Hemodialysis.com Research Interviews January 5 2013

Hemodialysis.com

Hemodialysis research, author interviews, dialysis updates and information on chronic
kidney disease and end stage renal failure.

Editor: Marie Benz, MD
info@hemodialysis.com
December 15 2012

For Informational Purposes Only: Not for Specific Medical Advice.

For Informational Purposes Only. Not for
Read more interviews on Hemodialysis.com
Specific Medical Advice

Hemodialysis.com Interviews
January 5 2013


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Microalbuminuria and hyperfiltration in subjects with nephro-urological disorders
Hemodialysis.com Author Interview:
Francois Cachat MD
Department of Pediatrics, Division of Pediatric Nephrology, University Hospital, Lausanne, Switzerland

• Hemodialysis.com Editor Marie Benz: What are the main findings of the study?

• In children with chronic nephro-urological disorders, there was only a weak
association between microalbuminuria and filtration fraction, and this only in
children with a single kidney and normal GFR.
In all other patients, there was no association between microalbuminuria and
filtration fraction.

• Hemodialysis.com: Were any of the findings unexpected?

• The fact that children with a single kidney showed only a weak association
between microalbuminuria and filtration fraction is surprising.
These children have lost 50% of their nephron mass, sometimes more, and one
would expect a much stronger association in that case. Their young age might
explain in part this negative finding.


Microalbuminuria and hyperfiltration in subjects with nephro-urological disorders
Francois Cachat MD
Department of Pediatrics, Division of Pediatric Nephrology, University Hospital, Lausanne, Switzerland
(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?

• Microalbuminuria should not be used to suspect or detect hyperfiltration in children with chronic
nephro-urological disorders.

• Hemodialysis.com: What recommendations do you have for future research as a result of this
study?

• It would be interesting to study subjects with a single kidney at a much later age, to see if they
finally develop microalbuminuria in relation to a high filtration rate.
Also, adult kidney donors would be interesting to study: adults might react differently to an acute
loss of nephron than children with congenital anomalies.

• Reference:
• Microalbuminuria and hyperfiltration in subjects with nephro-urological disorders
Francois Cachat, Christophe Combescure, Hassib Chehade, Gregory Zeier, Dolores Mosig, Blaise
Meyrat, Peter Frey, and Eric Girardin
Microalbuminuria and hyperfiltration in subjects with nephro-urological disorders Nephrol. Dial.
Transplant. first published online December 6, 2012 doi:10.1093/ndt/gfs494


Serum Adiponectin Levels and Mortality after Kidney Transplantation
Ahsan Alam, MD, CM, MS, FRCP(C)
Assistant Professor of Medicin Division of Nephrology
McGill University Health Centre - Royal Victoria Hospital Montreal, Quebec, Canada H3A 1A1


• Our study examined the association of an adipose-tissue derived hormone, adiponectin, on clinical
outcomes in prevalent kidney transplant recipients.
We found plasma levels of adiponectin to be associated with a 44% increase hazard for all-cause mortality in a
large cohort of prevalent, stable kidney transplant recipients.
This association was independent of estimated GFR and many conventional cardiovascular risk factors.


• Adiponectin has been identified to have anti-inflammatory and cardioprotective properties in healthy
individuals, although patients with CKD and on hemodialysis exhibit a paradoxical risk relationship where higher
levels are associated with adverse outcomes.
In stable kidney transplant recipients with partial restoration of kidney function we found this this protective
role was not re-established. Instead, all-cause mortality was higher in those with higher plasma adiponectin
levels.
Interestingly, death-censored graft failure was not associated with adiponectin.
Also, in our study we did not find the risk of adiponectin on all-cause mortality was accounted for by markers of
malnutrition or inflammation.


Serum Adiponectin Levels and Mortality after Kidney Transplantation
Ahsan Alam, MD, CM, MS, FRCP(C)
Assistant Professor of Medicin Division of Nephrology
McGill University Health Centre - Royal Victoria Hospital Montreal, Quebec, Canada H3A 1A1
(cont)


• Over the past several decades, advances in immunosuppression management have led to improved early graft and patient outcomes.
Nevertheless, the burden of cardiovascular mortality remains a central long-term challenge in this population. Attention should be placed on non-
traditional cardiovascular risk factors.
Adiponectin, a non-traditional atherosclerotic risk factor in those with kidney disease, may help to identify individuals at a higher risk of all-cause
mortality after kidney transplantation.

• Hemodialysis.com: What recommendations do you have for future research as a result of this study?

• It remains unclear from our study whether plasma adiponectin levels are indeed pathologic or simply a biomarker for increased mortality after
kidney transplantation.
Factors that modulate plasma adiponectin levels and its relationship with other novel biomarkers should be explored.
Whether modifying adiponectin levels could represent a therapeutic target or directly alter patient outcomes remains to be determined in future
clinical studies and trials.

• Reference:
• Serum Adiponectin Levels and Mortality after Kidney Transplantation.
Alam A, Molnar MZ, Czira ME, Rudas A, Ujszaszi A, Kalantar-Zadeh K, Rosivall L, Mucsi I.
Division of Nephrology, McGill University Health Centre, Montreal, Quebec, Canada;, †Institute of Pathophysiology and, ‡Institute of Behavioral
Sciences, Semmelweis University, Budapest, Hungary;, §Harold Simmons Center for Chronic Disease Research & Epidemiology, University of
California Irvine Medical Center, Irvine, California; Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California;,
‖Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada, ¶Division of
Nephrology & Hypertension, University of California Irvine Medical Center, Orange, California.
Clin J Am Soc Nephrol. 2012 Dec 6. [Epub ahead of print]


Cost effectiveness of the interferon-γ release assay for tuberculosis
screening of hemodialysis patients
Hemodialysis.com Author Interview: Akiko Kowada, MD, PhD
Kojiya Haneda Healthcare Service, Ota City Public Health Office, Tokyo, Japan

• The interferon-gamma release assay (IGRA) yields greater benefits
at a lower cost than tuberculin skin test and chest x-ray examination
for the tuberculosis screening of hemodialysis patients.

