Hemodialysis.com : Kidney Disease Research Interviews

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
July 9 2013
For Informational Purposes Only: Not for Specific Medical Advice.

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Toward a Wearable Portable Dialysis Machine:
Using Reusable Sorbents to Regenerate Dialysate
Hemodialysis.com Interview with Maarten Wester
Department of Nephrology and Hypertension,
University Medical Center Utrecht,|Utrecht, The Netherlands
• Hemodialysis.com Interview with Maarten Wester
Department of Nephrology and Hypertension, University Medical Center Utrecht,|Utrecht, The Netherlands
• Hemodialysis.com: What are the main findings of the study?
• Answer: Wearable or portable dialysis could provide benefit for dialysis patients by offering prolonged and
more frequent dialysis. This may be achieved by sorbent-based dialysate regeneration, by reducing the
amount of dialysate needed, thus limiting weight and size of dialysis machines.
• Our study shows that sodium polystyrene/divinylbenzenesulphonate and iron oxide hydroxide are suitable,
regenerable – and thereby reusable – sorbents for potassium and phosphate removal in dialysate
regeneration. We also showed that calcium and magnesium preloading could limit removal of these
electrolytes by the sorbents, which means that there will be no need for post sorbent cartridge infusion of
these electrolytes.
•
Hemodialysis.com: Were any of the findings unexpected?
• Answer: The tested sorbents performed surprisingly well, not only in the (static) batch binding assays but
also in the (dynamic) experiments with bovine blood. Combined with their substantial regenerability, this
may mean that relatively small amounts of sorbents will suffice to remove the daily required amounts of
potassium and phosphate.
Read the rest of the interview on Hemodialysis.com

Toward a Wearable Portable Dialysis Machine:
Using Reusable Sorbents to Regenerate Dialysate
Hemodialysis.com Interview with Maarten Wester
Department of Nephrology and Hypertension,
University Medical Center Utrecht,|Utrecht, The Netherlands
• Hemodialysis.com: What should clinicians and patients take away from this study?
• Answer: Dialysate regeneration based on toxin and excess electrolyte removal by reusable sorbents may
be the key to limiting dialysis device weight and dimensions. This offers the perspective of prolonged and
more frequent dialysis through wearable or portable devices.
• Hemodialysis.com: What recommendations do you have for future research as a result of your study?
• Answer: Future research should encompass more detailed, in vivo investigation into efficacy, possible
side-effects and toxicity of the sorbents that were used in our study.
• Citation:
• A regenerable potassium and phosphate sorbent system to enhance dialysis efficacy and device
portability: an in vitro study
• Maarten Wester, Frank Simonis, Karin G. Gerritsen, Walther H. Boer, Will K. Wodzig, Jeroen P. Kooman,
and Jaap A. Joles
• A regenerable potassium and phosphate sorbent system to enhance dialysis efficacy and device portability:
an in vitro study
Nephrol. Dial. Transplant. first published online July 3, 2013 doi:10.1093/ndt/gft205

Kidney Transplant Rejection and Withdrawal of Calcineurin Inhibition after PTLD Diagnosis
Hemodialysis.com Interview with: Olivier Thaunat
Service de Transplantation et d‟Immunologie Clinique
Hôpital Edouard Herriot, 5 Place d‟Arsonval, Lyon, France
• Response: Several data of the literature (Caillard et al 2012, Kasiske et al 2010) have reported an
increased incidence of graft rejection episodes and graft loss after the diagnosis of post transplant
lymphoproliferative disorder (PTLD).
This is likely the consequence of immunosuppression reduction introduced as the first line therapy to
restore immune surveillance mechanisms in recipients.
To our knowledge, there are no studies available comparing the impact of these different reduction
immunosuppression strategies on graft survival and overall survival.
• Our retrospective bicentric study shows that the withdrawal of calcineurin inhibition after PTLD diagnosis is
an independent risk factor for allograft
loss.
• Histological analysis revealed that maintaining a CNI at reduced dose (25 to 50% of the initial dose)
reduces the risk of developing de novo anti-HLA
antibodies and humoral rejection. Remarkably, the maintenance of calcineurin inhibition was not associated
with a worse PTLD outcome, suggesting that it is a safe therapeutic strategy.

• Hemodialysis.com: Were any of the findings unexpected?
• Response: Immunosuppression reduction strategies after the diagnosis of PTLD are not consensual.
If most transplant physicians agree to continue the steroids after a PTLD diagnosis, many are reluctant to
maintain calcineurin inhibitors, which
have direct pro-neoplasic effects. This attitude, was the one we were following in our center and before
initiating this study, we had the general impression
that graft outcome were good in patients left on corticosteroids alone after chemotherapy.
• Instead, statistical analyses revealed a higher risk for graft loss for patients left on corticosteroids alone.
This was mainly due to a defective control of the
humoral arm of recipients immune system, leading to more antibody-mediated rejection (both acute and
chronic). On the other hand, maintaining calcineurin
inhibition was safe and did not increase the rate of death or disease progression.

