Renal & Urology News March 2014 Issue by Haymarket Media

M A R C H 2014

VOLUME 13, ISSUE NUMBER 3

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CKD Raises Peptic Ulcer Disease Risk The risk is nearly 10 times greater among hemodialysis patients than individuals without CKD PEPTIC ULCERS AND CHRONIC KIDNEY DISEASE

A population-based study of 1998-2008 data in Taiwan

1.1

found a much higher incidence of peptic ulcer disease (PUD) among individuals with chronic

2.0

CKD

kidney disease (CKD) than those without CKD. The PUD incidences per 1,000 persons in 1999 and 2008 among individuals with and without CKD are shown here.

19.8

No CKD

13.2 ■ 1998 ■ 2008

Source: Liang C-C et al. Peptic ulcer disease risk in chronic kidney disease: Ten-year incidence, ulcer location, and ulcerogenic effect of medications. PLoS One (2014;9:e87952)

RA Ups Risk of Reduced eGFR REDUCED kidney function is more likely to develop in patients with rheumatoid arthritis (RA) than individuals without RA, a recently published study suggests. Cardiovascular disease (CVD) and associated factors appear to have a role. “The presence of RA in individuals with reduced kidney function may lead

to an increase in morbidity from CVD development, for which awareness may provide a means for optimizing care,” investigators concluded. LaTonya J. Hickson, MD, of Mayo Clinic in Rochester Minn., and colleagues compared with 813 patients with RA and 813 non-RA individuals. continued on page 6

LYCOPENE PROTECTIVE?

Greater dietary intake of the carotinoid lowers prostate cancer risk, study finds. SEE STORY PAGE 9

PATIENTS with chronic kidney disease (CKD) are at significantly increased risk of peptic ulcers, according to investigators in Taiwan. Over a 10-year period (1998-2008), researchers found an incidence of peptic ulcer disease (PUD) that was approximately 10-12 times higher among CKD patients than among individuals without CKD. Chih-Chia Liang, MD, of the China Medical University in Taichung, Taiwan, and colleagues conducted a nationwide, population-based study of data from Taiwan’s National Health Insurance Research (NHIR) database. The researchers compared 16,322 patients with newly diagnosed PUD with 32,644 controls without PUD.

Medications Show Promise for NODAT BY JODY A. CHARNOW IN SEPARATE studies, vildagliptin and sitagliptin demonstrated efficacy and safety in the treatment of newonset diabetes after kidney transplantation, potentially providing novel treatment alternatives for this form of diabetes. One study was a double-blind trial in which Marcus D. Säemann, MD, of the Medical University of Vienna, and colleagues randomly assigned 33 kidney transplant recipients (KTRs) with new-onset diabetes after transplantation (NODAT) to receive either 50 mg vildagliptin, which is a dipeptidyl peptidase-4 (DPP-4) inhibitor, or placebo once daily. Thirty-two patients completed the study (16 in each group). DPP-4 inhibitors selective foster insulin secretion without inducing hypoglycemia, the researchers explained. At baseline, the vildagliptin and placebo arms had two-hour plasma glucose levels of 256.4 and 236.9 mg/dL,

From 1998 to 2008, the incidence of PUD increased from 13.2 to 19.8 per 1,000 persons per year in CKD patients compared with 1.1 to 2.0 per 1,000 persons per year in individuals without CKD, study findings show. CKD patients aged 65 years and older experienced a rapid increase in PUD incidence after 2004, whereas CKD patients younger than 65 years experienced a slight decline in PUD incidence during the study period, the investigators reported. Compared with non-CKD individuals (the reference group), CKD patients not on hemodialysis (HD) and those on HD had a 3.8 and 9.7 times increased risk of PUD after adjustcontinued on page 6

IN THIS ISSUE 7 Live kidney donors are at slightly increased risk for ESRD 8 Elevated levels of uric acid raise diabetes risk 9 Sickle cell trait may increase the need for higher ESA doses

11 Kidney stone presentation rates rise during warmer months

16 NKF Preview: Guidelines and the older CKD patient

22 Higher dietary acid load increases CKD progression risk 22 New guideline advises deferring dialysis unless clinically indicated Expert Q&A Frank A. Critz, MD, discusses radiation vs. surgery for PCa PAGE 15

continued on page 6

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M A R C H 2014

VOLUME 13, ISSUE NUMBER 3

www.renalandurologynews.com

Observation Used for More PCa Cases Patients were 2.5 times more likely to be managed expectantly in 2011 than in 2004 MORE PATIENTS DELAYING TREATMENT A study of 2004-2011 data showed that growing proportions of patients with low-risk prostate cancer are receiving expectant management. 2004

9.8%

2005

9.7%

2006 2007 2008 2009

9.5% 9.1% 10.9% 13.6% 15.9%

2010

18.6%

2011 Source: Maurice M, et al. Abstract 68. Data presented at the 2014 Genitourinary Cancers Symposium in San Francisco.

Diabetes Ups RCC Pt Mortality SAN FRANCISCO—Diabetes mellitus is independently associated with decreased overall survival among patients with renal cell carcinoma (RCC) and decreased cancer-specific survival among patients with clear cell RCC, researchers reported at the 2014 Genitourinary Cancers Symposium. Sarah P. Psutka, MD, and colleagues

at Mayo Clinic in Rochester, Minn., reviewed 2,589 patients treated with nephrectomy for sporadic, unilateral RCC from 1990 to 2008 and identified 313 who had diabetes mellitus. Each of these patients was matched to two non-diabetic patients according to date of surgery, age, obesity, smoking status, continued on page 6

LYCOPENE PROTECTIVE?

Greater dietary intake of the carotinoid lowers prostate cancer risk, study finds. SEE STORY PAGE 9

SAN FRANCISCO—Expectant management for low-risk prostate cancer (PCa) is increasing and use of postprostatectomy adjuvant radiotherapy among PCa patients with adverse pathologic features is declining, according to two studies by the same research team presented at the 2014 Genitourinary Cancers Symposium. In one study, Matthew J. Maurice, MD, a urology resident at University Hospitals Case Medical Center in Cleveland, and colleagues used the National Cancer Database—a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society—to identify 287,562 men diagnosed with low-risk PCa from 2004 to 2011. Of

Libido Linked To Estradiol In TST Patients BY JODY A. CHARNOW ELEVATED serum estradiol is associated with increased libido in men receiving testosterone supplementation therapy (TST), according to researchers. In a study of 423 men on TST, Ranjith Ramasamy, MD, working with Larry Lipshultz, MD, at the Baylor College of Medicine in Houston, measured subjects’ testosterone and estradiol levels and asked the men to rate the quality of their libido using a five-point Likert scale (1= terrible, 5 = excellent). The researchers categorized the men as having low or high testosterone (below or above 300 ng/dL, respectively) and low or high estradiol (below 5 and above 5 ng/dL, respectively). Men with high serum testosterone levels reported significantly greater libido than men with low level and those with high serum estradiol levels had significantly greater libido than subjects with low levels. In all,

these, 34,132 received expectant management (EM), either active surveillance or watchful waiting. The investigators observed a significant and steady rise in EM usage beginning in 2008. Compared with patients diagnosed in 2004, those diagnosed in 2011 had a significant 2.5 times increased odds of receiving EM, the study found. Aside from year of diagnosis, older age and higher Charlson co-morbidity scores predicted increased use of EM usage. Hospital and insurance types also predicted EM use, “calling into question whether non-clinical factors are influencing EM selection,” the authors concluded in a poster presentation. continued on page 6

IN THIS ISSUE 6 Low testosterone before RP predicts worse PCa outcomes 7 Live kidney donors face a slightly increased risk of ESRD

11 Data may support targeted PSA screening for BRCA2 carriers

Kidney stone presentation rates rise during warmer months

Testosterone may weaken men’s response to vaccines

17 ED linked to uric acid in coronary artery disease patients

22 RCC rarely recurs after minimallyinvasive partial nephrectomy

Expert Q&A: Frank A. Critz, MD, discusses radiation vs. radical surgery for PCa. PAGE 15

continued on page 6

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Renal & Urology News 3

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Personalized Medicine in 2014

he term “personalized medicine” remains an overused promise to apply specific treatment plans matched to the unique aspects of a patient’s disease. It implies the ability to measure and manage a patient’s complex risk profile. In cancers, this means predicting a tumor’s inherent biology. Unfortunately, only crude methods of estimating tumor risk exist as genitourinary biomarkers demonstrate either low sensitivity/specificity (prostate/bladder markers) or are altogether unavailable (kidney biomarkers). Therefore, we are left with stage, grade and histology as the most relevant predictors of a tumor’s biology. A predominant theme at the recent Genitourinary Cancers Symposium was measuring tumor heterogeneity and beginning to manage it clinically—in other words, true “personalized medicine.” Moving the needle forward are the “omic” sciences (genomics, proteomics, kinomics, metabolomics). Perhaps nowhere is this better seen than in the case of kidney cancer. For decades, pathologists and clinicians have recognized that renal cell carcinoma (RCC) is not one but several distinct histological/clinical diseases. A new picture of RCC evolution is emerging. Investigators from the Royal Marsden Hospital in London have recently sequenced multiple areas in primary RCCs from 10 patients with their corresponding metastases and noted that biopsies from the same patient (and even in the same primary tumor) exhibited “unique and private” mutations as often as 65% of the time. Using these data, they developed a model of genetic mutational “branched” evolution in kidney cancer—analogous to a tree with its trunk and many branches.1 They demonstrate that in clear cell RCC, a VHL mutation, is a necessary event (the trunk) but that under unique selective pressures tumor cells can then “privately” evolve along different pathways (the branches) – with some branches overgrowing (metastases) and others thwarted (indolent cancers). They postulate that this clonal architecture itself may soon serve as a cancer biomarker (i.e., palm tree phenotypes—long trunk/few branches, perhaps as indolent cancers vs. baobab tree phenotypes—short trunk/many branches, perhaps an aggressive cancer). This model of “truncal drivers” and “branched evolution” appears to hold up in other cancers as well and has broad clinical implications for tumor risk stratification, drug development, therapeutic decisions, and understanding resistance. As the kinetics of data acquisition and analysis in the “omic” sciences increases, the moniker “personalized medicine” will be less about market hype and more about clinical hope for both oncologic and benign urologic disease. Robert G. Uzzo, MD, FACS, G. Willing “Wing” Pepper Chair in Cancer Research and Professor and Chairman, Department of Surgery, Fox Chase Cancer Center, Temple University, School of Medicine, Philadelphia.