• The cost-effectiveness was not sensitive to the rates of latent
tuberculosis infection and active tuberculosis in dialysis patients.

• Clinicians should recommend the IGRA for tuberculosis screening of
hemodialysis patients on the basis of the cost-effectiveness, as well
as its superior sensitivity and specificity, instead of tuberculin
skin test and chest x-ray examination.

• Future research is needed to evaluate the results of this cost
effectiveness by using the data of prospective cohort studies in
dialysis patients.

• Reference:
• Cost effectiveness of the interferon-γ release assay for tuberculosis screening of hemodialysis patients
Akiko Kowad Nephrol. Dial. Transplant. first published online December 13, 2012 doi:10.1093/ndt/gfs479


Reliability of Blood Pressure Parameters for Dry Weight Estimation in Hemodialysis Patients
Hemodialysis.com Authors' Interview:
Paweena Susantitaphong, MD Prof. Somchai Eiam-Ong, MD
Division of Nephrology, Department of Medicine,
Faculty of Medicine, King Chulalongkorn Memorial Hospital,
Chulalongkorn University Bangkok, Thailand

• Hemodialysis.com Editor Marie Benz: What is the Study Purpose?
• Chronic volume overload resulting from interdialytic weight gain and inadequate fluid removal
plays a significant role in poorly controlled high blood pressure (BP) in hemodialysis (HD)
patients. There was a direct relationship between decreased body weight and reduced BP during
follow-up. Clinical judgment could lead to over- or under-estimation of dry weight (DW).
Bioimpedance analysis (BIA) has been introduced for accurately assessing the ideal DW.
Because of the limited availability of BIA instrument, it is of interest to determine the role of BP
parameters in assessing hydration status. Therefore, we examined the correlation between the
hydration status measured by BIA and BP parameters. Extracellular water/total body water
(ECW/TBW) determined by sum of segments from BIA was utilized as an index of hydration
status.

• Hemodialysis.com: What are the main findings of the study?
• Pre-dialysis ECW/TBW was significantly correlated with only pulse pressure (PP) whereas
post-dialysis ECW/TBW had significant correlations with PP, systolic blood pressure (SBP), and
diastolic blood pressure (DBP).
ECW/TBW was used to classify the patients into normohydration (£0.4) and overhydration
(>0.4) groups. SBP, mean arterial pressure, and PP significantly reduced after dialysis in
normohydration group but did not significantly change in overhydration group. Pre-dialysis PP,
post-dialysis PP, and post-dialysis SBP in overhydration group were significantly higher than
normohydration group.


Reliability of Blood Pressure Parameters for Dry Weight Estimation in Hemodialysis Patients
Paweena Susantitaphong, MD Prof. Somchai Eiam-Ong, MD
Division of Nephrology, Department of Medicine,
Faculty of Medicine, King Chulalongkorn Memorial Hospital,
Chulalongkorn University Bangkok, Thailand
(cont)

• Achieving actual DW is the goal standard of HD care. Frequent and continuous DW assessments are of important
concerns. Due to the efficacy, simplicity, and cost reason, bed-side intervention such as monitoring of BP
parameters, especially PP, might be an alternative option in determining hydration status in HD patients.
In special population groups such as elderly and diabetes patients that might have non-volume factors, however,
it should be cautious to use these BP parameters alone to assess hydration status.


• The strength of the present study is the use of the bed-side intervention as BP parameters which are
simple and inexpensive to help the clinicians in assessing hydration status in HD patients. However, some
limitations should be emphasized.
1) we did not examine the long-term effect of fluid removal on BP parameters as well as hard outcomes such as
cardiovascular morbidity and mortality.
2) The exact cut-off value of ECW/TBW to determine the normohydration in HD patients is still unestablished.
Finally, the sample size was quite small, calling for the design of the larger sample size, randomized controlled
trials with long-term follow up.

• Reference:
• Reliability of Blood Pressure Parameters for Dry Weight Estimation in Hemodialysis Patients


Intravenous ferric carboxymaltose versus standard medical care in the treatment of iron deficiency anemia in patients with chronic kidney
disease: a randomized, active-controlled, multi-center study
Chaim Charytan, M.D.
Director, Nephrology, New York Hospital Medical Center of Queens, Flushing, NY,
Adjunct Clinical Professor of Medicine at Weill Medical College of Cornell University


• In this study, we evaluated Ferric carboxymaltose (FCM), a stable, iron formulation that does not
contain dextran or dextran derivatives. FCM was developed for rapid IV administration in high
doses.
The population studied had either hemodialysis dependent or nondialysis dependent chronic
kidney disease (HD-CKD or NDD-CKD).
We provided evidence that rapid administration of FCM in doses of 200 mg for HD-CKD patients
and up to 1000 mg in NDD-CKD patients were well tolerated and displayed comparable efficacy to
other IV iron formulations.


• There were no surprises in this study, in that the results were consistent with other studies
supporting the safety and efficacy of FCM in subjects with Iron Deficiency Anemia in the setting
of CKD as well as other clinical settings (including gastrointestinal disease, heavy uterine
bleeding, and the postpartum period).
We feel it is important for practitioners to have access to data comparing the safety of this new IV
iron formulation (FCM) to other available iron formulations.


Intravenous ferric carboxymaltose versus standard medical care in the treatment of iron deficiency anemia in patients with chronic kidney
disease: a randomized, active-controlled, multi-center study
Chaim Charytan, M.D.
Director, Nephrology, New York Hospital Medical Center of Queens, Flushing, NY,
Adjunct Clinical Professor of Medicine at Weill Medical College of Cornell University
(Cont)


• Currently available IV irons vary in indication, dosing regimens and safety profiles. Maximum doses given in a
single visit is limited by the in vivo stability of the iron-carbohydrate moieties.
In addition, the use of IV iron can be limited by anaphylactic reactions.
FCM, a non-dextran iron, was developed for rapid IV administration in high doses and in this study, FCM was
well tolerated and efficacious when compared to standard medical care.