• Response: At the diagnosis of PTLD, clinicians have to carefully take into consideration immunological
risks of each patient and the severity of PTLD in order to apply the fairest immunosuppression reduction
strategy.
• Over the past ten years, the standardization of chemotherapies‟ protocols and the use of rituximab have
considerably improved PTLD outcome. Consequently,the aim is now to cure PTLD with the concurrent goal
of preserving allograft function.
• To achieve this goal, our data suggests that most PTLD patients should be kept on a reduced dose (25 to
50% of the initial dose) of calcineurin inhibitor after
PTLD diagnosis.

• Hemodialysis.com: What recommendations do you have for future research as a result of your
study?
• Response: Our study is a first insight of the impact of immunosuppressive reduction strategies on graft
survival.
We are aware of the limitations of our work, especially due to its retrospective aspect and the small number
of patients included in the analysis.
• A similar study carried out in a larger population from national registries should be undertaken to validate
our findings on a larger scale.
In particular it would be interesting to better assess the risk for patient kept on steroid plus mTOR inhibitor.
• Citation:
• Maintaining calcineurin inhibition after the diagnosis of post-transplant lymphoproliferative
disorder improves renal graft survival
• Jean-Emmanuel Serre, David Michonneau, Emmanuel Bachy, Laure-Hélène Noël, Valérie Dubois, Caroline
Suberbielle, Henri Kreis, Christophe Legendre, Marie-France Mamzer-Bruneel, Emmanuel Morelon and
Olivier Thaunat
• Kidney International , (26 June 2013) | doi:10.1038/ki.2013.

Forty-eight hour kidney transplant admissions
Hemodialysis.com Interview with: Eric Siskind, MD
Department of Transplantation,
North Shore Long Island Jewish Health System,
306 Community Drive, 1E, Manhasset, NY 11030, USA.
• Dr. Siskind: Forty eight hour kidney transplantation admissions are a feasible option in selected recipients
of live donor allografts through the use of standardized postoperative protocols, multidisciplinary team
patient care, and intensive follow up at outpatient centers. Age, gender, and pretransplant dialysis status
did not impact the ability to achieve 48 hour admissions. We did not identify any other preoperative risk
factors that contributed to increased length of stay. Although ABO and highly sensitized recipients had
longer lengths of stay, the subgroup was too small to achieve statistical significance. We did not encounter
any readmissions within the first seven postoperative days. Further improvements in clinical management
will enhance the potential to shorten the length of hospital stay for all kidney transplant recipients.
• Dr. Siskind: Two-day renal transplant admissions are a novel approach and departure from the reported
standardized protocols that vary from six to ten days in uncomplicated cases. We were quite pleased with
our outcomes and believe this is the first such report.

Forty-eight hour kidney transplant admissions
Hemodialysis.com Interview with: Eric Siskind, MD
Department of Transplantation,
North Shore Long Island Jewish Health System,
306 Community Drive, 1E, Manhasset, NY 11030, USA.
• Dr. Siskind: With the use of standardized postoperative protocols, we have made living donor kidney
transplantation into a short stay procedure of only two days. This exemplifies the progress made in kidney
transplantation, transforming it into a more streamlined and predictable procedure. We hope these efforts
will enhance the view of kidney transplantation to end stage renal disease patients and their health care
providers, and encourage them to pursue transplantation as their best treatment option. We also hope that
these improved outcomes with living donor kidney transplantation will influence more donors to participate;
knowing their donation will be successful.
study?
• Dr. Siskind: We hope to expand our accelerated postoperative protocol to ABO incompatible and highly
sensitized recipients, as well as deceased donor kidney transplantation, as these subgroups
• Citation:
• Forty-eight hour kidney transplant admissions.
• Siskind E, Villa M, Jaimes N, Huntoon K, Alex A, Blum M, Tyrell R, Sameyah E, Kuncewitch M, Giangola M, Agorastos S, Deutsch G, Plumley L, Shen A,
Robinson M, Alexander M, Israel E, Lumermann L, Bhaskaran M, Calderon K, Jhaveri KD, Sachdeva M, Bellucci A, Mattana J, Fishbane S, D‟Agostino C,
Nicastro J, Coppa G, Molmenti E.
• Department of Transplantation, North Shore Long Island Jewish Health System, Manhasset, NY, USA.
Clin Transplant. 2013 Jun 27. doi: 10.1111/ctr.12178.
[Epub ahead of print]

Study addresses which uremic toxins are associated with mortality in hemodialysis patients?
Hemodialysis.com Interview with: Michal L. Melamed, MD, MHS
Associate Professor of Medicine and Epidemiology & Population Health
Nephrology Fellowship Program Director
Albert Einstein College of Medicine/ Montefiore Medical Center
• Dr. Melamed: The search for THE uremic toxin has been a long one. There are over 200 solutes retained
in patients with kidney disease and dialysis does not clear all of them. Urea in itself does not cause
significant toxicity in the body. In the study we found that of 4 retained solutes that we tested, methylamine,
dimethylamine, p-cresol sulfate and indoxyl sulfate, only high levels of indoxyl sulfate were associated with
a higher risk of all-cause mortality.
• Dr. Melamed: We expected to find that elevated p-cresol sulfate levels were also associated with poor
outcomes but they were not. There have been other studies that show that total levels, which is what we
tested, were not associated with poor outcomes but that free levels were. We intend to go back and
measure free p-cresol sulfate levels to see if there is an association.

