Renal Replacement Therapy

What the Non-Nephrologist

Should Know
Bernard G. Jaar, MD, MPH, FASN,FNKF
Johns Hopkins Medical Institutions
Nephrology Center of Maryland

Why is this topic relevant

to you?

Kidney Disease is a Public

Health Problem
Trends in Kidney Disease
Burden

Prevalence of CKD Stages in US Adults Aged

20 Years or Older:
NHANES 1988-1994 and NHANES 1999-2004

Coresh, J. et al. JAMA 2007;298:2038-2047

ESRD Prevalence The Forecast

Projected growth overall ESRD prevalence (5% / yr)
Number of patients (millions)
3.0

2.2 million
(60% diabetic)

2.0
618,160 pts
(2011)
1.3 million

1.0
0.7 million
0.4 million
0
1978

2000

2010
Year

2020

2030
Gilbertson et al. JASN 2003

Objectives
Describe treatment options for renal
replacement therapy
Understand the general principles of
dialysis modalities & compare their
outcomes
Importance of residual renal function
Describe kidney transplantation process

Case Presentation (I)

39 y/o AA man
PMHx: none
Routine physical exam:
BP 142 / 100
LE edema
4+ proteinuria (dipstick)

Case Presentation (II)

Initial Nephrology Clinic Visit
PE:
Unremarkable, except:
Weight 230 lbs (BMI 33)
BP 138 / 85
2+ LE edema

Treatment:
ACE inhibitor
Thiazide diuretics

Case Presentation (III)

Initial Laboratory Data
Labs:
12.3
7490

41.0

333

141
3.6

107
28

18
2.4

95

Albumin 2.5
eGFR 37 cc/min/1.73m2
T. cholesterol 398 mg/dL
Serology w-u (-)
UA: protein 4+, 0-2 RBC, 0-2 WBC
Spot u. prot. / creat. 413 mg/dL / 41 mg/dL 10

CKD Progression ESRD

Uremic
ESRD
Kidney Bx: FSGS

Initial presentation:
HTN, CKD, proteinuria

RRT

Indications for Renal

Replacement Therapy

Hyperkalemia
Metabolic acidosis
Fluid overload (recurrent CHF admissions)
Uremic pericarditis (rub)
Other non specific uremic symptoms:
anorexia and nausea, impaired nutritional
status, increased sleepiness, and
decreased energy level, attentiveness, and
cognitive tasking,

What are the Treatment

Options for Renal Replacement
Therapy for our Patient?

ESRD Treatment Options

ESRD

Comfort Care

Peritoneal Dialysis

Hemodialysis

Kidney Transplant

ESRD Treatment Options

ESRD

Hemodialysis

Comfort Care

Peritoneal Dialysis

Kidney Transplant

Dialysis options
Dialysis

Hemodialysis

Peritoneal Dialysis

In-Center HD (3 x week)
Home HD (short daily, nocturnal)

CAPD
CCPD

Home

Incident Patient Counts (USRDS)

by 1st Modality

USRDS 2013 ADR

CKD Education

CKD Progression ESRD

CKD
Education

Initial presentation:
HTN, CKD, proteinuria

Uremic
ESRD

RRT

CKD Education
Refer patients early, when eGFR < 30 cc/min
Education about types of renal replacement therapy:
Hemodialysis (vascular access +++)
Peritoneal Dialysis (QOL advantage +++)
Kidney Transplantation
Refer when eGFR <20
Living kidney transplant (family, friends)
Build time on list before dialysis initiation
Even transplant before dialysis initiation (pre-emptive)

Early Vaccination for Hepatitis B!

Patients with ESRD have response to vaccination

(2ary to general suppression of immune system)

To
o

fte
n

Fo
rg
ot

te

After Hepatitis B vaccination in ESRD patients:

50 60 % develop antibodies, compared to > 90%
in patients without renal failure
Have Lower titers
Have protective levels for shorter duration

Stevens CE et al. NEJM 1984; 311: 496

Buti M et al. Am J Nephrol 1992; 112: 144

Early Vaccination for Hepatitis B!