• Since FCM can be given in high doses, FCM is well suited for outpatient use.
A cost-effectiveness analysis would be interesting since FCM will require fewer clinical visits and venipunctures.
In addition studies evaluating effect on number of transfusion required and patient reported measures of
quality of life would be interesting.

• Reference:
• Intravenous ferric carboxymaltose versus standard medical care in the treatment of iron deficiency anemia in
patients with chronic kidney disease: a randomized, active-controlled, multi-center study
Nephrol. Dial. Transplant. first published online December 5, 2012 doi:10.1093/ndt/gfs528


Pentraxin 3, a Sensitive Early Marker of Hemodialysis-Induced Inflammation
Peter Bárány, MD, PhD
Renal Medicine, K56
Karolinska University Hospital Huddinge
SE–141 86 Stockholm (Sweden)


• Pentraxin 3 (PTX-3) is a sensitive marker of inflammation.
During hemodialysis, PTX-3 start to rise during the first hour and peaks at 180 minutes. The levels
of CRP and IL-6 did not change during dialysis and TNF-alpha concentrations decreased.
The effect of changing membrane from low-flux to high-flux or changing from hemodialysis to
hemodiafiltration had no significant effect on the intra-dialytic increase in PTX-3 levels.

• The rapid response with increase of PTX-3 during the first hour was not expected.
We believe that this early rise is mediated by release of stored PTX-3 from granulae in the
circulating neutrophils.
During repeated HD sessions the individual response was very similar, i.e. the amount of released
PTX-3, as estimated by area under the curve of the concentrations, did not change.


Pentraxin 3, a Sensitive Early Marker of Hemodialysis-Induced Inflammation
Peter Bárány, MD, PhD
Renal Medicine, K56
Karolinska University Hospital Huddinge
SE–141 86 Stockholm (Sweden)
(Cont)


• Sensitive methods are necessary to detect hemodialysis-induced inflammatory activity. PTX-3 is a
sensitive marker, but its role in the acute phase response and effect on the vasculature is not
clear.

study?

• PTX-3 appears to be a marker of endothelial dysfunction so it may be logical to follow-up with
studies of the effect of hemodialysis on the endothelium and the relationship to neutrophil
activation and PTX-3 release.

• Reference:
• Pentraxin 3, a Sensitive Early Marker of Hemodialysis-Induced Inflammation
• Sjöberg B, Qureshi AR, Anderstam B, Alvestrand A, Bárány P.
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and
Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Blood Purif. 2012 Dec 7;34(3-4):290-297. [Epub ahead of print]


Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome
Dr. Bart is Chief of Cardiology at Hennepin County Medical Center.
He is also the director of clinical programs including nuclear cardiology, EECP (enhanced external counterpulsation for the treatment of severe
angina), therapeutic hypothermia for the treatment of cardiac arrest survivors, and ultrafiltration for advanced heart failure at Hennepin
County Medical Center.


• The main result of CARRESS HF was that in patients with decompensated heart failure, worsened renal function and persistent congestion, an
aggressive diuretic-based stepped pharmacologic care algorithm was superior to ultrafiltration for change in creatinine 96 hours after enrollment
with similar weight loss. Creatinine increased by 0.23 mg/dL in the ultrafiltartion group at 96 hours and this increase in creatinine was transient.
In addition, rates of complete clinical decongestion were very low in both groups (10%) and clinical outcomes were poor with nearly 40% of
patients experiencing death or heart failure readmission within 60 days of enrollment.


• The transient increase in creatinine in the ultrafiltration group was
unexpected. One possible explanation for this is an overly aggressive
ultrafiltration prescription resulting in transient intravascular volume
depletion. However, there are few objective measures to support this
possibility - there was no drop in blood pressure or increase in heart
rate, there was no hemoconcentration measured by change in hemoglobin, there was no change in other measures of kidney function such as
eGFR, cystatin C or NGAL. Another possible explanation is the extensive use of IV diuretics in the ultrafiltration group.
Nine percent of the patients in the ultrafiltration group received IV diuretics instead of ultrafiltration and 30% of patients who did receive
ultrafiltration were treated with IV diuretics after the completion of ultrafiltration.

The presence of ischemic heart disease could also explain the unexpected finding of an increase in creatinine in the ultrafiltration group.
There were more patients with ischemic cardiomyopathy in the
ultrafiltration group. These patients had undergone more heart
catheterizations and revascularization procedures - repeated insults to the kidney not experienced by the pharmacologic care group. The
presence of atherosclerosis, the increased probability of renovascular
disease, and repeated exposures to catheterization and IV radiocontrast material could have predisposed patients in the ultrafiltration group to
be more susceptible to acute kidney injury during volume reduction therapies.


Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome
Dr. Bart is Chief of Cardiology at Hennepin County Medical Center.
He is also the director of clinical programs including nuclear cardiology, EECP (enhanced external counterpulsation for the treatment of severe
angina), therapeutic hypothermia for the treatment of cardiac arrest survivors, and ultrafiltration for advanced heart failure at Hennepin
County Medical Center.
(Cont)


• The most striking finding in CARRESS HF is the large unmet need among patients with decompensated heart failure, worsened renal function, and
persistent congestion.

• Success in relieving congestion is severely limited and the rates of death and rehospitalization continue to be unacceptably high. Small, transient
increases in creatinine are probably not a useful clinical surrogate and more research in the area of acute decongestion strategies is needed.


• Clinical decongestion is an important treatment goal with a large, unmet need.

