January 2010 Vol . 3 No.

www.nephrologytimes.com

P r a c t i c a l N e w s , Tr e n d s , a n d A n a l y s i s
In This Issue
Dr. Stephen Textor on ASTRAL: Shortcomings of Trial Limit Applicability ...............................2 Medicare Reimbursement for Nephrology Creeps Higher........7 Surprise Question plus Actuarial Factors Predict Prognosis.........10 Proposal: Invite Elective Surgery Patients to Become Organ Donors .....................................15

Nephrologists Using Social Media Connect with Far-Flung Colleagues, Health Care Consumers
By Brande Victorian

Sweet Dreams in CKD

Editorial Board member Dr. Alan Salama on identifying and managing sleep disturbance in patients with chronic kidney disease: pp. 14

ecommendations for electronic medical record providers, commentary on the latest medical research, and opinions on movies and sports are just a few of the topics being discussed by nephrologists on Twitter. Although so far only a handful of them have signed up for the social networking and microblogging service, those who have say that Twitter facilitates connections between people who may not otherwise have crossed paths. Twitter is very quick and easy and doesnt take a ton of preparation, said Simon Prince, MD, Founder of North Shore Nephrology PC in Manhasset, NY, who registered for the service about a year ago. Continued on page 16

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ASN RENAL WEEK 2009

Paricalcitol Reduces Albuminuria in Randomized Trial

By Michelle Hogan
reported here at the American Society of Nephrology (ASN) Renal Week 2009. Selective VDR [vitamin D receptor] activation with paricalcitol may be a novel approach to lowering the risk of kidney disease progression when used on top of ACE inhibitors and ARB therapy, said Dick de Zeeuw, MD, PhD, Professor and Chair of the Department of Clinical Pharmacology at University Medical Center Groningen in Groningen, the Netherlands, in his presentation of the trial results at the meeting. The results are promising but preliminary, said Alp Ikizler, MD, co-moderator of the session during which they were presented, when asked to comment in a phone interview. Dr. Ikizler is Catherine McLaughlin Hakim Professor of Medicine at Vanderbilt University School of Medicine. Continued on page 18

AN DIEGOParicalcitol lowers albuminuria in patients with type 2 diabetic nephropathy who are also receiving an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). This was the finding of a randomized clinical trial

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Nephrology Times

January 2010

SPECIALTY NEWS

Tom F. Parker III, MD, was selected as the recipient of the 2010 American Association of Kidney Patients (AAKP) Medal of Excellence, which recognizes significant contributions to patient education and disease treatment in the nephrology community. Dr. Parker is a consultant with the Baylor University Medical Center Transplant Program; Senior Attending at Parkland Memorial Hospital in Dallas, TX; Clinical Professor at the University of Texas Southwestern Medical Center at Dallas; and Chief Medical Officer of Renal Ventures Management. His major contribution has been the work he has done with his colleagues to define the quantity and quality of dialysis delivery, the AAKP noted in a news release. Most recently, Dr. Parker was course co-director of Harvard Medical Schools End-Stage Renal Disease: State of the Art and Charting the Challenges for the Future.

Tom F. Parker III, MD

John Raymond, MD

John Raymond, MD, of the Medical

University of South Carolina (MUSC) and the Ralph H. Johnson VA Medical Center, was named Patricia Gabow, MD the 2009 recipient of the Marcy Speer Outstanding Reviewer Award from the National Institutes of Health (NIH) Center for Scientific Review (CSR), the centers top honor for extraordinary commitment to peer review. The awards namesake exemplified this commitment by continuing to review grants during her treatment for breast cancer and extending her term as a regular member of one of CSRs genetics review panels to make up for meetings she missed during

chemotherapy. She died Aug. 4, 2007. Dr. John Raymond personifies the humbling dedication of our reviewers, who give so much to advance science and health here and around the world, said CSR Director Toni Scarpa, MD, PhD. He has served at nearly 100 review meetings, demonstrating a tireless commitment to fair and rigorous reviews. Dr. Raymond is Vice President for Academic Affairs, Provost, and Professor of Medicine at MUSC, as well as a practicing nephrologist and an NIHfunded researcher.

sion (MACPAC). Denver Health, an integrated safety net institution, is the largest provider of care to Medicaid and uninsured patients in Colorado. Dr. Gabow is also a member of the Commonwealth Funds Commission on a High-Performing Health System, the Center for Healthcare Quality and Payment Reform, and the New America Foundations Health CEOs for Health Reform. Her first MACPAC term is to expire in December 2012. Commissioners may be appointed for subsequent three-year terms.