Study addresses which uremic toxins are associated with mortality in hemodialysis patients?
Hemodialysis.com Interview with: Michal L. Melamed, MD, MHS
Associate Professor of Medicine and Epidemiology & Population Health
Nephrology Fellowship Program Director
Albert Einstein College of Medicine/ Montefiore Medical Center
• Dr. Melamed: Clinicians and patients need to remember that with our current dialysis therapy, there are
still many substances that are retained that may be causing toxicity. Of the 4 we tested, only one was
associated with all-cause mortality. Indoxyl sulfate is a protein bound molecule and as such, is not cleared
by current hemodialysis. There are ways to increase the removal of protein bound solutes, such as
increasing the dialyzer size and the dialysis flow rate during longer dialysis sessions. Once the toxicity of
solutes is firmly established, there are potentially easy methods to clear the toxic substances.
study?
• Dr. Melamed: I believe there needs to be more research into which substances are causing toxicity in
kidney disease patients so that we can tailor dialysis therapy to clear the actual substances that are causing
toxicity. These studies will include observational studies like the study we just completed and also
interventional studies to show if the uremic toxins are removed there are better patient outcomes.
• Citation:
• Retained organic solutes, patient characteristics and all-cause and cardiovascular mortality in hemodialysis: results
from the retained organic solutes and clinical outcomes (ROSCO) investigators.
• Melamed ML, Plantinga L, Shafi T, Parekh R, Meyer TW, Hostetter TH, Coresh J, Powe NR.
• BMC Nephrol. 2013 Jun 27;14(1):134. [Epub ahead of print]

Patient Survival after Onset of Acute Kidney Injury: Natural History
Hemodialysis.com Interview with: Dr. Jane H. Zhang
Cooperative Studies Program Coordinating Center
Veterans Affairs Connecticut Health Care System
950 Campbell A
venue, West Haven, CT 06516.
• Dr. Zhang: Based on our clinical impression of the natural history of acute kidney injury (AKI), we
hypothesized that survival curves after an episode of renal replacement therapy-requiring AKI might exhibit
distinct acute and convalescent phases. Using data from the Veterans Affairs/National Institutes of Health
Acute Renal Failure Trial Network (ATN) study, we analyzed the change in hazard of death over time within
the first year after an episode of severe AKI and confirmed the presence of these two distinct phases – an
early phase extending over the first 6 weeks and a late phase from 6 weeks to 1 year. Analyzing the
change in hazard function within each of these phases, we were able to identify an early hyper-acute phase
(day 0-4) and a subsequent phase extending from day 4 to day 42. Similarly, the convalescent phase
appears to have two components, an early convalescent phase extending from day 42 to approximately day
148 and a late convalescent phase after day 148. Through this analysis we have better defined the natural
history of survival after an episode of AKI – approximately half of the patients die during the acute phase of
AKI (from the start of dialysis to day 42) and another 1 in 7 die during the “convalescent” phase (day 42 to
one year).

950 Campbell Avenue, West Haven, CT 06516.
• Dr. Zhang: These findings were not surprising, but should help inform the design of future trials of AKI. For
example, prior studies of intensity of renal replacement therapy in AKI have utilized a variety of survival
endpoints, ranging from 15 days after discontinuation of therapy to 90 days after initiation of renal
support. Our results suggest that a primary survival endpoint of approximately within the 95% confidence
interval for the duration of the acute phase (22 days to 66 days) would be appropriate and support the use
follow-up intervals for primary survival endpoints of the survival endpoints of between 4 weeks and 2
months that have been used in the majority of previously conducted trials.
• Dr. Zhang: Our finding suggests that patients with an episode of severe AKI requiring renal support are at
greatest risk of death within the first 4 days after initiation of renal replacement therapy, with an acute phase
with high mortality risk extending out to six weeks. Although patients are still at increased risk of death, the
mortality risk is substantially attenuated after the first six weeks.