• Termination conditions need to be better defined for patients
• undergoing acute decongestion treatment (phamacologically or with extracorporal techniques).
•

• Improved technologies and better understanding of ultrafiltration prescription will lead to better patient outcomes.
• Reference:
• Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome
• Bradley A. Bart, M.D., Steven R. Goldsmith, M.D., Kerry L. Lee, Ph.D., Michael M. Givertz, M.D., Christopher M. O'Connor, M.D., David A. Bull, M.D.,
Margaret M. Redfield, M.D., Anita Deswal, M.D., M.P.H., Jean L. Rouleau, M.D., Martin M. LeWinter, M.D., Elizabeth O. Ofili, M.D., M.P.H., Lynne W.
Stevenson, M.D., Marc J. Semigran, M.D., G. Michael Felker, M.D., Horng H. Chen, M.D., Adrian F. Hernandez, M.D., Kevin J. Anstrom, Ph.D., Steven E.
McNulty, M.S., Eric J. Velazquez, M.D., Jenny C. Ibarra, R.N., M.S.N., Alice M. Mascette, M.D., and Eugene Braunwald, M.D. for the Heart Failure
Clinical Research Network

• November 6, 2012DOI: 10.1056/NEJMoa1210357


Comparison and clinical suitability of eight prediction models for cardiac surgery-related acute kidney injury
Peter Pickkers, M.D., Ph.D and Harmke Dorien Kiers
Department of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen,the Netherlands
Department of Cardiothoracic Surgery, Radboud University Nijmegen Medical Centre, Nijmegen,the Netherlands

• Hemodialysis.com Editor Marie Benz: What are the main findings of the
study?

• We analyzed eight different models that were designed to predict Acute
Kidney Injury and/or renal replacement therapy after cardiac surgery.
We found that the model of Thakar offered the best prediction on risk of
Acute Kidney Injury and dialysis.


• Not al models were widely applicable; some were not designed to
predict the risks of AKI and/or dialysis for all patient categories, and in
some models postoperative data was needed, making them not useful in
the pre-operative setting.


(cont)


• The model of Thakar is an easy to use tool which can be used in the pre-operative setting, it uses only variables
that are readily available in the pre-operative setting; so extra diagnostics are not needed.
When the score on this model is high, the risk of postoperative acute kidney injury or dialysis is increased. In
these patients, additional attention and monitoring of renal function may be beneficial.


• Knowing which patients are at risk of acute kidney injury and dialysis post-cardiac surgery is the first step
towards finding strategies to protect this group. Up to now, there are no known pharmacological or other
techniques proven to prevent these complications. However, identifying these patients will make it possible to
study new strategies on these particular high-risk patients.
The simplest way to have your interview posted is to reply to this email with your responses and I will upload
them promptly with a link to your interview.

• Reference:
• Comparison and clinical suitability of eight prediction models for cardiac surgery-related acute kidney injury
• Harmke D. Kiers, Mark van den Boogaard, Micha C.J. Schoenmakers, Johannes G. van der Hoeven, Henry A. van
Swieten, Suzanne Heemskerk, and Peter Pickkers
• Nephrol. Dial. Transplant. first published online December 4, 2012 doi:10.1093/ndt/gfs518


(cont)


• The model of Thakar is an easy to use tool which can be used in the pre-operative setting, it uses only variables
that are readily available in the pre-operative setting; so extra diagnostics are not needed.
When the score on this model is high, the risk of postoperative acute kidney injury or dialysis is increased. In
these patients, additional attention and monitoring of renal function may be beneficial.


• Knowing which patients are at risk of acute kidney injury and dialysis post-cardiac surgery is the first step
towards finding strategies to protect this group. Up to now, there are no known pharmacological or other
techniques proven to prevent these complications. However, identifying these patients will make it possible to
study new strategies on these particular high-risk patients.
Reference:
• Comparison and clinical suitability of eight prediction models for cardiac surgery-related acute kidney injury
• Harmke D. Kiers, Mark van den Boogaard, Micha C.J. Schoenmakers, Johannes G. van der Hoeven, Henry A. van
Swieten, Suzanne Heemskerk, and Peter Pickkers


Cause-Specific Excess Mortality Among Dialysis Patients: Comparison With the General Population in Japan
Minako Wakasugi, M.D., M.P.H., Ph.D.
Specially Appointed Assistant Professor
Center for Inter-organ Communication Research, Niigata University Graduate School of Medical and Dental Sciences
Asahimachi 1-757, Chuo-ku, Niigata 951-8510, JAPAN

• Hemodialysis.com Editor Marie Benz: What are the main findings of the
study?

• The age-adjusted mortality rate difference between dialysis patients and
the general population for cardiovascular diseases was similar to that for
non-cardiovascular diseases, indicating that preventing both
cardiovascular and non-cardiovascular deaths is important for decreasing
all-cause mortality among Japanese dialysis patients.


• Mortality due to accidental death was similar between dialysis patients
and the general population.
Because Japan experienced many different natural disasters during the
study period, Japanese disaster relief activity might protect dialysis
patients against mortality from these natural disasters.


Cause-Specific Excess Mortality Among Dialysis Patients: Comparison With the General Population in Japan
Minako Wakasugi, M.D., M.P.H., Ph.D.
Specially Appointed Assistant Professor
Center for Inter-organ Communication Research, Niigata University Graduate School of Medical and Dental Sciences
Asahimachi 1-757, Chuo-ku, Niigata 951-8510, JAPAN
(cot)


• There is still significant room for improvement in life prognosis for dialysis patients.
Preventing not only cardiovascular but also non-cardiovascular deaths is important.

study?
Because excess mortality in dialysis patients differed with cause of death, cause-specific mortality
studies should be planned to improve life expectancies of dialysis patients.

• Reference:
• Cause-Specific Excess Mortality Among Dialysis Patients: Comparison With the General
Population in Japan
Wakasugi, M., Kazama, J. J., Yamamoto, S., Kawamura, K. and Narita, I. (2012), Cause-Specific Excess
Mortality Among Dialysis Patients: Comparison With the General Population in Japan. Therapeutic
Apheresis and Dialysis. doi: 10.1111/j.1744-9987.2012.01144.x


The Relationship between Red Cell Distribution Width with Erythropoietin Resistance in Iron Replete Hemodialysis Patients
Baris Afsar,
Ass. Prof of Nephrology
Department of Medicine, Division of Nephrology, Konya Numune State Hospital, Konya, Turkey--


• The main and novel finding of the study is the independent relationship between red cell distribution width and
epo resistance.