Gerlinger et al Nature Genetics (in press)

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Medical Director, Urology

Medical Director, Nephrology

Robert G. Uzzo, MD, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman Department of Surgery Fox Chase Cancer Center Temple University School of Medicine Philadelphia

Kamyar Kalantar-Zadeh, MD, MPH, PhD Medical Director, Nephrology Professor & Chief Division of Nephrology & Hypertension University of California, Irvine School of Medicine Orange, Calif.

Nephrologists

Urologists Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto Stanton Honig, MD Associate Clinical Professor of Surgery/Urology University of Connecticut School of Medicine, Urology Center New Haven J. Stephen Jones, MD, FACS Chief of Surgical Operations Professor of Surgery CCLM Cleveland Clinic Regional Hospitals Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California, Irvine James M. McKiernan, MD Assistant Professor of Urology Columbia University College of Physicians and Surgeons New York City Kenneth Pace, MD, MSc, FRCSC Assistant Professor Division of Urology St. Michael’s Hospital University of Toronto Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, N.C. Suphamai Bunnapradist, MD Director of Research Department of Nephrology Kidney Transplant Research Center The David Geffen School of Medicine at UCLA Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center, Memphis Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc. Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center, Detroit Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J. Lynda Anne Szczech, MD, MSCE Medical Director, Pharmacovigilence and Global Product Development, PPD, Inc. Morrisville, N.C.

Renal & Urology News Staff Editor Executive editor Senior editor Web editor Editorial coordinator Art director Group art director, Haymarket Medical VP, audience development and operations Production manager Production director Product manager, digital products Circulation manager National accounts manager Editorial director Publisher VP medical magazines and digital products CEO, Haymarket Media Inc.

Jody A. Charnow Marina Galanakis Delicia Honen Yard Stephan Cho Candy Iemma Andrew Bass Jennifer Dvoretz John Crewe Krassi Varbanov Kathleen Millea Chris Bubeck Paul Silver William Canning Jeff Forster Dominic Barone Jim Burke Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 13, Number 3. Published monthly by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. Periodicals postage paid at New York, NY, and an additional mailing office. The subscription rates for one year are, in the U.S., $75.00; in Canada, $85.00; all other foreign countries, $110.00. Single issues, $20.00. www.renalandurologynews.com. Postmaster: Send address changes to Renal & Urology News, c/o DMD Data Inc., 2340 River Road, Des Plaines, IL 60018. For reprints, contact Wright’s Reprints at 1.877.652.5295. Copyright: All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2014.

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Contents

MARCH

2014

VOLUME

Nephrology

ONLINE

this month at renalandurologynews.com Expert Q&A

Suzanne Ildstad, MD, director of the Institute for Cellular Therapeutics at the University of Louisville in Louisville, Kentucky, talks about advances she has made in immunosuppression-free transplantation.

Take our latest quiz at renalandurologynews.com /clinical-quiz/. Answer correctly and you will be entered to win a $50 American Express gift card. Congratulations to our January winner: Robert Luangkhot, MD

Live Kidney Donors Face Elevated ESRD Risk The increased lifetime risk of end-stage renal disease is small compared with matched healthy non-donors.

Sickle Cell Trait May Up Need for Higher ESA Doses In African Americans, the presence of sickle cell or hemoglobin C trait may contribute to the need for higher doses of erythropoiesisstimulating agents during dialysis.

Guidelines and the Older CKD Patient Tomasz Beben, MD, and Dena Rifkin, MD, MS, discuss the challenges in managing geriatric patients with kidney disease.

2 2

Canadian Guideline: Defer Dialysis Initiation is recommended when clinical indications emerge or when the eGFR is 6 mL/min/1.73 m2 or below.

Drug Showcase

Read up on recently approved pharmaceuticals. Our latest include: • Fortesta (testosterone gel), for hypogonadism • Invokana (canagliflozin), for glycemic control in type 2 diabetics • Myrbetriq (mirabegron), for overactive bladder

Urology 6

0 1

News Coverage

Visit our website for timely reports from upcoming meetings.

2 2

European Association of Urology 2014 Congress Stockholm, Sweden April 11-15 National Kidney Foundation 2014 Spring Clinical Meetings Las Vegas April 22-26 American Urological Association Annual Meeting Orlando, Fla May 16-22 American Society of Hypertension Annual Meeting New York May 17-20 American Society of Clinical Oncology Annual Meeting Chicago May 30-June 3 European Renal Association-European Dialysis and Transplant Association Annual Meeting Amsterdam, The Netherlands May 30-June 3

Low T May Predict Worse PCa Levels below 300 ng/dL prior to radical prostatectomy are associated with an increased risk of positive surgical margins and seminal vesicle invasion. Greater Intake of Dietary Lycopene May Decrease Prostate Cancer Risk High intake of this carotenoid appears to be especially protective against lethal prostate cancer, according to researchers. Data Support Pre-Chemo Enzalutamide The drug decreased the risk of death by 30% versus placebo in patients with chemotherapy-naïve metastatic castrationresistant prostate cancer. Study: RCC Rarely Recurs After MIPN The estimated recurrence rate at 10 years following minimally invasive partial nephrectomy was 88.3%, data show.

Decreasing NEAP [net endogenous acid

production] may be an effective and safe kidney-protective strategy. See our story on page 7

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NUMBER

CALENDAR

Clinical Quiz

13, ISSUE

Departments 3

From the Medical Director “Personalized medicine” could become a reality

News in Brief High uric acid increases diabetes risk

Expert Q&A Radiation vs. radical surgery for PCa

Men’s Health Update Testosterone may weaken vaccine response

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Contents

MARCH

2014

VOLUME

Urology 6

ONLINE

this month at renalandurologynews.com Expert Q&A

0 1

2 2

Clinical Quiz

Drug Showcase

News Coverage

Visit our website for timely reports from upcoming meetings.

NUMBER

CALENDAR

Nephrology 7

Live Kidney Donors Face Elevated ESRD Risk The increased lifetime risk of end-stage renal disease is small compared with matched healthy non-donors.

Guidelines and the Older CKD Patient Tomasz Beben, MD, and Dena Rifkin, MD, MS, discuss the challenges in managing geriatric patients with kidney disease.

2 2

Canadian Guideline: Defer Dialysis Initiation is recommended when clinical indications emerge or when the eGFR is 6 mL/min/1.73 m2 or below.

Decreasing NEAP [net endogenous acid

production] may be an effective and safe kidney-protective strategy. See our story on page 7

RUN0314_TOC_Urology.indd 4

13, ISSUE

Departments 3

From the Medical Director “Personalized medicine” could become a reality

News in Brief High uric acid increases diabetes risk

Expert Q&A Radiation vs. radical surgery for PCa

Men’s Health Update Testosterone may weaken vaccine response

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RA Ups Risk continued from page 1

The researchers defined reduced kidney function as an estimated glomerular filtration rate (eGFR) below 60 mL/ min/1.73 m2. They also examined the effect of more advanced renal impairment (eGFR below 45). The 20-year cumulative incidence of an eGFR below 60 was significantly higher in RA than non-RA subjects (25% vs. 20%), but the 20-year cumulative incidence of an eGFR below 45 was not significantly different (9% vs. 10%), Dr. Hickson’s group reported in the American Journal of Kidney Diseases (2014;63:206-213). In RA patients, the presence of CVD at baseline was associated with a 77% increased risk of an eGFR below 60. An elevated erythrocyte sedimentation rate, obesity (body mass index [BMI] of 30 kg/m2 or higher), and dyslipidemia also were associated with an increased risk of an eGFR below 60. An eGFR below 60 was not associated with a significant increased risk of CVD development in patients with

CKD and peptic ulcers continued from page 1

ing for confounders, the investigators reported in PLoS One (2014;9:e87952). Maintenance HD patients were twice as likely to experience gastric rather than duodenal ulcers. Non-HD CKD patients had a similar risk for ulcers at both locations. “Overall, we suggest that CKD itself is a strong independent risk factor for PUD, and the incidence of PUD among elderly CKD patients is substantially increasing,” the authors wrote.