Patricia Gabow, MD, Chief Executive Officer of Denver Health and Hospital Authority and Professor of Medicine in the Division of Renal Diseases at the University of Colorado Denver School of Medicine, was one of 17 individuals appointed as commissioners of the new Medicaid and Childrens Health Insurance Program (CHIP) Payment and Access Commis-

Susan E. Quaggin, MD, of the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto, ON, was awarded the Kidney Foundation of Canadas 2009 Medal for Research Excellence. Dr. Quaggins research has resulted in the discovery of a gene critical for kidney, heart, and lung development. She is currently studying glomerulosclerosis.

Social Media
Continued from page 17 experiences, Dr.Topf said.The difference now is that the Internet leaves a trail of these discussions for the public to see. My sense is youre going to see a change in society where people are going to be less concerned about what comes up online. People have such a long history of online life, so the only way to deal with that is for people to become a little more forgiving of these old transgressions. I cant imagine that youre going to want employees, students, and residents to never be able to express a thought or idea, or that a minor transgression online would permanently scar them. I think during this transition, people will be harmed by this behavior, but I think in the long run the way society is going to react to this is were not going to exclude good people. Morals and ethics are not particularly different for students and younger physicians than they are for more established physicians, Dr. Topf said. We just didnt have this publishing platform. I think thats the long-term issue, but the reality is right now youve got to be careful with it. In spite of the various concerns, the most important rule of social networking is to embrace new technology and enjoy

yourself, the physicians interviewed agreed. Facebook and Twitter seem to be dominating the social media sphere, but we always need to be aware of what may be coming around the corner because what may be popular today may not be so tomorrow, Dr. Pho said. I think its an exciting place to be and really provides a change of pace from what I do in primary care.

Paricalcitol
Continued from page 1 Its a very interesting study actually. Clearly theres some suggestion that giving a high dose of active vitamin D3 seems to be decreasing the proteinuria versus the patients receiving placebo. However, it was not a large trial, Dr. Ikizler added. One of the biggest issues is that youre really looking at a small cohort of people, and it definitely should be considered as a pilot study rather than as a conclusive study. Another issue is its use of a surrogate endpoint. A decrease in proteinuria does not necessarily mean that youre going to see an improvement in progression of chronic kidney disease or improvement in the cardiovascular risk profile, so before you say that this drug should be used for that specific indication, I think a larger study looking at those more concrete outcomes, more clinically applicable outcomes, is definitely necessary, Dr. Ikizler said. Its a promising result that leads the way for a larger study. The trial, called the Selective Vitamin D Receptor Activator for Albuminuria Lowering (VITAL) study, was sponsored by Abbott.

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elective VDR activation with paricalcitol may be a novel approach to lowering the risk of kidney disease progression when used on top of ACE inhibitors and ARB therapy. Dick de Zeeuw, MD, PhD

Randomized Trial
A potential link between paricalcitol and proteinuria reduction had been incidentally identified in a previous post hoc analysis of dipstick proteinuria data from three randomized studies (Kidney Int 2005;68:2823-2828). The analysis was led by Rajiv Agarwal, MD, of Indiana University School of Medicine. To test this finding in a double-blind, placebo-controlled, randomized, multicenter study, Dr. de Zeeuw and colleagues enrolled 281 patients with Continued on page 19

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Nephrology Times

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Paricalcitol
Continued from page 18 a urine albumin-to-creatinine ratio (UACR) between 100 mg/g and 3,000 mg/g, estimated glomerular filtration rate (eGFR) between 15 mL/min/1.73 m2 and 90 mL/min/1.73 m2, corrected serum calcium level less than 9.8 mg/dL, and intact parathyroid hormone level between 35 pg/mL and 500 pg/mL. The participants also were required to have been on medication for their type 2 diabetes for at least 12 months and on a stable dose of an ACE inhibitor or an ARB for at least three months.