• Known factors such as inflammation, albumin and PTH did not related with epo resistance as an unexpected
finding.

• Should search for novel factors such as red cell distribution width for the epo resistance.

• Studies are needed to confirm and understand the underlying mechanism regarding RDW and EPO resistance.

• Reference:
• The Relationship between Red Cell Distribution Width with Erythropoietin Resistance in Iron Replete Hemodialysis
Patients
Baris Afsar , Mustafa Saglam , Cetin Yuceturk , Erhan Agca
European Journal of Internal Medicine, In Press, Corrected Proof, Available online 12 December 201


Associations among nocturnal sleep, daytime intradialytic sleep, and mortality risk in patients on daytime conventional hemodialysis: US
Renal Data System special study data
Donald L. Bliwise, Ph.D.
Professor of Neurology, Psychiatry and Behavioral Sciences, and Nursing, Director, Program in Sleep, Aging and Chronobiology,
Emory University School of Medicine, Atlanta, Georgia 30329


• The main finding from this study was that, even after controlling for many other
variables that are known to be associated with earlier mortality in patients with
renal disease, sleep (and more specifically a longer reported duration of sleep)
appeared to be an important correlate of survival.


• Yes and no. In our experience, nephrologists do not generally consider sleep,
sleep disturbance, sleep duration, or intra-dialytic sleep to be nearly as important
as comorbid diseases (e.g., obesity, albumin, adequacy of dialysis) when
discussing survival of ESRD patients. To the extent that we found that sleep was
important, this may be surprising to some.
As we point out in the Introduction, there is certainly ample literature from non-
dialysis populations to suggest that sleep durations, and possibly napping as well,
are important factors associated with mortality. In that sense, the results were
not at all unexpected to us.


Associations among nocturnal sleep, daytime intradialytic sleep, and mortality risk in patients on daytime conventional hemodialysis: US
Renal Data System special study data
Donald L. Bliwise, Ph.D.
Professor of Neurology, Psychiatry and Behavioral Sciences, and Nursing, Director, Program in Sleep, Aging and Chronobiology,
Emory University School of Medicine, Atlanta, Georgia 30329
(cont)

• At this point, it is far too premature to make recommendations for patient care regarding what should and should not be done in terms of an
individual patient’s treatment plan involving sleep. We would certainly agree with the suggestion, however, that physicians must be more aware
of these issues in their patients. For example, a patient sleeping excessively during the night (and perhaps during HD as well) should be evaluated
for specific sleep disorders, such as obstructive sleep apnea (OSA) or restless legs syndrome (RLS), that may be contributing to their high total
amounts of sleep.
Conditions such as OSA and RLS can be effectively and safely treated in a number of pharmacologic and occasionally non-pharmacologic
approaches in HD patients.


• There are many avenues for future research. First, it must be recalled that our data are all based on patients’ reports of their own sleep—not
objective measurements of sleep (i.e., polysomnography).
In order to achieve a more accurate rendering of such apparent tendencies, objective measurements should be made. Secondly, before
implementing routine changes in patient care, carefully performed interventional trials would be required, perhaps shortening sleep durations
(both nocturnally and perhaps intra-dialytically, as well) to determine whether there was any benefit.
Finally, any future study manipulating sleep in HD patients would need to appreciate fully the complex psychosocial matrix in which this basic
biologic drive occurs.
As can be seen on Table 1 of our study, HD patients are more likely to doze during HD if they have an early morning shift and/or if they are still
gainfully employed. In that sense, at least some sleep observed on the dialysis unit may well be compensatory for an inadequate amount of sleep
obtained elsewhere during the 24-hour day. Obviously, there may be many reasons that HD patients sleep or otherwise elect to sleep while they
dialyze. The best way to start to understand this phenomenon is to start to study it and collect data about it. To date, the number of studies that
have done this even descriptively could be summarized on a page not much longer than the one this is printed on.
• Reference:
• Associations among nocturnal sleep, daytime intradialytic sleep, and mortality risk in patients on daytime conventional hemodialysis: US Renal
Data System special study data
Kutner, N., Zhang, R., Johansen, K. and Bliwise, D. (2012), Associations among nocturnal sleep, daytime intradialytic sleep, and mortality risk in
patients on daytime conventional hemodialysis: US Renal Data System special study data. Hemodialysis International. doi: 10.1111/hdi.12005


Obesity and Kidney Transplant Candidates: How Big Is Too Big for Transplantation
Krista L. Lentine, MD, MS
Associate Professor of Medicine
Saint Louis University Center for Outcomes Research
& Department of Medicine/Division of Nephrology

• The obesity epidemic has not spared the ESRD population.
In the United States, the prevalence of obesity among kidney transplant recipients increased from 23 to 33% in the past decade. Obesity impacts
many inter-related considerations for transplant practice including candidate selection, outcomes prediction before and after transplant, and
waitlist management.
Our article describes an approach for applying available data on the importance of body composition to the kidney transplant population that
separates implications for candidate selection, risk stratification among selected candidates, and interventions to optimize health of the
individual


• Competing concerns and a lack of randomized evidence on obesity management has led to widely varying BMI limits for candidate selection
across transplant centers.
With respect to the question of appropriate thresholds for candidate listing, markers of increased adiposity (including BMI and waist
circumference) are associated with worse posttransplant outcomes (e.g. DGF, graft failure, cardiac disease, high costs) compared with ideal body
composition in most studies. However, current data have not identified limits of body composition that preclude clinical benefit from kidney
transplant compared to continued waiting on dialysis.

Regarding prognostication, BMI frequently shows ‘reverse’ associations with dialysis survival. But, as noted above, compared to recipients with
normal BMI, kidney transplant recipients with elevated BMI appear in many studies to face increased risk of adverse outcomes. Notably, BMI is a
surrogate measure of adiposity, and prediction may improve when combined with other measures, such as waist circumference and measures of
muscle mass.
With respect to the management of obese transplant candidates, observational studies have not shown benefits among dialysis patients who lost
weight before transplant. However, association studies cannot distinguish intentional from unintentional weight loss as a result of illness and
comorbidity, and offer little guidance on potential benefits of purposeful weight reduction.


