urea method is a
poor predictor of access outcome. ASAIO J 44:818-822,
1998
308. Sands J, Glidden D, Miranda C: Access flow
measured during hemodialysis. ASAIO J 42:M530-M532,
1996
309. Besarab A, Lubkowski T, Vu A, Aslam A, Frinak S:
Effects of systemic hemodynamics on flow within vascular
accesses used for hemodialysis. ASAIO J 47:501-506, 2001
310. Pandeya S, Lindsay RM: The relationship between
cardiac output and access flow during hemodialysis. ASAIO
J 45:135-138, 1999
311. Rehman SU, Pupim LB, Shyr Y, Hakim R, Ikizler
TA: Intradialytic serial vascular access flow measurements.
Am J Kidney Dis 34:471-477, 1999
312. Polkinghorne KR, Atkins RC, Kerr PG: Native
arteriovenous fistula blood flow and resistance during hemodialysis. Am J Kidney Dis 41:132-139, 2003
313. Depner TA, Rizwan S, Stasi TA: Pressure effects on
roller pump blood flow during hemodialysis. ASAIO Trans
36:M456-M459, 1990
314. Sands J, Glidden D, Jacavage W, Jones B: Difference between delivered and prescribed blood flow in hemodialysis. ASAIO J 42:M717-M719, 1996
315. Ahmed J, Besarab A, Lubkowski T, Frinak S: Effect
of differing blood lines on delivered blood flow during
316. Francos GC, Burke JF Jr, Besarab A, Martinez J,
Kirkwood RG, Hummel LA: An unsuspected cause of acute
hemolysis during hemodialysis. Trans Am Soc Artif Intern
Organs 29:140-145, 1983
317. Spergel LM, Holland JE, Fadem SZ, McAllister CJ,
Peacock EJ: Static intra-access pressure ratio does not
correlate with access blood flow. Kidney Int 66:1512-1516,
2004
318. Besarab A, Frinak S, Aslam M: Pressure measurements in the surveillance of vascular accesses, in Gray RJ,
Sands JJ (eds): Dialysis Access: A Multidisciplinary Approach. Philadelphia, PA, Lippincott Williams & Wilkins,
2002, pp 137-150
319. Besarab A, al-Saghir F, Alnabhan N, Lubkowski T,
Frinak S: Simplified measurement of intra-access pressure.
ASAIO J 42:M682-M687, 1996
320. Bosch JP, Barlee V, Valdecasas JG: Blood flow
measurement during hemodialysis. Adv Ren Replace Ther
1:83-88, 1994
321. Polaschegg HD: The extracorporeal circuit. Semin
Dial 8:299-304, 1995
322. Schwab SJ, Raymond JR, Saeed M, Newman GE,
Dennis PA, Bollinger RR: Prevention of hemodialysis fistula
thrombosis. Early detection of venous stenoses. Kidney Int
36:707-711, 1989
323. Agarwal R, Davis JL: Monitoring interposition graft
venous pressures at higher blood-flow rates improves sensitivity in predicting graft failure. Am J Kidney Dis 34:212217, 1999
S297
324. Polaschegg HD, Techert F, Wizemann V: Dynamic

pressure measurement for detection of blood access stenosis.
EDTNA ERCA J 24:39-44, 1998
325. Sirken GR, Shah C, Raja R: Slow-flow venous
pressure for detection of arteriovenous graft malfunction.
Kidney Int 63:1894-1898, 2003
326. Frinak S, Zasuwa G, Dunfee T, Besarab A, Yee J:
Dynamic venous access pressure ratio test for hemodialysis
access monitoring. Am J Kidney Dis 40:760-768, 2002
327. Collins DM, Lambert MB, Middleton JP, et al:
Fistula dysfunction: Effect on rapid hemodialysis. Kidney
Int 41:1292-1296, 1992
328. Alloatti S, Molino A, Bonfant G, Ratibondi S,
Bosticardo GM: Measurement of vascular access recirculation unaffected by cardiopulmonary recirculation: Evaluation of an ultrasound method. Nephron 81:25-30, 1999
329. Brancaccio D, Tessitore N, Carpani P, et al: Potassium-based dilutional method to measure hemodialysis
access recirculation. Int J Artif Organs 24:606-613, 2001
330. Magnasco A, Alloatti S, Bonfant G, Copello F,
Solari P: Glucose infusion test: A new screening test for
vascular access recirculation. Kidney Int 57:2123-2128,
2000
331. Hester RL, Curry E, Bower J: The determination of
hemodialysis blood recirculation using blood urea nitrogen
measurements. Am J Kidney Dis 20:598-602, 1992
332. Lopot F, Nejedly B, Sulkova S, Blaha J: Comparison of different techniques of hemodialysis vascular access
flow evaluation. Int J Artif Organs 26:1056-1063, 2003
333. Teruel JL, Fernandez Lucas M, Marcen R, et al:
Differences between blood flow as indicated by the hemodialysis blood roller pump and blood flow measured by an
ultrasonic sensor. Nephron 85:142-147, 2000
334. Krivitski NM, Gantela S: Access flow measurement
as a predictor of hemodialysis graft thrombosis: Making
clinical decisions. Semin Dial 14:181-185, 2001
335. Sands J, Glidden D, Miranda C: Hemodialysis
access flow measurement. Comparison of ultrasound dilution and duplex ultrasonography. ASAIO J 42:M899-M901,
1996
336. Lindsay RM, Bradfield E, Rothera C, Kianfar C,
Malek P, Blake PG: A comparison of methods for the
measurement of hemodialysis access recirculation and access blood flow rate. ASAIO J 44:62-67, 1998
337. Schwarz C, Mitterbauer C, Boczula M, et al: Flow
monitoring: Performance characteristics of ultrasound dilution versus color Doppler ultrasound compared with fistulography. Am J Kidney Dis 42:539-545, 2003
338. Planken RN, Tordoir JH, Dammers R, et al: Stenosis
detection in forearm hemodialysis arteriovenous fistulae by
multiphase contrast-enhanced magnetic resonance angiography: Preliminary experience. J Magn Reson Imaging 17:5464, 2003
339. Tessitore N, Bedogna V, Gammaro L, et al: Diagnostic accuracy of ultrasound dilution access blood flow measurement in detecting stenosis and predicting thrombosis in
native forearm arteriovenous fistulae for hemodialysis. Am J
Kidney Dis 42:331-341, 2003
340. Bosman PJ, Boereboom FT, Smits HF, Eikelboom
BC, Koomans HA, Blankestijn PJ: Pressure or flow record-
S298
ings for the surveillance of hemodialysis grafts. Kidney Int

52:1084-1088, 1997
341. Robbin ML, Oser RF, Allon M, et al: Hemodialysis
access graft stenosis: US detection. Radiology 208:655-661,
1998
342. Gadallah MF, Paulson WD, Vickers B, Work J:
Accuracy of Doppler ultrasound in diagnosing anatomic
stenosis of hemodialysis arteriovenous access as compared
with fistulography. Am J Kidney Dis 32:273-277, 1998
343. Lok CE, Bhola C, Croxford R, Richardson RM:
Reducing vascular access morbidity: A comparative trial of
two vascular access monitoring strategies. Nephrol Dial
Transplant 18:1174-1180, 2003
344. Arbab-Zadeh A, Mehta RL, Ziegler TW, et al:
Hemodialysis access assessment with intravascular ultrasound. Am J Kidney Dis 39:813-823, 2002
345. Pietura R, Janczarek M, Zaluska W, et al: Colour
Doppler ultrasound assessment of well-functioning mature
arteriovenous fistulas for haemodialysis access. Eur J Radiol
55:113-119, 2005
346. Grogan J, Castilla M, Lozanski L, Griffin A, Loth F,
Bassiouny H: Frequency of critical stenosis in primary
arteriovenous fistulae before hemodialysis access: Should
duplex ultrasound surveillance be the standard of care? J
Vasc Surg 41:1000-1006, 2005
347. Smits JH, van der Linden J, Hagen EC, et al: Graft
surveillance: Venous pressure, access flow, or the combination? Kidney Int 59:1551-1558, 2001
348. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Vascular Access: Update 2000. Am J
349. Hoeben H, Abu-Alfa AK, Reilly RF, Aruny JE,
Bouman K, Perazella MA: Vascular access surveillance:
Evaluation of combining dynamic venous pressure and
vascular access blood flow measurements. Am J Nephrol
23:403-408, 2003
350. Finlay DE, Longley DG, Foshager MC, Letourneau
JG: Duplex and color Doppler sonography of hemodialysis
arteriovenous fistulas and grafts. Radiographics 13:983-989,
1993
351. Kirschbaum B, Compton A: Study of vascular
access blood flow by angiodynography. Am J Kidney Dis
25:22-25, 1995
352. Safa AA, Valji K, Roberts AC, Ziegler TW, Hye RJ,
Oglevie SB: Detection and treatment of dysfunctional
hemodialysis access grafts: Effect of a surveillance program
on graft patency and the incidence of thrombosis. Radiology
199:653-657, 1996
353. Beathard GA: Percutaneous therapy of vascular
access dysfunction: Optimal management of access stenosis
and thrombosis. Semin Dial 7:165-167, 1994
354. Beathard GA: Percutaneous angioplasty for the
treatment of venous stenosis: A nephrologists view. Semin
Dial 8:166-170, 1995
355. Windus DW, Audrain J, Vanderson R, Jendrisak
MD, Picus D, Delmez JA: Optimization of high-efficiency
hemodialysis by detection and correction of fistula dysfunction. Kidney Int 38:337-341, 1990
356. Glanz S, Gordon DH, Butt KM, Hong J, Lipkowitz
GS: The role of percutaneous angioplasty in the manage-
VASCULAR ACCESS
ment of chronic hemodialysis fistulas. Ann Surg 206:777781, 1987