Patients with ESRD have response to vaccination
(2ary to general suppression of immune system)

After Hepatitis B vaccination in ESRD patients:

50 60 % develop antibodies, compared to > 90%
in patients without renal failure
Have Lower titers
Have protective levels for shorter duration

Stevens CE et al. NEJM 1984; 311: 496

Buti M et al. Am J Nephrol 1992; 112: 144

Hemodialysis (HD)

Principle of Hemodialysis
Vein
Artery

Hemodialysis Filter (Dialyzer)

Hemodialysis Filter (Dialyzer)

Hemodialysis Vascular Access

Polytetrafluoroethylene

Arteriovenous (AV) Fistula

Question 1
Which type of vascular access is associated
with better outcomes in hemodialysis
patients? (choose one answer):
1.Central venous cuffed catheter
2.Arteriovenous graft
3.Arteriovenous fistula
4.Temporary central venous catheter

Which Vascular Access and

When Should It Be Placed?

CKD Progression
Vascular
Access
(AVF)

Initial presentation:
HTN, CKD, proteinuria

HD

Adjusted* Relative Risk of Death

by Type of Vascular Access
Diabetes

No Diabetes

Cohort: 5,507 patients, followed for 2 years

*Adjusted for age, race, gender, BMI, history of smoking, PVD, CAD, CHF, neoplasm, ability to
ambulate and education level.
Prevalent diabetic pts: CVC vs. AVG (P = 0.42). Incident diabetic pts: CVC vs. AVG (P = 0.48).
Prev. nondiabetic pts: CVC vs. AVG (P < 0.0001). Inc. nondiabetic pts: CVC vs. AVG (P = 0.82).
Dhingra RK et al. Kidney Int 2001; 60: 14431451

Adjusted* Relative Risk of Death due to

Infection by VA Type and Diabetes Status

Cohort: 5,507 patients, followed for 2 years

*Adjusted for age, race, gender, BMI, history of smoking, PVD, CAD, CHF, neoplasm, ability to
ambulate and education level.
Prevalent diabetic pts: CVC vs. AVG (P = 0.81)
Prevalent nondiabetic pts: CVC vs. AVG (P < 0.13)
Dhingra RK et al. Kidney Int 2001; 60: 14431451

Patients who started using an AV access by

timing of first referral to a nephrologist

N=356 hemodialysis patients

Astor B. et al. Am J Kidney Dis 2001; 38 (3): 494-501

VASCULAR ACCESS GUIDELINES

Arm veins suitable for placement of vascular access
should be preserved, regardless of arm dominance.
Arm veins, particularly the cephalic veins of the nondominant arm should not be used.
Dorsum of the hand could be used for IV.
A Medic Alert bracelet should be worn to inform
hospital staff to avoid IV cannulation of essential
veins.
Subclavian vein catheterization should be avoided
for temporary access in all patients with CKD
( stenosis preclude use of ipsilateral arm for
vascular access)

SAVE the Non-Dominant ARM

for Vascular Access
When GFR < 30 mL/min
No BP measurement
No IV
No Blood Draws

On Non-Dominant
Arm

Place vascular access within a year of hemodialysis anticipation

Peritoneal Dialysis (PD)

Principle of PD Treatment

 Abdominal cavity is lined by peritoneal membrane

which acts as a semi-permeable membrane
Diffusion of solutes (urea, creatinine, ) from blood
into the dialysate contained in the abdominal cavity
Removal of excess water (ultrafiltration) due to
osmotic gradient generated by glucose in dialysate

Types of PD Catheters
Overall PD catheter survival : +/- 90% at 1 year
No particular catheter is superior

Placement of Peritoneal Dialysis

Catheter

Placement of PD Catheter
Exit Site

PD Catheter Exit Site

Peritoneal Dialysis (PD)

PD

Continuous

Intermittent

Continuous PD Regimens
Multiple sequential exchanges are performed during the day
and night so that dialysis occurs 24 hours a day, 7 days a week

CAPD: Continuous
Ambulatory PD

CCPD: Continuous
Cyclic PD

Intermittent PD Regimens
PD is performed every day but only during certain hours
DAPD: Daytime
Ambulatory PD.
Multiple manual exchanges
during waking hours

NPD: Nightly PD.

