Renal & Urology News January 2014 Issue

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Stents Do Not Improve RAS Outcomes

© CMSP / SPL

Optimal medical therapy prevented adverse events just as well in patients with CKD or hypertension

STENTS DO NOT significantly improve treatment of renal artery stenosis (shown above).

Microalbuminuria Predicts AF

BY WAYNE KUZNAR DALLAS—Microalbuminuria and microvascular abnormalities in the retina are independently associated with a higher risk of atrial fibrillation (AF).

The two together increase the risk of AF by more than 20-fold, Sunil K. Agarwal, MD, MPH, PhD, reported at the American Heart Association’s

Scientific Sessions 2013. “The processes that change small vessels in the heart should probably change the vessels of other organ systems,” said Dr. Agarwal in explaining the rationale for the study. “We wanted to see how microvessel changes in the eyes and also albumin in the urine, meancontinued on page 8

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BY WAYNE KUZNAR DALLAS—Renal artery stenting confers no additional benefit beyond optimal drug therapy for preventing adverse renal and cardiovascular events in patients with renal artery stenosis (RAS) and chronic kidney disease (CKD) or hypertension, according to data from a randomized clinical trial.

The research findings from CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, presented by Christopher J. Cooper, MD, at the American Heart Association’s Scientific Sessions 2013 and published online ahead of print in the New England Journal of Medicine, support those from other recent clinical trials of renal artery stenting and should prompt fur-

Dialysis Pts Have Higher Stroke Risk STROKE risk is elevated in dialysis patients compared with the general population, according to a study conducted in Taiwan.

In addition, the study demonstrated that the risk of hemorrhagic stroke is lower with peritoneal dialysis than hemodialysis.

Researchers analyzed data from 74,192 hemodialysis (HD) patients, 5,974 peritoneal dialysis (PD) patients, and 669,773 individuals in a reference cohort drawn from the general population and who were older than 18 years, not on dialysis, and had no history of stroke or cancer.

In the HD and PD patients, the incidence of hospitalization for ischemic stroke was 102.6 and 100.1 per 10,000 person-years, respectively, and the incidence of hospitalization for hemorrhagic stroke was 74.7 and 59.4 per 10,000 person-years, respectively. The incidences were significantly higher than those in age- and sex-matched

ther restriction of its use. After initial enthusiasm in the late 1990s and early 2000s for renal artery stenting for patients with atherosclerotic RAS or hypertension, use of the intervention had already been declining based on studies published prior to CORAL, said Mark Creager, MD, Director of the Vascular Center at Brigham and Women’s Hospital in Boston.

“I hope [the CORAL study] does alter how people take care of patients.

I think what it shows is, that with good medical therapy, the majority of patients can be managed without the need for a stent,” said Dr. Cooper, Chairman of the Department of Medicine at the University of Toledo in Ohio. continued on page 8

IN THIS ISSUE 8 High BMI raises renal decline risk in young adults 10 Mortality in CKD patients linked to gum disease 12 High-potency statins do not hike risk of kidney injury

13 Arthritis drug may benefit patients with FSGS

15 Transplanted kidneys can harbor HIV-1

17 Bacteremias linked to central venous catheters

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Reducing abdominal fat may halt CKD Testosterone therapy may help patients with Crohn’s disease PAGE 11

continued on page 8

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FDA Approves Peyronie’s Disease Drug

© IMAGE PROVIDED BY STANTON HONIG, MD.

It is the first medication approved by the agency for treating this erectile problem

XIAFLEX provides an alternative to surgery to treat Peyronie’s disease.

U.S. Faces Urologist Shortage

BY JODY A. CHARNOW THE SUPPLY of urologic surgeons in the U.S. has not kept pace with population growth, a trend that could be exacerbated by an aging urology workforce that is relatively older than surgeons in most other specialties, according to a new study.

From 1981-2009, the proportion of

urologic surgeons dropped from 3.23 to 3.18 per 100,000 population, a 1.3% decrease. Only general and thoracic surgeons experienced larger declines during this period. By comparison, the number of colorectal, pediatric, plastic, and vascular surgeons per 100,000 population increased by 34.9%, 43.2%, continued on page 8

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BY JODY A. CHARNOW UROLOGISTS for the first time have an FDA-approved drug to offer their patients with Peyronie’s disease.

The drug, collagenase clostridium histolyticum (Xiaflex), already had been approved as a treatment for Dupuytren’s contracture. It is an enzyme produced by Clostridium histolyticum that acts like a “chemical knife” to break up collagen. For Peyronie’s disease, the drug is administered through injections into the area where collagen scar tissue, known as Peyronie’s plaque, has formed.

Following injections, the treated area is massaged or “modeled” to break down the scar tissue. To date, off label use of intralesional verapamil and surgery

Blood Type May Affect RCC Prognosis 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, according to researchers. It is not associated with survival.