357. Rodkin RS, Bookstein JJ, Heeney DJ, Davis GB:
Streptokinase and transluminal angioplasty in the treatment
of acutely thrombosed hemodialysis access fistulas. Radiology 149:425-428, 1983
358. Burger H, Zijlstra JJ, Kluchert SA, Scholten AP,
Kootstra G: Percutaneous transluminal angioplasty improves longevity in fistulae and shunts for hemodialysis.
Nephrol Dial Transplant 5:608-611, 1990
359. Hakim R, Himmelfarb J: Hemodialysis access failure: A call to action. Kidney Int 54:1029-1040, 1998
360. Haruguchi H, Teraoka S: Intimal hyperplasia and
hemodynamic factors in arterial bypass and arteriovenous
grafts: A review. J Artif Organs 6:227-235, 2003
361. Kelly BS, Heffelfinger SC, Whiting JF, et al:
Aggressive venous neointimal hyperplasia in a pig model of
arteriovenous graft stenosis. Kidney Int 62:2272-2280, 2002
362. Roy-Chaudhury P, Kelly BS, Narayana A, et al:
Hemodialysis vascular access dysfunction from basic biology to clinical intervention. Adv Ren Replace Ther 9:74-84,
2002
363. Roy-Chaudhury P, Kelly BS, Melhem M, et al:
Novel therapies for hemodialysis vascular access dysfunction: Fact or fiction! Blood Purif 23:29-35, 2005
364. Neyra NR, Ikizler TA, May RE, et al: Change in
access blood flow over time predicts vascular access thrombosis. Kidney Int 54:1714-1719, 1998
365. Goldstein SL, Allsteadt A: Ultrasound dilution evaluation of pediatric hemodialysis vascular access. Kidney Int
59:2357-2360, 2001
366. McCarley P, Wingard RL, Shyr Y, Pettus W, Hakim
RM, Ikizler TA: Vascular access blood flow monitoring
reduces access morbidity and costs. Kidney Int 60:11641172, 2001
367. Mercadal L, Challier E, Cluzel P, et al: Detection of
vascular access stenosis by measurement of access blood
flow from ionic dialysance. Blood Purif 20:177-181, 2002
368. Sands JJ, Jabyac PA, Miranda CL, Kapsick BJ:
Intervention based on monthly monitoring decreases hemodialysis access thrombosis. ASAIO J 45:147-150, 1999
369. Schwab SJ, Oliver MJ, Suhocki P, McCann R:
Hemodialysis arteriovenous access: Detection of stenosis
and response to treatment by vascular access blood flow.
Kidney Int 59:358-362, 2001
370. Wang E, Schneditz D, Levin NW: Predictive value
of access blood flow and stenosis in detection of graft
failure. Clin Nephrol 54:393-399, 2000
371. Wang E, Schneditz D, Nepomuceno C, et al: Predictive value of access blood flow in detecting access thrombosis. ASAIO J 44:M555-M558, 1998
372. Bosman PJ, Boereboom FT, Eikelboom BC, Koomans HA, Blankestijn PJ: Graft flow as a predictor of
thrombosis in hemodialysis grafts. Kidney Int 54:17261730, 1998
373. Cayco AV, Abu-Alfa AK, Mahnensmith RL, Perazella MA: Reduction in arteriovenous graft impairment:
Results of a vascular access surveillance protocol. Am J
Kidney Dis 32:302-308, 1998
REFERENCES
374. Sands JJ, Miranda CL: Prolongation of hemodialysis access survival with elective revision. Clin Nephrol
44:329-333, 1995
375. Yeun JY, Depner TA: Role of access flow measurement, in Gray RJ, Sands JJ (eds): Dialysis Access: A Multidisciplinary Approach. Philadelphia, PA, Lippincott Williams
& Wilkins, 2002, pp 119-132
376. Paulson WD, Ram SJ, Birk CG, Work J: Does blood
flow accurately predict thrombosis or failure of hemodialysis synthetic grafts? A meta-analysis. Am J Kidney Dis
34:478-485, 1999
377. Paulson WD, Ram SJ, Birk CG, Zapczynski M,
Martin SR, Work J: Accuracy of decrease in blood flow in
predicting hemodialysis graft thrombosis. Am J Kidney Dis
35:1089-1095, 2000
378. Krivitski N, Gantela S: Access blood flow: Debate
continues. Semin Dial 14:460-461, 2001
379. Paulson WD: Blood flow surveillance of hemodialysis grafts and the dysfunction hypothesis. Semin Dial
14:175-180, 2001
380. Paulson WD, Ram SJ, Work J: Access blood flow:
Debate continues. Semin Dial 14:459-460, 2001
381. Roberts AB, Kahn MB, Bradford S, et al: Graft
surveillance and angioplasty prolongs dialysis graft patency.
J Am Coll Surg 183:486-492, 1996
382. Lumsden AB, MacDonald MJ, Kikeri D, Cotsonis
GA, Harker LA, Martin LG: Prophylactic balloon angioplasty fails to prolong the patency of expanded polytetrafluoroethylene arteriovenous grafts: Results of a prospective
randomized study. J Vasc Surg 26:382-390; discussion
390-382, 1997
383. Martin LG, MacDonald MJ, Kikeri D, Cotsonis GA,
Harker LA, Lumsden AB: Prophylactic angioplasty reduces
thrombosis in virgin ePTFE arteriovenous dialysis grafts
with greater than 50% stenosis: Subset analysis of a
prospectively randomized study. J Vasc Interv Radiol 10:389396, 1999
384. Dember LM, Holmberg EF, Kaufman JS: Randomized controlled trial of prophylactic repair of hemodialysis
arteriovenous graft stenosis. Kidney Int 66:390-398, 2004
385. Dember LM, Holmberg EF, Kaufman JS: Value of
static venous pressure for predicting arteriovenous graft
thrombosis. Kidney Int 61:1899-1904, 2002
386. Moist LM, Churchill DN, House AA, et al: Regular
monitoring of access flow compared with monitoring of
venous pressure fails to improve graft survival. J Am Soc
Nephrol 14:2645-2653, 2003
387. Ram SJ, Work J, Caldito GC, Eason JM, Pervez A,
Paulson WD: A randomized controlled trial of blood flow
and stenosis surveillance of hemodialysis grafts. Kidney Int
64:272-280, 2003
388. Schanter H: Overview of complications and management after vascular access creation, in Gray RJ, Sands JJ
(eds): Dialysis Access: A Multidisciplinary Approach. Philadelphia, PA, Lippincott Williams & Wilkins, 2002, pp 93-97
389. Tessitore N, Lipari G, Poli A, et al: Can blood flow
surveillance and pre-emptive repair of subclinical stenosis
prolong the useful life of arteriovenous fistulae? A randomized controlled study. Nephrol Dial Transplant 19:23252333, 2004
S299
390. Tessitore N, Mansueto G, Bedogna V, et al: A

prospective controlled trial on effect of percutaneous transluminal angioplasty on functioning arteriovenous fistulae
survival. J Am Soc Nephrol 14:1623-1627, 2003
391. Elseviers MM, Van Waeleghem JP: Identifying
vascular access complications among ESRD patients in
Europe. A prospective, multicenter study. Nephrol News
Issues 17:61-64, 66-68, 99, 2003
392. Paulson WD, Ram SJ, Zibari GB: Vascular access:
Anatomy, examination, management. Semin Nephrol 22:183194, 2002
393. Lockhart ME, Robbin ML: Hemodialysis access
ultrasound. Ultrasound Q 17:157-167, 2001
394. Brouwer DJ: . . . The road to improvement? Part 2.
The care and feeding of the AV fistula. Nephrol News Issues
17:48-51, 2003
395. Waterhouse D: Vascular access: A role for a renal
nurse clinician. EDTNA ERCA J 28:64-66, 69, 2002
396. Yang R, Humphrey S: Review of arteriovenous
fistula care. EDTNA ERCA J 26:11-14, 2000
397. Ross EA, Verlander JW, Koo LC, Hawkins IF:
Minimizing hemodialysis vascular access trauma with an
improved needle design. J Am Soc Nephrol 11:1325-1330,
2000
398. Toma S, Shinzato T, Fukui H, et al: A timesaving
method to create a fixed puncture route for the buttonhole
technique. Nephrol Dial Transplant 18:2118-2121, 2003
399. Paun M, Beach K, Ahmad S, et al: New ultrasound
approaches to dialysis access monitoring. Am J Kidney Dis
35:477-481, 2000
400. Comeax ME, Bryant PS, Harkrider WW: Preoperative evaluation of the the renal access patient with color flow
Doppler imaging. J Vasc Technol 17:247-250, 1993
401. Konner K: The initial creation of native arteriovenous fistulas: Surgical aspects and their impact on the
practice of nephrology. Semin Dial 16:291-298, 2003
402. Locatelli F, Pozzoni P, Del Vecchio L: Renal replacement therapy in patients with diabetes and end-stage renal
disease. J Am Soc Nephrol 15:S25-S29, 2004 (suppl 1)
403. Ernandez T, Saudan P, Berney T, Merminod T,
Bednarkiewicz M, Martin PY: Risk factors for early failure
of native arteriovenous fistulas. Nephron Clin Pract 101:c39c44, 2005
404. Chiang WC, Lin SL, Tsai TJ, Hsieh BS: High
resistive index of the radial artery is related to early primary
radiocephalic hemodialysis fistula failure. Clin Nephrol
56:236-240, 2001
405. US Renal Data System: Dialysis Morbidity and
Mortality Study (Wave 1). Bethesda, MD, The National
Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases, 1997, pp 45-67
406. Harter HR: Review of significant findings from the
National Cooperative Dialysis Study and recommendations.
Kidney Int Suppl 13:S107-S112, 1983
407. Sedlacek M, Teodorescu V, Falk A, Vassalotti JA,
Uribarri J: Hemodialysis access placement with preoperative noninvasive vascular mapping: Comparison between
patients with and without diabetes. Am J Kidney Dis
38:560-564, 2001
408. Prischl FC, Kirchgatterer A, Brandstatter E, et al:
Parameters of prognostic relevance to the patency of vascu-
S300
lar access in hemodialysis patients. J Am Soc Nephrol

6:1613-1618, 1995
409. Khan FA, Vesely TM: Arterial problems associated
with dysfunctional hemodialysis grafts: Evaluation of patients at high risk for arterial disease. J Vasc Interv Radiol
13:1109-1114, 2002
410. Manninen HI, Kaukanen ET, Ikaheimo R, et al:
Brachial arterial access: Endovascular treatment of failing
Brescia-Cimino hemodialysis fistulasInitial success and
long-term results. Radiology 218:711-718, 2001
411. Guerra A, Raynaud A, Beyssen B, Pagny JY,
Sapoval M, Angel C: Arterial percutaneous angioplasty in
upper limbs with vascular access devices for haemodialysis.
412. Anderson CB, Gilula LA, Harter HR, Etheredge EE:
Venous angiography and the surgical management of subcutaneous hemodialysis fistulas. Ann Surg 187:194-204, 1978
413. Krnung G: Plastic deformation of Cimino fistula
by repeated puncture. Dial Transplant 13:635-638, 1984
414. Sullivan K, Besarab A: Strategies for maintaining
dialysis access patency, in Cope C (ed): Current Techniques
in Interventional Radiology (ed 2). New York, NY, McGraw
Hill, 1996, pp 125-131
415. Turmel-Rodrigues L: Diagnosis and endovascular
treatment for autologous fistulae-related stenosis, in Gray
RJ, Sands JJ (eds): Dialysis Access: A Multidisciplinary
Approach. Philadelphia, PA, Lippincott Williams & Wilkins,
2002, pp 170-183
416. Vorwerk D, Adam G, Muller-Leisse C, Guenther
RW: Hemodialysis fistulas and grafts: Use of cutting balloons to dilate venous stenoses. Radiology 201:864-867,
1996
417. Turmel-Rodrigues L: Application of percutaneous
mechanical thrombectomy in autogenous fistulae. Tech Vasc
418. Turmel-Rodrigues L, Pengloan J, Rodrigue H, et al:
Treatment of failed native arteriovenous fistulae for hemodialysis by interventional radiology. Kidney Int 57:1124-1140,
2000
419. Turmel-Rodrigues L: Dilatation and declotting of
arteriovenous accesses. Ther Apher Dial 7:244-251, 2003
420. Schon D, Mishler R: Salvage of occluded autologous
arteriovenous fistulae. Am J Kidney Dis 36:804-810, 2000
421. Schon D, Mishler R: Pharmacomechanical thrombolysis of natural vein fistulas: Reduced dose of TPA and
long-term follow-up. Semin Dial 16:272-275, 2003
422. Rajan DK, Clark TW, Simons ME, Kachura JR,
Sniderman K: Procedural success and patency after percutaneous treatment of thrombosed autogenous arteriovenous
dialysis fistulas. J Vasc Interv Radiol 13:1211-1218, 2002
423. Hodges TC, Fillinger MF, Zwolak RM, Walsh DB,
Bech F, Cronenwett JL: Longitudinal comparison of dialysis
access methods: Risk factors for failure. J Vasc Surg 26:
1009-1019, 1997
424. Oakes DD, Sherck JP, Cobb LF: Surgical salvage of
failed radiocephalic arteriovenous fistulae: Techniques and
results in 29 patients. Kidney Int 53:480-487, 1998
425. Grochowiecki T, Szmidt J, Galazka Z, et al: Usefulness of arterialized cephalic vein of forearm of previously
thrombosed arteriovenous fistula for creating a new vascular
VASCULAR ACCESS
access for hemodialysis in patients with renal allograft