950 Campbell Avenue, West Haven, CT 06516.
study?
• Dr. Zhang: We believe that our findings can be used to inform the design of future clinical trials in acute
kidney injury and suggest that the optimal duration of follow-up for a primary mortality endpoint is at
approximately 6 weeks, although our results support the use of follow-up intervals ranging from
approximately four weeks to two months.
• We would like to acknowledge funding by the Cooperative Studies Program of the Department of Veterans
Affairs Office of Research and Development and by the National Institute of Diabetes and Digestive and
Kidney in support of this work.
• Citation:
• Piecewise Analysis of Patient Survival after Onset of AKI
• Jane H. Zhang, Paul M. Palevsky, Glenn M. Chertow, John Hartigan, Theresa Z. O‟Connor, Peter Guarino,
and Bingqing Zhou
• Piecewise Analysis of Patient Survival after Onset of AKI
CJASN CJN.07250712; published ahead of print June 27, 2013, doi:10.2215/CJN.07250712

Dialysis Fistula First Strategy: Best for the Elderly?
Hemodialysis.com Interview with:
Dr. Ranil N. DeSilva
Division of Nephrology, Beth Israel Deaconess Medical Center
185 Pilgrim Rd, FA 8, Boston, MA 02215.
• Dr. DeSilva: „Fistula First‟ is an intention to treat strategy, we hoped to better assess vascular access
outcomes based upon the access first placed rather than that first used at the start of hemodialysis in the
elderly ESRD population. It is well recognized and confirmed in our study that a central venous catheter is
a clearly inferior strategy with a much higher mortality than either a fistula or a graft. But since the elderly
have the highest rate of fistula complications, including failure to mature for use, patients over 80 years old
who underwent placement of a graft first did just as well as those with a fistula placed first (even in those
over 67 years old, a fistula first strategy was only little better). A large part of the explanation is likely
because in those with a fistula placed first 43% started dialysis with a catheter, whereas only 24% of those
with a graft placed first required a catheter at dialysis initiation.
• Hemodialysis.com What should clinicians and patients take away from this study?
• Dr. DeSilva: In an era using more standardized quality outcomes measures, we must remain cautious
generalizing many outcome measures to our growing elderly population. In the case of our study, „Fistula
First‟, a strategy that is clearly superior in young individuals requiring hemodialysis for ESRD, does not
appear to be the clearly superior strategy. When comparing placement of an arteriovenous fistula first to an
alternative placement of an arteriovenous graft first strategy in octogenarians and nonagenarians, both had
similar mortality results over 4 years of hemodialysis. It appears that the optimal vascular access choice
should be tailored to the specific patient in this elderly population.

Dialysis Fistula First Strategy: Best for the Elderly?
Dr. Ranil N. DeSilva
Division of Nephrology, Beth Israel Deaconess Medical Center
185 Pilgrim Rd, FA 8, Boston, MA 02215.
study?
• Dr. DeSilva: As our study aimed more to describe the mortality difference associated between first placing
a „Fistula First‟ versus a „Graft First‟ in the elderly population – we feel our results raised the option for a
more patient specific focused strategy in this elderly population rather than one size fits all. Understanding
more the patients‟ perspective in these different strategies in terms of quality of life I believe would add
more to our general understanding of this topic. In addition, a possible more comprehensive cost effective
analysis of these two strategies in the elderly may bring light to more „society‟s‟ perspective on this topic.
• Citation:
• Fistula First Is Not Always the Best Strategy For the Elderly
Ranil N. DeSilva, Bhanu K. Patibandla, Yael Vin, Akshita Narra, Varun Chawla, Robert S. Brown, and
Alexander S. Goldfarb-Rumyantzev
JASN ASN.2012060632; published ahead of print June 27, 2013, doi:10.1681/ASN.2012060632

CKD: Renal Clearance and Intestinal Generation of p-Cresyl Sulfate and Indoxyl Sulfate
Ruben Poesen, MD, On behalf of all C0-Authors
Department of Nephrology
University Hospitals Leuven, Belgium
• Answer: Chronic kidney disease is accompanied by the accumulation of a diverse panel of so-called
uremic retention solutes. Analyses show that the gut microbial metabolism contributes substantially to these
solutes with p-cresyl sulfate and indoxyl sulfate being among the most discriminating biomarkers of uremia.
However, serum levels of these 2 solutes are widely dispersed in patients with chronic kidney disease. We
demonstrated that, besides renal function, intestinal generation itself is an important determinant of the
interindividual variability of serum levels of both solutes. In addition, our group showed that the eGFR, the
currently used marker for renal function, provides an acceptable estimate for their renal handling, a finding
which was questioned in the past. Finally, renal clearances of indoxyl sulfate appeared approximately
threefold higher than those of p-cresyl sulfate.
• Answer: Until recently, factors determining interindividual variability of serum levels of p-cresyl sulfate and
indoxyl sulfate were largely unknown. It was assumed that differences in renal function, albeit not well
described by the currently used markers for renal function, were the main cause of differences in these
serum levels. We, however, demonstrated that eGFR does provide an acceptable marker for the renal
handling of these solutes, and that intestinal generation itself is an important determinant of this variability.