If you split that up between the two different [paricalcitol dose] groups, you see that there appears to be a dose-response effect, Dr. de Zeeuw said. Patients who received the 2 g/day dose of paricalcitol had a 19.5% reduction in UACR, which was a statistically significant difference, he added during a phone interview. That was sort of a weakness of the study, the fact that we combined in the primary endpoint two drug doses, of

which later on we found that actually one was doing the better job, the higher one. The percentage of patients who had at least a 15% reduction in urine albuminto-creatinine ratio was also compared across the groups. The proportion of subjects that reached more than a 15% reduction was significantly higher in the paricalcitol 2 g/day group as well as the combined group, Dr. de Zeeuw said at the meeting. Within four weeks of treatment with

higher-dose paricalcitol, eGFR showed a slight but significant fall of 4%. The pattern of the effect of paricalcitol on eGFRa decrease, followed by a period of stability that lasted for the duration of treatment, and then recovery after cessation of the drugis similar to what is observed with ACE inhibitor or ARB therapy, Dr. de Zeeuw noted. Blood pressure also was measured as part of the safety analysis.We didnt expect any Continued on page 20

decrease in proteinuria does not necessarily mean that you're going to see an improvement in progression of chronic kidney disease or improvement in the cardiovascular risk profile, so before you say that this drug should be used for that specific indication, I think a larger study looking at those more concrete outcomes, more clinically applicable outcomes, is definitely necessary.Alp Ikizler, MD

After a three-week run-in period, patients were randomized to receive 2 g/day of paricalcitol (n=95), 1 g/day of paricalcitol (n=93), or placebo (n=93).The three groups were similar in terms of baseline UACR, blood pressure, and GFR. They received their respective study treatments for a total of 24 weeks, but follow-up continued past that point, with measurements taken at 30 days and 60 days after the cessation of treatment.

Dose Response
The primary efficacy analysis compared the percent change from baseline to last on-treatment UACR for the combined group of patients receiving either paricalcitol dose versus patients receiving placebo. In the combined paricalcitol group, there was a 17% decrease in urine albumin-to-creatinine ratio. However, the difference between the combined group and the placebo group was not statistically significant.

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Nephrology Times

January 2010

CLINICAL TRIAL ALERT

Health and Wellness, Korea Contact: Shin-Wook Kang, MD, PhD Phone: 82-2-2228-5345 E-mail: kswkidney@yuhs.ac

he following is a partial list of new clinical trials recently added to the National Institutes of Healths ClinicalTrials.gov online registry. More information on these trials is available at www. clinicaltrials.gov.

Chronic Allograft Nephropathy

NCT00999258 Impact of Conversion from Tacrolimus to Sirolimus in African-American Renal Transplant Recipients Ages eligible for study: 18 years and older Sponsors and collaborators: Temple University and Wyeth Contact: Serban Constantinescu, MD, PhD Phone: 215-707-9171 E-mail: serban.constantinescu@ tuhs.temple.edu Contact: Sandra Amoroso, RN Phone: 215-707-7935 E-mail: sandra.amoroso@tuhs.temple.edu

Concentration-Time Curve in Subjects with Various Degrees of Renal Impairment and in Subjects with Normal Renal Function Ages eligible for study: 18 years to 85 years Sponsors and collaborators: Novo Nordisk Contact: Novo Nordisk E-mail: clinicaltrials@novonordisk.com

Contact: Professor Felix J. Frey Phone: 41-31-632-96-29 E-mail: felix.frey@insel.ch

Hypophosphatemia
NCT01011114 Using Cinacalcet to Treat the Hypophosphatemia of Early Kidney Transplant Ages eligible for study: 18 years and older Sponsors and collaborators: Montefiore Medical Center Contact: Maria Coco, MD, MS Phone: 718-920-4136 E-mail: mcoco@montefiore.org Contact: Daniel Glicklich, MD Phone: 718-920-5551 E-mail: dglich@montefiore.org

Graft Function
NCT00998972 N-acetyl-cysteine and Kidney Graft Function Ages eligible for study: 18 years to 70 years Sponsors and collaborators: Institut dAnesthesiologie des Alpes-Maritimes (Anesthesiology Institute of Alpes-Martimes) Contact: Carole R. Ichai, MD, PhD Phone: 00-33-4-92-03-33-00 E-mail: ichai@unice.fr

Immunosuppression
NCT01014234 Rapamycin and Regulatory T Cells in Kidney Transplantation Ages eligible for study: 18 years to 75 years Sponsors and collaborators: IRCCS Policlinico San Matteo (IRCCS San Matteo Polyclinic) Contact: Carmelo Libetta, MD Phone: 0039-0382-501813 E-mail: clibetta@smatteo.pv.it