insufficiency. Transplant Proc 32:1375-1376, 2000
426. Sivanesan S, How TV, Bakran A: Characterizing
flow distributions in AV fistulae for haemodialysis access.
427. Lazarides MK, Staramos DN, Kopadis G, Maltezos
C, Tzilalis VD, Georgiadis GS: Onset of arterial steal
following proximal angioaccess: Immediate and delayed
types. Nephrol Dial Transplant 18:2387-2390, 2003
428. Burrows L, Kwun K, Schanzer H, Haimov M:
Haemodynamic dangers of high flow arteriovenous fistulas.
Proc Eur Dial Transplant Assoc 16:686-687, 1979
429. Schanzer H, Schwartz M, Harrington E, Haimov M:
Treatment of ischemia due to steal by arteriovenous fistula
with distal artery ligation and revascularization. J Vasc Surg
7:770-773, 1988
430. Morsy AH, Kulbaski M, Chen C, Isiklar H, Lumsden AB: Incidence and characteristics of patients with hand
ischemia after a hemodialysis access procedure. J Surg Res
74:8-10, 1998
431. Miles AM: Vascular steal syndrome and ischaemic
monomelic neuropathy: Two variants of upper limb ischaemia after haemodialysis vascular access surgery. Nephrol
432. Sessa C, Pecher M, Maurizi-Balzan J, et al: Critical
hand ischemia after angioaccess surgery: Diagnosis and
treatment. Ann Vasc Surg 14:583-593, 2000
433. Knox RC, Berman SS, Hughes JD, Gentile AT, Mills
JL: Distal revascularization-interval ligation: A durable and
effective treatment for ischemic steal syndrome after hemodialysis access. J Vasc Surg 36:250-255; discussion 256,
2002
434. Zanow J, Petzold M, Petzold K, Kruger U, Scholz
H: Diagnosis and differentiated treatment of ischemia in
patients with arteriovenous vascular access, in Henry ML
(ed): Vascular Access for Hemodialysis-VII. Chicago, IL,
Gore, 2001, pp 201-209
435. Stevenson KB: Management of hemodialysis vascular access infection, in Gray RJ, Sands JJ (eds): Dialysis
Access: A Multidisciplinary Approach. Philadelphia, PA,
Lippincott Williams & Wilkins, 2002, pp 98-106
436. Surratt RS, Picus D, Hicks ME, Darcy MD, Kleinhoffer M, Jendrisak M: The importance of preoperative
evaluation of the subclavian vein in dialysis access planning.
AJR Am J Roentgenol 156:623-625, 1991
437. Davidson CJ, Newman GE, Sheikh KH, Kisslo K,
Stack RS, Schwab SJ: Mechanisms of angioplasty in hemodialysistk;1 fistula stenoses evaluated by intravascular ultrasound. Kidney Int 40:91-95, 1991
438. Kovalik EC, Newman GE, Suhocki P, Knelson M,
Schwab SJ: Correction of central venous stenoses: Use of
angioplasty and vascular Wallstents. Kidney Int 45:11771181, 1994
439. Maskova J, Komarkova J, Kivanek J, Danes J,
Slavikova M: Endovascular treatment of central vein stenoses and/or occlusions in hemodialysis patients. Cardiovasc
440. Oderich GS, Treiman GS, Schneider P, Bhirangi K:
Stent placement for treatment of central and peripheral
venous obstruction: A long-term multi-institutional experience. J Vasc Surg 32:760-769, 2000
REFERENCES
441. Shoenfeld R, Hermans H, Novick A, et al: Stenting

of proximal venous obstructions to maintain hemodialysis
access. J Vasc Surg 19:532-538; discussion 538-539, 1994
442. Vesely TM, Hovsepian DM, Pilgram TK, Coyne
DW, Shenoy S: Upper extremity central venous obstruction
in hemodialysis patients: Treatment with Wallstents. Radiology 204:343-348, 1997
443. Ayarragaray JE: Surgical treatment of hemodialysisrelated central venous stenosis or occlusion: Another option
to maintain vascular access. J Vasc Surg 37:1043-1046, 2003
444. Charara J, Guidoin R, Gill F, Guzman R: Morphologic assessment of ePTFE graft wall damage following
hemodialysis needle punctures. J Appl Biomater 1:279-287,
1990
445. Delorme JM, Guidoin R, Canizales S, et al: Vascular
access for hemodialysis: Pathologic features of surgically
excised ePTFE grafts. Ann Vasc Surg 6:517-524, 1992
446. Ballard JL, Bunt TJ, Malone JM: Major complications of angioaccess surgery. Am J Surg 164:229-232, 1992
447. Hausegger KA, Tiessenhausen K, Klimpfinger M,
Raith J, Hauser H, Tauss J: Aneurysms of hemodialysis
access grafts: Treatment with covered stents: A report of
three cases. Cardiovasc Interv Radiol 21:334-337, 1998
448. Blankestijn PJ, Smits JH: How to identify the haemodialysis access at risk of thrombosis? Are flow measurements
the answer? Nephrol Dial Transplant 14:1068-1071, 1999
449. May AG, Van De Berg L, Deweese JA, Rob CG:
Critical arterial stenosis. Surgery 54:250-259, 1963
450. Berguer R, Hwang NH: Critical arterial stenosis: A
theoretical and experimental solution. Ann Surg 180:39-50,
1974
451. Roberts AC, Valji K, Bookstein JJ, Hye RJ: Pulsespray pharmacomechanical thrombolysis for treatment of
thrombosed dialysis access grafts. Am J Surg 166:221-225;
discussion 225-226, 1993
452. Valji K, Bookstein JJ, Roberts AC, Davis GB:
Pharmacomechanical thrombolysis and angioplasty in the
management of clotted hemodialysis grafts: Early and late
clinical results. Radiology 178:243-247, 1991
453. Murray BM, Rajczak S, Ali B, Herman A, Mepani
B: Assessment of access blood flow after preemptive
angioplasty. Am J Kidney Dis 37:1029-1038, 2001
454. Trerotola SO, Lund GB, Scheel PJ Jr, Savader SJ,
Venbrux AC, Osterman FA Jr: Thrombosed dialysis access
grafts: Percutaneous mechanical declotting without urokinase. Radiology 191:721-726, 1994
455. Tordoir JH, Hoeneveld H, Eikelboom BC, Kitslaar
PJ: The correlation between clinical and duplex ultrasound
parameters and the development of complications in arteriovenous fistulae for haemodialysis. Eur J Vasc Surg 4:179184, 1990
456. Katz SG, Kohl RD: The percutaneous treatment of
angioaccess graft complications. Am J Surg 170:238-242,
1995
457. Gray RJ, Sacks D, Martin LG, Trerotola SO:
Reporting standards for percutaneous interventions in dialysis access. Technology Assessment Committee. J Vasc Interv
Radiol 10:1405-1415, 1999
458. Sidawy AN, Gray R, Besarab A, et al: Recommended standards for reports dealing with arteriovenous
hemodialysis accesses. J Vasc Surg 35:603-610, 2002
S301
459. Gray RJ, Horton KM, Dolmatch BL, et al: Use of

Wallstents for hemodialysis access-related venous stenoses
and occlusions untreatable with balloon angioplasty. Radiology 195:479-484, 1995
460. Hoffer EK, Sultan S, Herskowitz MM, Daniels ID,
Sclafani SJ: Prospective randomized trial of a metallic
intravascular stent in hemodialysis graft maintenance. J Vasc
461. Patel RI, Peck SH, Cooper SG, et al: Patency of
Wallstents placed across the venous anastomosis of hemodialysis grafts after percutaneous recanalization. Radiology
209:365-370, 1998
462. Funaki B, Szymski GX, Leef JA, Rosenblum JD,
Burke R, Hackworth CA: Wallstent deployment to salvage
dialysis graft thrombolysis complicated by venous rupture:
Early and intermediate results. AJR Am J Roentgenol 169:
1435-1437, 1997
463. Rajan DK, Clark TW: Patency of Wallstents placed
at the venous anastomosis of dialysis grafts for salvage of
angioplasty-induced rupture. Cardiovasc Interv Radiol 26:
242-245, 2003
464. Welber A, Schur I, Sofocleous CT, Cooper SG, Patel
RI, Peck SH: Endovascular stent placement for angioplastyinduced venous rupture related to the treatment of hemodialysis grafts. J Vasc Interv Radiol 10:547-551, 1999
465. Brooks JL, Sigley RD, May KJ Jr, Mack RM:
Transluminal angioplasty versus surgical repair for stenosis
of hemodialysis grafts. A randomized study. Am J Surg
153:530-531, 1987
466. Dapunt O, Feurstein M, Rendl KH, Prenner K:
Transluminal angioplasty versus conventional operation in
the treatment of haemodialysis fistula stenosis: Results from
a 5-year study. Br J Surg 74:1004-1005, 1987
467. Green LD, Lee DS, Kucey DS: A metaanalysis
comparing surgical thrombectomy, mechanical thrombectomy, and pharmacomechanical thrombolysis for thrombosed dialysis grafts. J Vasc Surg 36:939-945, 2002
468. Marston WA, Criado E, Jaques PF, Mauro MA,
Burnham SJ, Keagy BA: Prospective randomized comparison of surgical versus endovascular management of thrombosed dialysis access grafts. J Vasc Surg 26:373-380; discussion 380-371, 1997
469. Sands JJ, Patel S, Plaviak DJ, Miranda CL: Pharmacomechanical thrombolysis with urokinase for treatment of
thrombosed hemodialysis access grafts. A comparison with
surgical thrombectomy. ASAIO J 40:M886-M888, 1994
470. Schwartz CI, McBrayer CV, Sloan JH, Meneses P,
Ennis WJ: Thrombosed dialysis grafts: Comparison of
treatment with transluminal angioplasty and surgical revision. Radiology 194:337-341, 1995
471. Beathard GA, Litchfield T: Effectiveness and safety
of dialysis vascular access procedures performed by interventional nephrologists. Kidney Int 66:1622-1632, 2004
472. Dougherty MJ, Calligaro KD, Schindler N, Raviola
CA, Ntoso A: Endovascular versus surgical treatment for
thrombosed hemodialysis grafts: A prospective, randomized
study. J Vasc Surg 30:1016-1023, 1999
473. Falk A, Guller J, Nowakowski FS, et al: Reteplase in
the treatment of thrombosed hemodialysis grafts. J Vasc
Interv Radiol 12:1257-1262, 2001
S302
474. Gmelin E, Winterhoff R, Rinast E: Insufficient