CKD: Renal Clearance and Intestinal Generation of p-Cresyl Sulfate and Indoxyl Sulfate
Ruben Poesen, MD, On behalf of all C0-Authors
Department of Nephrology
University Hospitals Leuven, Belgium
• Answer: Clinicians must be aware that the eGFR can be used to estimate the renal clearance of both
solutes in patients not yet on dialysis, and that renal clearances of indoxyl sulfate are approximately
threefold higher than those of p-cresyl sulfate. Additionally, for both renal patients and clinicians, it is
intriguing to know that intestinal generation itself is an important determinant of serum levels of both
solutes, making the gut a novel target for therapeutic intervention in the future.
study?
• Answer: As the intestinal generation of p-cresyl sulfate and indoxyl sulfate is an important determinant of
their serum levels, and both solutes are related with cardiovascular disease, overall mortality and renal
disease progression, effort should be made to gain more insights in mechanisms governing this intestinal
generation. In turn, this could lead to novel treatment strategies in patients with chronic kidney disease.
• Citation:
• Renal Clearance and Intestinal Generation of p-Cresyl Sulfate and Indoxyl Sulfate in CKD
• Ruben Poesen, Liesbeth Viaene, Kristin Verbeke, Kathleen Claes, Bert Bammens, Ben Sprangers, Maarten
Naesens, Yves Vanrenterghem, Dirk Kuypers, Pieter Evenepoel, and Björn Meijers
• CJASN CJN.00300113; published ahead of print June 27, 2013, doi:10.2215/CJN.00300113

Kidney Dialysis: Initial Impact of Medicare’s New Prospective Payment System
Hemodialysis.com Interview with: Richard A. Hirth, Ph.D
Associate Chair, Department of Health Management and Policy
Professor Department of Health Management and Policy
Ann Arbor, Michigan 48109-202
• Dr. Hirth: There were substantial changes in practice patterns in the year following the implementation of
the expanded bundled payment system for dialysis. These included a reduction per treatment use of
injectable medications, a shift in agents (more patients received iron relative to ESAs, and changes in the
mix of iron and vitamin D products). In terms of home dialysis, the pre-bundle growth trend in the share of
patients receiving home hemodialysis was unchanged, but there was a substantial acceleration in the share
of first and second year patients receiving peritoneal dialysis.
• Dr. Hirth: The most surprising aspect of the findings was that when we looked at monthly trends the
decline in use of injectables continued throughout the first year after the bundle. Therefore, we will need to
track 2012 in 2013 trends to determine when steady-state practice patterns are reached.

Kidney Dialysis: Initial Impact of Medicare’s New Prospective Payment System
Hemodialysis.com Interview with: Richard A. Hirth, Ph.D
Associate Chair, Department of Health Management and Policy
Professor Department of Health Management and Policy
Ann Arbor, Michigan
• Dr. Hirth: Practices appear quite responsive to changes in financial incentives and other factors such as
the new FDA warning label on ESAs that was issued in June 2011. This makes monitoring quality of care a
significant issue. The trend towards an increase in the use of peritoneal dialysis is encouraging and
clinicians and patients should actively assess the best modality for the patient‟s individual circumstances.
study?
• Dr. Hirth: Clearly, ongoing monitoring of utilization, access to care, and quality of care is necessary. It is yet
to be established what the steady-state level of utilization of injectables will be, and what the long-term
effect on the distribution of patients across dialysis modalities will be.
• Finally, we would like to acknowledge funding by CMS in support of this work while noting that the opinions
and interpretations of the data expressed here are solely those of the manuscript authors and may not
reflect CMS‟ views.
• Citation:
• The Initial Impact of Medicare’s New Prospective Payment System for Kidney Dialysis
Richard A. Hirth, Marc N. Turenne, John R.C. Wheeler, Tammie A. Nahra, Kathryn K. Sleeman, Wei
Zhang, Joseph A. Messana
American Journal of Kidney Diseases – 17 June 2013 (10.1053/j.ajkd.2013.03.044)

Preventing Cyclosporin Renal Toxicity with a New Antioxidant
Hemodialysis.com Interview with: Francesco Trepiccione
Division of Nephrology
Department of Cardio-Thoracic and Respiratory Sciences
Second University of Naples, Naples, Italy
• Answer: In this study we investigated the potential role of a new antioxidant molecule, rMnSOD, in
preventing the renal toxic effect of Cyclosporin A. Cyclosporin A is an immunosuppressant drug that
completely renewed the history of transplantation. However, its long term usage leads to renal failure and
hypertension. The main outcome of this study is the prevention of cyclosporine A-induced impairment of
GFR in rats co-treated with rMnSOD. Quenching the radical oxygen species is the underlying mechanisms
we propose. rMnSOD could be a potential novel therapeutic strategy for patients taking
immunosuppressant.
• Answer: Whether rMnSOD, a novel antioxidant, can prevent the cyclosporin induced renal side effect was
the question behind the study.
Our data confirmed this hypothesis. It was surprising the entity of rMnSOD effect on GFR.

