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February 2017 | Vol.

9, Number 2

Depression Undertreated in Patients

Receiving Chronic Dialysis Inside
By Tracy Hampton
Journal of the American Society of Neph- the Centers for Medicare & Medicaid
Report: Kidney
rology, also found that when patients are Services Quality Improvement Program Disease Research
willing to accept treatment for depression, (QIP) for end stage renal disease recently Underfunded
renal providers commonly do not pre- mandated that all dialysis facilities report US government spends
scribe it. individual patient screening and treat- more on the Medicare ESRD
Depression affects nearly one- ment plans for depression for payment program (nearly $32 billion)
quarter of people receiving chronic year 2018. Little information, however, than it invests in the entire
hemodialysis, compared with an is available on the effectiveness of anti- NIH budget (approximately
average population lifetime risk depressant therapy in patients on chronic $31 billion)
of between 8.3% and 9%. These hemodialysis or the acceptance of treat-
high rates likely reflect the various ment by patients and clinicians.
physiological and psychosocial con- To investigate, a team led by Steven Kidney Workforce
sequences of living with impaired Weisbord, MD, MSc, and Julio Pena-Po- Trends to watch in 2017
kidney functionfrom the adverse ef- lanco, MD, of the VA Pittsburgh Health- include shifts in nephrology
fects of frequent treatment to the poten- care System and University of Pittsburgh GME, new training offerings,
tial loss of social support and vocational School of Medicine, asked 101 patients and the changing healthcare
capacity. on hemodialysis who were participating landscape
Depression in dialysis patients affects in the Symptom Management Involv-
not only their mental health and quality ing ESRD (SMILE) trial to complete the
of life but has also been linked to missed Patient Health Questionnaire 9 (PHQ-
Fellows Corner

ew research indicates that many and abbreviated dialysis treatments, more A fellow looks at the clinical
9) each month. The prospective, multi-
patients who are receiving chron- implications of low health
frequent emergency department visits center, cluster-randomized SMILE trial
ic hemodialysis have depressive literacy
and hospitalizations, and an increased compared 2 strategies for the manage-
symptoms but do not wish to receive ag- risk of premature death. To address the ment of 3 common symptoms in cog-
gressive treatment to alleviate them. The negative effects that depression can have nitively intact adults receiving chronic, Findings
study, which is published in the Clinical on dialysis patients health and survival, Continued on page 2 Mortality differs acccording to
reason for starting dialysis

Why Is Low Blood Pressure Related to Increased Practice Pointers

Pregnancy and kidney failure
Cardiovascular Risk in CKD?
Study Suggests Reverse Causality from Subclinical Cardiac Disease

any studies have noted a U- Confounding by disease is the chief Oxford. Such confounding masks a causal
shaped association between explanation for the apparent weakening association between blood pressure and
blood pressure and cardiovas- and reversal of the association between risk in patients with CKD with established
cular risk in patients with chronic kidney systolic BP and cardiovascular risk in mod- cardiovascular disease.
disease (CKD). A report in Hypertension erate-to-advanced CKD, said William Together with other recent evidence,
suggests a possible explanation for this par- G. Herrington, MD, MRCP(UK) of the these results add weight to the hypothesis
adoxical relationship: a confounding effect Clinical Trial Service Unit & Epidemio- that more-intensive BP reductions might
by subclinical cardiac disease. logical Studies Unit (CTSU), University of reduce cardiovascular risk in patients with
CKD, including those on dialysis.

U-shaped association between

BP and mortality in CKD
The researchers analyzed data from The
Study of Heart and Renal Protection
Continued on page 2
2 | ASN Kidney News | February 2017

Depression In most cases, patients refused the that when patients do request treatment, In an accompanying editorial, Maree
recommendations because they felt their renal providers commonly do not pre- Hackett, PhD, and Meg Jardine, PhD,
Undertreated depression was attributable to an acute scribe treatment. of the University of Sydney, in Australia,
Continued from page 1 event, chronic illness, or dialysis. Fac- Weisbord and his colleagues pointed noted that there are many challenges to
tors associated with refusal of treatment to past research indicating that 90% of the detection and treatment of depression
recommendations were older age, being nephrologists provide primary care to in people on dialysis. The importance of
thrice-weekly outpatient hemodialysis at married, and African American race, al- their patients who are on dialysis and that the inner experience may get lost by pa-
9 dialysis units in western Pennsylvania. though only the association of older age as few as 20% of patients on chronic dial- tients, carers and clinicians in a setting of
For depressed patients (PHQ-9 score with treatment refusal was statistically ysis have a separate primary care provider. intensive medical intervention, intercur-
10), trained nurses generated treatment significant. The apparent unwillingness of renal rent comorbidities, and high rates of un-
recommendations and helped implement In 11 of 18 instances (61%) in which providers to consider implementing treat- welcome events, they wrote. They argued
therapy if patients and renal providers ac- patients accepted the recommendation ment for depression, particularly in the that a safe, effective, low-cost treatment
cepted the recommendations. related to treatment for depression, re- absence of primary providers who might for managing depression could help pa-
Of the 101 patients who were followed nal providers were unwilling to provide assume this responsibility, represents a tients live well, rather than just survive,
for at least 1 year, 39 met criteria for de- treatment. In 8 of these 11 instances, the major obstacle to the systematic provision while on dialysis.
pression based on their PHQ-9 scores. renal provider offered no explanation for of therapy, they wrote.
These 39 patients had depression on 147 not accepting the recommendation; in 2 Considering Medicares recently re- ______________________
of 373 (39%) monthly assessments. At instances, the provider deferred treatment leased criteria for the end stage renal
70% of these 147 assessments, patients recommendations to the patients pri- disease QIP, the authors noted that the Article: Acceptance of Anti-Depressant
were receiving anti-depressant therapy. mary care provider; and in 1 instance, the implementation of a performance meas- Treatment by Patients on Hemodialysis
and at 51 of 70 (70%) assessments, pa- provider did not accept the recommenda- ure based on screening and treatment is and their Renal Providers. doi: 10.2215/
tients did not accept nurses recommen- tion because the patient was hospitalized. logically based on the assumption that pa- CJN.07720716
dations to intensify treatment. At 44 as- We discovered that some patients are tients wish to have the condition treated.
sessments, patients with depression were on anti-depressant treatment that does Therefore, the results of this study suggest Editorial: We Need to Talk about De-
not receiving anti-depressant therapy and not appear to be effective, and most who that the requirement to universally docu- pression and Dialysis: But What Ques-
in 40 instances (91%) did not accept rec- are not on treatment do not wish to be ment and provide care for depression in tions Should We Ask and Does Anyone
ommendations to start treatment. treated, Weisbord said. We also noted dialysis patients may be premature. Know the Answers?

Low BP Related to Increased

Cardiovascular Risk
Ure-Na is lemon-lime Continued from page 1

flavored urea used

(SHARP)a seminal trial in which 9270 patients with CKD were randomly
assigned to ezetimibe/simvastatin versus placebo. The principal investiga-
tors of the SHARP Study (www.sharpinfo.org) were Colin Baigent, FRCP,

to manage hyponatremia.
FFPH, and Martin J. Landray, PhD, FRCP, also of CTSU.
The main SHARP resultspublished in The Lancet in 2011showed
that cholesterol-lowering therapy can substantially reduce the risk of major
atherosclerotic events in CKD. Subsequent analyses of the SHARP data have
. Now being used coast to coast. yielded further insights on the outcomes and prognostic factors among peo-

. Cost effective. ple with CKD. In this new analysis, the SHARP investigators explored the
paradoxical relationship between BP and cardiovascular risk in patients with
. Used in in-patient & out-patient settings. CKD.

. Guideline supported . *
In apparently healthy adults, as BP increases so does the risk of death from
ischemic heart disease, stroke, or heart failure. Risk is approximately doubled
. Typical dosing of ure-Na is 1-3 packets for each 20 mm Hg increase in usual systolic BP and each 10 mm Hg in-
crease in diastolic BPthere is no threshold below which lower SBP is not
per day (15-45g/day) .
. A single packet of ure-Na mixes with associated with lower risk.
However, in CKD, the association curve is often U-shapedcardiovascu-
3-4 ounces of water or juice.
. For outpatient use, patients can access
lar risk is increased at both higher and lower BP values, including low-normal
BP. One suggested reason is reverse causality: longstanding hypertension may
ure-Na by calling 1-844-980-9922 or lead to changes in cardiac structure and function, thus lowering BP while at
at www.ure-na.com. the same time increasing cardiovascular risk.
. Ure-Na may be a tax deduction Previous studies have found that at least half of patients with stage 4 to
5 CKD show cardiac structural abnormalities, often without signs or symp-
qualified medical expense. toms. In the Chronic Renal Insufficiency Cohort (CRIC) study, 75% of pa-
tients with an estimated glomerular filtration rate less than 30 mL/min per
Hospital pharmacies can order ure-Na from McKesson, 1.73 m2 had left ventricular hypertrophy on echocardiography.
Cardinal or AmerisourceBergen. Herrington and colleagues tested the hypothesis that the association be-
tween BP and cardiovascular risk might be confounded by the presence of
For questions, contact sales@nephcentric.com
such cardiac damagepatients who have CKD but have not yet developed
cardiac disease might exhibit a positive loglinear association similar to that
observed in apparently healthy adults.
To do this, the researchers needed a marker of cardiovascular risk. The
investigative trick was to use blood troponin to identify those at lowest risk of
Learn more at: www.ure-na.com
subclinical heart disease, Herrington explained. This was based on several
Oral Urea Made Palatable previous studies showing that troponin-I is positively correlated with left ven-
*The European clinical practice guideline recommend the use of oral urea tricular mass and negatively correlated with cardiac function.
as a treatment option in SIADH for moderate to profound hyponatremia. In the SHARP cohort, higher baseline troponin-I was associated with
male sex, older age, higher systolic BP, a higher prevalence of diabetes, and
February 2017 | ASN Kidney News | 3