hemodialysis access fistulas: Late results of treatment with
percutaneous balloon angioplasty. Radiology 171:657-660,
1989
475. Mori Y, Horikawa K, Sato K, Mimuro N, Toriyama
T, Kawahara H: Stenotic lesions in vascular access: Treatment with transluminal angioplasty using high-pressure
balloons. Intern Med 33:284-287, 1994
476. Sofocleous CT, Hinrichs CR, Weiss SH, et al:
Alteplase for hemodialysis access graft thrombolysis. J Vasc
477. Turmel-Rodrigues L, Pengloan J, Blanchier D, et al:
Insufficient dialysis shunts: Improved long-term patency
rates with close hemodynamic monitoring, repeated percutaneous balloon angioplasty, and stent placement. Radiology
187:273-278, 1993
478. Vogel PM, Bansal V, Marshall MW: Thrombosed
hemodialysis grafts: Lyse and wait with tissue plasminogen
activator or urokinase compared to mechanical thrombolysis
with the Arrow-Trerotola Percutaneous Thrombolytic Device. J Vasc Interv Radiol 12:1157-1165, 2001
479. Zibari GB, Rohr MS, Landreneau MD, et al: Complications from permanent hemodialysis vascular access.
Surgery 104:681-686, 1988
480. Cohen MA, Kumpe DA, Durham JD, Zwerdlinger
SC: Improved treatment of thrombosed hemodialysis access
sites with thrombolysis and angioplasty. Kidney Int 46:13751380, 1994
481. Trerotola SO, Vesely TM, Lund GB, Soulen MC,
Ehrman KO, Cardella JF: Treatment of thrombosed hemodialysis access grafts: Arrow-Trerotola percutaneous
thrombolytic device versus pulse-spray thrombolysis. Arrow-Trerotola Percutaneous Thrombolytic Device Clinical
Trial. Radiology 206:403-414, 1998
482. Ryan SV, Calligaro KD, Scharff J, Dougherty MJ:
Management of infected prosthetic dialysis arteriovenous
grafts. J Vasc Surg 39:73-78, 2004
483. Berns JS, Tokars JI: Preventing bacterial infections
and antimicrobial resistance in dialysis patients. Am J Kidney
Dis 40:886-898, 2002
484. Deneuville M: Infection of PTFE grafts used to
create arteriovenous fistulas for hemodialysis access. Ann
Vasc Surg 14:473-479, 2000
485. American College of Radiology: Practice Guidelines for Percutaneous Management of the Thrombosed or
Dysfunctional Dialysis Access. Reston, VA, American College of Radiology, 2000, pp 473-485
486. Develter W, De Cubber A, Van Biesen W, Vanholder
R, Lameire N: Survival and complications of indwelling
venous catheters for permanent use in hemodialysis patients.
Artif Organs 29:399-405, 2005
487. Little MA, ORiordan A, Lucey B, et al: A prospective study of complications associated with cuffed, tunnelled
haemodialysis catheters. Nephrol Dial Transplant 16:21942200, 2001
488. Ponikvar R, Buturovic-Ponikvar J: Temporary hemodialysis catheters as a long-term vascular access in chronic
hemodialysis patients. Ther Apher Dial 9:250-253, 2005
489. Leblanc M, Fedak S, Mokris G, Paganini EP: Blood
recirculation in temporary central catheters for acute hemodialysis. Clin Nephrol 45:315-319, 1996
VASCULAR ACCESS
490. Little MA, Conlon PJ, Walshe JJ: Access recirculation in temporary hemodialysis catheters as measured by the
saline dilution technique. Am J Kidney Dis 36:1135-1139,
2000
491. Carson RC, Kiaii M, MacRae JM: Urea clearance in
dysfunctional catheters is improved by reversing the line
position despite increased access recirculation. Am J Kidney
Dis 45:883-890, 2005
492. Blankestijn PJ: Cuffed tunneled catheters for longterm vascular access, in Conlon PJ, Nicholson ML, Schwab
SJ (eds): Hemodialysis Vascular Access: Practice and Problems. London, UK, Oxford, 2000, pp 64-84
493. Leblanc M, Bosc JY, Paganini EP, Canaud B:
Central venous dialysis catheter dysfunction. Adv Ren
Replace Ther 4:377-389, 1997
494. Trerotola SO: Hemodialysis catheter placement and
management. Radiology 215:651-658, 2000
495. Mokrzycki MH, Jean-Jerome K, Rush H, Zdunek
MP, Rosenberg SO: A randomized trial of minidose warfarin
for the prevention of late malfunction in tunneled, cuffed
hemodialysis catheters. Kidney Int 59:1935-1942, 2001
496. Daeihagh P, Jordan J, Chen J, Rocco M: Efficacy of
tissue plasminogen activator administration on patency of
hemodialysis access catheters. Am J Kidney Dis 36:75-79,
2000
497. Kaufman JS, OConnor TZ, Zhang JH, et al: Randomized controlled trial of clopidogrel plus aspirin to
prevent hemodialysis access graft thrombosis. J Am Soc
Nephrol 14:2313-2321, 2003
498. Obialo CI, Conner AC, Lebon LF: Maintaining
patency of tunneled hemodialysis cathetersEfficacy of
aspirin compared to warfarin. Scand J Urol Nephrol 37:172176, 2003
499. Vesely TM: Central venous catheter tip position: A
continuing controversy. J Vasc Interv Radiol 14:527-534,
2003
500. Bayes B, Bonal J, Romero R: Sodium citrate for
filling haemodialysis catheters. Nephrol Dial Transplant 14:
2532-2533, 1999
501. Karaaslan H, Peyronnet P, Benevent D, Lagarde C,
Rince M, Leroux-Robert C: Risk of heparin lock-related
bleeding when using indwelling venous catheter in haemodialysis. Nephrol Dial Transplant 16:2072-2074, 2001
502. Agharazii M, Plamondon I, Lebel M, Douville P,
Desmeules S: Estimation of heparin leak into the systemic
circulation after central venous catheter heparin lock. Nephrol Dial Transplant 20:1238-1240, 2005
503. Polaschegg HD: Loss of catheter locking solution
caused by fluid density. ASAIO J 51:230-235, 2005
504. Bolz KD, Fjermeros G, Wideroe TE, Hatlinghus S:
Catheter malfunction and thrombus formation on doublelumen hemodialysis catheters: An intravascular ultrasonographic study. Am J Kidney Dis 25:597-602, 1995
505. Negulescu O, Coco M, Croll J, Mokrzycki MH:
Large atrial thrombus formation associated with tunneled
cuffed hemodialysis catheters. Clin Nephrol 59:40-46, 2003
506. Twardowski ZJ: The clotted central vein catheter for
haemodialysis. Nephrol Dial Transplant 13:2203-2206, 1998
507. McFarland HF, Dinwiddie L, Ferrell J, ForloinesLynn S: Lytic therapy in central venous catheters for
REFERENCES
hemodialysis. Nephrol Nurs J 29:355-360; quiz 361-352,