NODAT continued from page 1

respectively, a non-significant difference between the groups. Both groups had HbA1c levels of 6.7%. Two-hour plasma glucose levels decreased profoundly and significantly in the vildagliptin group compared with the placebo arm, the investigators reported in the American Journal of Transplantation (2014;14:115-123). They decreased by 73.7 mg/dL from baseline to three months after treatment in the vildagliptin arm compared with a 5.7 mg/dL decrease in the placebo arm. At one month after the discontinuation of treatment, the HbA1c was 6.1% in the vildagliptin group compared with 6.5%

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RA, but a greater reduction in GFR (eGFR below 45) was associated with a significant 93% increased risk of CVD. Some characteristics were associated with a decreased likelihood of developing reduced kidney function, including a BMI below 20 and use of non-steroidal anti-inflammatory agents (NSAIDs). The investigators found no association between use of NSAIDs and development of CVD, hypertension, or diabetes during follow-up. “A combination of RA disease characteristics and CVD-associated factor appear to play a role in reduced kidney function development,” Dr. Hickson’s team concluded. Additionally, they noted that RA disease did not appear to affect survival among patients in whom reduced kidney function developed. RA disease in patients with reduced kidney function may lead to an increase in morbidity from CVD development, primarily among individuals who have advanced kidney disease. “Based on these findings,” the authors concluded, “therapeutic strategies to modify nontraditional risk

factors for CVD and consistent kidney function monitoring when appropriate may be used to minimize the risk of reduced kidney function and subsequent complications, including CVD and death, in our RA population.” During follow-up, 392 patients died—229 with and 163 without RA. An eGFR below 60 was associated with

increased risk of death in both groups, but the effect of an eGFR below 60 on mortality was significantly less in RA patients, the researchers found. An eGFR below 45 was associated with a nearly twofold increased risk of developing CVD among RA patients, but had no significant effect on CVD risk in non-RA patients. n

CKD patients receiving a non-steroidal anti-inflammatory drug (NSAID) or clopidogrel were at increased risk for PUD compared with CKD patients not receiving these medications. Among subjects taking an NSAID or clopidogrel, non-HD CKD patients had a 4.6 times and 3.1 times increased risk of PUD, respectively, compared with non-CKD patients in adjusted analyses. “Unexpectedly, the peptic ulcer risk in CKD patients on aspirin was quite distinct from that in CKD patients on [an] NSAID,” the authors wrote. “The

use of aspirin did not increase the risk for PUD, which seems contradictory to the well-documented increase in peptic ulcer risk.” Dr. Liang’s group pointed out that the strengths of their study included use of a national population database, which minimizes selection bias and provides sufficient statistical power. In addition, they looked at inpatients and outpatients as well as PUD with and without bleeding, which allows for generalization to clinical practice for general CKD patients, they noted. The study also examined the risk

for PUD, not upper gastrointestinal bleeding (UGIB). “UGIB consists of many diseases, which presents challenges in conducting appropriate and meaningful analyses.” The investigators acknowledged study limitations, noting, for example, that the NHIR database does not provide relevant laboratory values and data on lifestyle risk factors such as smoking and alcohol consumption. The researchers also stated that they did not have information available on the location of gastric ulcers (for example, cardia or pylorus). n

in the placebo group. Adverse events generally were mild and occurred at similar rates in both groups.

insulin secretion and lowered fasting and postprandial plasma glucose levels. The drug was well tolerated, and the researchers observed no effect on plasma markers of cardiovascular risk and no serious adverse events. “Thus, sitagliptin represents a novel treatment alternative for renal transplant recipients with NODAT, but long-term data on such therapy are warranted,” the authors wrote. Oral therapeutic options for treating hyperglycemia in these patients are limited because of reduced renal function, potential interactions with immunosuppressive drugs, and adverse effects such as hypoglycemic events that may increase cardiovascular risk, they explained.

BMI affects NODAT risk In a separate development related to NODAT in KTRs, Diane D. Stadler, PhD, RD, LD, and colleagues at Oregon Health & Science University in Portland, found that increasing body mass index (BMI) was associated with increasing risk of NODAT, according to a report in the Journal of Renal Nutrition (published online ahead of print). The researchers reviewed the medical records of 204 adults who had received their first renal transplant. The odds of developing NODAT by discharge or three or six months post-transplant increased by 11%, 13%, and 15%, respectively, for each per unit increase in pre-transplant BMI. n

Sitagliptin The other study, which was published online ahead of print in Nephrology Dialysis Transplantation, evaluated the use of sitagliptin—another DPP-4 inhibitor—in 19 long-term stable KTRs with NODAT. Thea Anine Strøm Halden, MD, of the University of Oslo in Norway, and colleagues randomized subjects to receive either sitagliptin 50-100 mg/day for four weeks followed by a sitagliptin-free period of four weeks, or vice versa. Results showed that sitagliptin significantly increased first- and second-phase

Impaired Renal Function in Rheumatoid Arthritis In a study, patients with rheumatoid arthritis (RA) had a significantly higher 20-year cumulative incidence of an estimated glomerular filtration rate below 60 mL/min/1.73 m2 than patients without RA, but the 20-year cumulative incidence of an eGFR below 45 did not differ by significantly RA status. 25

n RA n No RA

25% 20% Less than 60

9% 10% Less than 45

eGFR (mL/min/1.73 m2) Source: Hickson RJ et al. Development of reduced kidney function in rheumatoid arthritis. Am J Kidney Dis 2014;63:206-213.

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RCC continued from page 1

histologic subtype, and other characteristics. The patients with diabetes were significantly older non-diabetics at RCC diagnosis, more likely to be obese, and had higher Charlson scores. They also were significantly more likely to have clear cell RCC (83% vs. 76%). Of the 939 matched cases and controls, 463 died within a median of 5.5 years after nephrectomy, Dr. Psutka’s group found. Survivors had a median follow-up of 8.6 years. The five-year cancer-specific survival rates did not

differ significantly among diabetics and non-diabetics (84% vs. 87%), but five-year overall survival was significantly lower among the diabetic patients (66% vs. 75%). Even after adjusting for Charlson score, diabetic patients had a significant 33% increased risk of all-cause mortality. In a sub-analysis of patients with clear cell RCC, diabetics had a significant 44% increased risk of cancer-related death than non-diabetics after adjusting for potential confounders. The new findings differ from those of some recently published studies. For example, a study 492 patients with non-

Observation for PCa continued from page 1

Patients treated at comprehensive cancer centers had a significant 37% decreased likelihood of receiving EM than patients treated at community hospitals, and patients with private health insurance had a significant 10% decreased odds of receiving EM compared with those who had publicly funded health coverage. Although the study was not designed to explain the reasons behind these practice patterns, Dr. Maurice told Renal & Urology News: “Patient preference is a well known driving force behind treat-

Estradiol continued from page 1

60.4% of men with both high testosterone and estradiol levels reported very good or excellent libido (score as 4 or 5) compared with 31.3% of participants with both low testosterone and estradiol levels, the researchers reported in European Urology (published online ahead of print). These results are expected to be presented at the American Urological Association annual meeting in Orlando this May.

Study limitations In multivariable analysis, men with high levels of estradiol were twice as likely as those with low levels to report very good or excellent libido, according to the investigators. Although their study highlights the importance of estrogen in men on TST, the authors explained, limitations include a lack of a control group and absence of score comparisons before and after start of TST. They also noted that a larger sample size might have unmasked a confounding relationship between testosterone and libido.

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Matthew J. Maurice, MD

Prior findings confirmed “Estradiol plays an important role in libido in men taking testosterone supplementation,” Dr. Ramasamy said, adding that this finding is similar to what was identified in a recently published study by Joel S. Finkelstein, MD, and collaborators at Massachusetts General Hospital in Boston. The study of 198 healthy men aged 20-50 years demonstrated that libido declines dramatically in conjunction with decreased levels of serum estrogen. Results were published in the New England Journal of Medicine (2013;369:1011-1022). Additionally, according to Dr. Finkelstein’s group, the study demonstrated that testosterone deficiency in men accounts for decreases in lean mass, muscle size, and strength, whereas estrogen deficiency primarily accounts for increases in body fat. “Aromatase inhibitors to reduce estrogen should be used judiciously to treat symptoms, such as gynecomastia and breast tenderness, and not for the sole purpose of reducing a high estrogen laboratory value,” Dr. Ramasamy cautioned. n

metastatic RCC—62 with type 2 diabetes and 430 without—found that the presence of type 2 diabetes was not an independent prognostic factor for RCC. Although disease-specific and overall survival rates were lower in the diabetics than non-diabetics, the differences

were not statistically significant, according to a report published in the Korean Journal of Urology (2013;54:499-503). A study published online ahead of print in the World Journal of Urology found that type 2 diabetes at the time of radical or partial nephrectomy for localized RCC had no significant impact on cancer-specific and recurrence-free survival in patients. T he Genitouri nar y Ca ncer Symposium is co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. n

ment decisions, and it is possible that patients who seek care at comprehensive cancer centers or who have private health insurance may be more involved in their own medical care and at the same time less willing to accept EM.” Alternatively, there may be financial disincentives for healthcare systems or healthcare providers to offer EM, as this approach may cost less—and presumably, reimburse less—than the initial active treatment of PCa, he said. For the other study, Dr. Maurice’s group used the National Cancer Database to identify 103,092 men who had either pT3 disease (81% of the cohort) or pT2 disease with posi-

tive surgical margins (19%). Of these subjects, 10,043 (9.7%) received aRT. Use of aRT declined from 11.5% of cases in 2004 to 7.8% of cases in 2011, the investigators reported. Men diagnosed in 2011 had a significant 22% decreased odds of receiving aRT than those diagnosed in 2004. In addition, compared with patients who received care at community hospitals, those treated at comprehensive cancer centers or teaching hospitals had a significant 37% and 58% decreased likelihood of receiving aRT, respectively. The investigators said the lower use of aRT at teaching hospitals may reflect greater use of salvage radiation. n

Cancer-specific mortality is higher in diabetics with clear cell RCC.