worse renal function. During a median fol- diastolic BP remained U-shaped among unknown, and current recommenda- Baigent noted: The observational data
low-up of nearly five years, 2188 subjects patients with a low troponin-I. tions vary widely. Recent studies, includ- in SHARP only appear to show that lower
had one or more cardiovascular eventsa ing SPRINT, taken together with the BP associates with higher risk of cardio-
rate of 6.7% per year. Support for studies of lower BP evidence of reverse causality in the present vascular events. We argue that, if correctly
On adjusted analysis, higher baseline targets in CKD analysis in the SHARP trial, suggest that analyzed with due regard to the presence of
troponin-I was a strong predictor of future The findings add to previous data on the trials of lower BP targets in patients with confounding by subclinical cardiac disease,
cardiovascular events. Risk was increased complex relationship between BP and car- CKD are indicated, the researchers write. the true association between BP and risk
61% for CKD patients with baseline tro- diovascular risk in CKD. Herrington and Such studies would also address the po- of major cardiovascular events is positive
ponin-I over 0.01 ng/mL and 182% for coauthors write: The presence of a clear tential harms as well as benefits of lower throughout the range studied.
those over 0.03 ng/mL (compared to the positive loglinear relationship between BP targets; in SPRINT, more intensive BP
reference value of 0.01 ng/mL or less). This SBP (or pulse pressure) and cardiovascular control was associated with an increased Suggested Reading
association was apparent in both dialysis events in patients with CKD at lowest risk risk of acute kidney injury. 1. Herrington W, et al. Evidence for re-
and non-dialysis CKD patients. of cardiac disease in SHARP suggests that The findings in this paper probably are verse causality in the association be-
In the full cohort, the association be- reverse causality is a plausible explanation most applicable to people with CKD not tween blood pressure and cardiovascu-
tween systolic BP and cardiovascular risk for previously observed U-shaped asso- on dialysis, commented Rajiv Agarwal, lar risk in patients with chronic kidney
was U-shaped. However, among the 7278 ciations among patients with moderate-to- MBBS, of Indiana University School of disease. Hypertension 2017; 69:314
patients without previous cardiovascular advanced CKD. Medicine, Indianapolis. In a 2004 review 322.
disease, there was a positive loglinear asso- Herrington commented: This suggests in Hemodialysis International, Agarwal 2. Agarwal R. Exploring the paradoxical
ciation. On adjusted analysis, each 10 mm that guidelines should not be using obser- hypothesized that reverse causality might relationship of hypertension with mor-
Hg increment in usual systolic BP was as- vational analyses of BP to define optimum account for the U-shaped association be- tality in chronic hemodialysis. Hemo-
sociated with a 16% increase in cardiovas- BP targets in diseased populations, as such tween blood pressure and cardiovascular dial Int 2004; 8:207213.
cular risk. This risk increased to 27% per analyses may wrongly conclude that lower risk in CKD. 3. Baigent C, et al. The effects of lower-
10 mm Hg when analyses were further re- BP is dangerous, when the opposite may To understand the association between ing LDL cholesterol with simvasta-
stricted to those patients without evidence be the case. BP and cardiovascular risk would require tin plus ezetimibe in patients with
of subclinical cardiac diseasei.e., baseline Randomized trials, which control for home or ambulatory BP recordings chronic kidney disease (Study of Heart
troponin of 0.01 ng/mL or less. The asso- such confounding, have supported the ef- which werent available in the SHARP and Renal Protection): a randomised
ciation was little affected by adjustment fectiveness of lowering BP in other popu- data. placebo-controlled trial. Lancet 2011;
for baseline albumin:creatinine ratio, was lation groups where U-shaped associations Nonetheless, observational studies 377:21812192.
about the same for atherosclerotic and between BP and cardiovascular risk have show that low BP associates with higher 4. Park M, et al. Associations between
nonatherosclerotic events, in dialysis and been observed, including patients with pri- mortality in dialysis, while meta-analyses kidney function and subclinical cardiac
nondialysis patients, and among patients or cardiovascular disease and older adults of randomized trials suggest the opposite, abnormalities in CKD. J Am Soc Neph-
younger than 62 (the study median age) (e.g., the Systolic Blood Pressure Interven- Agarwal said. While we dont have a de- rol 2012; 23:17251734.
and those 62 years or older. tion Trial, or SPRINT). The same may finitive trial on BP level and outcomes in 5. The SPRINT Research Group: A ran-
In the full cohort, however, there were therefore be true in CKD. dialysis, I believe that the meta-analyses domized trial of intensive versus stand-
also U-shaped associations for diastolic BP In the absence of sufficiently large tri- trump the observational data. Clearly there ard blood-pressure control. N Engl J
(but not pulse pressure). Associations with als, the optimal BP target in CKD remains is room for research in this important area. Med 2015; 373:21032116.

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4 | ASN Kidney News | February 2017

Corporate Supporters
Editorial Staff ASN gratefully acknowledges the Societys
Editor-in-Chief: Richard Lafayette, MD
Executive Editor: Dawn McCoy Diamond and Platinum Corporate Supporters
Design: Lisa Cain Design
Communications Assistant: Sara Leeds for their contributions in 2016.
Editorial Board:
Joseph Mattana, Kings County Hospital Center, Brooklyn, NY
Andrew King, MD, Scripps, San Diego, CA
Pascale Lane, MD, FASN, University of Oklahoma Health Sciences
Diamond Level
Edgar V. Lerma, MD, FASN, University of Illinois Chicago /Associates in Nephrology, SC
Uday S. Nori, MD, Ohio State University Wexner Medical Center
Glenda Payne, MS, RN, CNN, Nephrology Clinical Solutions
Jeffrey Petersen, MD, Amgen
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President-elect: Mark D. Okusa, MD, FASN
Past-President: Raymond C. Harris, MD, FASN
Secretary-Treasurer: John R. Sedor, MD, FASN
Councilors: Mark E. Rosenberg, MD, FASN, Anupam Agarwal, MD, FASN,
Susan E. Quaggin, MD, Barbara Murphy, MD

Executive Vice President: Tod Ibrahim

Director of Communications: Robert Henkel

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knowledge and clinical practice of that discipline through stimulation of basic and clinical
investigation, providing access to new knowledge through the publication of journals and the
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Copyright 2016 All rights reserved
February 2017 | ASN Kidney News | 5

Policy Update

GAO Report Reveals Extent of Underfunding of Kidney Disease Research

Relative to Health Burden Cost

T he American Society of Nephrology (ASN)

has repeatedly cautioned health care policy-
makers that kidney diseases are at staggering
levels and, for decades, there have been too few new
ports research personnel working at universities, med-
ical schools, and other institutions. The National In-
stitute of Diabetes and Digestive and Kidney Diseases
(NIDDK)one of NIHs 27 institutes and centers
ASN analysis of the report reveals that the equivalent
of 1.7% of the annual total cost of care for kidney
failure is invested in research to improve therapies and
discover cures.
therapies for treating patients. Now, the US Govern- (IC)has primary responsibility for kidney disease Kidney diseases are devastating the lives of mil-
ment Accountability Office (GAO) has conducted a research. lions of Americans, said ASN President Eleanor
study and published its findings in a new report re- GAO began by identifying diseases and condi- Lederer, MD, FASN. Innovation has not kept pace
leased January 18, 2017, National Institutes of Health: tions with a high disease burden in the United States with the magnitude of the diseases, and the current
Kidney Disease Research Funding and Priority Setting, relative to other conditions based on data from the underinvestment in kidney research is detrimental to
that statistically validates these points. The report Centers for Disease Control and Prevention (CDC). patients and taxpayers. Todays GAO report highlights
highlights the inadequacies of federally funded medi- Investigators analyzed CDCs national survey data, the extent of the gap between our investment in inno-
cal research for kidney diseases in the face of a stagger- and interviewed CDC officials to identify conditions vation to treat and cure kidney diseases and the out-
ing burden on patients and taxpayers. that had high mortality, or were chronic conditions sized burden they place on every American.
GAO conducted the study at the request of mem- with high prevalence, or both. They then matched ASN announced at a White House Organ Summit
bers of Congress from both the House of Representa- the diseases and conditions identified with fiscal year last year its pledge of the first $7 million to launch
tives and the Senate. Prior to that request in 2015, 2015 datathe most current availablefrom NIHs a prize competition incentivizing the development of
ASN had formally requested these members of Con- Research, Condition, and Disease Categorization novel technologies for renal replacement therapy to
gress to call on GAO to conduct the study. GAO is a (RCDC) system, which categorizes NIH research pro- improve quality of life for patients with kidney diseas-
part of the federal legislative branch, and only mem- jects (and associated funding) into categories. es. The society has also pledged to work with Congress
bers of Congress can direct the agency to undertake One unique aspect of kidney diseases in terms of to ensure the United States investment in research to
studies. policy is that Medicare covers every American suf- cure kidney diseases is adequate to meet the challenge
The study, a performance audit, was conducted fering from kidney failureregardless of ageand it poses to patients and taxpayers.
from February 2016 to December 2016 and exam- guarantees them access to dialysis or kidney trans- Despite the federal governments commitment to
ined two primary factors affecting federally funded plants through the End-Stage Renal Disease (ESRD) care for patients with kidney failure, for decades we
kidney disease research: 1) the level of NIH fund- Program. Kidney failure is the only condition covered have seen too few new therapies for kidney patients,
ing for biomedical research on kidney diseases, and by Medicare for patients under 65 years of age. More said Crystal Gadegbeku, MD, Chair of the ASN Pol-
for other leading diseases and conditions; and 2) how than 20 million Americans have kidney diseases and icy and Advocacy Committee. This report strength-
the National Institute of Diabetes and Digestive and more than 650,000 have kidney failure. ens ASNs resolve to foster innovation that improves
Kidney Diseases (NIDDK) sets priorities for kidney Despite this commitment to care for patients with patients lives and extends the value to the Medicare
disease research. kidney diseases, the report demonstrates a significant program that has saved so many lives.
GAO reported that the NIH, within the Depart- gap between investment in research and the disease
ment of Health and Human Services, is the primary burden. Annually, the federal government spends Requesters of the GAO report were Congressional Kidney
federal agency that conducts biomedical research on more on the Medicare ESRD program (nearly $32 Caucus co-chair Rep. Tom Marino (R-PA), Rep. Barbara
kidney disease, as well as various other diseases and billion) than it invests in the entire National Institutes Comstock (R-VA), House Science Committee chair Rep.
conditions. NIHs budget$30 billion in fiscal year of Health (NIH) budget ($30 billion). With just $564 Lamar Smith (R-TX), Sen. Ben Cardin (D-MD), and
2015mostly funds extramural research that sup- million dedicated to kidney disease research at NIH, Sen. Bill Nelson (D-FL).