Cardiovascular Disease Hypertension

NCT01002118 Feasibility Study of Omega-3 Fatty Acids in Dialysis Patients Ages eligible for study: 18 years to 70 years Sponsors and collaborators: GlaxoSmithKline and the University of Iowa Contact: Heather A. Muster, MD, MS Phone: 319-384-8197 E-mail: heather-muster@uiowa.edu NCT00999453 The Effects of Lowering LowDensity Lipoprotein Cholesterol Levels to New Targets on Cardiovascular Complications in Peritoneal Dialysis Patients Ages eligible for study: 20 years to 70 years Sponsors and collaborators: Clinical Research Center for End-Stage Renal Disease, Korea; and the Ministry of

Chronic Kidney Disease

NCT01016613 Clinical Phenotyping Resource and Biobank Core of the Michigan OBrien Renal Center (C-PROBE) Sponsors and collaborators: University of Michigan, St. Johns Health System, University of Illinois, Wayne State University Contact: Jennifer J. Hawkins, MPH Phone: 734-615-8304 E-mail: jenjoyce@med.umich.edu Contact: Chrysta Lienczewski Phone: 734-615-5021 E-mail: boridley@med.umich.edu NCT01007994 Reduction of Nighttime Blood Pressure in Pediatric Renal Transplant Recipients Ages eligible for study: 5 years to 21 years Sponsors and collaborators: North ShoreLong Island Jewish Health System and Childrens Hospital of Philadelphia Contact: Christine B. Sethna, MD, EdM Phone: 718-470-3423 E-mail: csethna@nshs.edu NCT01009229 Reduced 11b-HSD Activity, a Novel Mechanism of Salt Sensitivity and Hypertension after Renal Allograft Donation? Ages eligible for study: 20 years to 70 years Sponsors and collaborators: University Hospital (Inselspital), Bern

Nutrition
NCT01015313 Effects of Intensified Sodium Management in Hemodialysis Patients Ages eligible for study: 18 years and older Sponsors and collaborators: Renal Research Institute Contact: Lars Penne, MD Phone: 212-360-4954 E-mail: lpenne@rriny.com Continued on page 21

Diabetes Mellitus
NCT01006057 A Trial Investigating the NN1250

Paricalcitol
Continued from page 19 effect there, but, to our surprise, we saw that there is in the 2-g paricalcitol group a five percent, on average, decrease in systolic blood pressure that reached significance, Dr. de Zeeuw said. There was a trend for recovery after 30 to 60 days. The safety of both doses of paricalcitol was similar to that with placebo, though the study was relatively small, Dr. de Zeeuw noted. There was, notably, no hypercalcemia in excess found in either dose of the paricalcitol group compared with placebo.

Nor were there differences among the groups in adverse events or serious adverse events, though study discontinuation was more common in the higherdose paricalcitol group. Paricalcitol, at least at the dose of 2 g/day, appears to lower albuminuria in patients with diabetic nephropathy who are stable on intervention in the renin-angiotensin system, Dr. de Zeeuw said.Paricalcitol is found to be generally safe.

Need for Large Trial

The relationship between paricalcitol and albuminuria lowering in the study prompts questions for further study.

The immediate follow-up question is: And what would that mean for the long-term effect on progressive kidney function loss? Dr. de Zeeuw said in the phone interview. Ultimately you dont want to lower blood pressure; ultimately you dont want to lower cholesterol; ultimately you dont want to lower albuminuria, but you want to protect the patient against cardiovascular or renal events, and that is obviously what now needs to be done. During the question-and-answer session at the ASN meeting, Dr. de Zeeuw was asked whether the albuminuria reduction could have been caused by the

drop in blood pressure instead of by the drug itself. There is a possibility that that would be the case, Dr. de Zeeuw said. We can not test that other than correct for that effect, but the blood pressure effect appears to be extremely small compared with what we saw in albuminuria. Further research would be needed to determine the mechanism behind the albuminuria lowering. And a trial examining the effect of the drug on hard outcomes is in order, Dr. de Zeeuw added. I would suggest a large cardiovascular renal outcome trial comparing paricalcitol with placebo on top of existing therapies.