Low T Predicts Worse PCa LOW testosterone levels prior to radical prostatectomy (RP) for prostate cancer (PCa) are associated with worse oncologic outcomes, new findings suggest. In a study o 177 men who had their preoperative testosterone levels measured and underwent RP, a team led by R. Jeffrey Karnes, MD, of Mayo Clinic in Rochester, Minn., found that patients with a low preoperative testosterone level (below 300 ng/dL) had a significantly higher risk of positive surgical margins and seminal vesicle invasion compared with men who had normal testosterone levels before surgery. Low testosterone was associated with a slightly, but not significantly, higher rate of biochemical failure, the investigators reported in the Journal of Men’s Health (2014;10:129-133). Patients had a median preoperative testosterone level of 423 ng/dL and a median age of 65 years. Of the 177 patients, 40 had low and 137 had normal testosterone. The study had a median follow-up of about 15 years, making it the longest follow-up to date correlating preoperative testosterone levels with biochemical failure in men undergoing RP, the researchers noted. Positive surgical margins and seminal vesicle invasion were found in 47.5% and 22.5%, respectively, of the low testosterone group compared with 29.9% and 8%, respectively, of the normal testosterone group. Additionally, the study showed that higher body mass index was associated with lower testosterone levels. “The data add to the accumulating evidence that low testosterone levels could potentially be an adverse factor in prostate cancer patients,” Dr. Karnes’ group concluded. n

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www.renalandurologynews.com MARCH 2014

Renal & Urology News 7

Live Kidney Donors Face Elevated ESRD Risk BY DELICIA HONEN YARD INDIVIDUALS who donate a kidney have a small increased lifetime risk of developing end-stage renal disease (ESRD) compared with healthy nondonors, but they are much less likely than the general population to develop ESRD. Both findings are probably due to the fact that potential organ donors are thoroughly tested to ensure they will be able to survive with just one kidney. “Compared with matched healthy non-donors, kidney donors had an increased risk of ESRD over a median of 7.6 years; however, the magnitude of the absolute risk increase was small,” Dorry L. Segev, MD, PhD, and fellow investigators wrote in the Journal of the American Medical Association (2014;311:579-586). Dr. Segev, a transplant surgeon at The Johns Hopkins Hospital in Baltimore, led what is believed to be the larg-

ESRD risk is higher in donors compared with matched healthy non-donors. est study of ESRD risk in living kidney donors, according to information from Johns Hopkins Medicine. The researchers analyzed medical records from all 96,217 living U.S. adults who donated a kidney from April 1994 to November 2011. They compared data obtained from these records with information from 20,024 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were linked to Centers for Medicare & Medicaid Services data to ascertain development of ESRD. The investigators defined ESRD as the initiation of maintenance dialysis, placement on the transplant waiting list, or receipt of a living or deceased donor kidney transplant. By age 80 years, the estimated lifetime risk of ESRD was 90 per 10,000 live donors, 14 per 10,000 healthy nondonors, and 326 per 10,000 unscreened non-donors (general population). During a median follow-up of 7.6 years (maximum 15.0 years), ESRD developed in 99 live donors in a mean of 8.6 years after donation, according to the investigators. By comparison, during a median follow-up of 15.0 years (maximum 15.0 years), ESRD developed in

RUN0314_DonorESRD.indd 7

36 matched healthy non-donors in 10.7 years. The estimated risk of ESRD at 15 years after donation was 30.8 per 10,000 donors, and 3.9 per 10,000 matched healthy non-donors. Dr. Segev’s group observed this difference in both black and white individuals.

Blacks had the highest absolute risk of ESRD regardless of donor status. As stated in the information from Johns Hopkins Medicine, all increased risk of ESRD in the white donors studied could be attributed to the donation itself, but one-third of ESRD cases in the black donors appeared to come

from an inherent risk—something not identified during the donor screening process. Dr. Segev and his team have launched a study to understand the increased risks for black kidney donors and to develop a more sensitive screening tool for this population. n

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2/21/14 1:21 PM

8 Renal & Urology News

MARCH 2014 www.renalandurologynews.com

News in Brief

Please visit us at www.renalandurologynews.com for the latest news updates from the fields of urology and nephrology

Short Takes Surgical Quality Not Just Related to Volume

compared with 0.5% for patients

Prostate cancer patients who undergo

associated with development of AKI in-

radical prostatectomy by a urologist

cluded ST-segment elevation myocar-

different from the one who diagnosed

dial infarction, severe chronic kidney

their prostate cancer are less likely to

disease, and cardiogenic shock.

without AKI. Factors most strongly

suffer surgical complications within 30 not change urologists, a study pub-

High Uric Acid Raises Risk of Diabetes

lished online ahead of print in Health

Elevated levels of uric acid are asso-

Services Research noted. Men who

ciated with an increased likelihood of

changed urologists between diagnosis

diabetes, but uric acid levels decline

and treatment had a significant 18%

after diabetes is diagnosed.

days after surgery than those who did

decreased odds of 30-day surgical

The study of 11,134 participants

complications versus those who did

in the Atherosclerosis Risk in Com-

not change urologists.

munities Study, researchers led by Elizabeth Selvin, MD, of Johns Hopkins

Study: AKI Develops in 7% of PCI Patients

University in Baltimore, showed that

Acute kidney injury (AKI) develops in

was associated with a significant 18%

7% of patients undergoing percuta-

increased risk of diabetes, after ad-

neous coronary intervention (PCI),

justing for potential confounders. The

researchers reported in JACC: Cardio-

association remained significant even

vascular Interventions (2014;7:1-9).

after adjusting for fasting glucose

each 1 mg/dL increment in uric acid

In a study of 985,737 consecutive

and insulin levels, the researchers re-

patients who underwent PCIs at 1,253

ported online in the American Journal

sites, 69,658 (7%) experienced AKI,

of Epidemiology. Among subjects with

with 3,005 (0.3%) requiring new dialy-

diabetes, each additional five years’

sis treatment. The in-hospital mortality

duration of diabetes was associated

rate was 9.7% for patients with AKI

with a 0.10 mg/dL lower uric acid

and 34% for those requiring dialysis

level in adjusted analyses.

Suing Patients Not Welcome In a recent online poll, Renal & Urology News asked nephrologists and urologists, “Would you accept a new patient who has sued another doctor for malpractice?” A plurality of respondents said “no.” Here are the results based on 110 responses.

Yes: 22.73%

No: 48.18%

Do not know: 29.09%

RUN0314.NewsInBrief.indd 8

Complications of PCa Treatment Characterized C

omplications other than urinary incontinence or erectile dysfunction occur frequently following treatment for prostate cancer (PCa), according to new findings published online in The Lancet Oncology. In a retrospective study of 32,465 PCa patients who underwent radical prostatectomy or radiotherapy alone, the five-year cumulative incidence of hospital admission for a treatment-related complication, needing a urologic procedure, a rectal or anal procedure, or an open surgical procedure was 22.2%, 32.0%, 13.7%, and 0.9%, respectively, Robert K. Nam, MD, of the University of Toronto, and colleagues reported. The fiveyear cumulative incidence of a second malignancy was 3.0%. At five years, patients who received radiotherapy had more rectal or anal procedures, open surgical procedures, and second malignancies than those who had surgery, but surgery patients had more urologic procedures.

IV Iron Drugs Demonstrate Similar Efficacy, AE Rates F

erumoxytol and iron sucrose have comparable safety and efficacy in the treatment of iron deficiency anemia in patients with chronic kidney disease, according to the results of a head-to-head randomized, controlled trial. The trial, by Iain C. Macdougall, MD, of King’s College Hospital in London, and colleagues included 162 anemic CKD patients randomly assigned to receive either ferumoxytol (80 patients, two 510 mg injections) or iron sucrose (82 patients, 1.0 g iron sucrose administered either as a slow injection or infusion). Overall, the treatment arms experienced similar increases in hemoglobin from baseline to week 5, the researchers reported in the Clinical Journal of the American Society of Nephrology. The rate of adverse events (AEs) was 48% for ferumoxytol and 65% for iron sucrose. The rate of AEs related to treatment was 10% and 16%, respectively. The rate of serious AEs was 9% and 7%, respectively, and the rate of serious AEs related to treatment was 1% and 1%, respectively.

Bladder Cancer Linked to Breast Cancer Gene H

uman epidermal growth factor receptor 2 (HER2), a known driver of some breast cancers, is amplified in the micropapillary urothelial carcinoma form of bladder cancer compared with typical urothelial carcinomas, and this amplification is associated with a greater risk of cancer-related death, according to the findings of a recent study published online ahead of print in Modern Pathology. John C. Cheville, MD, a pathologist at the Mayo Clinic in Rochester, Minn., and colleagues reached this conclusion after reviewing pathologic material and data from patients undergoing cystectomy at the facility from 1980 to 2008. They identified amplification of HER2 (referred to as ERBB2 in the study) in 9 of 61 micropapillary carcinomas (15%) compared with 9 of 100 typical urothelial carcinomas (9%). Patients with HER2 amplification in micropapillary carcinoma demonstrated a nearly threefold increased risk of bladder cancer death, a risk that remained significantly elevated on multivariate analysis. The researchers observed no association between cancer-specific survival and HER2 amplification in patients with typical urothelial carcinoma.

2/19/14 3:20 PM

www.renalandurologynews.com MARCH 2014

Renal & Urology News 9

Greater Intake of Dietary Lycopene May Lower Prostate Cancer Risk BY JODY A. CHARNOW TWO recently published studies suggest that lycopene may help protect against the development of prostate cancer (PCa). In one study, researchers led by Edward Giovannucci, MD, ScD, of the Harvard School of Public Health in Boston, found that increased dietary intake of lycopene is associated with a decreased risk of PCa, especially lethal PCa. The investigators also demonstrated that higher lycopene intake is associated with lower angiogenic potential in tumors based on vessel size and shape. “Based on these results, we hypothesize that the consumption of a diet rich in lycopene-containing foods reduces the aggressive potential of prostate cancer by inhibiting the neoangiogenesis that occurs in tumor development,” Dr. Giovannucci’s team reported online ahead of print in the Journal of the National Cancer Institute. In the other study, Simone Mariani, MD, of Sant’Andrea Hospital and Fabia Mater Hospital, both in Rome, and collaborators found that low prostatic lycopene levels are associated with a greater likelihood of PCa. In a paper published in the International Journal of Molecular Sciences (2014;15:1433-1440), the investigators said their findings point to prostatic lycopene level as a promising biomarker of PCa.