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Education | The ASN Advantage

February 2017 | ASN Kidney News | 7

Looking Ahead at the Nephrology


ephrology workforce research Only 64 US MDs matched in nephrology in AY ASN initiatives and programs by collecting, man-
conducted last year by George 2017, down 21% from last year and 52% from aging, analyzing, and synthesizing data relevant to
Washington UniversityHealth AY 2009. nephrology and nephrology professionals.
Workforce Institute (GWU-HWI)
investigators and others revealed 2017 Workforce research portfolio Data Analytics Program activities in 2016 included:
some interesting facets of the nephrology work-
Nephrology workforce research is one part of ASNs ASN Pediatric Nephrology Fellows Survey Re-
force that will inform ongoing research activities in sponsesBrief Analysis Authored for the ASPN
commitment to empower current and future mem-
2017. Heres a brief look back at nephrology work- Workforce Committee. The full report is avail-
bers of the nephrology workforce and advance their
force research in 2016 and trends to watch for in able at http://asn.kdny.info/TZpf305BEAy
professional goals and success. This years portfolio
the year ahead. Kidney News Online ASN Data Bytes Series.
Quick takes on items of interest to ASN mem-
2016 GWU-HWI report GWU-HWI Workforce Surveys bers. List of current articles available at http://
The most recent report from GWU-HWI inves- Researchers from GWU-HWI will focus on ad- www.kidneynews.org/search/node/Pivert
tigators led by Edward Salsberg, MPA, uncovered ministering three surveys assessing nephrology fel-
some interesting data points: lows and early career nephrologists: In 2017, the Program will focus on development of
The number of nephrology fellows in training 2017 Nephrology Fellows Survey ASN GME Database
has remained steady, despite a large number of 4th iteration of the annual fellows survey will Allows monitoring of trends among training
positions going unfilled in the Match. capture longitudinal data on job market experi- programs and nephrology fellows
University of North Carolina Sheps Center re- ences Data Collection Efforts
searchers working in collaboration with GWU Survey of Nephrologists One Year Out of Assessing and enumerating knowledge and data
project the number of adult nephrologists per Training resource gaps, as well as potential approaches to
10,000 population will grow by 58% between Assessment of nephrologists practice and em- address them
2016 and 2030. ployment settings and experiences 1 year after ASN Data Resource Center
A central repository for ASNs ongoing nephrol-
ogy workforce research and data collection

Workforce, Training, and Career

Advancement Department
In April 2016, ASN coalesced its workforce-cen-
tered programs into a new Workforce, Training,
and Career Advancement Department to foster ca-
reer development for all kidney health profession-
als. Among the departments portfolio are Kidney
STARS, Kidney TREKS, and the ASN Foundation
for Kidney Research grants programs to which
Overall, the report details a mixed picture for graduation, conducted in concert with/fulfilling ASN commits more than $3 million each year.
the specialty. The job market for US medical gradu- ACGME-required 1-year postgraduate program More than 40 physician volunteers serving on the
ates is improving although it remains challenging assessments newly created Career Advancement, Diversity and
for international medical graduates. However, the Survey of Nephrologists Five Years Out of Inclusion, and Workforce and Training Commit-
inflow of new nephrologists is outpacing the rate of Training tees will inform the departments strategic initia-
retirement for older physicians. Detailed investigation of early career nephrolo- tives. Expanding the range of resources available to
Our third annual report on the nephrology gists, including the first graduating class who kidney professionals across the entire career trajec-
workforce finds both positive and negative signs, completed the ASN Nephrology Fellows Survey tory, from student to senior clinicians and inves-
said Salsberg. For example, while the job market assessments of training tigators, will advance their professional lives and
for new nephrologists is still challenging, there improve treatment of kidney diseases.
were some bright spots especially for US medical Best Practices Project: Internal Medicine Residencies
school graduates as job prospects improved along The Best Practices Project is one of several initia- Trends to watch
with incomes. And a new survey of nephrologists tives designed by the ASN Workforce Committee Among the trends to watch in 2017 are:
over 55 found that most were satisfied with their to assess best practices of institutions that success-
specialty, practice, and income. Shifts in nephrology GME
fully attract trainees, in order to increase interest The AY 2017 Match was flat year over year, yet
In addition to surveying nephrologists 55 and in nephrology careers among the brightest medical
older, GWU conducted the annual Nephrology positions have continued to fill. Growing anec-
students and residents. The project identified top dotal evidence demonstrates a shift in reducing
Fellows Survey and outlined the potential of re- internal medicine residency producing physicians
cently introduced ESRD Seamless Care Organiza- the number of fellowship positions.
who subsequently specialize in nephrology and will Evolution of the Specialty
tion (ESCO) demonstration projects to influence isolate potentially translatable practices that could
nephrologist demand, which they determined may New training offerings, such as critical care
be disseminated and implemented at other institu- nephrology, could kindle interest in the special-
make the specialty more fulfilling and economically tions. Results of the first phasefocusing on medi-
rewarding. ty.
cal schoolswere presented at ASN Kidney Week A new Congress and administration
2016. A new healthcare landscape could result in
Appointment year (AY) 2017 Match
changing regulations and practice patterns and
Results of the AY 2017 nephrology Match released ASN Data Analytics Program may influence specialty choice among trainees
on December 7, 2016, were essentially flat to the The Data Analytics Program was created in April and future physician demand.
previous year. An ASN Data Brief (http://asn.kdny. 2016 to advance the goals of ASNs new strategic
info/dyo6307Gh2r) highlighted several key points: plan. ASN is conducting in-house research and Workforce research reports and other resources are
Despite a 4.4% increase in the number of train- analysis projects, building on collaborations with available at http://www.asn-online.org/workforce.
ing tracks compared with AY 2016, the number GWU-HWI and expanding into new areas. The If you have questions, concerns, or suggestions for
of slots offered was flat, suggesting nephrology Data Analytics Program will support informed, future workforce research, data or knowledge gaps,
training positions may be contracting slightly. strategic decision-making and implementation of please contact workforce@asn-online.org.
8 | ASN Kidney News | February 2017

Delay for CMS Rule on Premium

By Bridget M. Kuehn

new CMS regulation that would comment letter. For many patients in the vul- But a New York Times investigation, published
potentially curtail third party pay- nerable dialysis population, third party assistance December 25, 2016, suggested that the AKF had
ments for insurance for dialysis pa- currently helps them achieve their goals, be it to in some instances resisted offering assistance to
tients has been delayed by a U.S. work part time, gain access to transplant, or afford patients from dialysis clinics not associated with
District Court judge in Texas. medications, and the society is concerned that the companies that donated to the charity, contrary to
Fresenius Medical Care, Davita, U.S. Renal proposals in this [rule] would inadvertently jeop- OIG guidelines.
Care, along with Dialysis Patient Citizens, filed ardize some individuals access to care. In a statement, the AKF argued the article was
a lawsuit to block the CMS rule on Jan. 6, 2017. factually incorrect, that it had never turned away
Issued as an interim rule in August 2016, the reg- a patient who was financially qualified, and that
ulation was set to go into effect Jan. 13, 2017. 40% of dialysis providers who have patients re-
The judges temporary restraining order delaying ceiving AKF assistance do not contribute to the
the rule may stay in place for up to 14 days post- fund. But the AKF also expressed concern that so-
issuance. cial workers from independent dialysis clinics who
In its lawsuit, the groups stated that the rule
were interviewed by the New York Times believe
was pushed through without the proper notice or
that the fund is favoring patients from large dialy-
comment period that usually occurs before a new
sis companies who donate.
rule is adopted.
This is simply not the case, and we want to
The U.S. District Court judge agreed, stating
correct the record, as well as take ownership of any
the organizations likely showed that the Depart-
way that AKF itself may have contributed to this
ment of Health and Human Services (HHS) im-
plemented the final rule without time for thor- misperception, the statement said.
ough review and comment. In a fact sheet, CMS noted that in recent years
In a statement about the temporary restrain- dialysis providers have been offering premium as-
ing order, Fresenius Medical Care said: We are sistance, either directly or through charities, as
pleased that the court has issued a temporary re- a way to boost reimbursements. Premiums cost
straining order preventing this improperly issued about $6000, but private insurance may pay as
regulation from going into effect. Todays ruling much as 4 times more for dialysis care than Medi-
will help ensure that Americans with kidney fail- Premium support scrutiny care, resulting in up to an additional $100,000 to
ure have the same right as every other American In mid-August 2016, CMS announced it was $200,000 in reimbursement.
to receive charitable assistance to pay their health investigating reports of inappropriate steering of AKF said in a statement that it supported ef-
insurance premiums. We look forward to working dialysis patients into private insurance by dialy- forts to stop steering but had urged the agency to
with the new administration on regulations that sis providers to boost their own reimbursements. withdraw the rule, saying it would leave kidney
protect the sustainability of the Medicare program According to CMS, the investigation yielded re- disease patients with fewer options.
while protecting the ability of Americans to select ports of abuse with negative health and financial HHS is irresponsibly upending the entire
the health coverage of their choosing, free from consequences for patients. This led CMS to issue safety net that exists for dialysis patients who cant
discrimination based on their health status or dis- the interim rule requiring that dialysis facilities afford their health coverage, said Burton. This
ability. disclose the risks of various coverage options to cannot be the result that the agency intended to
achieve when it set out to protect ESRD patients
from improper steering.
[The rule requires] that dialysis facilities disclose the risks of various
Insurance discrimination
coverage options to their patients, be more transparent about how The regulation also drew sharp criticism from the
the provider benefits, and prevent potential disruptions in coverage patient advocacy group Dialysis Patient Citizens,
by seeking insurer approval for coverage. which said the rule, which requires insurance
companies to approve private coverage, allows in-
surers the chance to veto a patients choice of
private coverage.
The rule grew out of a CMS investigation of their patients, be more transparent about how the It basically creates a two-tier system, said
reports that dialysis companies were paying for provider benefits, and prevent potential disrup-
Hrant Jamgochian, chief executive officer of Di-
private insurance in order to boost their reim- tions in coverage by seeking insurer approval for
bursements. It requires dialysis companies to fully alysis Patient Citizens, which joined dialysis pro-
disclose to a patient their insurance options, how viders in the lawsuit to block the rule. If you can
Third parties, including nonprofits, have long
the providers would benefit from a patients receiv- afford private coverage, you are protected from
offered patients who require dialysis help paying
ing private coverage, and would require insurance discrimination [under ACA], but if you cant af-
for insurance. For example, the American Kidney
company approval of coverage for the patient. Fund (AKF) offers such payment assistance for ford it [without premium assistance] you arent.
In a Jan. 11, 2017, letter to CMS commenting low-income patients to purchase Medicare Part Patients with HIV are protected from such
on the rule, the American Society of Nephrology B, Medigap, and private or employer-based insur- discrimination, Jamgochian noted, because in-
(ASN) urged the agency to take more time and ance. Currently, the organization provides payment surers are required to accept charitable assistance
gather more input from stakeholders before final- assistance to 80,000 patients, including 6400 in for these patients under the Ryan White Care
izing the rule. Affordable Care Act marketplace plans, according Act. His organization has proposed similar pro-
The ASN firmly agrees with CMS that pay- to a press release. The organization runs a health tection for patients with kidney failure and has
ment of premiums and cost-sharing by third party insurance premium assistance program established urged CMS to crack down on insurance compa-
entities should only be used to promote the best in 1997 according to guidelines laid out by the US nies steering dialysis patients who could benefit
interests of the beneficiary, ASN stated in its Office of the Inspector General (OIG). from private insurance into Medicare.
February 2017 | ASN Kidney News | 9