2002
508. Clase CM, Crowther MA, Ingram AJ, Cina CS:
Thrombolysis for restoration of patency to haemodialysis
central venous catheters: A systematic review. J Thromb
Thrombolysis 11:127-136, 2001
509. Estess JM, Moliterno DJ: Thrombolytic therapy for
acute myocardial infarction. Catheter Cardiovasc Interv
53:489-498, 2001
510. Falk A, Samson W, Uribarri J, Vassalotti JA: Efficacy of reteplase in poorly functioning hemodialysis catheters. Clin Nephrol 61:47-53, 2004
511. Hannah A, Buttimore AL: Thrombolysis of blocked
hemodialysis catheter using recombinant tissue-type plasminogen activator. Nephron 59:517-518, 1991
512. Hathiwala SC, Hristea I, Khalili V: Alteplase (TPA)
for clotted dialysis catheters. Int J Artif Organs 23:668-669,
2000
513. Haymond J, Shalansky K, Jastrzebski J: Efficacy of
low-dose alteplase for treatment of hemodialysis catheter
occlusions. J Vasc Access 6:76-82, 2005
514. Hilleman DE, Dunlay RW, Packard KA: Reteplase
for dysfunctional hemodialysis catheter clearance. Pharmacotherapy 23:137-141, 2003
515. Knofler R, Dinger J, Kabus M, et al: Thrombolytic
therapy in childrenClinical experiences with recombinant
tissue-plasminogen activator. Semin Thromb Hemost 27:169174, 2001
516. Little MA, Walshe JJ: A longitudinal study of the
repeated use of alteplase as therapy for tunneled hemodialysis catheter dysfunction. Am J Kidney Dis 39:86-91, 2002
517. Meers C, Toffelmire EB: Urokinase efficacy in the
restoration of hemodialysis catheter function. J Cannt 8:1719, 1998
518. Moser M, Nordt T, Peter K, et al: Platelet function
during and after thrombolytic therapy for acute myocardial
infarction with reteplase, alteplase, or streptokinase. Circulation 100:1858-1864, 1999
519. Northsea C: Continuous quality improvement:
Improving hemodialysis catheter patency using urokinase.
ANNA J 23:567-571, 615, 1996
520. OMara NB, Ali S, Bivens K, Sherman RA, Kapoian
T: Efficacy of tissue plasminogen activator for thrombolysis
in central venous dialysis catheters. Hemodial Int 7:130134, 2003
521. Paulsen D, Reisoether A, Aasen M, Fauchald P: Use
of tissue plasminogen activator for reopening of clotted
dialysis catheters. Nephron 64:468-470, 1993
522. Peska DN, DeLange B, Gratch JO, Bleicher JN,
Pertusi RM, Mueller D: Short-term continuous infusion
thrombolytic therapy for occluded central nervous venous
dialysis catheters. Am J Manag Care 3:261-264, 1997
523. Semba CP, Bakal CW, Calis KA, et al: Alteplase as
an alternative to urokinase. Advisory Panel on CatheterDirected Thrombolytic Therapy. J Vasc Interv Radiol 11:279287, 2000
524. Welik RA, Josselson J, Shen SY, Reed WR, Sadler
JH: Repeated low-dose streptokinase infusions into occluded permanent, central-venous hemodialysis catheters.
Kidney Int 31:1210-1212, 1987
S303
525. Zacharias JM, Weatherston CP, Spewak CR, Vercaigne LM: Alteplase versus urokinase for occluded hemodialysis catheters. Ann Pharmacother 37:27-33, 2003
525A. Prescribing information for Abbokinase [urokinase]. Chicago, IL, Abbott Laboratories, 2003
525B. Prescribing information for Reteplase [reteplase]. Boehringer Mannheim GmbH, 2000
525C. Prescribing information for Cathflo Activase
[alteplase]. South San Francisco, CA, Genentech, 2001
526. Deitcher SR, Fesen MR, Kiproff PM, et al: Safety
and efficacy of alteplase for restoring function in occluded
central venous catheters: Results of The Cardiovascular
Thrombolytic to Open Occluded Lines Trial. J Clin Oncol
20:317-324, 2002
527. Ponec D, Irwin D, Haire WD, Hill PA, Li X,
McCluskey ER: Recombinant tissue plasminogen activator
(alteplase) for restoration of flow in occluded central venous
access devices: A double-blind placebo-controlled trial
The Cardiovascular Thrombolytic to Open Occluded Lines
(COOL) efficacy trial. J Vasc Interv Radiol 12:951-955,
2001
528. Tranter SA, Donoghue J: Brushing has made a
sweeping change: Use of the endoluminal FAS brush in
haemodialysis central venous catheter management. Aust
Crit Care 13:10-13, 2000
529. Crowther MA, Stevens L, Ingram AJ, Clase CM,
Chan AKC: Effectiveness of reconstituted and then frozen
tPA for dysfunctional percutaneous dialysis catheters. Blood
96:92bA, 2000 (abstr)
530. Gray RJ, Levitin A, Buck D, et al: Percutaneous
fibrin sheath stripping versus transcatheter urokinase infusion for malfunctioning well-positioned tunneled central
venous dialysis catheters: A prospective, randomized trial.
J Vasc Interv Radiol 11:1121-1129, 2000
531. Merport M, Murphy TP, Egglin TK, Dubel GJ:
Fibrin sheath stripping versus catheter exchange for the
treatment of failed tunneled hemodialysis catheters: Randomized clinical trial. J Vasc Interv Radiol 11:1115-1120, 2000
532. Jean G, Charra B, Chazot C, et al: Risk factor
analysis for long-term tunneled dialysis catheter-related bacteremias. Nephron 91:399-405, 2002
533. Marr KA, Sexton DJ, Conlon PJ, Corey GR, Schwab
SJ, Kirkland KB: Catheter-related bacteremia and outcome
of attempted catheter salvage in patients undergoing hemodialysis. Ann Intern Med 127:275-280, 1997
534. Fernandez-Cean J, Alvarez A, Burguez S, Baldovinos G, Larre-Borges P, Cha M: Infective endocarditis in
chronic haemodialysis: Two treatment strategies. Nephrol
535. Manian FA: Vascular and cardiac infections in
end-stage renal disease. Am J Med Sci 325:243-250, 2003
536. Robinson DL, Fowler VG, Sexton DJ, Corey RG,
Conlon PJ: Bacterial endocarditis in hemodialysis patients.
Am J Kidney Dis 30:521-524, 1997
537. Saeed Abdulrahman I, Al-Mueilo SH, Bokhary HA,
Ladipo GO, Al-Rubaish A: A prospective study of hemodialysis access-related bacterial infections. J Infect Chemother
8:242-246, 2002
538. Sandroni S, McGill R, Brouwer D: Hemodialysis
catheter-associated endocarditis: Clinical features, risks,
and costs. Semin Dial 16:263-265, 2003
S304
539. Spies C, Madison JR, Schatz IJ: Infective endocarditis in patients with end-stage renal disease: Clinical presentation and outcome. Arch Intern Med 164:71-75, 2004
540. Safdar N, Fine JP, Maki DG: Meta-analysis: Methods for diagnosing intravascular device-related bloodstream
infection. Ann Intern Med 142:451-466, 2005
541. Tovbin D, Mashal A, Friger M, et al: High incidence
of severe twin hemodialysis catheter infections in elderly
women. Possible roles of insufficient nutrition and social
support. Nephron 89:26-30, 2001
542. Hannah EL, Stevenson KB, Lowder CA, et al:
Outbreak of hemodialysis vascular access site infections
related to malfunctioning permanent tunneled catheters:
Making the case for active infection surveillance. Infect
Control Hosp Epidemiol 23:538-541, 2002
543. Stevenson KB, Adcox MJ, Mallea MC, Narasimhan
N, Wagnild JP: Standardized surveillance of hemodialysis
vascular access infections: 18-Month experience at an outpatient, multifacility hemodialysis center. Infect Control
Hosp Epidemiol 21:200-203, 2000
544. Zaleski GX, Funaki B, Lorenz JM, et al: Experience
with tunneled femoral hemodialysis catheters. AJR Am J
Roentgenol 172:493-496, 1999
545. Maya ID, Allon M: Outcomes of tunneled femoral
hemodialysis catheters: Comparison with internal jugular
vein catheters. Kidney Int 68:2886-2889, 2005
546. Raad I, Costerton W, Sabharwal U, Sacilowski M,
Anaissie E, Bodey GP: Ultrastructural analysis of indwelling vascular catheters: A quantitative relationship between
luminal colonization and duration of placement. J Infect Dis
168:400-407, 1993
547. Lewis K: Riddle of biofilm resistance. Antimicrob
Agents Chemother 45:999-1007, 2001
548. Saxena AK, Panhorota BR, Al-Mulhim AS: Vascular access related infections in hemodialysis patients. Saudi J
Kidney Dis Transplant 16:46-71, 2005
549. Bastani B, Minton J, Islam S: Insufficient penetration of systemic vancomycin into the PermCath lumen.
550. Mermel LA, Farr BM, Sherertz RJ, et al: Guidelines
for the management of intravascular catheter-related infections. J Intraven Nurs 24:180-205, 2001
551. Beathard GA: Management of bacteremia associated with tunneled-cuffed hemodialysis catheters. J Am Soc
Nephrol 10:1045-1049, 1999
552. Saad TF: Bacteremia associated with tunneled,
cuffed hemodialysis catheters. Am J Kidney Dis 34:11141124, 1999
553. Tanriover B, Carlton D, Saddekni S, et al: Bacteremia associated with tunneled dialysis catheters: Comparison
of two treatment strategies. Kidney Int 57:2151-2155, 2000
554. Mokrzycki MH, Singhal A: Cost-effectiveness of
three strategies of managing tunnelled, cuffed haemodialysis
catheters in clinically mild or asymptomatic bacteraemias.
555. Allon M: Saving infected catheters: Why and how.
Blood Purif 23:23-28, 2005
556. Boorgu R, Dubrow AJ, Levin NW, et al: Adjunctive
antibiotic/anticoagulant lock therapy in the treatment of
bacteremia associated with the use of a subcutaneously
VASCULAR ACCESS
implanted hemodialysis access device. ASAIO J 46:767770, 2000

557. Capdevila JA, Segarra A, Planes AM, et al: Successful treatment of haemodialysis catheter-related sepsis without catheter removal. Nephrol Dial Transplant 8:231-234,
1993
558. Krishnasami Z, Carlton D, Bimbo L, et al: Management of hemodialysis catheter-related bacteremia with an
adjunctive antibiotic lock solution. Kidney Int 61:11361142, 2002
559. Poole CV, Carlton D, Bimbo L, Allon M: Treatment
of catheter-related bacteraemia with an antibiotic lock
protocol: Effect of bacterial pathogen. Nephrol Dial Transplant 19:1237-1244, 2004
560. Trerotola SO, Johnson MS, Shah H, et al: Tunneled
hemodialysis catheters: Use of a silver-coated catheter for
prevention of infectionA randomized study. Radiology
207:491-496, 1998
561. Dogra GK, Herson H, Hutchison B, et al: Prevention
of tunneled hemodialysis catheter-related infections using
catheter-restricted filling with gentamicin and citrate: A
randomized controlled study. J Am Soc Nephrol 13:21332139, 2002
562. Allon M: Prophylaxis against dialysis catheterrelated bacteremia with a novel antimicrobial lock solution.
Clin Infect Dis 36:1539-1544, 2003
563. Betjes MG, van Agteren M: Prevention of dialysis
catheter-related sepsis with a citrate-taurolidine-containing
lock solution. Nephrol Dial Transplant 19:1546-1551, 2004
564. Allon M: Dialysis catheter-related bacteremia: Treatment and prophylaxis. Am J Kidney Dis 44:779-791, 2004
565. Lok CE, Stanley KE, Hux JE, Richardson R, Tobe
SW, Conly J: Hemodialysis infection prevention with polysporin ointment. J Am Soc Nephrol 14:169-179, 2003
566. Sesso R, Barbosa D, Leme IL, et al: Staphylococcus
aureus prophylaxis in hemodialysis patients using central
venous catheter: Effect of mupirocin ointment. J Am Soc
Nephrol 9:1085-1092, 1998
567. Quarello F, Forneris G: Prevention of hemodialysis
catheter-related bloodstream infection using an antimicrobial lock. Blood Purif 20:87-92, 2002
568. Johnson DW, van Eps C, Mudge DW, et al: Randomized, controlled trial of topical exit-site application of honey
(Medihoney) versus mupirocin for the prevention of catheterassociated infections in hemodialysis patients. J Am Soc
Nephrol 16:1456-1462, 2005
569. Lok CE, Oliver MJ: Overcoming barriers to arteriovenous fistula creation and use. Semin Dial 16:189-196,
2003
570. Gibson KD, Gillen DL, Caps MT, Kohler TR,
Sherrard DJ, Stehman-Breen CO: Vascular access survival
and incidence of revisions: A comparison of prosthetic
grafts, simple autogenous fistulas, and venous transposition
fistulas from the United States Renal Data System Dialysis
Morbidity and Mortality Study. J Vasc Surg 34:694-700,
2001
571. Windus DW, Jendrisak MD, Delmez JA: Prosthetic
fistula survival and complications in hemodialysis patients:
Effects of diabetes and age. Am J Kidney Dis 19:448-452,
1992
REFERENCES
572. Sands J, Young S, Miranda C: The effect of Doppler