Preventing Cyclosporin Renal Toxicity with a New Antioxidant
Hemodialysis.com Interview with: Francesco Trepiccione
Division of Nephrology
Department of Cardio-Thoracic and Respiratory Sciences
Second University of Naples, Naples, Italy
• Answer: Over the years novel immunosuppressant drugs come up and the management for the transplant
patients improved. However the clinicians cannot get rid of the use of cyclosporin yet. It seems crucial
especially at the beginning of the transplantation. Thus, the interest of the researchers in preventing
cyclosporin side effects is very active and probably new option will be available in a reasonable time. Up to
now, this study is in line with previous ones pointing on the importance of antioxidants in this field.
study?
• Answer: We are interesting to test whether this antioxidant could be efficacious also in the prevention of
the cyclosporine-induced hypertension. A deeper understanding of the pathogenesis of cyclosporine –
related hypertension could be helpful not only for transplant patients, but also to generate novel anti-
hypertensive approaches.
• Citation:
• A new recombinant MnSOD prevents the Cyclosporine A-induced renal impairment.
• Damiano S, Trepiccione F, Ciarcia R, Scanni R, Spagnuolo M, Manco L, Borrelli A, Capasso C, Mancini R,
Schiattarella A, Iervolino A, Zacchia E, Bata-Csere A, Florio S, Anastasio P, Pollastro R, Mancini A,
Capasso G.
• Division of Nephrology, Department of Cardio-Thoracic and Respiratory Sciences, Second University of
Naples, Naples, Italy.Nephrol Dial Transplant. 2013 May 15.[Epub ahead of print]

Low-Protein Vegetarian Diets Supplemented with Keto Analogues
Vegetarian low-protein diets supplemented with keto analogues:
a niche for the few or an option for many?
Martina Ferraresi and Giorgina B. Piccoli
SS Nephrology, University of Turin, Orbassano, Turin, Italy
Hemodialysis.com: What are the main findings of the study?
• Answer: The diet schema prescribed is based on a simplified approach using a „not-too-strict‟ diet (protein
intake of 0.6 g/kg/day), based on allowed and forbidden foods and 1-3 free-choice meals, to reduce the
psychological burden and to avoid malnutrition. We wanted to know if there are some clinical and
demographic elements for an a priori deﬁnition of „good‟ candidates for LPD-KA, considering „prescription
success‟ as at least 6 months of follow-up.
• Our analysis demonstrates that educational level, diabetes, overall comorbidity and old age are not
confirmed as strong relevant factors in attaining the medium-term follow-up of the diet. In this small series,
the start of dialysis was the main cause of discontinuation of the diet.
• The flexible policy, the allowance of free-choice meals and the strict control policy, probably reduce clinical
reasons for discontinuation, and avoid case of malnutrition.
• Conversely, psychological reasons for dropping out were more common, underlining the strong negative
effect of monotony of the dietary regimen and the need for several „pills‟, usually in the context of a complex
polypharmacy.
• The low mortality rates (4.4 cases per 100 patient-year), within the limits of relatively small numbers and
short follow-up, give further reassurance that there is no negative impact of LPD-KA in our population.
• Another interesting aspect of the analysis is the potential reduction of costs of the treatment of kidney
patients: in our area, 1 year of dialysis corresponds to 35–60 patient-years on LPD-KA, (35-60000 Euros
per year vs 1000 Euros per year).

• Answer: Interestingly, in stable patients with at least 6 months of follow-up, compliance was impressive,
with a median protein intake of 0.5 g/kg/day, calculated at distance from the free meals. This supports the
hypothesis that subtle personal preferences, as well as clear motivations, are fundamental in the
relationship with food and diet. Therefore, the diet should be proposed to all patients without preclusion.
• Answer: Our study was neither designed nor sufficiently powerful to demonstrate an effect on the
progression of CKD. Routine laboratory data, such as creatinine clearance, lack the precision of isotopic or
inulin clearances. Within these limits, the analysis of the progression rate (performed to allow
contextualization of our results), suggests that at least patients with longer follow-up may stabilize on the
LPD-KA diet, an issue to be confirmed on larger numbers and longer follow-up. Moreover, every patient can
follow the diet, without a piori characteristics to expect the diet prescription success.

study?
• Answer: Our favorable data on progression and mortality should be considered as a stimulus for further
analysis with larger samples of patients. More importantly, a control group of patients who choose either no
diet or a different LPD (for example with commercial food) was not available for the present analysis; such
an analysis is planned in the context of a perspective study, including all CKD Stage IV–V patients followed
in our unit.
• Citation:
• Giorgina B. Piccoli, Martina Ferraresi,, Maria C. Deagostini, Federica Neve Vigotti, Valentina Consiglio,
Stefania Scognamiglio, Irene Moro, Roberta Clari, Federica Fassio, Marilisa Biolcati, and Francesco
Porpiglia
• Vegetarian low-protein diets supplemented with keto analogues: a niche for the few or an option for many?
Nephrol. Dial. Transplant. first published online June 9, 2013 doi:10.1093/ndt/gft092

Adiponectin in Hypertensive Patients and Kidney Transplant Recipients
Hemodialysis.com Interview with: Avshalom Leibowitz, MD
Internal Medicine D and Hypertension Unit,
The Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.
• Hemodialysis.com: What is adiponectin and what is its importance?
• Dr. Leibowitz: Adiponectin is an adipocytokine, a hormone secreted exclusively by adipocytes. It circulates
in the blood in a relatively high concentration. Unlike other adipocytokines, which are considered
proinflammatory hormones, adiponectin appears to have anti-inflammatory, anti-diabetic and anti-
atherogenic properties. Overall, clinical data suggests that adiponectin plays a protective role in the
cardiovascular system.
• Hemodialysis.com: What was the aim of the study?
• Dr. Leibowitz: In general, there is an inverse correlation between serum adiponectin levels and traditional
cardiovascular risk factors such as obesity, diabetes mellitus, hypertension and an abnormal lipid profile.
On the other hand, patients with chronic kidney disease exhibit higher levels of adiponectin. Data regarding
adiponectin levels in kidney transplant recipients is ambiguous. Our study was conducted in order to gain
more information regarding the role that adiponectin plays in this unique population.