Fellows Corner

Health Literacy in CKD:

A Fellows Perspective By Devika Nair

Lower health literacy has been linked to to help bridge the literacy gap between Table 1
worsened glomerular filtration rates (1,2). ourselves and our patients. We can ask Clinical red flags for lim-
Patients with CKD and poor health lit- open-ended questions, speak slowly with
eracy tend to access preventive health patient-oriented language, and limit the
ited health literacy
services less frequently and have poorer information we discuss at each visit. The
self-care methods, all of which can con- teach-back method, or asking our pa-
Patient registration forms
tribute to rising healthcare costs. In addi- tients to repeat back and explain any in- that are incomplete or
tion, one study showed that patients on structions given to them, can also be a inaccurately completed
dialysis with limited health literacy were useful tool to help confirm patient com-
Non-adherence with
78% less likely to be referred for a renal prehension.
medications or treatments
transplant (3). Patients with no medical background
Further complicating this matter, the seem to know what it means to have Frequently missed
Department of Education has reported heart disease and diabetes, but many still appointments
that 21% of adults in the United States struggle with understanding the impli- Lack of follow-through with
read below a fifth-grade level, and 14% cations of kidney disease. Not only is it labs, imaging tests, or
of the population is illiterate. A study of referrals
Devika Nair important to collaborate with educators
kidney diseaserelated patient education and policy leaders to develop educational Unable to name

edical students and residents tools from the United States, Australia, tools that provide simple representations medications, explain
are often intimidated by renal and the United Kingdom revealed that of this complex disease process, it is also what medications are
physiology and struggle to un- most materials required a ninth-grade crucial to support health literacy training for, or explain timing of
derstand the many aspects of the kidneys reading level for adequate comprehen- in the medical community. It is impor- medication administration
role in medical disease. If trainees have sion. In addition, many of these tools tant that more of these efforts be geared May offer excuses to
trouble grasping the complexities of the were geared toward those who had pro- toward patients during earlier stages of deflect reading tasks
kidney, it should come as no surprise that gressed to hemodialysis with little focus kidney disease as well as toward adoles- I forgot my glasses
our patients feel the same way. on patients with earlier stages of kidney cents.
Health literacy, or the ability of an in- Let me bring this home
disease (4). Low health literacy, a high pill Each of us has a right to knowledge so I can discuss it with my
dividual to be actively engaged in a dia- burden, and an unfamiliar health system that informs decisions about our own children
logue about his health, has been linked can be an overwhelming combination for health. It is our responsibility to ensure
to patient outcomes. Adequate health lit- Seldom have questions
a patient with kidney disease. that this knowledge is delivered in a way
eracy is particularly important in chronic It is also important to realize that we that is both understandable and beneficial Seek help only when
kidney disease (CKD), which often re- as providers may fail to recognize existing to our patients. Our health interventions illness is advanced
quires patients to navigate a complex health literacy issues that are downplayed are only as effective as our patients abil- Have difficulty explaining
health system and make drastic lifestyle out of fear or embarrassment. When I ity to carry them outa challenge that medical concerns
changes. Patients may be faced with such asked one of my patients to read back we must continue to try to overcome with
critical decisions as choosing to begin re- the medication instructions I had writ- regard to kidney disease.
nal replacement therapy with little to no ten for him, it was only when he held
understanding of its implications. the paper upside down that I realized he Devika Nair, MD, is currently a first-year EJ, Hsu C. Health literacy and access
As a first-year Nephrology fellow, most could not read. nephrology fellow at Vanderbilt Univer- to kidney transplantation. Clin J Am
of the patients I see are new to me as well Table 1 provides a helpful list of pa- sity. She completed her medical training Soc Nephrol 2009; 4:195200.
as new to the clinic. I quickly realized that tient characteristics that may be associated and chief residency in Internal Medicine 4. Morony S, Flynn M, McCaffery KJ,
despite being referred to a clinic that ex- with low health literacy (5). at Tulane University and her undergradu- Jansen J, Webster AC. Readability of
clusively sees patients with kidney disease, How can providers continue to ad- ate studies at the University of California, written materials for CKD patients:
several of my patients were wholly una- dress concerns about patient health liter- Berkeley. a systematic review. Am J Kidney Dis
ware of having renal dysfunction in the acy? Tools such as the Rapid Estimate of 2015; 65:842.
first place. When I asked them what they Adult Literacy in Medicine (REALM), References 5. Jain D, Green JA. Health literacy
had trouble understanding, they often re- Test of Functional Health Literacy in 1. Devraj R, et al. Relationship between in kidney disease: Review of the lit-
plied with, everything, and didnt know Adults (TOFHLA), and Brief Health health literacy and kidney function. erature and implications for clini-
where to begin. Literacy Screen (BHLS) have all been Nephrology 2015; 20:360367. cal practice. World J Nephrol 2016;
used to successfully screen dialysis pa- 2. Ricardo AC, et al. Limited health lit- 5:147151.
Clinical implications of low tients for poor health literacy (5,6), al- eracy is associated with low glomeru- 6. Dageforde LA, Cavanaugh KL.
health literacy though studies regarding their effective- lar filtration in the Chronic Renal Health literacy: Emerging evidence
The clinical implications of low health ness in earlier stages of kidney disease are Insufficiency Cohort (CRIC) study. and applications in kidney disease
literacy in kidney disease are being rec- lacking. In addition to using these tools, Clin Nephrol 2014; 81:3037. care. Adv Chronic Kidney Dis 2013;
ognized by the nephrology community. there are simple steps that we can take 3. Grubbs V, Gregorich S, Perez-Stable 20:311319.

Have a tip or idea youd like to share with your fellow

peers and the broader kidney community?
Send your idea to the Kidney News Fellows Corner column at kidneynews@asn-online.org

A New Direction in SHPT

Rayaldee is the first and only extended-release prohormone of the
active form of vitamin D3 that raises 25-hydroxyvitamin D and lowers iPTH levels.
Indication and Limitations of Use
Rayaldee (calcifediol) extended-release 30 mcg capsules is indicated for the treatment of
secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease and serum
total 25-hydroxyvitamin D levels less than 30 ng/mL. Rayaldee is not indicated in patients
with stage 5 chronic kidney disease or end-stage renal disease on dialysis.
Important Safety Information
Hypercalcemia: Excessive administration of vitamin D compounds, including Rayaldee, can
cause hypercalcemia and hypercalciuria. Severe hypercalcemia due to substantial overdosage
of vitamin D and its metabolites may require emergency attention. Patients should be informed
about the symptoms of elevated calcium. Digitalis toxicity: Potentiated by hypercalcemia of
any cause. Monitor serum calcium and signs and symptoms of digitalis toxicity more frequently when


initiating or adjusting the dose of Rayaldee. Adynamic Bone Disease: Monitor for abnormally low
levels of intact PTH levels when using Rayaldee, and adjust dose if needed. The most common
adverse reactions (3% and more frequent than placebo) were anemia, nasopharyngitis, increased
blood creatinine, dyspnea, cough, congestive heart failure and constipation. Care should be taken
while dosing Rayaldee with cytochrome P450 inhibitors, thiazides, cholestyramine or drugs stimulating
microsomal hydroxylation due to the potential for drug interactions. Serum calcium should be below
9.8 mg/dL before initiating treatment. Monitor serum calcium, phosphorus, 25-hydroxyvitamin D
and intact parathyroid hormone (iPTH) 3 months after starting therapy or changing dose.
Please see Brief Summary of Prescribing Information on following page, and Full Prescribing Information at RAYALDEE.com.
RAYALDEE is a registered trademark of OPKO Ireland Global Holdings Ltd. 2016 OPKO Pharmaceuticals, LLC. OP-US-0092-102016v.1
12 | ASN Kidney News | February 2017