Obesity and Kidney Transplant Candidates: How Big Is Too Big for Transplantation
Krista L. Lentine, MD, MS
Saint Louis University Center for Outcomes Research
& Department of Medicine/Division of Nephrology
(cont)

• Pending more urgently needed research, the answer to ‘How big is too big for transplant?’ is that it appears to depend on the experience and risk
tolerance of the individual transplant center at this time.

• A main objective of our report is to remind future investigators in the broad field of transplant obesity to be explicit about the purpose and scope
of inferences from a particular study. We encourage research relevant to the following topic areas as follows:
• Candidate selection.

• Defining whether there are limits of body composition that preclude clinical benefit from kidney transplant compared to continued dialysis.
• Formal cost-effectiveness studies, including appropriate quality of life adjustments that capture impact of complications, to determine if payers
and society should be compensating centers for clinical and financial risks of transplanting obese ESRD patients
• Risk stratification among selected candidates.

• Defining practical measures of body composition that refine accuracy for outcomes prediction, including attention to subgroups
• Interventions to optimize health of the individual
• Prospective evaluations of the impact of intentional weight loss efforts among obese ESRD patients including dietary changes, monitored exercise
programs, and bariatric surgery.

• Reference:
•
Obesity and Kidney Transplant Candidates: How Big Is Too Big for Transplantation.
• Lentine KL, Delos Santos R, Axelrod D, Schnitzler MA, Brennan DC, Tuttle-Newhall JE:
Am J Nephrol 2012;36:575-586 (DOI: 10.1159/000345476)


BK polyoma virus nephropathy in the native kidney
Hemodialysis.com Author Interview: Dr Shree Gopal Sharma
Shree G Sharma, M.D.
Assistant Professor of Pathology
University of Arkansas for Medical Sciences
Little Rock, AR


• The present series describes the risk factors and clinical course of polyoma virus nephropathy
(PVN) in the native kidney. All 8 of our cases had an immunocompromised state, including 6
patients with hematological malignancies, 1 with double lung transplant for cystic fibrosis and 1
with diabetes and tuberculosis. In addition, 3 of the patients with hematologic malignancy had
undergone bone marrow transplant (2 allo- and 1 haploidentical) for which they were receiving
antirejection immunosuppressive therapy for up to 4 years. The patients were all male,
predominantly Caucasian, and varied in age from young to elderly (mean 47.4 yr; range 16-66 yr).
From these data and our review of 18 cases reported in the literature, we conclude that patients
with hematologic malignancy and non-renal organ transplants are particularly at risk for
development of PVN in the native kidney.


• BK polyoma virus nephropathy is not commonly thought outside the setting of renal
transplantation. It is reported in patients with other organ transplants. Two of the patients
reported in the series had unusual combination of diseases. One patient was without
hematological malignancy or organ transplant had both diabetes mellitus and tuberculosis as
potential predisposing conditions to an immunocompromised state, a combination that has not
been reported previously as associated with PVN. The other patient with chronic lymphocytic
leukemia had BK PVN and subsequently also developed progressive multifocal
leukoencephalopathy due to JC virus. To our knowledge this is the first such reported case.


BK polyoma virus nephropathy in the native kidney
Hemodialysis.com Author Interview: Dr Shree Gopal Sharma
Shree G Sharma, M.D.
Assistant Professor of Pathology
University of Arkansas for Medical Sciences
Little Rock, AR
(cont)

• A high level of suspicion in immunocompromised patients is needed to diagnose PVN in an early stage that may
respond more favorably to antiviral therapy.


• As the number of solid organ transplants continues to rise, the incidence of renal dysfunction in this population
has also increased. It will be important to distinguish the rare development of PVN in this population from the
more common situation of BKV activation. These outcome data underscore importance of careful screening and
prompt use of a renal biopsy for early detection of PVN involving the native kidney in at risk patients with
hematologic malignancies and/or organ transplants who develop AKI. Ideally, monitoring of at risk patients with
urinary decoy cell screening, serum PCR assays for BKV and renal functional studies coupled with the judicious
use of renal biopsy are potential strategies for earlier detection. Greater awareness of the potential
development of PVN in the native kidney is needed to avoid under-recognition of this newly emerging entity.

• Reference:
• BK polyoma virus nephropathy in the native kidney
• Shree G. Sharma, Volker Nickeleit, Leal C. Herlitz, Anne K. de Gonzalez, Michael B. Stokes, Harsharan K. Singh,
Glen S. Markowitz, and Vivette D. D'Agati


Multivessel coronary artery bypass grafting versus percutaneous coronary intervention in ESRD
Dr. Tara I. Chang MD
Stanford University,
Division of Nephrology, Palo Alto, CA 94304

• Hemodialysis.com Editor Marie Benz: What is the background of the study?
•
The study included patients (n=21,981) from the United States Renal Data System, a database of
all patients on dialysis in the United States with primary Medicare coverage. Patients received
initial coronary revascularization with either multivessel CABG or PCI between 1997 and 2009 and
had at least 6 months of prior Medicare coverage as their primary payer.
Overall, 5-year survival for patients was low — 22% to 25% — regardless of revascularization
strategy. Multivariable-adjusted proportional hazards regression analysis revealed that CABG
compared with PCI led to a significantly lower risk for all-cause death (HR=0.87; 95% CI, 0.84-
0.90) and the composite of all-cause death or MI (HR=0.88; 95% CI, 0.86-0.91). Results were
similar in analyses using a propensity score-matched cohort.


• We found that in a cohort of more than 20,000 patients with multivessel coronary disease who
were on dialysis, CABG was associated with 10-16% lower rate of all-cause death when compared
with PCI. However, the overall mortality rates were very high in this cohort, with 5-year life
expectancy of only 22-25%, irrespective of revascularization strategy.