• Dr. Leibowitz: Our study attempted to answer two main questions:
• 1. What is the level of serum adiponectin in kidney transplant recipients compared to controls (both healthy
and hypertensive)?
• 2. Is there a correlation between adiponectin levels and traditional risk factors in kidney transplant
recipients?
• In our study, we found that adiponectin levels were similar in both kidney transplant recipients and the
healthy control group. However, we found a strong correlation between adiponectin levels and traditional
metabolic risk factors such as triglycerides and body weight in the healthy control group. There was no such
correlation in kidney transplant recipients or the hypertensive control group.
• Dr. Leibowitz: We believed that the ambiguity found in literature is due to non-selective patient selection.
Renal function and glucose metabolism have major effects on adiponectin levels. As a result, in our study
we chose only transplant recipients with normal kidney function and without diabetes. Sure enough,
adiponectin levels were found to be at the same level as healthy participants. However, the lack of
correlation to metabolic risk factors may suggest that the metabolic “behavior” of adiponectin in kidney
transplant recipients is different than in the healthy population.

• Dr. Leibowitz: In my opinion, the lesson to be gained from this study is that until more data is available
regarding new protective cardiovascular factors, we as physicians should adhere to traditional evidence-
based treatments. Patients should receive the best preventive treatment available, especially blood
pressure control.
• Citation:
• Normal adiponectin levels in kidney transplant patients with hypertension.
• Leibowitz A, Peleg E, Ben-David A, Sharabi Y, Kamari Y, Holzman E, Grossman E.
• Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer,
Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Clin Transplant. 2013 Jun 13. doi: 10.1111/ctr.12169. [Epub ahead of print]

Ethnicity, medical insurance, and living kidney donation
Hemodialysis.com Interview with Amber M. Reeves-Daniel, D.O.
Assistant Professor Internal Medicine- Nephrology at Wake Forest Baptist Medical Center.
• Answer: This single-center study examined relationships between ethnicity, medical insurance, and living
donation in 447 kidney transplant patients and identified that recipient private medical insurance was
positively associated with the likelihood of living donor kidney transplantation (LKT), as well as with
preemptive transplantation. In addition, Medicaid insurance was negatively associated with the likelihood of
either LKT or preemptive transplantation. These findings were more pronounced in African
Americans. African Americans with private medical insurance were 14 times more likely than African
Americans without private medical insurance to receive a live donor kidney and African Americans with
Medicaid were unlikely to receive LKT. In comparison, European Americans with private medical insurance
were 2.2 times more likely than European Americans without private medical insurance to receive LKT.
• Answer: Yes. An alarming finding is that despite apparent access to kidney transplantation, with
successful transplantation of 175 African Americans (40% Medicaid recipients), no African American
Medicaid recipient received a living donor kidney transplant during the 2.5 year study period. We suggest
that presence or absence of Medicaid insurance may influence the likelihood of LKT or deceased donor
transplantation among African Americans at our transplant center.

• Answer: Recipient insurance status is associated with the likelihood of Iiving donor kidney transplantation
(LKT), positively with private insurance and negatively with Medicaid. African Americans were markedly
impacted by this phenomenon, potentially contributing to their lower rates of LKT. African American
Medicaid recipients appear unlikely to receive LKT. Efforts to assist this population overburdened with
chronic kidney disease and underserved with LKT might include utilization of live donor
champions. Greater efforts to protect donor employment, including re-imbursement for lost wages from
time away from work and assistance with family obligations, may expand the living donor benefit to all
Americans eligible under Medicare, but unable to overcome the social constraints seen in those eligible for
Medicaid.

study?
• Answer: Future studies could examine the effectiveness of a live donor champion in the Medicaid
population.
• Citation:
• Ethnicity, medical insurance, and living kidney donation
• Reeves-Daniel AM, Farney AC, Fletcher AJ, Assimos D, Westcott C, Rogers J,
Stratta RJ, Rocco MV, Freedman BI.
• Clin Transplant. 2013 Jun 19. doi: 10.1111/ctr.12168. [Epub ahead of print]
• PMID: 23781870 [PubMed - as supplied by publisher]

Risk Kidney Injury after Acute Coronary Events same with High-or-Low Potency Statins
Amy Sarma, M.D., Brigham and Women’s Hospital, Boston, Mass;
• Dr. Sarma: Statins have been shown to reduce the risk of recurrent cardiovascular events in patients after
an acute coronary syndrome (heart attack or unstable angina). However, two recent studies from large
observational databases raised concerns that high-potency statins may increase the risk of acute kidney
injury. Since these analyses were observational in nature, the authors could not exclude the possibility that
their findings were explained by other factors that may influence the decision to treat with a high-potency
statin. To address this issue, we examined the incidence of kidney injury in two randomized trials of
intensive versus moderate statin therapy in patients after an acute coronary syndrome. We found that the
incidence of kidney injury was the same regardless of whether the patients were treated with a high- or low
potency statin. Similarly, the change in serum creatinine (a marker of kidney function) was similar between
treatment arms over time.