Diet Quality Affects Risk of eGFR Decline in Urban Patients
In a diverse urban population, low dietary rate (eGFR) of 60 mL/min/1.73 m2 or Accordance with the DASH diet was incident chronic kidney disease or eGFR
quality is associated with an increased higher. Mean age was 48 years; 59% of minimalmedian score 1.5 on a 08 decline greater than 25%.
risk of declining kidney function among participants were African American. scale. At a median 5 years follow-up, Previous studies have linked a health-
adults with hypertension, reports a study A Dietary Approaches to Stop Hy- rapid eGFR decline occurred in 13.4% ier diet to a lower risk of kidney disease
in the Journal of Renal Nutrition. pertension (DASH) score, based on nine of patients overall, 15.2% of those with outcomes, but none of these studies have
The study included data on 1534 par- target nutrients, was calculated for each a DASH score of 1 or less, and 12.0% focused on urban populations. The new
ticipants in the Healthy Aging in Neigh- participant. Diet score was evaluated for with a DASH score greater than 1. On results show that a low DASH score is as-
borhoods of Diversity across the Life association with rapid decline in kidney adjusted analysis, the association with sociated with an increased risk of rapid
Span (HANDLS) study: African Ameri- function (greater than 3 mL/min/1.73 m2 rapid eGFR decline was significant only decline in eGFR, among urban adults
cans and whites, aged 30 to 64 years, with per year), incident chronic kidney disease, for subjects with hypertension: risk ratio with hypertension. The investigators
a baseline estimated glomerular filtration and eGFR decline greater than 25%. 1.68. The DASH score was unrelated to conclude: [D]iet quality may play an
important role in determining kidney
outcomes among individuals with risk
factors for CKD [Liu Y, et al. Dietary
habits and risk of kidney function de-
BRIEF SUMMARY compound was teratogenic at doses of 25 and 50 mcg/kg/day. A dose of 5 Increase in Serum Calcium: Patients randomized to RAYALDEE experienced cline in an urban population. J Renal
CONSULT PACKAGE INSERT FOR mcg/kg/day was not teratogenic. In a similar study in rats, calcifediol was not a greater mean (SE) increase in serum calcium (P<0.001) than patients Nutr 2017; 27: 625].
FULL PRESCRIBING INFORMATION teratogenic at doses up to and including 60 mcg/kg/day. randomized to placebo [i.e., 0.2 (0.02) mg/dL on RAYALDEE versus 0.1 (0.03)
mg/dL on placebo from baseline to trial end]. Six subjects (2%) in the RAYALDEE
RAYALDEE (calcifediol) extended-release capsules, for oral use Carcinogenesis, Mutagenesis, Impairment of Fertility
treatment group and no subjects (0%) in the placebo group required dose
No neoplastic changes attributable to calcifediol were observed at subcutaneous
reductions for protocol-defined hypercalcemia (two consecutive serum calcium
doses of 3, 10 and 33 mcg/kg/day in a 26-week rasH2 transgenic mouse study.
In vitro or in vivo mutagenicity studies have not been performed with RAYALDEE.
values greater than 10.3 mg/dL). A total of 4.2% of RAYALDEE treated subjects
and 2.1% of placebo treated subjects experienced at least 1 elevation in serum
Mortality Differs by
Reason for Starting
No genotoxic or mutagenic effects have been reported with calcifediol.
calcium above the upper limit of normal (10.5 mg/dL).
Calcifediol has not been shown to have significant effects on fertility in rats.
Increase in Serum Phosphorus: Patients randomized to RAYALDEE experienced
Labor and Delivery: The effect of this drug on the mother and fetus during
labor and delivery is not known.
Nursing Mothers: Limited available evidence indicates that calcifediol is
a greater mean (SE) increase in serum phosphorus than patients randomized
to placebo [i.e., 0.2 (0.03) mg/dL on RAYALDEE versus 0.1 (0.04) mg/dL Dialysis
RAYALDEE is a vitamin D3 analog indicated for the treatment of secondary

on placebo from baseline to trial end]. One subject (0.4%) in the RAYALDEE
poorly excreted in human milk. Caution should be exercised when RAYALDEE is Among patients initiating dialysis, mor-
hyperparathyroidism in adult patients with stage 3 or 4 chronic kidney disease and treatment group met protocol-defined hyperphosphatemia (two consecutive serum
administered to a nursing woman.
serum total 25-hydroxyvitamin D levels less than 30 ng/mL. RAYALDEE is not indi- phosphorus values >5.5 mg/dL deemed to be study drug related) compared to tality is higher for those with a primary
Pediatric Use: The safety and efficacy of RAYALDEE have not been established
cated for the treatment of secondary hyperparathyroidism in patients with stage 5 no subjects in the placebo group. A total of 45% of RAYALDEE treated subjects
in pediatric patients.
chronic kidney disease or in patients with end-stage renal disease on dialysis.
Geriatric Use: Of the total number of subjects in phase 3 placebo-controlled
and 44% of placebo treated subjects experienced at least one elevation in serum indication of volume overload or hyper-
phosphorus above the upper limit of normal (4.5 mg/dL).
CONTRAINDICATIONS: clinical studies of RAYALDEE, 63% were 65 years of age and 22% were 75 tension, suggests a study in the American
None years of age. No overall differences in the safety or efficacy of RAYALDEE were To report SUSPECTED ADVERSE REACTIONS, contact OPKO
observed between subjects older than 65 years and younger subjects. Pharmaceuticals, LLC at 1-844-729-2539 or FDA at 1-800-FDA-
Journal of Kidney Diseases.
Hypercalcemia may occur during RAYALDEE treatment. Acute hypercalcemia may
Renal Impairment 1088 or www.fda.gov/medwatch The retrospective analysis included
No difference in efficacy was observed between patients with stage 3 chronic
increase the risk of cardiac arrhythmias and seizures and may potentiate the effect
kidney disease or those with stage 4 disease in subgroup analysis. Safety
DRUG INTERACTIONS 461 patients who initiated hemodialysis
of digitalis on the heart. Chronic hypercalcemia can lead to generalized vascular
calcification and other soft-tissue calcification. Severe hypercalcemia may require
outcomes were similar in these subgroups. The safety and efficacy of RAYALDEE in CYP3A Inhibitors or peritoneal dialysis (24 patients) from
the treatment of secondary hyperparathyroidism in patients with stage 2 or stage Cytochrome P450 inhibitors, such as ketoconazole, atazanavir, clarithromycin,
emergency attention.
5 chronic kidney disease and patients with end-stage renal disease on dialysis indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin or 2004 through 2012 at 14 facilities. All-
Hypercalcemia may be exacerbated by concomitant administration of high
have not been established [see Indications and Usage]. voriconazole, may inhibit enzymes involved in vitamin D metabolism (CYP24A1 cause mortality was analyzed for patients
doses of calcium containing preparations, thiazide diuretics, or other vitamin D
Overdosage and CYP27B1), and may alter serum levels of calcifediol. Dose adjustment of
compounds. In addition, high intake of calcium and phosphate concomitantly with differing primary indications for
Excessive administration of RAYALDEE can cause hypercalciuria, hypercalcemia, RAYALDEE may be required, and serum 25-hydroxyvitamin D, intact PTH and
with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia.
hyperphosphatemia, or oversuppression of intact PTH. Common symptoms of serum calcium concentrations should be closely monitored if a patient initiates or
In these circumstances, frequent serum calcium monitoring and RAYALDEE dose
vitamin D overdosage may include constipation, decreased appetite, dehydration, discontinues therapy with a strong CYP3A4 inhibitor.
dialysis initiation: laboratory evidence of
adjustments may be required. Patients with a history of hypercalcemia prior to
initiating therapy with RAYALDEE should be monitored more frequently for possible
fatigue, irritability, muscle weakness, or vomiting.
kidney function decline (reference cat-
Treatment of acute accidental overdosage with RAYALDEE should consist of general
hypercalcemia during therapy.
supportive measures. If the overdosage is discovered within a short time, induce
Thiazides are known to induce hypercalcemia by reducing excretion of calcium in egory), uremic symptoms, volume over-
Patients should be informed about the symptoms of elevated serum calcium, the urine.
which include feeling tired, difficulty thinking clearly, loss of appetite, nausea,
emesis or perform gastric lavage to prevent further absorption. Obtain serial
Concomitant administration of thiazides with RAYALDEE may cause hypercalcemia. load, hypertension, or other/unknown.
serum and urine calcium measurements, and assess any electrocardiographic
vomiting, constipation, increased thirst, increased urination, and weight loss.
abnormalities due to hypercalcemia. Discontinue supplemental calcium. Treat
Patients may require more frequent serum calcium monitoring in this setting. At a median follow-up of 2.4 years,
Hypercalcemia of any cause, including RAYALDEE, increases the risk of digitalis
toxicity. In patients using RAYALDEE concomitantly with digitalis compounds,
with standard medical care if persistent and markedly elevated serum calcium Cholestyramine 40% percent of patients had died. Crude
levels occur. Cholestyramine has been reported to reduce intestinal absorption of fat-soluble
monitor both serum calcium and patients for signs and symptoms of digitalis
Calcifediol is not significantly removed by dialysis. vitamins and may impair the absorption of calcifediol, the active ingredient in mortality was 21.7 per 100 patient-years
toxicity and increase the frequency of monitoring when initiating or adjusting the
RAYALDEE. Dose adjustment of RAYALDEE may be required, and serum total for patients with volume overload or hy-
25-hydroxyvitamin D, intact PTH and serum calcium concentrations should be
Adynamic bone disease with subsequent increased risk of fractures may develop if The data in Table 1 are derived from two pivotal studies described below. These pertension, compared to 10.0 for those
closely monitored if a patient initiates or discontinues therapy with cholestyramine.
intact PTH levels are suppressed by RAYALDEE to abnormally low levels. Monitor data reflect exposure of 285 subjects to RAYALDEE 30 or 60 mcg daily for up to
intact PTH levels and adjust RAYALDEE dose, if needed. 6 months (mean 24 weeks, range 1 to 31 weeks). The mean age of the study Other Agents with kidney function decline, 12.7 with
population was 66 years old (range 25-85 years). Half of the subjects were Phenobarbital or other anticonvulsants or other compounds that stimulate
male, 65% were White, and 32% were African-American or Black. At baseline, microsomal hydroxylation reduce the half-life of calcifediol, the active ingredient
uremic symptoms, and 12.2 for the oth-
Important Dosage and Administration Information
Ensure serum calcium is below 9.8 mg/dL before initiating treatment.
subjects had secondary hyperparathyroidism, stage 3 (52%) or 4 (48%) chronic in RAYALDEE. Dose adjustment of RAYALDEE may be required, and serum total er/unknown category.
kidney disease without macroalbuminuria and serum total 25-hydroxyvitamin D 25-hydroxyvitamin D, intact PTH and serum calcium concentrations should be
Instruct patients to swallow RAYALDEE capsules whole.
levels less than 30 ng/mL. The most common causes of chronic kidney disease closely monitored if a patient initiates or discontinues therapy with phenobarbital On adjusted analysis, volume over-
Instruct patients to skip a missed dose and to resume taking the medicine at
the next regularly scheduled time. Do not administer an extra dose.
were diabetes and hypertension and the mean estimated GFR at baseline was 31 or other anticonvulsants. load or hypertension was the only cate-
mL/min/1.73 m . At baseline, mean plasma intact PTH was 148 pg/mL, mean