Lycopene is a carotenoid found in abundance in tomato, tomato-based products, pink grapefruit, and watermelon, Dr. Giovannucci and his colleagues explained. In a meta-analysis of studies published up to 2003, high intakes of tomato or tomato-based products was associated with a 10%20% decrease in PCa risk and high serum or plasma concentrations of lycopene were associated with a 25% decreased risk, they noted. Dr. Giovannucci and his group studied 49,898 male health professionals who provided dietary information through questionnaires. Men in the highest quintile of dietary lycopene intake had a significant 9% decreased risk of PCa overall and a 28% decreased risk of lethal PCa compared with those in the bottom quintile, after adjusting for multiple variables. When the researchers limited their analysis to men who had at least one negative PSA screening test, subjects in the highest quintile had a significant 53% decreased risk of lethal PCa compared with those in the lowest quintile. Study subjects were participants in the Health Professionals Follow-up study, an ongoing prospective cohort study consisting of 51,529 U.S. male dentists, osteopaths, podiatrists, pharmacists, and veterinarians aged 40-75 years at baseline in 1986. The study by Dr. Mariani and colleagues included 32 patients with pros-

Increased consumption appears to be especially protective against lethal PCa, data show

Tomatoes are a rich source of lycopene.

tatic high-grade intraepithelial neoplasia (HGPIN), a pre-cancerous lesion. The investigators instructed subjects to consume 20-25 mg/day of lycopene through dietary supplementation for six months. Patients underwent a six-month follow-up prostate biopsy and were classified into three groups based on histopathologic findings: prostatitis (seven patients), HGPIN (16 patients), and PCa (nine patients). The researchers measured PSA and plasma lycopene levels before and after the lycopene supplementation, but measured prostatic lycopene level only after supplementation. Only prostatic lycopene level was significantly different among the three groups, with a level below 1 ng/mg sig-

nificantly associated only with PCa. Of the nine patients with PCa, seven (77.8%) had a prostatic lycopene level below 1 ng/mg compared with only one (6.3%) of 16 patients with HGPIN and none of the seven patients with prostatitis, the researchers reported. In a recently published systematic review and meta-analysis in the Journal of Nutritional Science and Vitaminology (2013;59:213-223), Chinese investigators found that consumers of the highest intake of raw tomato had a 19% decreased risk of PCa compared with those who had the lowest intake. Additionally, the meta-analysis, which examined data from six prospective cohort studies and 11 prospective nested case-control studies, found that consumers of the highest levels of cooked tomato intake versus the lowest intake had a 15% decreased risk. The highest intake of lycopene was associated with a 7% decreased risk of PCa compared with the lowest intake. The researchers noted that their meta-analysis does not strongly support a positive association between lycopene or tomato intake with decreasing PCa, but it does provide “reasonable evidence that research on lycopene/tomato intake in association of prostate health should be carried out among more geographical and age groups and correlation of lycopene intake and plasma lycopene should be examined.” n

Sickle Cell Trait May Up Need for Higher ESA Doses IN AFRICAN Americans, the presence of sickle cell or hemoglobin C trait may contribute to the need for higher doses of erythropoiesis-stimulating agents (ESAs) during dialysis to manage anemia. Investigators made this discovery after conducting a cross-sectional study of a cohort of 5,319 African American adults undergoing hemodialysis in the United States. To determine the prevalence of hemoglobinopathy traits and quantify their influence on ESA dosing, Vimal K. Derebail, MD, MPH, of the University of North Carolina

RUN0314_Lycopene.indd 9

Kidney Center in Chapel Hill, and colleagues examined laboratory and clinical data obtained from these patients over a six-month period in 2011. A total of 542 patients (10.2%) had sickle cell trait—a more common rate than the 6.5% to 8.7% seen in the general African-American population. In addition, 129 patients (2.4%) had hemoglobin C trait. No other hemoglobinopathy traits were present, Dr. Derebail and colleagues reported online ahead of print in Journal of the American Society of Nephrology. Of the 5,002 patients receiving

ESAs, 10.3% had sickle cell trait and 2.4% had hemoglobin C trait. The two groups had similar demographic and clinical variables, and achieved hemoglobin levels were nearly identical. Patients with these hemoglobinopathy traits received higher median doses of ESA than did patients with normal hemoglobin (4,737.4 vs. 4,364.1 units/ treatment). Multivariable analyses showed hemoglobinopathy traits to be associated with 13.2% more ESA per treatment. Within subgroups, patients with sickle cell trait received a 13.2%

higher dose, similar to the 12.9% higher dose recorded for patients with hemoglobin C trait. “Our findings suggest that the presence of sickle cell trait and hemoglobin C trait may explain, at least in part, prior observations of greater ESA doses administered to African-American dialysis patients relative to Caucasian patients,” the authors wrote. It is unknown whether this higher dose of medication is associated with any adverse consequences, Dr. Derebail said in a statement from the American Society of Nephrology. n

2/19/14 3:22 PM

10 Renal & Urology News

■ GUCS 2014

MARCH 2014 www.renalandurologynews.com

2014 Genitourinary Cancers Symposium, San Francisco

Data Support Pre-Chemo Enzalutamide The drug decreased the risk of death by 29% versus placebo in chemotherapy-naïve mCRPC patients BY JODY A. CHARNOW Enzalutamide significantly improves survival in men with metastatic castration-resistant prostate cancer (mCRPC) who have not prior chemotherapy, according to study findings. The double-blind PREVAIL study included 1,717 chemotherapy-naïve men with mCRPC randomly assigned to receive enzalutamide—an androgen receptor inhibitor—or placebo. Patients in the enzalutamide arm had a 29% decreased risk of death and an 81% decreased risk of radiographic progression or death, investigators reported. Cancer burden seen on imaging studies was decreased in 59% of patients in the enzalutamide arm compared with only 5% in the placebo arm. In addition, patients taking enzalutamide on average required chemotherapy about 17 months later than those on placebo (28.0 vs. 10.8 months), which translated into

Docs Favoring Newer Tools For UTUC Dx MODERN diagnostics such as endoscopy have supplanted traditional methods of diagnosing upper tract urothelial carcinoma (UTUC), researchers at Washington University School of Medicine in Saint Louis, Mo., reported. Goutham Vemana, MD, and colleagues identified patients aged 66-90 who underwent

a 65% decreased risk of needing chemotherapy. “Enzalutamide is likely to become an important new treatment option that has a significant impact on the progression of prostate cancer,” said lead author Tomasz Beer, MD, Professor of Medicine at Oregon Health and Science University in Portland. The estimated median overall survival was estimated at 32.4 months in the enzalutamide arm compared with 30.2 months in the placebo group; however, because the median follow-up was approximately 22 months—about 10 months short of the estimated overall survival—the hazard ratio is a more accurate way to express the survival benefit, Dr. Beer noted. The median radiographic progression-free survival was not yet reached in the enzalutamide arm and 3.9 months in the placebo arm, researchers said. In addition, 78% of enzalutamidetreated patients had a PSA decline of

50% or more compared with 3.5% of placebo recipients. Seizures occurred one patient in each study arm (one-tenth of 1% of patients in both arms). Both patients had a history of seizures that was not known to the investigators at the time of enrollment.

Enzalutamide recipients had a 65% lower risk of needing chemotherapy. Based on these positive interim data, the Independent Data Monitoring Committee recommended that the trial be stopped and patients receiving placebo be offered enzalutamide. Study findings showed that enzalutamide’s effects translated into improved quality of life. “As measured

by how long patients’ quality of life was maintained, enzalutamide was much more effective than placebo,” Dr. Beer told Renal & Urology News. The FDA approved enzalutamide on August 31, 2012 to treat mCRPC in patients previously treated with docetaxel. The drug is co-marketed under the brand name Xtandi by Astellas Pharma U.S., Inc., of Northbrook, Ill., and Medivation, Inc., of San Francisco. The FDA approval was based on the findings of the AFFIRM trial, which included 1,199 patients with metastatic CRPC who had received prior treatment with docetaxel. The median overall survival was 18.4 months for men who received the drug compared with 13.6 months for patients who received placebo. In this trial, the most common adverse effects observed in study participants taking enzalutamide included fatigue, back pain, constipation, and joint pain. n

AB Blood Predicts Less Lethal PCa MEN with blood group AB are less likely to develop lethal prostate cancer (PCa) than men with blood group O, researchers reported. Yuksel Urun, MD, of the DanaFarber Cancer Institute in Boston, and colleagues prospectively evaluated the association between ABO blood group and risk of lethal PCa in the Health Professionals Follow-up Study from 1996-2008. A total of 2,793 cases of incidence PCa were documented during 12 years of follow-up of 26,602 men, including 289 lethal cases (either

death from PCa or distant metastases). The frequency of ABO blood type was similar between men who developed PCa and other subjects. On multivariate analysis, blood type was not associated with overall PCa incidence, but compared with men who had blood group O, those with blood group AB were 61% less likely to develop lethal PCa. Compared with blood group O, blood group A or B was not associated with an increased risk of lethal PCa. Additionally, ABO blood type was not significantly associated with the risk

of advanced stage or high-grade cancers (Gleason score 8-10). In a recently published study in BJU International, researchers found that blood group O in patients with renal cell carcinoma (RCC) is associated with a lower risk of lymph node metastases but a higher risk of bilateral disease. In addition, the study of 556 patients who underwent surgery for RCC showed that blood group O was not associated with survival and ABO blood group overall was not associated with RCC prognosis. n

treatment for UTUC from 1992-2009. They found a downward trend in the use of intravenous pyelograms and retrograde pyelograms, and an increase in the use of endoscopy, computed tomography urograms, and magnetic resonance urography. The researchers observed no change in the incidence of lower stage disease over time. n

RUN0314_GU_Cancers.indd 10

BP Drugs May Improve mRCC Patient Survival PATIENTS with metastatic renal cell carcinoma (mRCC) may experience significant improvements in overall and progression-free survival if they receive concomitant antihypertensive treatment with an angiotensin system inhibitor (ASI), according to a recent study.