flow screening studies and elective revisions on dialysis
access failure. ASAIO J 38:M524-M527, 1992
573. Bhat DJ, Tellis VA, Kohlberg WI, Driscoll B, Veith
FJ: Management of sepsis involving expanded polytetrafluoroethylene grafts for hemodialysis access. Surgery 87:445450, 1980
574. Foley RN, Guo H, Snyder JJ, Gilbertson DT, Collins
AJ: Septicemia in the United States dialysis population,
1991 to 1999. J Am Soc Nephrol 15:1038-1045, 2004
575. Klevens RM, Tokars JI, Andrus M: Electronic
reporting of infections associated with hemodialysis. Nephrol News Issues 19:37-38, 43, 2005
576. Odurny A, Slapak M: The use of Goretex (P.T.F.E.)
for angio-access for chronic haemodialysis. The place of
peri-operative antibiotics. Br J Clin Pract 38:134-137, 1984
577. Powe NR, Jaar B, Furth SL, Hermann J, Briggs W:
Septicemia in dialysis patients: Incidence, risk factors, and
prognosis. Kidney Int 55:1081-1090, 1999
578. Levin A, Mason AJ, Jindal KK, Fong IW, Goldstein
MB: Prevention of hemodialysis subclavian vein catheter
infections by topical povidone-iodine. Kidney Int 40:934938, 1991
579. Lund GB, Trerotola SO, Scheel PF Jr, et al: Outcome of tunneled hemodialysis catheters placed by radiologists. Radiology 198:467-472, 1996
580. Maki DG, Weise CE, Sarafin HW: A semiquantitative culture method for identifying intravenous-catheterrelated infection. N Engl J Med 296:1305-1309, 1977
581. Jarvis WR: Benchmarking for prevention: The Centers for Disease Control and Preventions National Nosocomial Infections Surveillance (NNIS) system experience.
Infection 31:S44-S48, 2003 (suppl 2)
582. Maki DG, Ringer M, Alvarado CJ: Prospective
randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central
venous and arterial catheters. Lancet 338:339-343, 1991
583. Maki DG, Band JD: A comparative study of polyantibiotic and iodophor ointments in prevention of vascular
catheter-related infection. Am J Med 70:739-744, 1981
584. Conly JM, Grieves K, Peters B: A prospective,
randomized study comparing transparent and dry gauze
dressings for central venous catheters. J Infect Dis 159:310319, 1989
585. Vanherweghem JL, Dhaene M, Goldman M, et al:
Infections associated with subclavian dialysis catheters: The
key role of nurse training. Nephron 42:116-119, 1986
586. Gann M Jr, Sardi A: Improved results using ultrasound guidance for central venous access. Am Surg 69:11041107, 2003
587. Hind D, Calvert N, McWilliams R, et al: Ultrasonic
locating devices for central venous cannulation: Metaanalysis. BMJ 327:361, 2003
588. Skolnick ML: The role of sonography in the placement and management of jugular and subclavian central
venous catheters. AJR Am J Roentgenol 163:291-295, 1994
589. Jean G, Charra B, Chazot C, Vanel T, Terrat JC,
Hurot JM: Long-term outcome of permanent hemodialysis
catheters: A controlled study. Blood Purif 19:401-407, 2001
S305
590. Schuman E, Quinn S, Standage B, Gross G: Thrombolysis versus thrombectomy for occluded hemodyalisis
grafts. Am J Surg 167:473-476, 1994
591. Glazer S, Crooks P, Shapiro M, Diesto J: Using CQI
and the DOQI guidelines to improve vascular access outcomes: The Southern California Kaiser Permanente experience. Nephrol News Issues 14:21-26; discussion 27, 2000
592. Rodriguez JA, Lopez J, Cleries M, Vela E: Vascular
access for haemodialysisAn epidemiological study of the
Catalan Renal Registry. Nephrol Dial Transplant 14:16511657, 1999
593. Golledge J, Smith CJ, Emery J, Farrington K,
Thompson HH: Outcome of primary radiocephalic fistula
for haemodialysis. Br J Surg 86:211-216, 1999
594. Kennedy MT, Quinton H, Bubolz TA, Wennberg JE,
Wilson SE: An analysis of the patency of vascular access
grafts for hemodialysis using the Medicare Part B claims
database. Semin Vasc Surg 9:262-265, 1996
595. Miller PE, Carlton D, Deierhoi MH, Redden DT,
Allon M: Natural history of arteriovenous grafts in hemodialysis patients. Am J Kidney Dis 36:68-74, 2000
596. Mosquera D: Regarding Vascular access survival
and incidence of revisions: A comparison of prosthetic
grafts, simple autogenous fistulas, and venous transposition
fistulas from the United States Renal Data System Dialysis
Morbidity and Mortality Study. J Vasc Surg 37:238-239,
2003
597. Quintaliani G, Buoncristiani U, Fagugli R, et al:
Survival of vascular access during daily and three times a
week hemodialysis. Clin Nephrol 53:372-377, 2000
598. Young EW, Dykstra DM, Goodkin DA, Mapes DL,
Wolfe RA, Held PJ: Hemodialysis vascular access preferences and outcomes in the Dialysis Outcomes and Practice
Patterns Study (DOPPS). Kidney Int 61:2266-2271, 2002
599. Saran R, Dykstra DM, Pisoni RL, et al: Timing of
first cannulation and vascular access failure in haemodialysis: An analysis of practice patterns at dialysis facilities in
the DOPPS. Nephrol Dial Transplant 19:2334-2340, 2004
600. Twardowski ZJ: High-dose intradialytic urokinase
to restore the patency of permanent central vein hemodialysis catheters. Am J Kidney Dis 31:841-847, 1998
601. Dowling K, Sansivero G, Stainken B, et al: The use
of tissue plasminogen activator infusion to re-establish
function of tunneled hemodialysis catheters. Nephrol Nurs J
31:199-200, 2004
602. Savader SJ, Ehrman KO, Porter DJ, Haikal LC,
Oteham AC: Treatment of hemodialysis catheter-associated
fibrin sheaths by rt-PA infusion: Critical analysis of 124
procedures. J Vasc Interv Radiol 12:711-715, 2001
603. Davies J, Casey J, Li C, Crowe AV, McClelland P:
Restoration of flow following haemodialysis catheter thrombus. Analysis of rt-PA infusion in tunnelled dialysis catheters. J Clin Pharm Ther 29:517-520, 2004
604. Eyrich H, Walton T, Macon EJ, Howe A: Alteplase
versus urokinase in restoring blood flow in hemodialysiscatheter thrombosis. Am J Health Syst Pharm 59:1437-1440,
2002
605. Haire WD, Atkinson JB, Stephens LC, Kotulak GD:
Urokinase versus recombinant tissue plasminogen activator
in thrombosed central venous catheters: A double-blinded,
randomized trial. Thromb Haemost 72:543-547, 1994
S306
606. Theriault RL, Buzdar AU: Acute superior vena

caval thrombosis after central venous catheter removal:
Successful treatment with thrombolytic therapy. Med Pediatr Oncol 18:77-80, 1990
607. Beathard GA: Dysfunction of new catheters by old
fibrin sheaths. Semin Dial 17:243-244, 2004
608. Prabhu PN, Kerns SR, Sabatelli FW, Hawkins IF,
Ross EA: Long-term performance and complications of the
Tesio twin catheter system for hemodialysis access. Am J
Kidney Dis 30:213-218, 1997
609. Rockall AG, Harris A, Wetton CW, Taube D,
Gedroyc W, Al-Kutoubi MA: Stripping of failing haemodialysis catheters using the Ampltaz gooseneck snare. Clin
Radiol 52:616-620, 1997
610. USRDS: The United States Renal Data System.
611. Bourquelot P, Raynaud F, Pirozzi N: Microsurgery
in children for creation of arteriovenous fistulas in renal and
non-renal diseases. Ther Apher Dial 7:498-503, 2003
612. Sanabia J, Polo JR, Morales MD, Canals MJ, Polo J,
Serantes A: Microsurgery in gaining paediatric vascular
access for haemodialysis. Microsurgery 14:276-279, 1993
613. Sheth RD, Brandt ML, Brewer ED, Nuchtern JG,
Kale AS, Goldstein SL: Permanent hemodialysis vascular
access survival in children and adolescents with end-stage
renal disease. Kidney Int 62:1864-1869, 2002
614. Goldstein SL, Macierowski CT, Jabs K: Hemodialysis catheter survival and complications in children and
adolescents. Pediatr Nephrol 11:74-77, 1997
615. Sharma A, Zilleruelo G, Abitbol C, Montane B,
Strauss J: Survival and complications of cuffed catheters in
children on chronic hemodialysis. Pediatr Nephrol 13:245248, 1999
616. Sheth RD, Kale AS, Brewer ED, Brandt ML,
Nuchtern JG, Goldstein SL: Successful use of Tesio catheters in pediatric patients receiving chronic hemodialysis.
Am J Kidney Dis 38:553-559, 2001
618. Bourquelot P, Cussenot O, Corbi P, et al: Microsurgical creation and follow-up of arteriovenous fistulae for
chronic haemodialysis in children. Pediatr Nephrol 4:156159, 1990
619. Lumsden AB, MacDonald MJ, Allen RC, Dodson
TF: Hemodialysis access in the pediatric patient population.
Am J Surg 168:197-201, 1994
620. Lahoche A, Beregi JP, Kherbek K, Willoteaux S,
Desmoucelle F, Foulard M: Percutaneous angioplasty of
arteriovenous (Brescia-Cimino) fistulae in children. Pediatr
Nephrol 11:468-472, 1997
621. McDonald SP, Craig JC: Long-term survival of
children with end-stage renal disease. N Engl J Med
350:2654-2662, 2004
622. Goldstein SL, Allsteadt A, Smith CM, Currier H:
Proactive monitoring of pediatric hemodialysis vascular
access: Effects of ultrasound dilution on thrombosis rates.
Kidney Int 62:272-275, 2002
623. Goldstein SL, Smith CM, Currier H: Noninvasive
interventions to decrease hospitalization and associated
VASCULAR ACCESS
costs for pediatric patients receiving hemodialysis. J Am Soc

Nephrol 14:2127-2131, 2003
624. Chand DH, Poe SA, Strife CF: Venous pressure
monitoring does not accurately predict access failure in
children. Pediatr Nephrol 17:765-769, 2002
625. Goldstein SL, Jabs K: Pediatric hemodialysis, in
Avner ED, Harmon WE, Niaudet P (eds): Pediatric Nephrology (ed 5). Philadelphia, PA, Lippincott Williams & Wilkins,
2003, pp 1395-1410
626. Jenkins RD, Kuhn RJ, Funk JE: Clinical implications of catheter variability on neonatal continuous arteriovenous hemofiltration. ASAIO Trans 34:108-111, 1988
627. Swartz RD, Messana JM, Boyer CJ, Lunde NM,
Weitzel WF, Hartman TL: Successful use of cuffed central
venous hemodialysis catheters inserted percutaneously. J Am
Soc Nephrol 4:1719-1725, 1994
628. Donckerwolcke RA, Bunchman TE: Hemodialysis
in infants and small children. Pediatr Nephrol 8:103-106,
1994
629. Strippoli GF, Craig JC, Schena FP: The number,
quality, and coverage of randomized controlled trials in
nephrology. J Am Soc Nephrol 15:411-419, 2004
630. Clark TW, Hirsch DA, Jindal KJ, Veugelers PJ,
LeBlanc J: Outcome and prognostic factors of restenosis
after percutaneous treatment of native hemodialysis fistulas.
J Vasc Interv Radiol 13:51-59, 2002
631. Krivitski NM, Gantela S: Relationship between
vascular access flow and hemodynamically significant stenoses in arteriovenous grafts. Hemodial Int 7:23-27, 2003
632. Vogel PM, Parise C: SMART stent for salvage of
hemodialysis access grafts. J Vasc Interv Radiol 15:10511060, 2004
633. Aschwanden M, Hess P, Labs KH, Dickenmann M,
Jaeger KA: Dialysis access-associated steal syndrome: The
intraoperative use of duplex ultrasound scan. J Vasc Surg
37:211-213, 2003
634. Diehl L, Johansen K, Watson J: Operative management of distal ischemia complicating upper extremity dialysis access. Am J Surg 186:17-19, 2003
635. Korzets A, Kantarovsky A, Lehmann J, et al: The
DRIL procedureA neglected way to treat the steal
syndrome of the hemodialysed patient. Isr Med Assoc J
5:782-785, 2003
636. Shemesh D, Mabjeesh NJ, Abramowitz HB: Management of dialysis access-associated steal syndrome: Use of
intraoperative duplex ultrasound scanning for optimal flow
reduction. J Vasc Surg 30:193-195, 1999
637. Wixon CL, Mills JL Sr, Berman SS: Distal revascularization-interval ligation for maintenance of dialysis access and restoration of distal perfusion in ischemic steal
syndrome. Semin Vasc Surg 13:77-82, 2000
638. Yeager RA, Moneta GL, Edwards JM, et al: Relationship of hemodialysis access to finger gangrene in patients
with end-stage renal disease. J Vasc Surg 36:245-249; discussion 249, 2002
639. Kian K, Wyatt C, Schon D, Packer J, Vassalotti J,
Mischler R: Safety of low-dose radiocontrast for interventional AV fistula salvage in stage 4 chronic kidney disease

AVF
AVG
BP
CHF
CPR
CrCl
CVD
DOQI
GFR
HD
HTN
KDOQI
Kt/V
LVH
NKF
PD
RCT
ROC
SGA
TPA
UOP
UrCl
US
Arteriovenous fistula
Arteriovenous graft
Blood pressure
Clinical Practice Recommendations
Hemodialysis
Hypertension
Measure of dialysis adequacy calculated from K (dialyzer clearance), t (time) and V (volume
of body water in a given patient)
Peritoneal dialysis
Receiver operating characteristics
Tissue plasminogen activator
Urine output
Urea clearance
Ultrasonography
S307
APPENDIX 1. METHODS FOR EVALUATING EVIDENCE

AIM
The overall aim of the project was to update
the 2000 Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines on
Hemodialysis and Peritoneal Dialysis Adequacy,
and Vascular Access. The Work Group sought to
update the guidelines using an evidence-based
approach. After topics and relevant clinical questions were identified for the updates, the available scientific literature on those topics was
systematically searched and summarized.
OVERVIEW OF PROCESS
Update of the guidelines required many concurrent steps to:
Form the Work Groups and Evidence Review