Starting Dose and Dose Titration serum calcium was 9.2 mg/dL, mean serum phosphorus was 3.7 mg/dL and
HOW SUPPLIED gory associated with increased mortality:
mean serum 25-hydroxyvitamin D was 20 ng/mL. RAYALDEE is supplied as 30 mcg calcifediol in blue, oval extended-release hazard ratio 1.69. Among patients using
The initial dose of RAYALDEE is 30 mcg administered orally once daily at
Table 1 shows common adverse reactions associated with the use of RAYALDEE in capsules, imprinted O:
bedtime. a permanent dialysis access, the risk of
the pooled placebo-controlled trials. These adverse reactions were not present at
The maintenance dose of RAYALDEE should target serum total 25-hydroxyvita- Bottles of 30 [NDC 70301-1001-1]
baseline, occurred more commonly on RAYALDEE than on placebo, and occurred in
min D levels between 30 and 100 ng/mL, intact parathyroid hormone (PTH)
at least 1.4% of patients treated with RAYALDEE. Bottles of 60 [NDC 70301-1001-2]
death was eight times higher for those
levels within the desired therapeutic range, serum calcium (corrected for low
albumin) within the normal range and serum phosphorus below 5.5 mg/dL. STORAGE AND HANDLING
in the volume overload/hypertension
Table 1. Common Adverse Reactions in Placebo-controlled Trials
Monitor serum calcium, serum phosphorus, serum total 25-hydroxyvitamin D
Reported in 1.4% of RAYALDEE-Treated Subjects Store at 20-25C (68-77F); excursions permitted to 15-30C (59-86F)
group, compared to those with decreased
and intact PTH levels at a minimum of 3 months after initiation of therapy or
dose adjustment, and subsequently at least every 6 to 12 months. Placebo RAYALDEE
[see USP Controlled Room Temperature]. kidney function.
Increase the dose to 60 mcg orally once daily at bedtime after approximately Adverse Reaction N=144 N=285 RAYALDEE is a registered trademark of OPKO Ireland Global Holdings Ltd. The results suggest increased mortal-
3 months, if intact PTH remains above the desired therapeutic range. Prior to
raising the dose, ensure serum calcium is below 9.8 mg/dL, serum phosphorus % % Patent: http://www.opko.com/products/patents/ ity among patients initiating dialysis due
is below 5.5 mg/dL and serum total 25-hydroxyvitamin D is below Anemia 3.5 4.9 Rev. 06/2016 to volume overload, relative to those with
100 ng/mL. Nasopharyngitis 2.8 4.9
Suspend dosing if intact PTH is persistently and abnormally low to reduce the
Blood creatinine increased 1.4 4.9
laboratory evidence of kidney function
risk of adynamic bone disease [see Warnings and Precautions], if serum calcium decline. The researchers write: Improved
is consistently above the normal range to reduce the risk of hypercalcemia [see Dyspnea 2.8 4.2
Warnings and Precautions], or if serum total 25-hydroxyvitamin D is consistently Cough 2.1 3.5 understanding of symptoms and clinical
above 100 ng/mL. Restart at a reduced dose after these laboratory values Cardiac failure congestive 0.7 3.5
have normalized. Constipation 2.8 3.2 decision making at the time of the transi-
Bronchitis 0.7 2.8 Manufactured for: tion to dialysis therapy has the potential
Hyperkalemia 0.7 2.5 OPKO Pharmaceuticals, LLC
Teratogenic Effects - Pregnancy Category C: Calcifediol has been
Osteoarthritis 0.7 2.1 4400 Biscayne Blvd
to lead to innovation in identifying the
shown to be teratogenic in rabbits when given in doses of 8 to 16 times the
human dose of 60 mcg/day, based on body surface area. There are no adequate Hyperuricemia 0.7 1.8 Miami FL 33137 optimal timing for the initiation of main-
and well-controlled studies in pregnant women. RAYALDEE should be used during Contusion 0.0 1.8 2016 OPKO Ireland Global Holdings Ltd. OP-US-0071-092016v.1 tenance dialysis therapy [Rivara MB, et
pregnancy only if the potential benefit justifies potential risk to the fetus. Pneumonia 0.7 1.4
When calcifediol was given orally to bred rabbits on the 6th through the 18th day Chronic obstructive pulmonary disease 0.0 1.4 al. Indication for dialysis initiation and
of gestation, gross visceral and skeletal examination of pups indicated that the mortality in patients with chronic kidney
failure: a retrospective cohort study. Am J
Kidney Dis 2017; 69:4150].
RAYA16AGRX4627_Brief_PI_V2_1_r3_FSU.indd 1 10/18/16 5:17 PM
February 2017 | ASN Kidney News | 13

Obese Living Kidney Donors at Increased ESRD Risk

Among living kidney donors, the long- ment for potential confounders. risk is significantly higher for obese
term risk of ESRD is close to doubled Twenty years after living kidney donors. The increase in risk begins at
for those who are obese, reports a study donation, the cumulative incidence of a donor BMI of 27 kg/m2below
in Kidney International. ESRD was 93.9 per 10,000 for obese the standard cutoff for obesity. The
The study included data on 119,769 donors versus 39.7 per 10,000 for non- authors discuss the implications
living kidney donors, linked to Cent- obese donors. In adjusted models, obe- for living donor selection prac-
ers for Medicare & Medicaid Services sity was the only potentially modifiable tices, including the possibility
data to determine ESRD status. There risk factor associated with increased of predonation rehabilitation or
were 20,588 obese donors, body mass ESRD risk: adjusted hazard ratio 1.86. weight loss programs [Locke JE,
index (BMI) 30 kg/m2 or higher; and For each one-unit increase in BMI over et al. Obesity increases the risk of
58,004 nonobese donors. (The remain- 27 kg/m2, there was a 7% increase in end-stage renal disease among liv-
ing 41,177 donors had missing data on ESRD risk. ing kidney donors. Kidney Int 2016;
BMI.) Postdonation risk of ESRD was While the absolute risk of ESRD af- DOI: http://dx.doi.org/10.1016/j.
compared between groups, with adjust- ter living kidney donation is low, the kint.2016.10.014].

Albuminuria Screening May Predict Rapid eGFR Decline

Screening for elevated albuminuria and first morning urine sample, confirmed by 0.81mL/min/1.73 m2 per year. lation screening for albuminuria might
hypertension may identify a group of pa- an albumin excretion of 30 mg/d or higher The association was strongest in par- aid in identifying patients at risk of faster
tients at increased risk of faster decline in in two 24-hour urine collections. Hyper- ticipants aged 55 or older and in men. decline in kidney function, who could
kidney function, reports a study in Neph- tension was defined as a blood pressure of Participants with elevated albuminuria benefit from treatment. This strategy may
rology Dialysis Transplantation. 140/90 mm Hg or higher or use of antihy- had consistently higher blood pressure. be most effective in men and in older pa-
The study included 6471 participants pertensive drugs. Elevated albuminuria and as yet un- tients; the authors suggest the possibility
from the population-based Prevention Participants with elevated albuminu- known hypertension was associated with of combining albuminuria screening with
of Renal and Vascular End-stage Disease ria had a faster rate of decline in eGFR the highest blood pressure. This combi- colorectal cancer screening [zyilmaz A,
(PREVEND) study. All had at least two during follow-up. This was so in subjects nation was more than twice as common et al. Screening for elevated albuminuria
(median four) measurements of estimated with known hypertension, 1.84 ver- as elevated albuminuria with known hy- and subsequently hypertension identifies
glomerular filtration rate (eGFR) over a sus 1.16mL/min/1.73 m2 per year; pertension. subjects in which treatment may be war-
median 11.3 years follow-up. Elevated newly diagnosed hypertension, 1.59 Identifying CKD at an early stage ranted to prevent renal function decline.
albuminuria was defined as an albumin versus 1.14mL/min/1.73 m2 per year; might help to prevent ESRD by manag- Nephrol Dial Transpl 2016; doi: 10.1093/
concentration of 20 mg/L or higher in a and normal blood pressure, 1.18versus ing hypertension and albuminuria. Popu- ndt/gfw414].

AKI Linked to Unplanned Readmissions

Acute kidney injury (AKI) is strongly asso- and death without readmission in 363. On consistent, and independent risk factor
ciated with an increased risk of unplanned multivariable analysis, AKI was a strong for unplanned hospital readmissions.
hospital readmissionsespecially for acute risk factor for the combined outcome: More than one-fourth of readmissions
pulmonary edema, according to a study in odds ratio 1.50 for stage 1, 2.23 for stage in AKI patients may be related to acute
BMC Nephrology. 2, and 2.80 for stage 3. The reason for re- pulmonary edemaa potentially
The researchers analyzed Scottish admission was acute pulmonary edema in modifiable condition. Some readmis-
population-based data on 16,453 patients 26.6% of AKI cases, compared to 4.0% sions may be avoidable by careful
who were hospitalized and survived to dis- of those with no AKI and normal kidney pre-emptive planning after AKI to
charge in 2003. Of these, 2623 patients function. Although AKI was a strong pre- prevent the development of pulmo-
had AKI, based on KDIGO criteria. AKI dictor, it added little incremental value nary edema, the investigators con-
and other candidate predictors were ana- when added to other predictive models. clude [Sawhney S, et al. Acute kidney
lyzed as risk factors for unplanned read- Acute kidney injury is a common and injury as an independent risk factor for
mission or death within 90 days. serious condition; coordinated care is need- unplanned 90-day hospital readmissions.
The main study outcome occurred in ed to prevent avoidable complications. The BMC Nephrol 2017; 18: 9 DOI: 10.1186/
18.6% of patients: readmission in 2701 new analysis finds that AKI is a strong, s12882-016-0430-4].