For the study, researchers analyzed data from clinical trials of medications to treat mRCC. The study population totaled 4,736 patients. The investigators found that the median overall survival was 26 months for patients receiving ASIs—which include ACE inhibitors and angio-

tensin receptor blockers—compared with 17 months for non-ASI users. The median progression-free survival was 8.3 months for ASI users versus 6.5 months for non-users, according to researchers led by Rana McKay, MD, a clinical oncology fellow at Dana-Farber Cancer Institute in Boston. n

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www.renalandurologynews.com MARCH 2014

Renal & Urology News 11

Mutations ID Men at Higher PCa Risk A new study supports the use of targeted PSA screening of BRCA2 carriers, researchers concluded MEN WHO have the BRCA2 gene mutation are significantly more likely than non-carriers to have intermediate- or high-risk prostate cancer (PCa) found on prostate biopsy, according to a study. The results support the use of targeted PSA screening of BRCA2 carriers, researchers concluded. Previous research has found that PCa is more likely to develop in men with BRCA1 or BRCA2 gene mutations than in men without these mutations. The study enrolled 2,481 men from 62 centers in 20 countries. The cohort consisted of 791 BRCA1 carriers, 531 BRCA1 controls, 731 BRCA2 carriers, and 428 BRCA2 controls. A total of 199 subjects (8%) presented with a PSA level above 3.0 ng/mL and were offered a prostate biopsy. In all, 162 biopsies were performed and 59 patients were diagnosed with PCa (18 BRCA1 carriers, 10 BRCA1 controls, 24 BRCA2 carriers, and seven BRCA2 controls). The positive predictive value (PPV) of

Study: Stone Rates Highest In August THE FIRST study to examine the role of climate on stone presentation in a large city above the Southern “stone belt” states found that emergency department (ED) visits for renal colic increase during warmer months and decrease in colder months. Mohit Sirohi, MD, and Benjamin F. Katz, MD, of Beth Israel Medical Center in New York, and colleagues analyzed 3,647 ED visits for renal colic at their hospital from January 2007 through December 2012. The highest average monthly rate of renal colic occurred in August (43.8 per 1,000 ED visits) and the lowest occurred in February (28.8 per 1,000 ED visits), the researchers reported online ahead of print in the Journal of Endourology. On multivariate analysis, only average monthly temperature was significantly associated with monthly urinary calculi presentation rate, according to the investigators. “Urologists should recognize that warmer seasons might result in an increased incidence of patients pre-

RUN0314_BRCA2.indd 11

a prostate biopsy using a PSA threshold of 3.0 ng/mL for detecting intermediate- and high-risk PCa was 2.38% for men carrying the BRCA2 mutation compared with 0.71% for controls (men who tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families). “These early findings indicate that the tumours detected [in BRCA2 carriers] are more likely to need treatment based on national guidelines for management of more aggressive PCa,” Rosalind A. Eeles, PhD, of The Institute of Cancer Research in London, U.K., and colleagues concluded in an online report in European Urology. The results are from the initial screening round of the IMPACT study. The overall PPV of biopsies using a 3.0 ng/mL PSA threshold was 36% (59 of 162 biopsies). The PPV was 37.5% for BRCA1 carriers, 23.3% for BRCA1 controls, 48% for BRCA2 carriers, and 33.3% for BRCA2 controls. The

senting to the ED with renal colic,” the authors concluded. “We can combat this effect by instructing patients to take several known preventative measures such as increasing fluid intake and decreasing protein consumption.” Male and female patients accounted for 63% and 37% of ED visits for renal colic, respectively, according to the study. In addition, 50% of patients were aged 21-44 years, 42% were aged 45-64 years, and 8% were aged 65 and older. Approximately 14% of all patients presenting with a stone were admitted as inpatients, with the remainder discharged from the ED, the researchers reported. In their discussion of study limitations, they noted that their study was a single-institution retrospective investigation looking at billing codes as a surrogate for renal stone presentation. “There could be errors in coding, misdiagnosis, or a patient presenting with more than one medical issue,” the researchers noted. “Another limitation to the study is that patients may have presented multiple times, with each presentation assigned as a unique visit,” they stated. “This could lead to a falsely high number of new presentations related to the monthly temperature.” n

Positive Predictive Values of BRCA1 and BRCA2 For detecting intermediate- or high-risk prostate cancer, here are the positive predictive values for BRCA1 and BRCA2 gene mutation carriers and controls based on a 3.0 ng/mL PSA threshold for prostate biopsy, according to a new study. 50 40 30 20 10 0

37.5%

23.3%

48%

33.2%

BRCA1 carriers

BRCA1 controls

BRCA2 carriers

BRCA2 controls

Source: Bancroft EK et al. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: Results from the initial screening round of the IMPACT study. Eur Urol 2014 (published online ahead of print).

researchers found no statistically significant difference among the groups. Although the observed differences in PCa detection rates between carriers and controls were not statistically significant, the trend is clear, they wrote. With larger numbers of PCa cases in the follow-up phase of the study (five

years), “these differences, if sustained, are likely to be significant.” “Future screening rounds will determine the optimal frequency of PSA testing, determine the utility of PSA screening in BRCA1 carriers, and provide further data on the value of annual screening in BRCA2 carriers.” n

Perinephric Fat Thickness Predicts RAPN Blood Loss PERINEPHRIC fat thickness could aid

renal masses, and, if validated, pro-

in preoperative risk assessment in

spectively, may have a role in develop-

patients undergoing robot-assisted

ment of enhanced clinical prediction

partial nephrectomy (RAPN), according

tools,” the authors concluded.

to researchers.

Dr. Harper and his colleagues

In a study of 53 patients undergo-

explained that obesity frequently is cat-

ing RAPN, a team at the University of

egorized by body mass index (BMI), but

Washington in Seattle led by Jonathan

visceral and abdominal wall fat quantity

D. Harper, MD, found that increases

vary with equivalent BMI. “Because peri-

in perinephric fat, especially medial

nephric fat around the kidney impacts

and posterior fat, were associated

the operative field, it is expected to be

with increased estimated blood loss

a superior predictor of complexity.”

(EBL) and operative time during the

Of the 53 patients, 27 had a BMI

procedure. Each 1 mm increment in

below 30 kg/m2 and 26 had a BMI of

medial and posterior perinephric fat

30 kg/m2 or higher (obese). The mean

was associated with a 24 mL and 19

EBL differed significantly between the

mL increase in EBL, respectively, and

obese and non-obese patients (300 vs.

3.3 minute and 3.3 minute increase

212 mL). Although obese patients had

in operative time, Dr. Harper’s group

a 37 minute longer operative time on

reported online ahead of print in the

average, this difference did not reach

Journal of Endourology.

statistical significance. On multivariate

“Perinephric fat measurements

analysis, however, increasing BMI was

are independently associated with

associated with increased operative

increased EBL and operative time in

time, but was not independently associ-

patients undergoing RAPN for small

ated with EBL. n

2/19/14 3:24 PM

www.renalandurologynews.com MARCH 2014

Renal & Urology News 15

Radiation vs. Radical Surgery for PCa Some may find it surprising that Frank A. Critz, MD—a radiation oncologist who focuses on prostate cancer— generally considers radical prostatectomy to be the go-to treatment for localized disease. But now that he and fellow investigators have completed a 25-year study showing radiation therapy outcomes to be equal to those of radical prostatectomy under the strict surgical definition of prostate cancer control (The Journal of Urology 2013;189[3]:878-883), Dr. Critz—the founder and medical director of Radiotherapy Clinics of Georgia–Decatur (an affiliate of Vantage Oncology), can comfortably recommend both options to patients. Other than the impressively long followup period, what sets your findings apart?

Dr. Critz: An equally important factor in our report is how the 25-year diseasefree-survival rates were calculated. They were calculated with the surgical definition of recurrence following radical prostatectomy instead of the universally used ASTRO [American Society for Radiation Oncology] or Phoenix definition of recurrence used by radiation oncologists when calculating disease-free-survival rates. Use of the surgical definition of recurrence was placed in the title of this study since this factor is so important. The surgical definition of recurrence is based upon a PSA rise above 0.2 ng/ mL or a nadir above this level. In contrast, neither of the radiation oncology definitions of recurrence requires any specific PSA level. Thus, the radiation definitions have completely different meanings relative to the surgical definition of recurrence. From a practical standpoint, as documented both after radical prostatectomy and after irradiation, calculation with the two radiation definitions significantly inflates disease-free-survival rates relative to calculations using the surgical definition of recurrence.

On The Web RUN0314_ExpertQA.indd 15

When radiation oncologists write research papers comparing irradiation and surgical disease freedom, the effect of the definition of disease freedom on calculations is virtually always ignored. In fact, this is the only radiotherapy publication on disease-freesurvival rates for prostate cancer that compares PSA-defined disease-freesurvival rates of surgery with irradiation using the same definition of recurrence—the surgical definition.

Dr. Critz: Our study is ongoing, but whether there will be any value to analyzing men after 25-year follow-up may be questionable. The reason we continue to analyze our men is to add to the sample size at 15-, 20-, and 25-year follow-up. Is there a point at which follow-up data no longer contribute to the scientific knowledge on this subject?

Dr. Critz: Due to the small sample size at 20-year follow-up (30 men) and 25-year follow-up (five men), I do not think one can make a definitive statement about length of follow-up except to say that it should continue indefinitely for the present time until we get more information. For example, when I wrote the paper, the longest time to recurrence was at 15.5-year follow-up. Subsequent to writing the paper, we have had four more recurrences, with the longest time to recurrence now being 17 years. Were you surprised by the finding that radiation was equal to radical prostatectomy in terms of the risk of late recurrence?

Will you publish findings at 30-year follow-up and beyond? Or does the relatively late age of diagnosis for this disease diminish the usefulness, or even the possibility, of data collected after that point?

What has been the reaction of the urology community toward these findings?

Dr. Critz: The response to the report has been overwhelmingly positive both from urologists in academic settings and those in private practice. In fact, I have not heard any negative comments. I think urologists respect the findings from our program because we stress that there should be a universal PSA definition of recurrence following either radiation or radical prostatectomy for prostate cancer and not the current status of a radiation definition separate from a surgical definition. Have your findings changed the way you advise men seeking treatment for prostate cancer?

Dr. Critz: Since I have continually monitored the disease-free-survival results of our program, which have always been calculated with the surgical definition of recurrence, I was not surprised by the findings and, thus, our paper has had no real impact on how we advise men seeking treatment for prostate cancer. Due to the 5% of recurrences occurring after 10-year follow-up, I have stressed that men continue follow-up indefinitely. This is especially important when we treat young men who have a projected life span of 20 to 30 years.