Multivessel coronary artery bypass grafting versus percutaneous coronary intervention in ESRD
Dr. Tara I. Chang MD
Stanford University,
Division of Nephrology, Palo Alto, CA 94304
(cont)


• We were surprised to see that the overall mortality rates had not improved over the past 15-20
years in this population.

• It is important to note that because our study was observational, our results cannot prove that
CABG is better. But our study suggests that in carefully selected patients on dialysis with
multivessel coronary disease, CABG may be preferred rather than PCI.

• Reference:
• Multivessel coronary artery bypass grafting versus percutaneous coronary intervention in ESRD
Chang TI, Shilane D, Kazi DS, Montez-Rath ME, Hlatky MA, Winkelmayer WC.
Stanford University, Division of Nephrology, 780 Welch Road Suite 106, Palo Alto, CA 94304.
J Am Soc Nephrol. 2012 Dec;23(12):2042-9. doi: 10.1681/ASN.2012060554.


Anti-glomerular basement membrane antibody disease is an uncommon cause of end-stage renal disease
Professor David Johnson
MB BS (Hons), FRACP, PhD (Syd), PSM
Director, Metro South and Ipswich Nephrology & Transplant Services (MINTS)
Professor of Medicine (University of Queensland)


• This retrospective, multi-centre, multi-country registry analysis examined the outcomes of 449
end-stage renal disease (ESRD) patients with anti-glomerular basement membrane antibody
(anti-GBM) disease compared to 57,973 patients with ESRD due to other causes, using data from
the Australian and New Zealand Dialysis and Transplant (ANZDATA) Registry.
We found that anti-GBM disease was associated with comparable dialysis survival, renal
transplant patient survival and renal allograft survival, although it was associated with an
increased probability of recovery of dialysis-independent renal function.
In addition, older age and a history of pulmonary haemorrhage in patients with anti-GBM disease
was associated with an increased risk of mortality on dialysis.


• The outcomes of patients with ESRD due to anti-GBM disease have been uncertain until now
because the rarity of anti-GBM disease as a cause of ESRD has impeded the study of outcomes of
this condition once renal replacement therapy has commenced.


Anti-glomerular basement membrane antibody disease is an uncommon cause of end-stage renal disease
Professor David Johnson
MB BS (Hons), FRACP, PhD (Syd), PSM
Director, Metro South and Ipswich Nephrology & Transplant Services (MINTS)
Professor of Medicine (University of Queensland)
(Cont)

• Anti-GBM disease is an uncommon cause of ESRD.
Patients with anti-GBM disease who commence renal replacement therapy can expect similar
dialysis and transplant outcomes (in terms of patient survival and renal allograft survival) to the
remaining patients with other causes of ESRD.
Older age and a history of pulmonary haemorrhage are associated with poorer survival of
patients with anti-GBM disease on dialysis.

study?
• Comparison of anti-GBM ESRD patient outcomes with those of other national registries would be
useful.

• Reference:
• Anti-glomerular basement membrane antibody disease is an uncommon cause of end-stage renal
disease
• Wen Tang, Stephen P McDonald, Carmel M Hawley, Sunil V Badve, Neil C Boudville, Fiona
G Brown, Philip A Clayton, Scott B Campbell, Janak R de Zoysa and David W Johnson
Kidney Int advance online publication, December 19, 2012; doi:10.1038/ki.2012.375


Timing of dialysis initiation in AKI in ICU: international survey.
Charuhas V. Thakar, MD, FASN
Division of Nephrology and Hypertension University of Cincinnati Cincinnati OH 4526

• Our analysis of survey of nephrologists found that severity of illness in ICU patients with AKI
influences the timing of dialysis initiation. So, survey respondents were more likely to initiate
early dialysis in case scenarios portraying higher severity of illness. Whether early dialysis
initiation in a higher severity of illness group would modify their outcome remains to be
examined.
Also, the study found that decision to initiate dialysis in ICU patients with AKI is still largely driven
by imminent indications of dialysis (e.g. hyperkalemia, or hypoxemia) rather than a proactive
decision based on degree of severity of kidney injury.

• Another important finding was that 1-in-3 respondents indicated that early dialysis could be
associated with more risk than benefit, given the present state of evidence. Additionally, we
found that despite the widespread dissemination of the information related to acute kidney
injury definitions, and the data related to severity of kidney injury and related outcome, it seems
like dialysis decisions were more heavily influenced by absolute levels of BUN or creatinine rather
than degree of elevation from baseline.

• In a way, yes, as we think that we tend to start early dialysis, but when asked objectively, the
indications are still the traditional indications of dialysis. Thus, dialysis remains a subjective
clinical decision.


Timing of dialysis initiation in AKI in ICU: international survey.
Charuhas V. Thakar, MD, FASN
Division of Nephrology and Hypertension University of Cincinnati Cincinnati OH 4526
(cont)

• Hemodialysis.com: What should clinicians and patients take away from your
report?
• Until we have prospective clinical trials, timing of dialysis will remain a subjective
decision, one that is dependent on several factors including severity of illness.
Whether our decisions modify outcome is unclear.

• Hemodialysis.com: What recommendations do you have for future research as a
result of this study?
• We recommend that prospective trials are needed to come to a consensus in this
area. Also, we may have to stratify patients based on expected mortality/severity
of illness when such trials are designed, otherwise, interventions such as early
dialysis may not necessarily modify hard endpoints.

• Reference:
• Timing of dialysis initiation in AKI in ICU: international survey.
Thakar CV, Rousseau J, Leonard AC.
Crit Care. 2012 Dec 19;16(6):R237. [Epub ahead of print]


Comparison of the glomerular filtration rate in children by the new revised Schwartz formula and a new generalized formula
Dr Hassib Chehade
Médecin associé
Service de néphrologie pédiatrique


• This study is the first one to describe a precise cutoff for the validity of the new revised Schwartz formula, and leads to deriving a new generalized
Quadratic formula applicable for all glomerular filtration rate (GFR) values, and also to children with failure to thrive.