No Reduction in AVF Failure with Fish Oil and Aspirin

Treatment with fish oil and/or aspirin tion. with no difference in the composite significant difference in AVF failure over
does not reduce the risk of arteriovenous Patients were randomly assigned outcome or its individual components. 12 months, with either fish oil, aspirin,
fistula (AVF) failure, reports a rand- to receive fish oil, 4 g/d, or placebo. A There was also no difference between the or the combination of the two. The high
omized trial in JAMA Internal Medicine. subset of 406 patients were further as- aspirin and placebo groups: fistula failure failure rate of nearly 50% emphasizes the
The Omega-3 Fatty Acids (Fish Oils) signed to aspirin, 100 mg/d, or placebo. rate 45% and 43%, respectively. Adverse urgent need to improve AVF outcomes
and Aspirin in Vascular Access Outcomes Study treatments began 1 day before sur- events, including bleeding, were similar [Irish AB, et al. Effect of fish oil sup-
in Renal Disease (FAVOURED) study gery and continued for 12 weeks. At 12 between groups. plementation and aspirin use on arterio-
included 567 patients at 35 dialysis cent- months, a composite endpoint of fistula Fish oil and aspirin have differing ef- venous fistula failure in patients requiring
ers in Australia, Malaysia, New Zealand, thrombosis or abandonment or cannula- fects that might make them useful for re- hemodialysis: a randomized clinical trial.
and the United Kingdom. All patients tion failure was assessed. ducing the high rates of early thrombosis JAMA Intern Med 2017; doi:10.1001/ja-
had stage 4 or 5 chronic kidney disease The fistula failure rate was 47% in and maturation failure in AVFs. How- mainternmed.2016.8029].
and were undergoing surgical AVF crea- patients assigned to fish oil or placebo, ever, the FAVOURED results show no Continued on page 14
14 | ASN Kidney News | February 2017

Continued from page 13

Worldwide Trends in Hypertension: 40-Year Analysis
More than 1 billion people worldwide In 2015, global age-standardized mean tral and eastern Europe, sub-Saharan Af- tries, especially in sub-Saharan Africa. The
now have hypertension, with the highest blood pressure increased systolic blood rica, and south Asia. total number of adults with raised blood
levels now seen in low-income countries pressure was 127.0/78.7 mm Hg in men The overall number of adults with pressure has increased by 90%. The au-
in south Asia and sub-Saharan Africa, ac- and 122.3/76.7 mm Hg in women. The raised blood pressure increased from 594 thors call for multifaceted approaches to
cording to a report in The Lancet. age-standardized prevalence of raised million in 1975 to 1.13 billion in 2015, address the large and inequitable burden
The NCD Risk Factor Collaboration blood pressure was 24.1% and 20.1%, re- with most of the increase occurring in of cardiovascular diseases and kidney dis-
analyzed pooled data from 1479 studies spectively. low- and middle-income countries. The ease associated with high blood pressure
that had measured blood pressure in 19.1 High-income western and Asia Pacific global increase was attributable to popu- [NCD Risk Factor Collaboration: World-
million adults. The researchers analyzed countries went from having some of the lation growth and ageing, partly offset by wide trends in blood pressure from 1975
trends in mean systolic and diastolic blood highest measured blood pressure values in decreases in age-specific prevalence. to 2015: a pooled analysis of 1479 pop-
pressure from 1975 to 2015, as well as the the world in 1975 to the lowest in 2015. Over the past 40 years, the high- ulation-based measurement studies with
prevalence of raised blood pressure (140/90 By 2015, the regions with the highest est measured blood pressure values have 19.1 million participants. Lancet 2017;
mm Hg or higher) in 200 countries. measured blood pressure levels were cen- shifted from high- to low-income coun- 389:3755].

How Does Switching to HDHPs Affect Diabetes Care?

For patients with diabetesincluding on low-deductible plans only. er, high-priority specialist visits decreased However, rates of ED visits for prevent-
but not limited to low-income patients The effects of switching to an HDHP by 5.5% in the first year and 7.1% in the able acute diabetes complications are
switching to high-deductible health plan on diabetes outpatient care and acute second year. substantially increased, particularly for
(HDHPs) leads to major increases in complications were assessed, including After the switch to an HDHP, outpa- low-income, high-morbidity, and HSA-
emergency department visits for prevent- ED visits for preventable complications. tient visits for acute diabetes complica- eligible patients. With the increasing fo-
able acute diabetic complications, reports Subgroup analyses focused on 4121 low- tions were delayed in both the overall and cus on HDHPs in the US healthcare sys-
a study in JAMA Internal Medicine. income patients and 1899 patients eligi- low-income cohorts: adjusted hazard ratio tem, the authors discuss implications for
The researchers analyzed the effects of ble for health savings accounts (HSAs). 0.94 and 0.89, respectively. Annual ED preventing adverse effects on diabetes care
an employer-mandated switch to HDHPs Out-of-pocket costs increased for dia- visits for acute complications increased by [Wharam FJ, et al. Diabetes outpatient
in 12,084 diabetic patients, aged 12 to 64 betic patients in the year after switching 8.0% for all patients, 15.5% in HSA-eli- care and acute complications before and
years. All were enrolled in a low-deducti- to HDHPs: by 49.4% overall, 51.7% gible patients, and 21.7% in low-income after high-deductible insurance enroll-
ble plan ($500 or less) for 1 year, followed for low-income patients, and 67.8% patients. ment: a Natural Experiment for Transla-
by 2 years in an HDHP ($1000 or high- for HSA-eligible patients. There was no Switching to an HDHP does not ap- tion in Diabetes (NEXT-D) study. JAMA
er). The HDHP patients were propensity change in high-priority primary care visits pear to affect outpatient visits and dis- Intern Med 2017; doi:10.1001/jamain-
score-matched to patients who remained or use of disease monitoring tests. Howev- ease monitoring for diabetic patients. ternmed.2016.8411].

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January 2017 | ASN Kidney News | 15

Better Data
on Living
Donor Risks
By Bridget M. Kuehn

growing understanding of the health
and psychosocial risks associated with
being a living kidney donor is helping
drive innovations that will improve the
informed consent process, according
to recent research.
Receiving a kidney donated by a living donor
greatly improves the outcomes of patients with kidney
failure. But it also creates risks for the 30,000 otherwise
healthy donors around the world who donate kidneys
each year. Ensuring that living donors give proper
informed consent is essential. Now, a growing body
of evidence on the risks associated with living kidney
donation and emerging tools to help clinicians and
patients assess them are helping to improve the process
of informed consent.
Our ability to walk donors through informed
consent has exponentially improved, said Robert
S. Gaston, MD, director of the Comprehensive
Transplantation Institute at the University of Alabama-
Birmingham. I think we will be able to plug [infor-
mation] into a calculator really soon and give an
absolute risk. Gaston spoke at a Kidney Week 2016
symposium. donated a kidney may have worse pregnancy outcomes. We really wanted to make sure we did things con-
Women who donate a kidney have an elevated risk sistently, she said.
Modeling risk of gestational hypertension compared with those who Many donors report unchanged or even improved
have never donated a kidney (OR 2.4; 95% confidence quality of life and other psychosocial function after
Scientists have created models that can help clinicians
interval, 1.2 to 5.0; p=0.01) (Garg AX, et al. N Engl J donating a kidney (Clemens KK, et al. Am J Transplant
assess the risks faced by an individual donor based on
Med 2015; 372:124133). 2006; 6:29652977). But a small number may face
several demographic and health characteristics (Grams
Another study that compared donors pre- and post- poor psychosocial outcomes, Jacobs noted.
ME, et al. N Engl J Med 2016; 374:411421). Living
donation pregnancies found a higher risk of preterm A number of factors, including having good family
donors have about a 3.5- to 5.3-fold higher risk of
delivery, fetal loss, gestational diabetes, hypertension, or other support, viewing the donation process posi-
kidney failure than comparable individuals in the US
proteinuria, and preeclampsia postdonation (Ibrahim tively, having a higher level of education, and greater
population, said Robert Foley, MD, associate profes-
HN, et al. Am J Transplant 2009; 9:825834). comfort with the decision to donate, all appear to
sor of medicine in the division of renal diseases at the
The absolute risks of these outcomes are low, and protect against poor outcomes, Jacobs said. But other
University of Minnesota. Fagan noted that the absolute
generally on par with or lower than the risk of this factors, including having poor mental health, lim-
risks of end stage renal disease (ESRD) are still low.
outcome in the general population because donors ited support, a longer recovery, or financial hardships
Among the factors that increase the risk of living
are healthier than the general population, said Mirna related to the donation, may lead to poorer outcomes.
donors developing ESRD are the development of post-
Boumitri, MD, an assistant professor of medicine Many donors report lost income, dependent care
donation diabetes or hypertension, which boost the
in the division of renal diseases at the University of costs, as well as travel and health care costs related to
risk of proteinuria fourfold and the risk of ESRD by
Minnesota. Still, women should be counseled about their donation. One study found that 89% of donors
more than twofold, respectively (Ibrahim HN, et al. J
postdonation risks to pregnancy, Boumitri said. suffered a financial loss during the first year after dona-
Am Soc Nephrol 2016; 27:28852893).
tion, with one-third reporting a loss of more than
Even then, predonation factors can help identify Paying to donate $2500 (Rodrigue JR, et al. Am J Transplant 2016;
individuals at greatest risk.
Living kidney donors may also face financial or psy- 16:869876)
What Id really like to get to is a clinical model
chosocial consequences of their decision to donate. But Donors are paying to donate, Jacobs said.
that would help donors, Foley said. Ideally, he said
better and more consistent screening can help identify Donors may also have a harder time accessing health
such a tool would be very simple and use a spreadsheet
donors at risk. or life insurance, Jacobs said. Some programs have
program or graphs to explain individual risks and how
Cheryl Jacobs, MSW, a clinical transplant social been created to help neutralize the costs to donors.
they might be managed, for example, by keeping blood
worker at the University of Minnesota Medical Center, For example, travel grants may be available for some
pressure within the normal range or making lifestyle
said her institution has taken steps to ensure that donors. Additionally, the US Living Donor Protection
choices to minimize the risk of diabetes posttransplant.
donors are properly screened. They also use a donor Act, which would prevent insurers from punishing
Pregnancy risks advocate who is not involved in the donors medi- donors, was introduced recently.
cal care, which is now required by the Centers for We owe it to donors to advocate where there are
Emerging data also suggest that women who have gaps, Jacobs said.
Medicare & Medicaid Services.
16 | ASN Kidney News | February 2017