• Dr. Sarma: Because two large observational data sets had raised concerns that high-potency statin therapy
may be associated with an increased risk of acute kidney injury, we were reassured to find that this was not
the case when we looked at two large randomized trial databases.
• Several studies have demonstrated that the use of high-potency statins reduces the risk of recurrent
cardiovascular events in patients after an acute coronary syndrome. These new findings provide important
reassurance to clinicians and patients that the use of high-potency statins in this population will not increase
the risk of kidney injury.

study?
• Dr. Sarma: Dr. Sarma: As we enter an era of personalized medicine, further study is warranted to identify
patients who might derive both greater cardiovascular benefit from statin therapy, as well as those who are
at greater risk for adverse events. For example, patients on dialysis or with very poor renal function
(estimated glomerular filtration rate of less than 30 ml/min/1.73m2) were not included in our analysis,
therefore further exploration is needed within this high-risk group of patients. However, we did not see any
signal toward an increased risk of kidney injury in those patients with moderately diminished renal
function. As we increasingly treat patients with a multitude of comorbidities at presentation, a thorough
understanding of individualized risk and benefit profiles will be important to optimizing clinical care after an
acute coronary syndrome.
• Citation:
• Sarma A, et al “The incidence of kidney injury for patients treated with intensive versus less potent statin
therapy after an acute coronary syndrome” AHA‟s Emerging Science Series, Abstract.

Change in Blood Pressure during Hemodialysis Treatment and Survival
Jongha Park, MD, PhD
Division of Nephrology, Ulsan University Hospital
Dr. Kalantar-Zadeh, MD, MPH, PhD
University of Ulsan College of MedicineProfessor & Chief, Division of Nephrology & Hypertension
University of California Irvine, School of Medicine
• Response: This large cohort study sought to find an association of blood pressure (BP) change during
hemodialysis (HD) treatment (post-HD BP minus pre-HD BP) with mortality. In 113,255 HD patients,
unadjusted models revealed U-shaped associations between Δ systolic and diastolic BP and all-cause
mortality. After adjustment for other potential covariates, the U-shaped associations were persisted. In fully
adjusted model, modest declines in Δ systolic BP between -30 – 0 mmHg were associated with better
survival, while both Δ systolic BP <-30 mmHg and Δ systolic BP >0 mmHg were associated with increased
mortality. The greatest survival was observed at Δ systolic BP of -14 mmHg [adjusted hazard ratio (aHR),
0.92; 95% confidence interval (CI), 0.91 – 0.93]. Similarly, Δ diastolic BP between -15 – 5 mmHg showed
better survival and the greatest survival was observed at -6 mmHg (aHR, 0.93; 95% CI, 0.91 – 0.94]. When
the outcome of interest was cardiovascular mortality, similar U-shaped associations were still observed.

University
of California Irvine, School of Medicine
• Response: Intradialytic hypotension is a frequent complication of HD that may be associated with reduced
survival, but emerging data suggests that increases in BP during or after HD may also be associated with
adverse outcomes. Our study showed modest declines in BP after HD are associated with the greatest
survival, whereas any rise as well as large declines in BP is associated with worsened survival. Given on-
going debates on strategies of BP control in HD patients, BP changes during HD would have important
clinical implications.

University of California Irvine, School of Medicine
study?
• Response: It is possible that large decline in BP during HD causes reduction in coronary blood flow and
asymptomatic HD-associated cardiac ischemia, so that is associated with adverse outcome. Further trials
are warranted to find effective strategies that promote hemodynamic stability during HD. However, it has
been unclear why BP rises during HD in some patients and also how this rise in BP relates to adverse
outcomes. Exploration of possible mechanisms underlying intradialytic hypertension warrants further
studies. Lastly, it would be interesting to evaluate whether or not a modest BP drop by HD can lead to
better survival in clinical trial.
• Citation:
• A comparative effectiveness research study of the change in blood pressure during hemodialysis
treatment and survival
• Kidney International , (19 June 2013) | doi:10.1038/ki.2013.237
• Jongha Park, Connie M Rhee, John J Sim, Yong-Lim Kim, Joni Ricks, Elani Streja, Tania Vashistha, Ramin
Tolouian, Csaba P Kovesdy and Kamyar Kalantar-Zadeh

Hemodialysis.com : Kidney Disease Research Interviews

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