Performed while patient
asleep using an automated
cycler machine.
Sometimes,
1 or 2 day-time manual
exchanges are added to
enhance solute clearances

CCPD Treatment Setup

Question 2
What is the most common cause of
technique failure in peritoneal dialysis?
(choose one answer):
1.Ultrafiltration failure
2.Malnutrition
3.Peritonitis
4.Non-adherence to the treatment regimen

Cumulative percentage of PD
patients by time from 1st dialysis to
1st switch to HD
25% of PD
patients
switched to HD
within 5-7 years

Jaar BG et al. BMC Nephrol 2009; 10: 3

Causes of PD Technique Failure

(Switching from PD to HD)
Psychological Issues
Abdominal Surgery

Peritonitis
Malnutrition

Ultrafiltration Failure
Jaar BG et al. BMC Nephrol 2009; 10: 3

Which Dialysis Modality

Provides the Best Outcomes?

Factors Influencing Dialysis Choice

Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,

Dialysis Modality

Absolute contraindications for PD

Documented loss of peritoneal function or
extensive abdominal adhesions (previous abd.
Surgeries) limit dialysate flow
Uncorrectable mechanical defects
(e.g., diaphragmatic hernia)
In the absence of a suitable assistant, a patient
who is physically or mentally incapable of
performing PD.
NKF K/DOQI Guidelines 2000

Peritoneal Adhesions

Factors Influencing Dialysis Choice

Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,

Dialysis Modality

Best Study Design to Compare

Dialysis Modalities
Prospective, randomized, clinical trial
Significant barriers to performing this type of study1
We are left with the analysis of observational data
from well-conducted prospective studies

Quinn RR et al. 2011 (I)

Country:
Enrollment Years:
Follow-Up:

Ontario, Canada
7-1-1998 to 3-31-2006
8 years

Population Type:

Incident Elective Outpatient

(databases @ Institute for Clinical
Evaluative Sciences)

Sample Size:
Switching Modality:

HD: 4,538 PD: 2,035

No

Model(s)

Intention-to-Treat (baseline
modality)
Quinn RR et al. J Am Soc Nephrol 2011; 22: 1534-1542

Adjusted Survival between PD and HD,

(received > 4 months of predialysis care
and Started as outpatient)
Adjusted HR: 0.96, p = 0.44

Quinn RR et al. J Am Soc Nephrol 2011; 22: 1534-1542

Biases
Residual confounding: limited adjustment for known
factors associated with mortality (e.g., comorbidities,
lab data [albumin, ])
Short follow-up (1-2 years) in some studies
Lead-time bias: baseline GFR
Selection bias: patient characteristics
Statistical Methodology:
Center Effect: confounding by clinic as patient
characteristics varied by center and treatment
How to handle modality switching: As-Treated vs
Intention-to-Treat
No causal relationship, just association!

Other Issues: PD vs HD
Beyond Survival
In considering choice of dialysis technique,
other issues must be considered

Factors Influencing Dialysis Choice

Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Cost of Care,
Late Referral,

Dialysis Modality

CHOICE - Quality of Life:

PD vs HD (I)
PD patients reported better QOL then HD
patients in the following domains:
Bodily pain
Travel
Diet restrictions
Dialysis access
Financial well-being
Physical functioning (only at baseline, not at 1
year)
Wu A et al. JASN 2004; 15: 743-753

CHOICE - Quality of Life:

PD vs HD (II)
At one year,
HD patients improved more on aspects of
general health-related QOL than patients on
PD
HD patients had greater improvement on:
Physical functioning
Sexual functioning
General health perceptions
Wu A et al. JASN 2004; 15: 743-753