Practice Pointers

Pregnancy and End Stage Renal Disease

By Rakhi Khanna

How frequent is pregnancy in ESRD? What are the current out- Is anemia management different? Are there concerns regarding
comes? erythropoietin or transfusion?
Fertility is reduced in dialysis patients. The reasons are multifactorial and include hor- Anemia, especially hemoglobin levels <8 g/dL, can have adverse effects on the fetus
monal abnormalities, such as hyperprolactinemia and hypergonadotrophic hypog- (2). Erythropoietic agents can be used in pregnancy, because there are no reports of
onadism, anovulatory cycles, and sexual dysfunction (1). In the United States, among teratogenicity (10). Previous studies do not show transfer of epoetin alfa (epogen)
women of childbearing age on dialysis, frequency of pregnancy is around 0.5% per across the placenta (11). Multidose formulations containing benzyl alcohol are con-
year on the basis of survey results (1). Some countries have reported up to 1.4% per traindicated, and single-dose preparations should be used. Dose requirements are 50
year frequency rates. For reasons that are not well understood, patients on hemo- to 100% more for pregnant women on dialysis and can be increased right away (1).
dialysis have a two to three times greater likelihood of conception than patients on Intravenous iron preparations can be continued as well, although safety data are lack-
peritoneal dialysis (2). Experts think peritoneal solution may cause interference with ing. There are sparse reports about packed red blood cell transfusion during preg-
implantation and ovum transport. nancy; therefore, it should be used cautiously following current transfusion guidelines.
Approximately 50% of pregnancies result in survival of infants. However, many
of these infants are premature and small for gestational age. These infants can have What are the postpartum issues for the mother and the baby?
multiple medical and developmental problems (1).
The pregnant dialysis patient requires a highly specialized team, including the neph-
rologist, a high-risk pregnancy obstetrician, and a neonatologist. The number one
What treatment modalities are best for mother and child? When is issue encountered in pregnant dialysis patients is prematurity, which in turn, is the
fetal monitoring initiated? greatest cause of morbidity and mortality in the infants (1).
Pregnancy requires more aggressive dialysis. This means more frequent dialysis, at least Other complications include preeclampsia, polyhydramnios, and premature labor.
six times a week with a target BUN <45 mg/dL (3). Better outcomes are reported for Most commonly used medicines, such as intravenous magnesium to stop preterm
infants born to pregnant women dialyzed more than 36 hours per week. Intense dialy- labor, are difficult to use, because they can lead to magnesium toxicity and cause
sis improves uremic and maternal volume status. Therefore, these infants have a higher respiratory depression (12). Timing of delivery is usually around 34 to 36 weeks, but
live birth rate compared with those of pregnant women who were dialyzed less fre- the mean gestational age has been noted to be only 32 to 36 weeks. Infants of dialysis
quently (4). Kidney Disease Outcomes Quality Initiative guidelines also recommend patients are born with BUN and creatinine levels similar to the levels of the mother.
long frequent dialysis. However, the standard method to calculate Spkt/V cannot be After birth, these infants can have an osmotic diuresis and develop volume contraction
used, because the equation applies to thrice weekly hemodialysis. with metabolic alkalosis (13).
It is also a challenge to adjust the ultrafiltration goal and/or establish a dry weight
for the patient. Elevated BP in pregnancy may not always be volume mediated and Acknowledgments
may be related to preeclampsia. Careful attention is needed to avoid hypotension,
As a practicing nephrologist, I am indebted to my patients for giving me the opportu-
which can lead to placental hypoperfusion. Daily dialysis does help in assisting vol-
nity to provide care for them and the inspiration to learn.
ume balance.
Frequent hemodialysis will mean very careful adjustments in potassium, calcium,
and bicarbonate to avoid hypercalcemia and alkalosis (5). A regimen of daily dialysis
can lead to alkalosis, and the the bicarbonate bath needs to be adjusted to maintain Search for this topic revealed multiple review articles but few prospective studies ex-
bicarbonate levels around 20 mEq/L (1). Typical dialysate potassium of 3 mEq/L and amining management and outcomes of pregnant dialysis patients. I recommend an
bicarbonate concentration of 25 mEq/L are needed. ongoing registry for pregnant patients on dialysis.
Peritoneal dialysis may be used and may also be useful in avoiding rapid metabolic
changes. However, as pregnancy progresses, it can become difficult to tolerate the References
exchange volumes (1). 1. Hou S. Pregnancy in chronic renal insufficiency and end stage renal disease. Am
Fetal monitoring is done as per obstetric guidelines using serial ultrasound to ex- J Kidney Dis 1999; 33:22352252.
amine fetal growth and evaluate the placenta and amniotic fluid. Weekly fetal surveil- 2. Okyndaye IB, Abrinko P, Hou S. Registry for pregnancy in dialysis patients. Am
lance is started around 24 to 26 weeks using ultrasound and biophysical profile (6). J Kidney Dis 1998; 31:766773.
3. August P. Pregnancy in Women with Underlying Renal Disease. www.uptodate.
What medications are safe? com.
Antihypertensive medications that are safe and commonly used are methyldopa, la- 4. Hiadunewich MA, et al. Intensive hemodialysis associated with improved preg-
betalol, hydralazine, and dihydropyridine calcium channel blockers. b-blockers other nancy outcomes: A Canadian and United States Cohort Comparison. J Am Soc
than labetalol can cause fetal bradycardia. Angiotensin-converting enzyme inhibitors Nephrol 2014; 25:11031109.
and angiotensin receptor blockers are contraindicated, because they can increase the 5. Hou S. Pregnancy in dialysis patients: Where do we go from here? Semin Dial
risk of major congenital malformations (7). 2003; 16:376378.
As patients
Continued from pageare
15 dialyzed more often, caution and proper medication adjustment 6. Bagon JA, et al. Pregnancy and dialysis. Am J Kidney Dis 1998; 31:756765.
are needed to avoid hypotension. Target postdialysis BP should be less than 140/90 7. Krane NK, Hamrahian M. Pregnancy: Kidney diseases and hypertension. Am J
mm Hg. Kidney Dis 2007; 49:336345.
In terms of anticoagulation, heparin can be used in dialysis. It does not cross the 8. Ginsberg JS, et al. Heparin therapy during pregnancy. Risks to the fetus and
placenta, and it is not teratogenic (8). Coumadin cannot be used, and patients who mother. Arch Intern Med 1989; 149:22332236.
are on Coumadin for access-related clotting problems will have to be changed to sub- 9. Briggs GG, Freeman RK, Jaffe SJ. Drugs in Pregnancy and Lactation, Baltimore,
cutaneous heparin (9). Low molecular weight heparins, such as enoxaparin, and novel MD, Williams and Wilkins, 1994.
oral anticoagulants, such as rivoraxaban, dabigatran, and apixaban, are not approved 10. Hou SH, et al. Pregnancy in women with end stage renal disease: Treatment of
for use in dialysis patients. anemia and premature labor. Am J Kidney Dis 1993; 21:1622.
Calcium-based phosphorus binders are probably the safest to continue as long 11. Zanjani ED, et al. Erythropoietin does not cross the placenta into the fetus.
as calcium concentration is monitored and maintained within normal limits. Active Pathobiology 1993; 61:211215.
vitamin D derivatives and vinacalcet are all category C drugs with only case reports 12. Redrow M, et al. Dialysis in the management of pregnant patients with renal
of their use. There are not enough reports to show safety. A higher dose of folic acid insufficiency. Medicine (Baltimore) 1998; 67:199208.
(at least 5 mg/d) is also needed during pregnancy owing to higher dosage needs and 13. Bolwey DL, Warady BA. Neonatal outcome in pregnancies associated with renal
removal of water-soluble vitamins caused by intensive dialysis. The multivitamin dose replacement therapy. Adv Ren Replace Ther 1998; 5:4552.
is also doubled daily. Rhaki Khanna, DO, is a nephrologist in Gurnee, IL.
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February 2017 | ASN Kidney News | 19

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Email Address
Return the completed form to:
Bob Henkel, 1510 H Street NW, #800, Washington, DC 20005
Signature Date
or Fax: 202-403-3615 or Email: bhenkel@asn-online.org

Index to Advertisers
Mount Sinai . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 3
Nephcentric . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 2
OPKO Renal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pages 10-12
Kidney Self-Assessment Program
Challenge your knowledge and diagnostic skills.
The Kidney Self-Assessment Program (KSAP) is a CME and Part 2 MOC product
designed to review the essentials of nephrology. Assess your understanding of the core
elements of nephrology through challenging, clinically-oriented questions.

Based on the ABIM nephrology examination blueprint, KSAP is an excellent resource

for fellows preparing for initial certification or practicing nephrologists preparing for

Module 1 and 2 are now available for each volume

Volume 1 (2015): 25 MOC Points, 15 CME Credits (per module)
Volume 2 (2016): 25 MOC Points, 25 CME Credits (per module)

Learn more and get started at www.asn-online.org/ksap

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