At the 25-year mark, median followup was 11 years. What was the average age of your study patients at enrollment?

Dr. Critz: At the time of seed implantation, the average age of men was 65 years. This is an interesting point for, as I recall, men in the United States live an average 77 years. Thus, it requires a large sample size to find enough men who live into their late 80s and 90s to be evaluated for a 25-year study.

Dr. Critz: Yes, I was surprised to find that our late recurrence rate, defined as recurrence after 10-year follow-up, of 5% was essentially the same as the 6.4% following radical prostatectomy at Johns Hopkins. I believe the similarity is, again, based on using the same definition of recurrence.

There is a strong move to build multidisciplinary centers. — Frank A. Critz, MD

Do you think your findings might change how men in general are advised regarding prostate cancer treatment?

Dr. Critz: The major way this report might affect how men are advised regarding prostate cancer treatment is to suggest to men that when speaking with physicians they should not ask about “cure rates” but more precisely ask what their chance is of having a PSA level below 0.2 ng/mL 10 to 15 years after treatment. n

Continue the conversation online! We have many experts who weigh in on controversial topics important to you. Catch our discussions at www.renalandurologynews/expertqa.

2/19/14 3:25 PM

16 Renal & Urology News

■ NKF 2014, Las Vegas

MARCH 2014 www.renalandurologynews.com

The article below is a preview of a talk scheduled for presentation at the National Kidney Foundation Spring Clinical Meetings.

Guidelines and the Older CKD Patient BY TOMASZ BEBEN, MD, AND DENA RIFKIN, MD, MS Editor’s note: Dr. Rifkin, together with Mark Sarnak, MD, and Paul Stevens, MD, will participate in a session on this topic during presentations at the National Kidney Foundation 2014 Spring Clinical Meetings, April 22-26, at the MGM Grand in Las Vegas.

GERIATRIC patients with chronic kidney disease (CKD) are at high risk for morbidity and mortality not only from their underlying diseases, but also from the potential side effects of treatments. Often, treatment decisions need to be individualized, taking into account a patient’s preferences, comorbidities, life expectancy, and quality of life. This is a heterogeneous population in which a healthy and active 80-year-old with CKD 3A is quite different from a chronically ill 80-year-old with CKD 5. While the former patient may live to see the benefit of a given treatment, the latter patient may be more likely to be harmed by its adverse effects. Thus, crafting unified comprehensive practice guidelines is often difficult, and it is made more problematic by the fact that this population tends to be under-represented in trials that serve as a basis for guidelines. This article will illustrate some of the challenges with integrating potentially incomplete and conflicting guidelines into clinical practice.

Hypertension Although hypertension is highly prevalent in elderly patients with CKD and contributes to significant cardiovascular morbidity and mortality, its optimal management in this population is unknown. Most of the available data have been extrapolated either from studies of younger populations with CKD or elderly populations without advanced CKD. The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines on hypertension concluded that there is insufficient evidence to recommend any particular blood pressure (BP) goals in the elderly with CKD. Instead, a general recom-

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mendation was made to individualize therapy while carefully considering comorbidities and potential side effects, such as orthostatic hypotension. The guidelines also recommended that clinicians take into account the deleterious effects on quality of life that pharmacotherapy and certain lifestyle interventions, such as strict sodium restriction, may have. More recently, members of the Eighth Joint National Committee (JNC 8) published their 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults in which they discussed treatment of hypertension in the CKD and elderly populations.1 They provided a recommendation to treat hypertension to a goal of less than 150/90 mmHg in those older than 60 years and found no evidence that lower BP goals in this population are beneficial. In contrast, for patients with diabetes or CKD aged 18-70 years, a goal BP of less than 140/90 was recommended based on expert opinion. No specific recommendations were made for patients aged 70 years or older with a glomerular filtration rate less than 60 mL/min/1.73m2 based on a lack of outcomes data in this population. However, there was

Treatment decisions for geriatric CKD patients often need to be individualized. dissent among panel members, reflecting uncertainty even in the expert community;2 the ongoing multicenter Systolic Blood Pressure Intervention Trial (SPRINT), which encompasses a large proportion of patients with CKD and advanced age, hopefully will shed more light on this topic, although its intensive arm (less than 120 mm Hg systolic BP) is less than either of the debated targets by the members of the JNC committee.

Diabetes Diabetes and CKD often coexist and impart a very high risk for cardiovascular disease. The National Kidney Foundation’s Kidney Disease

Outcomes Quality Initiative (KDOQI) issued an update to their diabetes guidelines in 2012, recommending a goal hemoglobin A1C of 7% for diabetics with CKD. However, they suggested that goals may be liberalized for those who are at risk for hypoglycemia, have comorbidities, or a limited life expectancy. Furthermore, it has been hypothesized that elderly patients with a long duration of diabetes (more than 15 years) and established atherosclerosis are less likely to benefit from intensive glucose control.3 Thus, the American Diabetes Association, in conjunction with the American Geriatrics Society, provided more specific A1C goals in the elderly based on patient characteristics: less than 7.5% in healthy people with long life expectancies, less than 8.0% in those with moderate comorbidities and intermediate life expectancies, and less than 8.5% in those with multiple comorbidities and short life expectancies. Preference was also given to drug regimens that avoid imposing an undue burden on patients or their caretakers while minimizing adverse effects.

Lipids Both KDOQI and the ADA recommend LDL lowering with statins in patients with CKD and diabetes who are not yet on dialysis. The cardiovascular benefit from statins in the elderly has been observed within just 3.5 ± 1.5 years of follow-up in meta-analysis.3 The SHARP study also demonstrated improved cardiovascular outcomes with LDL lowering in patients with an average age of 62 and eGFR of 26 mL/min/1.73 m2, lending support to their usage in older patients with CKD. However, multiple studies have not shown statins to have a beneficial cardiovascular effect in ESRD populations. Furthermore, side effects, such as myopathy, may be more common in the elderly and should be monitored. Anemia For anemia management in CKD, KDIGO recommends that erythropoietin-stimulating agent (ESA) therapy should be initiated in dialysis patients and considered in pre-dialysis patients with Hb levels below 10 g/dL and should be avoided when Hb levels are above 11.5 g/dL. They further recom-

mend individualizing these choices based on the risks of ESA therapy and the degree of anemia symptoms. There are no specific data on optimal hemoglobin levels in the elderly with CKD. Yet, prior studies have shown an improvement in quality of life with ESA usage in this population.5

Vascular Access KDOQI recommends the placement of an arteriovenous (AV) fistula for initiation of dialysis, but the benefit of AV fistulas over AV grafts may not be realized in all elderly patients. AV fistulas are associated with longer maturation times and higher primary failure rates in the elderly, leading to additional procedures and an increased time using a catheter. For certain patients, an AV graft may be a more optimal choice, and certain studies have shown similar mortality outcomes compared with AV fistulas in the elderly.6 As with most treatments in this population, a patient’s comorbidities and life expectancy should be taken into account when considering the type and timing of access placement. n For more information about the NKF 2014 Spring Clinical Meetings visit www. nkfclinicalmeetings.org Tomasz Beben, MD, is a geriatrician and is currently a nephrology fellow at the University of California, San Diego. Dena Rifkin, MD, MS, is a nephrologist who is an Assistant Professor of Medicine at the University of California San Diego and an attending physician at the Veterans’ Affairs Medical Center in San Diego. REFERENCES 1. James PA, Oparil S. Carter BL, et al. 2014 Evidencebased guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2013 Epub ahead of print. 2. Wright Jr, JT, Fine LJ, Lackland DT, et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: The minority view. Ann Intern Med 2014 (Epub ahead of print). 3. Sue Kirkman M, Brisco VJ, Clark N, et al. Diabetes in older adults: a consensus report. J Am Geriatr Soc 2012;60:2342–2356. 4. Savarese G, Gotto AM Jr, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: A meta-analysis. J Am Coll Cardiol 2013;62:2090–2099. 5. Moreno F, Aracil FJ, Pérez R, Valderrábano F. Controlled study on the improvement of quality of life in elderly hemodialysis patients after correcting endstage renal disease-related anemia with erythropoietin. Am J Kidney Dis 1996;27:548–556. 6. DeSilva RN, Patibandla BK, Vin Y, et al. Fistula first is not always the best strategy for the elderly. J Am Soc Nephrol 2013;24:1297–1304.

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Renal & Urology News 17

Men’s Health Update Please visit us at www.renalandurologynews.com for the latest news updates from the fields of urology and nephrology

Night-Shift Work Increases Diabetes Risk A study published recently in the Journal of Biological Rhythms (2013;28:356-359) shows that diabetes is more likely to develop in people who do any amount of nightshift work. The study, by Timothy H. Monk, PhD, DSc, and Daniel J. Buysse, MD, of the University of Pittsburgh, included a heterogenous sample of 1,111 retired men and women, stratified by the number of years doing night shift work (past 9 pm, non-overtime basis). The rates of diabetes and elevated BMI were higher among individuals who had done any shiftwork compared with those who worked only daytime jobs. The rates did not differ based on the number of years spent working the night shift. The focus for physicians treating patients working night shifts should be encouraging healthy lifestyle habits, maintaining normal rhythms, and an adequate sleep schedule, and decreasing night-shift work whenever possible.

Elevated Melatonin May Cut Risk of Advanced PCa Higher levels of melatonin may decrease a man’s risk of prostate cancer (PCa), according to new findings presented in January at the American Association for Cancer Research-Prostate Cancer Foundation Conference on Advances in Prostate Cancer Research. In a study of 928 Icelandic men, Sarah C. Markt, MPH, a doctoral candidate in the Department of Epidemiology at the Harvard School of Public Health in Boston, and colleagues found that men with higher melatonin levels (above the median level for the cohort) had a significant 75% decreased risk for developing advanced PCa compared with subjects who had lower levels. The study also found a 31% reduced risk of PCa overall, but this was not statistically significantly. For the study, the researchers measured urine levels of 6-sulfatoxymelatonin, the main breakdown product of melatonin. The study subjects had a median 6-sulfatoxymelatonin urine level of 17.14 ng/mL.