Team that were to be responsible for different
aspects of the process;
Confer to discuss process, methods, and results;
Develop and refine topics;
Define exact populations of interest;
Create draft guideline statements and rationales;
Create data extraction forms;
Create and standardize quality assessment and
applicability metrics;
Develop and perform literature search strategies;
Screen abstracts and retrieve full articles;
Review articles;
Extract data and perform critical appraisal of the
literature;
Tabulate data from articles into summary
tables;
Write guideline statements and rationales based
on literature and Work Group consensus.
Separate Work Groups were created for each

subject area: hemodialysis adequacy, peritoneal dialysis adequacy, and vascular access. The 3 groups
worked in parallel to create the guidelines. The
Work Group Chairs conferred regarding overlapping topics across guidelines. The Evidence Review Team, comprised of experts in systematic
review and guideline development, guided the Work
Groups in all methods and aspects of guideline
development.
Creation of Groups
The KDOQI Advisory Board selected the Work
Group Chairs and the Director of the Evidence
S308
Review Team then assembled groups to be responsible for the development of the updates. These
Work Groups and the Evidence Review Team collaborated closely throughout the project.
The Work Groups consisted of domain experts,
including individuals with expertise in nephrology,
surgery, radiology, pediatrics, nursing and nutrition. For each guideline update, the first task of the
Work Group members was to define the overall
topics and goals of the updates. They then further
developed and refined each topic, literature search
strategies, and data extraction forms (described
below). The Work Group members were the principal reviewers of the literature, and from their reviews and detailed data extractions, they summarized the available evidence and took the primary
roles of writing the guidelines and rationale statements. Completed data extractions were posted on
a National Kidney Foundation (NKF) website for
direct access by Work Group members.
The Evidence Review Team consisted of nephrologists (1 senior nephrologist and 2 nephrology
fellows), methodologists, and research assistants
from Tufts-New England Medical Center with expertise in systematic review of the medical literature. They instructed the Work Group members in
all steps of systematic review and critical literature
appraisal. The Evidence Review Team also coordinated the methodological and analytical process of
the report, defined and standardized the methodology of performing literature searches, of data extraction, and of summarizing the evidence in summary
tables. They organized abstract and article screening, created forms to extract relevant data from
articles, organized Work Group member data extraction, and tabulated results. Throughout the project
the Evidence Review Team led discussions on
systematic review, literature searches, data extraction, assessment of quality and applicability of
articles, evidence synthesis, and grading of the
quality of the body of evidence and the strength of
guideline recommendations.
Refinement of Update Topics and Development
of Materials
The Work Group reviewed the 1995 Dialysis
Outcomes Quality Initiative (DOQI) Clinical Practice Guidelines and the 2000 KDOQI updates and
decided which of the guideline recommendations
required updates and which should remain un-
METHODS FOR EVALUATING EVIDENCE
changed. These assessments were based primarily

on expert opinion regarding the currency of the
previous guidelines and the likelihood of availability of new evidence. Preliminary literature searches
were made to inform this process. To allow for
timely review, it was determined that each set of
guidelines would be able to have systematic reviews on only a limited number of topics. After
literature review, the experts decided which recommendations would be supported by evidence or by
opinion. As described below, recommendations
based on adequate evidence were categorized as
Guidelines (CPGs), while opinion-based statements were categorized as Clinical Practice Recommendations (CPRs).
The Work Groups and Evidence Review Team
developed: a) draft guideline statements; b) draft
rationale statements that summarized the expected
pertinent evidence; and c) data extraction forms
containing the data elements to be retrieved from
the primary articles. The topic refinement process
began prior to literature retrieval and continued
through the process of reviewing individual articles.
Literature Search
Based on the draft guideline statements, the
Work Group members agreed on topics that would
be systematically reviewed and formulated questions defining predictors, interventions, comparators, and outcomes of interest. Search strategies
were developed based on these questions and topics, in addition to the study designs and years of
publications of interest to the Work Group. Articles
of interest were identified through MEDLINE
searches of English language literature of human
studies in May through July 2004. Broad search
terms were used to avoid missing potentially pertinent articles. The searches were supplemented by
articles identified by Work Group members through
June 2005.
Only full journal articles of original data were
included. The searches were limited to studies
published since January 1997 since earlier publications were reviewed in the previous DOQI guidelines. Editorials, letters, abstracts, and unpublished
reports were not included. Selected review articles,
however, were included for background material.
No systematic process was followed to obtain review articles.
S309
Abstracts and titles from the MEDLINE search

results were prescreened by members of the Evidence Review Team for general relevance. A second round of screening was performed on the
abstracts by Work Group members for relevance
using predefined eligibility criteria, described below. Articles were retrieved by the Evidence Review Team and then rescreened by Work Group
members and/or the Evidence Review Team. Eligible studies were extracted using standardized
extraction forms. Domain experts made the final
decisions regarding the eligibility of all articles.
Generation of Data Extraction Forms
Data extraction forms were designed to capture information on various aspects of the primary articles. Forms for all topics included study
setting and demographics, eligibility criteria,
causes of kidney disease, numbers of subjects,
study design, study funding source, dialysis characteristics, comorbid conditions, descriptions of
relevant risk factors or interventions, description
of outcomes, statistical methods, results, study
quality (based on criteria appropriate for each
study design (see below), study applicability (see
below), and sections for comments and assessment of biases. Training of the Work Group
members to extract data from primary articles
occurred by emails and teleconferences. Work
Group members were assigned the task of data
extraction of articles.
Generation of Evidence Tables
The Evidence Review Team condensed the
information from the data extraction forms into
evidence tables, which summarized individual
studies. These tables were created for the Work
Group members to assist them with review of the
evidence and are not included in the guidelines.
All Work Group members (within each Update)
received copies of all extracted articles and all
evidence tables. During the development of the
evidence tables, the Evidence Review Team
checked the data extraction for accuracy and
re-screened the accepted articles to verify that
each of them met the initial screening criteria
determined by the Work Group. If the criteria
were not met, the article was rejected, in consultation with the Work Group.
S310
Format for Summary Tables

Summary Tables describe the studies according
to the following dimensions: study size and follow-up duration, applicability or generalizability,
results, and methodological quality. Within each
table, the studies are first grouped by outcome type.
Data entered into Summary Tables were derived
from the data extraction forms, evidence tables,
and/or the articles by the Evidence Review Team.
All Summary Tables were reviewed by the Work
Group members.
Within each outcome, studies are ordered first
by methodological quality (best to worst), then
by applicability (most to least), and then by study
size (largest to smallest). When relevant, outcome thresholds (eg, of access flow measurement) are included. Results are presented by
using the appropriate metric or summary symbols, as defined in the table footnotes.
APPENDIX 1
Systematic Review Topics, Study Eligibility

Criteria, and Studies Evaluated
The topics for each Update were selected by
the respective Work Group members for systematic review (Table 1, Table 2, Table 3). The
eligibility criteria were defined by the Work
Group members of each Update in conjunction
with the Evidence Review Team.
Literature Yield for Hemodialysis Adequacy
(Table 4)
A total of 2,526 citations were screened, of
which 319 were review articles and 14 were added
by Work Group members. There were 223 articles
(191 studies in adults and 32 in children) that were
potentially relevant. These articles were retrieved
for full review. Of these, 87 adult articles were
accepted for full data extraction by the Work Group
members. Eight articles in children were formally
data extracted by a pediatric nephrologist on the
Work Group. Articles in adults were randomly

assigned to individual Work Group members for
data extraction. Of these, 23 studies answered questions pertinent to topics chosen for systematic listing in Summary Tables.
Literature Yield for Peritoneal
Dialysis Adequacy (Table 4)
A total of 2,307 citations were screened and 7
were added by Work Group members. There
were 293 articles (263 studies in adults and 30 in
children) that were potentially relevant. These
articles were retrieved for full review. Of these,
101 adult articles were accepted for full data
extraction by the Work Group members. Nine
articles in children were formally data extracted
S311
by a pediatric nephrologist on the Work Group.

Articles in adults were randomly assigned to
individual Work Group members for data extraction. Of these, 27 studies answered questions
pertinent to topics chosen for systematic listing
in Summary Tables.
Literature Yield for Vascular Access (Table 4)
A total of 2,892 citations were screened, of
which 388 were review articles. There were 112
articles (89 studies in adults, 13 in children, 10
review articles) that were potentially relevant.
These articles were retrieved for full review. Of
these, 58 articles were accepted for full data
extraction by the Work Group members. Because
of small sample sizes, articles in children were
S312
APPENDIX 1
not formally data extracted but reviewed in detail

by the 2 pediatric nephrologists on the Work
Group and used to write the narrative summary
in the pediatric section. Articles in adults were
randomly assigned to individual Work Group
members for data extraction. Five additional
articles were added by Work Group experts and
the Evidence Review Team. Finally, 24 studies
answered questions pertinent to topics chosen for
systematic listing in Summary Tables.
Search terms for all updates are shown in
Appendix 2.
Grading of Individual Studies
Study Size and Duration
The study (sample) size is used as a measure
of the weight of the evidence. In general, large
S313
studies provide more precise estimates of prevalence and associations. In addition, large studies
are more likely to be generalizable; however,
large size alone, does not guarantee applicability.
A study that enrolled a large number of selected
patients may be less generalizable than several
smaller studies that included a broad spectrum of
patient populations. Similarly, longer duration
studies may be of better quality and more applicable, depending on other factors.
Applicability
Applicability (also known as generalizability
or external validity) addresses the issue of whether
the study population is sufficiently broad so that
the results can be generalized to the population
of interest at large. The study population is
S314
APPENDIX 1
typically defined primarily by the inclusion and

exclusion criteria. The target population was
defined to include patients with kidney failure,
specifically those on dialysis. A designation for
applicability was assigned to each article, according to a three-level scale. In making this assessment, sociodemographic characteristics were considered, as well as comorbid conditions and prior
treatments. Applicability is graded in reference
to the population of interest as defined in the
clinical question. For example for the question of
treatment of catheter-related infections the reference population is that of HD patients with
infected cuffed tunneled HD catheters.
Sample is representative of the target
population, or results are definitely
applicable to the target population
irrespective of study sample.
Sample is representative of a relevant subgroup of the target population. For
example, sample is only representative of
people with virgin arteriovenous fistulas, or
only a specific relevant subgroup, such as
elderly individuals or incident dialysis
patients.
Sample is representative of a narrow
subgroup of patients only, and not well
generalizable to other subgroups. For
example, the study includes only a small
number of patients or patients with a rare
disease or virgin fistulas with no access
dysfunction. Studies of such narrow
subgroups may be extremely valuable for
demonstrating exceptions to the rule.
Results
The type of results available in each study is
determined by the study design, the purpose of
the study, and the question(s) being asked. The
Work Group decided on the eligibility criteria
and outcomes of interest (see Tables 1-3).
Diagnostic Test Studies
For studies of diagnostic tests, sensitivity
and specificity data or area under the curve
were included when reported. When necessary,
sensitivity and specificity data were calculated
from the reported data. Diagnostic tests were
evaluated according to a hierarchy of diagnos-
tic tests.* Each test was assessed according to