Factors Influencing Dialysis Choice

Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,

Dialysis Modality

CHOICE - Treatment Satisfaction:

PD vs HD
PD patients were significantly more likely to give
excellent ratings of dialysis care overall compared
to HD patients (85% vs 56%).
Also PD patients were more likely to give excellent
ratings for specific aspects of care:
information on choosing a dialysis modality
information on fluid removal
staff and nephrologist availability
coordination with other physicians
caring of nurses or staff

Rubin HR et al. JAMA 2004; 291: 697-703

Implications
Each modality has distinct advantages or disadvantages
Physicians should be as explicit as possible in describing specific
tradeoffs and attempt to elicit individual preferences at start of
dialysis
Although there is no conclusive evidence that the choice of PD or HD
provide a specific survival advantage:
Better selection of PD patients (PD underutilized)
PD patients should be monitored closely after the 2 nd or 3rd year of dialysis
Consider a timely transfer to HD (if or when PD problems arise)

What is the best long-term treatment?

1. PD
2. HD in-center
3. HD home/
self-care
Ask the nephrology providers which dialysis modality they
would select if they had ESRD?

What is the best long-term treatment?

Opinion vs Reality

1. PD
2. HD in-center
3. HD home/
self-care

Ledebo I., Ronco C. NDT Plus 2008; 6:403-408

Question 3
Which one of the following patients characteristic
or comorbidity is associated with better overall
outcome on dialysis (choose one answer):
1.Diabetes Mellitus + end-organ damage
2.BMI > 30
3.Residual urine output of > 500 cc / day
4.Colon cancer
5.Early initiation of dialysis (eGFR > 15)

Is Timing of Dialysis
Initiation Important in
ESRD Patients?
(Controversial)

IDEAL Study: KM Curves for Time to the

Initiation of Dialysis & for Time to Death
Between July 2000 &
November 2008
Australia / New Zealand
828 adults
Early start:
eGFR 10-14 cc/min
Late start:
eGFR 5-7 cc/min
mean age 60.4 years
542 men & 286 women
355 with diabetes
Median follow-up 3.6
years
Cooper BA et al. N Engl J Med 2010;363:609-619

Implications
A total of 75.9% of the patients in the late-start group
started dialysis when eGFR was > 7.0 cc/minute,
owing to the development of symptoms!
In this study, planned early initiation of dialysis in
patients with stage V CKD was not associated with an
improvement in survival or clinical outcomes (QOL)
OK to delay initiation of dialysis (eGFR < 7-10 cc/min)
Dialysis initiation should be based upon clinical
factors (symptoms) rather than eGFR alone
Cooper BA et al. N Engl J Med 2010;363:609-619

Why is Residual Renal

Function Important in
Dialysis Patients?

Why is baseline residual renal

function important?
Remaining GFR at start of dialysis make a
significant contribution to the removal of
potential uremic toxins
Also facilitates regulation of fluid, electrolytes,
and may enhance nutritional status and QOL
Offers survival advantage in both HD and PD
Suda T et al. Nephrol Dial Transplant 2000; 15: 396
Shemin D et al. Am J Kidney Dis 2001; 38: 85
Szeto C et al. Nephrol Dial Transplant 2003; 18: 977

Cumulative Incidence of All-Cause Mortality in 579

HD Patients by Urine Status at 1 Year (CHOICE)
Adjusted Hazard Ratio: 0.70 (0.52-0.93) p = 0.02

Shafi T., Jaar B., et al. Am J Kidney Dis. 2010;56:348-58

Implications
Try to preserve residual renal function in
dialysis patients!
Less dietary restriction
Better quality of life
Better survival
Try to avoid nephrotoxins if your dialysis
patient still makes urine!