Erectile Dysfunction, Uric Acid Linked in Patients with Coronary Artery Disease Patients with coronary artery disease (CAD) are more likely to have erectile dysfunction (ED) if they have elevated uric acid levels, according to researchers. In a cross-sectional study of 312 men with suspected CAD, 149 (47.7%) had ED as determined using the short ver-

Lung, Colorectal Cancer Less Likely in Physically Fit Men M

en who maintain good physical fitness have a lower risk of lung and colorectal cancer, according to study findings presented at the 2013 American Society of Clinical Oncology annual meeting. The study, by Susan G. Lakowski, MD, and colleagues, prospectively followed a cohort of 17,049 men with a mean age of 50 years undergoing preventative health at the Cooper Clinic in Dallas over more than 20 years. The V02max was calculated for each patient during a treadmill test to assess cardiorespiratory fitness. The investigators used Medicare claims data to determine who died or developed lung, colorectal, or prostate cancer (PCa). Men in the highest quintile of cardiorespiratory fitness levels had a 68% and 38% decreased risk of lung cancer and colorectal cancer, respectively, compared with men in the lowest quintile. The researchers found no significant effect of fitness on PCa. Among men who developed any of the three cancers, the risk of death was 64% lower among those in the highest versus lowest quintile of fitness.

Testosterone May Weaken Vaccine Response T

estosterone could at least partly explain why men have less robust immune responses to vaccines than women, according to a new study. In a study of 53 women and 34 men, David Furman, PhD, of Stanford University in Stanford, Calif., and colleagues analyzed the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) as well as immune system components, such as serum cytokines and chemokines. They found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of women compared with men regardless of age, the researchers reported online ahead of print in the Proceedings of the National Academy of Sciences. In addition, Dr. Furman’s team identified a cluster of genes involved in lipid biosynthesis that correlated with poor virus-neutralizing activity in men. This cluster of genes had been shown previously to be up-regulated by testosterone. Men with elevated serum testosterone levels and associated gene signatures exhibited the poorest antibody responses to TIV.

sion of the International Index of Erectile Function questionnaire. After adjusting for age and CAD, each 1 mg/dL increment in serum uric acid was associated of Sexual Medicine (2014;11:165-172). After further adjustment for estimated glomerular filtration rate, each 1 mg/dL increment in uric acid was associated with a non-significantly 21% increased risk of ED. The investigators, led by Mehmet Kanbay, MD, of Istanbul Medeniyet University in Turkey, noted that ED is associated with CAD, with prospective observational studies suggest that men with ED are at risk for future cardiovascular events. They hypothesized that increased serum uric acid levels may be one of the missing links between CAD and ED.

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MEDISTAT

with a significant 31% increased risk of ED, researchers reported in The Journal

29 PERCENT

The proportion of osteoporosis-related fractures accounted for by men in the U.S.

Source: Burge R et al. J Bone Miner Res 2007;22:465-475.

Short Takes

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22 Renal & Urology News

MARCH 2014 www.renalandurologynews.com

Canadian Guideline: Defer Dialysis Initiation is recommended when clinical indications emerge or when the eGFR is 6 mL/min/1.73 m2 or below BY DELICIA HONEN YARD The Canadian Society of Nephrology recommends an “intent to defer” rather than an “intent to start early” approach to dialysis initiation for patients with chronic kidney disease (CKD) in a new clinical practice guideline focused on timing the initiation of chronic dialysis. In the intent-to-defer strategy, patients with an estimated glomerular filtration rate (eGFR) below 15 mL/ min/1.73m2 are closely monitored by a nephrologist. Dialysis is initiated when clinical indications emerge or when the eGFR is 6 mL/min/1.73m2 or less—whichever occurs first, according to a report in the Canadian Medical Association Journal (2014;186: 112-117). In the guideline, developed by a panel nominated by the Canadian Society of Nephrology Clinical Practice Guidelines Committee, clinical indications for the initiation of dialysis include symptoms of uremia, fluid overload, refractory hyperkalemia or acidemia, or other conditions or symptoms that are likely to be ameliorated by dialysis. “Our recommendation places a high value on the avoidance of a burden-

some and resource-intensive therapy that does not provide measurable benefit when started before the development of a clinical indication, such as uremic symptoms,” wrote guideline chair Louise M. Moist, MD, MSc, a professor of medicine and epidemiology at the Schulich School of Medicine and Dentistry at Western University in London, Ontario, and coauthors.

Panel cited an absence of detectable evidence that early initiation improves outcomes. The group based the recommendation on findings from the Initiating Dialysis Early and Late (IDEAL) clinical trial as well as 22 other studies. Neither the randomized controlled trials nor the observational studies yielded any detectable evidence that early initiation of dialysis improved survival, quality of life, or hospital admission rates compared with late or deferred initiation, according to the guideline panel.

“The intent-to-defer strategy pertains specifically to dialysis initiation, and does not imply that patients should be referred to nephrologists at a lower level of kidney function,” the authors wrote. “Patients should be referred according to previously published guidelines.” Separately, in a recently published study, researchers in Norway found that an early dialysis start—defined as an eGFR of 10 mL/min/1.73 m 2 or higher—was not associated with improved quality of life. Inger Karin Lægreid, MD, of the Norwegian University of Science and Technology in Trondheim, and colleagues assessed QoL in 194 patients aged 75 years and older, 52 of whom started dialysis early and 142 started late (at an eGFR below 10 mL/min/1.73 m2). Previously, a meta-analysis of data from 15 studies totaling 1,285,747 patients indicated that early initiation of dialysis was associated with an increased risk of death. The researchers, who published their findings in Nephron Clinical Practice (2012;120:c121-c131), concluded that older age, greater likelihood of diabetes, and the presence of severe comorbid diseases partly explain this effect. n

Study: RCC Rarely Recurs After MIPN PATIENTS who undergo minimally invasive partial nephrectomy (MIPN) for renal cell carcinoma rarely experience recurrence of the cancer, according to researchers. In a study of 417 patients who underwent MIPN for mostly pT1 tumors, the estimated recurrencefree survival rates at two, five, and 10 years were 98.2%, 93.5%, and 88.3%, respectively, J. Stuart Wolf, Jr., MD, and colleagues at the University of Michigan Hospitals and Health Centers in Ann Arbor reported online ahead of print in the Journal of Endourology. The estimated overall survival rates were 95.6%, 89.1%, and 70.7%, respectively. Only one cancer-related death occurred. Study subjects had a mean tumor size of 2.9 cm and only 6.7% of patients had a pathologic stage T2 or greater. The median overall and oncologic follow-up was 3.3 and 2.9 years, respectively. Patients underwent standard, hand-assisted, or robotic-assisted laparoscopy. On multivariate analysis, only tumor stage was associated

Higher Dietary Acid Load Ups CKD Progression Risk

with recurrence and only patient

INCREASED dietary acid load is associated with progression of chronic kidney disease (CKD) in elderly patients, according to Japanese investigators. Eiichiro Kanda, MD, MPH, PhD, of Tokyo Kyosai Hospital, and colleagues studied 217 CKD patients with an average age of 70.6 years. All patients were on a low-protein diet with normal serum bicarbonate levels. The primary outcome was a 25% decline in estimated glomerular filtration rate (eGFR). The investigators grouped subjects into quartiles of net endogenous acid production (NEAP)—a measure of dietary acid load—every three months. Compared with patients in the lowest quartile of NEAP, those in the second, third, and fourth quartiles had a 3.9 times, 4.7 times, and 4.3 times increased odds of the primary outcome in adjusted analyses, according to a report in the American Journal of Nephrology (2014;39:145-152).

associated with overall survival.

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Mean NEAP values for the first, second, third, and fourth quartiles were 41.5, 60.6, 76.4, and 126.7 mEq/day, respectively. “Decreasing NEAP may be an effective and safe kidney-protective strategy,” Dr. Kanda’s group concluded. The researchers analyzed the effect of NEAP quartiles on the primary outcome according to bicarbonate level. Among patients with a low bicarbonate level, patients in the second, third, and fourth NEAP quartiles had a 2.3, 3.1, and 2.9 times increased odds of the primary outcome compared with those in the first quartile, Dr. Kanda and colleagues reported. Among patients with a high bicarbonate level, patients in the second, third, and fourth NEAP quartiles had a 9.4, 7.9, and 11.4 times increased odds of the primary outcome. In addition, the study showed that hypoalbuminemia or hyperkalemia

were associated with low serum bicarbonate and pre-existing conditions, but not NEAP. At Kidney Week 2013, Tanushree Banerjee, PhD, of the University of California San Francisco, and colleagues presented study findings showing that higher dietary acid load is associated with the development of end-stage renal disease among patients with CKD. The study included 1,486 adults with CKD who participated in the National Health and Nutrition Examination Survey III. ESRD developed in 311 participants (20.9%) during a median of 14.2 years of follow-up. Compared with subjects in the lowest tertile of net acid excretion (NAE), those in the middle and highest tertiles had a 3.8 times and 8.6 times increased risk for ESRD, the study found. The investigations ascertained NAE by 24-hour dietary recall questionnaire. n

age and American Society of Anesthesiologists (ASA) score were Compared with patients who had stage pT1a tumors, those with pT1b and pT2 or greater tumors were 4.8 times and 19 times more likely to experience recurrence, respectively. Each additional year of age was associated with a 5% increased risk of death. Compared with an ASA score of 1 or 2, a score of 3 or 4 was associated with a 3.5 times increased risk of death, Dr. Wolf’s group reported. “With limited impact of these small renal cancers on mortality, the clinician’s operative decisions should be guided by the understanding that recurrence-free survival is influenced by tumor stage and that overall survival is influenced by patients’ age and medical condition,” the authors concluded. n

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