diagnostic technical capacity, accuracy, diagnostic and therapeutic impact, and patient outcome. This ultimately affected the overall
strength of a recommendation regarding a diagnostic test.
Methodological Quality
Methodological quality (or internal validity)
refers to the design, conduct, and reporting of the
clinical study. Because studies with a variety of
types of design were evaluated, a 3-level classification of study quality was devised:
Least bias; results are valid. A study that
mostly adheres to the commonly held
concepts of high quality, including the
following: a formal study; clear description
of the population and setting; clear
description of an appropriate reference
standard; proper measurement techniques;
appropriate statistical and analytical
methods; no reporting errors; and no
obvious bias. Not retrospective studies or
case series.
Susceptible to some bias, but not sufficient
to invalidate the results. A study that does
not meet all the criteria in the category
above. It has some deficiencies but none
likely to cause major bias.
Significant bias that may invalidate the
results. A study with serious errors in
design or reporting. These studies may
have large amounts of missing information
or discrepancies in reporting.
Summarizing Reviews and Selected
Original Articles
Work Group members had wide latitude in
summarizing reviews and selected original articles for topics that were determined not to
require a systemic review of the literature.
Guideline Format
The format for each guideline chapter is outlined in Table 5. Each guideline contains 1 or
* Fineberg HV, Bauman R, Sosman M: Computerized

cranial tomography. Effect on diagnostic and therapeutic
plans. JAMA 238:224-227, 1977
S315
Table 5. Format for Guidelines
Introductory Statement
Guideline or CPR Statement 1
Guideline or CPR Statement 2
BACKGROUND
RATIONALE
Definitions (if appropriate)
Rationale statement 1
Supporting text and tables
Rationale statement 2
Supporting text and tables
LIMITATIONS
Research Recommendations are presented in a separate chapter.
more specific guideline statements that represent recommendations to the target audience.
Each guideline contains background information, which is generally sufficient to interpret the
guideline. The rationale for each guideline describes the evidence upon which each guideline
recommendation is based. The guideline concludes with a discussion of limitations of the
evidence review and a brief discussion of clinical
applications, and implementation issues regarding the topic. Research recommendations for
each guideline update are summarized in a separate section at the end of each guideline update.
Rating the Strength of Recommendations
After literature review, the experts decided
which recommendations were supported by
evidence and which were supported by consensus of Work Group opinion. Evidence-based
guideline recommendations were graded as
strong (A) or moderate (B). Recommendations
based on weak evidence (C) and/or consensus
of expert opinion were labeled as Clinical
Practice Recommendations (CPRs). An A
rating indicates it is strongly recommended
that clinicians routinely follow the guideline
for eligible patients. There is strong evidence
that the practice improves health outcomes,
and benefits substantially outweigh harm. The
B rating indicates it is recommended that
clinicians routinely follow the guideline for
eligible patients. There is moderately strong

evidence that the practice improves health outcomes. A CPR rating indicates it is recommended that clinicians consider following the
guideline for eligible patients. This recommendation is predominantly based on consensus of
opinions of the Work Group and reviewers that
the practice might improve health outcomes.
(See Table 6).
The strength of each guideline recommendation is based on the quality of the supporting
evidence as well as additional considerations.
Additional considerations, such as cost, feasibility, and incremental benefit were implicitly
considered. The quality of evidence was not
explicitly graded. It was implicitly assessed
according to the criteria outlined in Table 7,
and considered: i) the methodological quality
of the studies; ii) whether or not the studies were
carried out in the target population, ie, patients
on dialysis, or in other populations; and iii)
whether the studies examined health outcomes
directly, or examined surrogate measures for
those outcomes, eg, blood flow instead of access
survival.
Limitations of Approach
While the literature searches were intended
to be comprehensive, they were not exhaustive. MEDLINE was the only database
searched, and searches were limited to English
S316
APPENDIX 1
Table 6. Rating the Strength of Guideline Recommendations

Grade
A
B
CPR
Recommendation
It is strongly recommended that clinicians routinely follow the guideline for eligible patients. There is strong
evidence that the practice improves health outcomes.
It is recommended that clinicians routinely follow the guideline for eligible patients. There is moderately
strong evidence that the practice improves health outcomes.
It is recommended that clinicians consider following the guideline for eligible patients. This recommendation
is based on either weak evidence or on the opinions of the Work Group and reviewers that the practice
might improve health outcomes.
Health outcomes are health-related events, conditions, or symptoms that can be perceived by individuals to have an important effect on their
lives. Improving health outcomes implies that benefits outweigh any adverse effects.
language publications. Hand searches of journals were not performed, and review articles
and textbook chapters were not systematically
searched. However, important studies known
to the domain experts that were missed by the
literature search were included in the review.
Because of resource limitations and other
practical considerations, there were several
deviations from the original protocol for several of the update topics. These primarily re-
sulted in nephrologists in the Evidence Review

Team, rather than Work Group members, performing the primary article screening and the
data extraction for articles included in several
Summary Tables. However, all articles that
met criteria for all topics, all completed data
extraction forms, and all Summary Tables were
distributed to relevant Work Group members
for critical review and incorporation into guidelines.
Table 7. Rating the Quality of Evidence
Outcome
Health outcome(s)
Health outcome(s)
Surrogate measure for
health outcome(s)
Surrogate measure for
health outcome(s)
Population
Target population
Other than the target
population
Target population
Other than the target
population
Well designed and

analyzed (little, if any,
potential bias)
Stronga
Methodological Quality
Some problems in
design and/or analysis
(some potential bias)
Moderately strongb
Poorly designed and/or

analyzed (large
potential bias)
Weakh
Moderately strongc
Moderately strongd
Weakh
Moderately stronge
Weakf
Weakh
Weakg
Weakg
Weakg,h
Strong- aEvidence includes results from well-designed, well-conducted study/studies in the target population that directly assess effects on health outcomes.
Moderately strong- bEvidence is sufficient to determine effects on health outcomes in the target population, but the strength of the evidence is limited by the
number, quality, or consistency of the individual studies; OR cevidence is from a population other than the target population, but from well-designed, wellconducted studies; OR devidence is from studies with some problems in design and/or analysis; OR eevidence is from well-designed, well-conducted studies
on surrogate endpoints for efficacy and/or safety in the target population.
Weak- fEvidence is insufficient to assess the effects on net health outcomes because it is from studies with some problems in design and/or analysis on
surrogate endpoints for efficacy and/or safety in the target population; OR gthe evidence is only for surrogate measures in a population other than the target
population; OR hthe evidence is from studies that are poorly designed and/or analyzed.
APPENDIX 2. MEDLINE SEARCH STRATEGIES

HEMODIALYSIS ADEQUACY, UPDATE 2006
Ovid MEDLINE, Ovid MEDLINE Daily Update, Ovid MEDLINE In-Process
Search from 1/1/97 through 6/22/04
S317
S318
APPENDIX 2
Ovid MEDLINE, Ovid MEDLINE Daily Update, Ovid MEDLINE In-Process

Search from 1/1/97 through 10/27/04 (search from 6/22/04 with Artificial Kidney added)
MEDLINE SEARCH STRATEGIES
PERITONEAL DIALYSIS ADEQUACY, UPDATE 2006

Ovid MEDLINE, Ovid MEDLINE Daily Update, Ovid MEDLINE In-Process.
VASCULAR ACCESS, UPDATE 2006

Search #1. Ovid MEDLINE, Ovid MEDLINE Daily Update, Ovid MEDLINE In-Process.
S319
S320
VASCULAR ACCESS, UPDATE 2006

PEDIATRIC SEARCHa
Ovid MEDLINE 1996 to July Week 3 2004
APPENDIX 2
MEDLINE SEARCH STRATEGIES
S321
VASCULAR ACCESS, UPDATE 2006 SEARCH #2

Ovid MEDLINE 1966 to August Week 2 2004
Search from 1/1/97 through 8/19/2004 (original search date 5/5/04 with terms shunt and graft
added)
S322
APPENDIX 2

American Journal of Kidney Diseases

Enviado por

Dados do documento

Direitos autorais

Formatos disponíveis

Compartilhar este documento

Compartilhar ou incorporar documento

Opções de compartilhamento

Você considera este documento útil?

Este conteúdo é inapropriado?

Direitos autorais:

Formatos disponíveis

American Journal of Kidney Diseases

Enviado por

Direitos autorais:

Formatos disponíveis

AJKD

Associate Managing Editor

VOL 48, NO 1, SUPPL 1, JULY 2006

KDOQI Advisory Board Members ..................................................................................

CLINICAL PRACTICE GUIDELINES FOR HEMODIALYSIS ADEQUACY, UPDATE

Abbreviations and Acronyms ........................................................................................

I. Clinical Practice Guidelines for Hemodialysis Adequacy ..................................

Guideline 1. Initiation of Dialysis..............................................................................

Clinical Practice Recommendation for Guideline 1: Initiation of Dialysis ................

III. Research Recommendations ...............................................................................

Appendix. Methods for Adding Residual Clearance to Hemodialyzer Clearance ....

Work Group Biographies................................................................................................

CLINICAL PRACTICE GUIDELINES FOR PERITONEAL DIALYSIS ADEQUACY,

Abbreviations and Acronyms ........................................................................................

I. Clinical Practice Guidelines for Peritoneal Dialysis Adequacy .........................

Guideline 1. Initiation of Dialysis..............................................................................

Clinical Practice Recommendation for Guideline 1: Initiation of Dialysis ................

III. Research Recommendations ...............................................................................

Work Group Biographies................................................................................................

CLINICAL PRACTICE GUIDELINES FOR VASCULAR ACCESS, UPDATE 2006

Abbreviations and Acronyms ........................................................................................

I. Clinical Practice Guidelines for Vascular Access...............................................

II. Clinical Practice Recommendations for Vascular Access .................................

III. Research Recommendations ...............................................................................

Work Group Biographies................................................................................................

Abbreviations and Acronyms ........................................................................................

Appendix 1. Methods for Evaluating Evidence ............................................................

Appendix 2. Medline Search Strategies ........................................................................

Hemodialysis Adequacy 2006

Evidence Review Team

Priscilla Chew, MPH

In addition, oversight was provided by:

Validated GFR-Estimating Equations................................................................................ S14

American Journal of Kidney Diseases, Vol 48, No 1, Suppl 1 (July), 2006: p S3

Abbreviations and Acronyms

ABBREVIATIONS AND ACRONYMS

Residual native kidney urea clearance

VOL 48, NO 1, SUPPL 1, JULY 2006

he publication of the second update of the

This document has been divided into 3 major

debt of gratitude is due to the members of the

Adeera Levin, MD, FACP

be given to residual kidney function (RKF) in

ings, remains 1.2 Kt/V units per dialysis for

GUIDELINES FOR HEMODIALYSIS ADEQUACY

population depending on HD for life support.

I. CLINICAL PRACTICE GUIDELINES FOR

GUIDELINE 1. INITIATION OF DIALYSIS

GUIDELINES FOR HEMODIALYSIS ADEQUACY

planned treatment initiation using the permanent

the decision about whether to attempt AV fistula

Table 2. Causes of Unusually Low or High Endogenous Creatinine Generation

Table 3. Causes of Unusually Low or High Kidney Tubular Creatinine Secretion

clearance does not offer a more accurate estimate

such patients. However, they should consider

(10 to 10.5 mL/min/1.73 m2) for children and

GUIDELINES FOR HEMODIALYSIS ADEQUACY

ing Dialysis Early and Late (IDEAL) Study from

GUIDELINE 2. METHODS FOR MEASURING AND

lyzed solutes. To account for variations in the

GUIDELINES FOR HEMODIALYSIS ADEQUACY

cause dialysis most effectively removes small

METHODS FOR MEASURING AND EXPRESSING THE HEMODIALYSIS DOSE

where V is postdialysis urea distribution volume, G is urea generation rate, Kr is residual