• When we conducted this study, we aimed to provide additional data that assess the accuracy of the revised Schwartz formula by using another
gold standard method of GFR measurement, i.e. inulin clearance, in a cohort of children with renal failure, and also in children with normal renal
function or even with supra-normal GFR.
What we found out was very interesting: The new Quadratic formula we developed is a tool for bedside GFR estimation in children applicable
across all GFR values.

• The new Quadratic formula assesses GFR equally well or more precisely than the new Schwartz formula and allows pediatricians to have a more
precise estimation of high GFR values particularly in cases of hyperfiltration.
A more precise GFR estimation will lead to a proper classification of the patients’ chronic kidney disease stages for appropriate treatment.
• We recommend conducting further studies to perform an external validation of the new Quadratic formula in other pediatric population groups
and also assess the accuracy of this formula in adults.

• Reference:
• Comparison of the glomerular filtration rate in children by the new revised Schwartz formula and a new generalized formula
• Anja Gao, Francois Cachat, Mohamed Faouzi, Daniel Bardy, Dolores Mosig, Blaise-Julien Meyrat, Eric Girardin and Hassib Chehade
• Kidney Int advance online publication, December 19, 2012; doi:10.1038/ki.2012.388


Evaluation of Potential Renal Transplant Recipients With Computed Tomography Angiography
Matthew Cooper, MD
Director, Kidney and Pancreas Transplantation
Medstar Georgetown Transplant Institute
Washington, DC 20007
(cont)


• The concern for contrast-induced nephropathy or overt renal failure in patients who are
considered for CT studies has limited its use in what may be a greatly valued test for clinical (or
surgical) decision-making.
•
• In addition to a complete history and physical exam, this study indicated the value of a limited-
contrast enhanced CT for all potential recipients of a living donor kidney allograft.
Of the 149 patients evaluated using this technique, over 22% had a change in their original
operative plan (ie. need for additional surgery, change in operative site location, et al.) based
upon the findings on the CT scan. While not necessary in all patients, the study clearly indicates
the value of the best non-invasive testing available to plan accordingly for the risk associated with
not only the recipient transplant but also that associated with the donor nephrectomy.


• The study was not limited to potential recipients currently on dialysis. Of the total number of
patients, 42 were currently not dialysis-dependent (although all had Stage 4 or 5 CKD). None of
these patients following the administration of 100ml of Visipaque required hemodialysis
following testing and there was no change in the in the mean SCr value for this cohort compared
to pre-test values.


Evaluation of Potential Renal Transplant Recipients With Computed Tomography Angiography
Matthew Cooper, MD
Director, Kidney and Pancreas Transplantation
Medstar Georgetown Transplant Institute
Washington, DC 20007


• While clinicians should always appreciate the risk associated with all testing including contast
enhanced CT, if there is an expected benefit in its use including a potential deviation from
standard practice, the fear of contrast induced nephropathy is more lore than data-driven. With
appropriate hydration pre- and post- contrast as well as a judicious use of contrast by a
knowledgeable radiologic team, most patients will not see a nephrologic effect.
• Our study demonstrated an overall cost savings in the use of CTA for this cohort of patients.

study?

• As there will still be controversy in the use of CTA v. physical exam alone, a well-constructed
multi-center trial comparing the use of CTA in all patients v. PE alone with a careful and critical
analysis of both intra-operative complications and long-term outcomes would be warranted.

• Reference:
• Evaluation of Potential Renal Transplant Recipients With Computed Tomography Angiography
• Smith D, Chudgar A, Daly B, Cooper M.
Arch Surg. 2012 Dec 1;147(12):1114-22. doi: 10.1001/archsurg.2012.1466.


Hypothyroidism and Mortality among Dialysis Patients.
Connie Rhee, MD, MSc,
on behalf of the co-authors
Rhee CM, Alexander EK, Bhan I, Brunelli SM.


• Patients with impaired kidney function have a disproportionately higher
prevalence of hypothyroidism compared to the general population.
Although hypothyroidism has been associated with adverse cardiovascular
outcomes in non-kidney disease populations, the prognostic implications of
hypothyroidism in dialysis patients have not been well defined.
• In the general population, there has been controversy as to whether subclinical
(“mild”) hypothyroidism is associated with increased death risk, but there has
been a tendency towards positive associations in high cardiovascular risk
populations. Thus, we were surprised to find that, compared to dialysis patients
with TSH levels in the low-normal range, those with mild hypothyroidism had a
significantly higher death risk, and there was a trend towards greater death
among those with TSH levels in the high-normal range. This may potentially be
due to the high underlying cardiovascular risk in dialysis patients.


Hypothyroidism and Mortality among Dialysis Patients.
Connie Rhee, MD, MSc,
on behalf of the co-authors
Rhee CM, Alexander EK, Bhan I, Brunelli SM. (cont)


• It should be noted that because this was an observational study, we are unable to
show that there is a causal association between hypothyroidism and death in dialysis patients. However, our
findings do suggest that hypothyroidism is a negative prognostic indicator in dialysis patients.


• There are two key findings in our study that prompt future investigation. First, dialysis patients receiving
exogenous thyroid hormone with normal thyroid function at baseline (presumed to adequately-treated
hypothyroid patients) appear to have a similar mortality risk as those with spontaneously normal thyroid
function. This suggests that normalization of thyroid function with treatment may reduce mortality risk
associated with hypothyroidism, but future studies examining the effectiveness and safety of longitudinal
exogenous thyroid hormone treatment in dialysis patients are needed.
Second, we observed that adjustment for cardiovascular risk factors markedly attenuated the hypothyroidism—
mortality association. This suggests that hypothyroidism may increase mortality in dialysis patients through
cardiovascular pathways. However, future research is needed to identify possible mechanisms by which
hypothyroidism may increase death risk in dialysis patients.

• Reference:
• Rhee CM, Alexander EK, Bhan I, Brunelli SM. Hypothyroidism and Mortality among Dialysis Patients. Clin J Am Soc
Nephrol. 2012 Dec 20. [Epub ahead of print]


Hemodialysis.com Research Interviews January 5 2013

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Hemodialysis.com Research Interviews January 5 2013