Kidney Transplantation

Principle of Kidney Transplantation

Iliac Fossa

Question 4
Which one of the following statements is
correct? (choose one answer):
1.CKD patients can be referred to a transplant
center when their GFR is < 20 cc/min/1.73m 2
2.Pre-emptive and live kidney transplants are
associated with better graft survival
3.Most common cause of kidney transplant loss is
death with a functional transplant
4.All of the above

Trends in Transplantation:
patients age 20 years & older

USRDS ADR 2012

Adjusted Relative Risk of Death among 23,275

Recipients of a 1st Cadaveric Transplant

Wolfe RA et al. N Engl J Med 1999;341:1725-1730

K-M Estimates of Allograft Survival According to

the Use or Nonuse of Long-Term Dialysis before
Kidney Transplantation from a Living Donor
Adjusted Rate Ratio (95% CI): 0.16 (0.070.35)

P = 0.009

Mange K et al. N Engl J Med

Acute Rejection within

the 1st Year Post-Transplant

Patients age 18
& older with a
functioning
graft at
discharge.

USRDS ADR 2012

Cumulative incidence of
post-transplant diabetes

Patients
receiving a
first-time,
kidney-only
transplant,
20032007
combined.

USRDS ADR 2012

Causes of Death in Kidney Transplant

Patients with Functioning Graft
20062010
First-time,
kidney-only
transplant
recipients,
age 18 &
older, 2006
2010, who
died with
functioning
graft.

USRDS ADR 2012

Posttransplant Malignancy
Risk is 4X to 100X compared rates of malignancy in
the general population
No comprehensive reporting system
Available data suggesting 2- to 3-fold under-reporting
The precise rate is UNKNOWN
Accounts for 10% of deaths in kidney recipients with
functioning graft
SCREENING is KEY!

Immunization for Kidney Transplant

Recipients
Recommended
Influenza types A and B
(yearly)
Pneumovax (every 3-5
years)
Diphteria-PertussisTetanus
Haemophilus influenza B
Hepatitis A and B
Inactivated polio
Meningococcus

Not Recommended

Varicella zoster
Intranasal influenza
BCG
Live oral typhoid
Measles, Mumps, Rubella
Oral polio
Yellow fever
Smallpox
Live Japanese B encephalitis
vaccine

Key Concepts (I)

Kidney transplantation is the most cost-effective
modality of renal replacement
Transplanted patients have a longer life and
better quality of life
Early transplantation (before [pre-emptive] or
within 1 year of dialysis initiation) yields the best
results
Living donor kidney outcomes are superior to
deceased donor kidney outcomes

Key Concepts (2)

Early transplantation is more likely to occur in
patients that are referred early to nephrologists
Refer for transplant evaluation when eGFR <
20 cc/min/1.73m2
Success of transplantation results from a
delicate balance between the suppression of
the immune system to prevent rejection and the
long-term side-effects of immunosuppression

Key Concepts (3)

The most common cause of transplant loss is
death with a functional transplant due to
Heart disease +++
Infections
Malignancies

Immunosuppressants are essential to prevent

immunological loss of the transplant but side
effects can also lead to transplant loss

What are the Costs of the

Different Renal Replacement
Therapy Modalities?

Costs (in Billion) of Medicare and

ESRD Programs in 2010
ESRD Cost
$32.9 (6.3%)

Total Medicare Costs

$522.8
488,938 ESRD patients representing
less than 1% Medicare population

USRDS ADR 2012

Total Medicare ESRD expenditures

per person per year, by modality
$87,561
$66,751

$32,914

Period prevalent ESRD patients

Patients with Medicare as secondary payor are excluded
USRDS ADR 2012

What About No Renal

Replacement Therapy Option?

Starting Dialysis in the Elderly

Or Not?
Among patients > 75 yrs with stage 5 CKD who
chose NOT to start dialysis:
Overall, more likely to die over next 1-2 years
But if they had ischemic heart disease or other
significant comorbidity NO DIFFERENCE in
survival
Active disease management and supportive care
may be appropriate without starting dialysis in the ill
elderly
Must have end-of-life discussions!
Murtagh, et al. Nephrol Dial Transplant. 2007; 22(7): 1955-1962

The Future

 Regenerative Medicine
Stem Cell Therapy
Wearable Artificial Kidney

Thank You !
QUESTIONS?