A team led by Tobias Klatte, MD, of the Medical University of Vienna in Austria reviewed data from 556 patients who underwent surgery for RCC to evaluate the relationship between blood groups and clinical and pathologic variables. The researchers noted that subjects had a median follow-up of 39 months.

Blood group O was associated with a significantly lower risk of lymph node metastases (1% vs. 4%), the investigators reported online ahead of print in BJU International.

Of 16 patients with positive nodes, 14 (87.5%) had a non-O blood group.

In multivariable analysis, patients with a non-O blood group had a 5.8 times increased risk for lymph node metas-

have been the standard treatment for Peyronie’s disease.

Based on U.S. historical medical claims data, it is estimated that 65,000 to 120,000 PD cases are diagnosed annually but only 5,000 to 6,500 patients are treated each year, the drug’s maker, Auxillium, said in a press release.

The FDA based its approval on the results of the pivotal IMPRESS I and IMPRESS II trials, in which Xiaflex was compared with placebo.

Xiaflex is indicated for the treatment of Peyronie’s disease in men with a palpable plaque and a curvature of 30 degrees or more at the start of treatment. The dose of Xiaflex is 0.58 mg continued on page 8

IN THIS ISSUE 8 Protein in biopsied prostate tissue can predict PCa risk 9 Bladder instillations of heparin may prevent UTIs 9 Mind-body activity found to ease fatigue in PCa patients

11 Optimal testosterone levels

associated with better survival

15 Smoking at the start of sunitinib therapy shortens survival

21 Prostate cancer risk lower in statin users

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Sacral neuromodulation promising for refractory OAB Testosterone therapy may help patients with Crohn’s disease PAGE 11

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A VIRT UAL CO N FE RE N CE

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Register for FREE to attend Kidney Care Congress. You will hear from Nephrology experts, chat with your

Acute Kidney Injury: Challenges and Opportunities

Ravindra L. Mehta, MBBS, MD Professor of Clinical Medicine at

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Csaba P. Kovesdy, MD

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Coming in March: Men’s Health Update for Urologists

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JANUARY 2014 www.renalandurologynews.com

FROM THE EDITOR EDITORIAL ADVISORY BOARD

Why Not A Federal Medical License?

W

hen we move from one state to another, typically we must obtain a driver’s license from the state to which we are relocating. For the most part, the process is routine, and mainly involves just filling out a few forms, paying a fee, and getting your photo license at a local office of the state department of motor vehicles. Still, the process can be a hassle in light of all the other challenges of moving. I have moved between states several times in my career, and each time I had to swap one state’s license for another, a thought occurred to me: Wouldn’t it be great if we could get a federal driver’s license that is valid in all states and all that would be required when we move is a change of address?

The process of moving from one state to another is more involved for physicians. Not only do they have to get their new state’s driver’s license (and set up residence, etc.), they have to get that state’s medical license as well, a process that could be much more challenging.

It is not uncommon for physicians to relocate from one part of the country to another. So why not give physicians an option of getting a federal medical license?

Standards of medical competence, that is, clinical knowledge and ability, probably vary little, if at all, from state to state, so why not just establish a national standard of competence, the licensing equivalent of the board-certification examination?

Doctors would still be obligated to follow each state’s laws, rules, and regulations governing certain aspects of medical practice, such as prescribing and reporting requirements.

If the U.S. government issued federal medical licenses, it likely would also have to establish federal medical boards to oversee doctors who hold those licenses, and, like state medical boards, administer penalties such as reprimands and license suspensions. Such federal oversight could make it difficult for doctors who get in professional trouble in one state to start practicing in another state, although some physicians (and other people) might not welcome another layer of federal bureaucracy.

Renal & Urology News recently asked readers in an online poll whether they thought there should be a federal medical license, and nearly three-quarters of the 392 respondents indicated “yes.” Although other issues related to healthcare are more pressing right now, perhaps federal medical licenses are worth considering at some point.

Sincerely, Jody A. Charnow Editor

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

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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 1. 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

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JANUARY 2014

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VOLUME 13, ISSUE NUMBER 1

Nephrology

ONLINE

this month at renalandurologynews.com Expert Q&A

Aydogan Ozcan, PhD, of the University of California Los Angeles, discusses a new albumin self-testing platform he and his team developed.

0 1

Gum Disease Ups Death Risk in CKD Periodontal disease is associated with increased death risk in patients with chronic kidney disease, new findings suggest.

12

No Kidney Injury Risk from High-Potency Statins Pooled analysis of data from two large randomized trials show no link patients with acute coronary syndromes.

13

The Medical Minute

Visit renalandurologynews.com /the-medical-minute/ to hear podcast reports on new studies.

Our latest include: • Chemical in Dialyzers May Be Toxic to Immune Cells • Primary CKD Screening in the General Population Not Cost-Effective • Light Drinking Plus Acetaminophen May Raise Renal Impairment Risk

Transplanted Kidneys Can Harbor HIV-1 HIV-1 can infect kidney allografts after transplantation despite undetectable viremia, researchers concluded.

2 1

NSM Raises Death Risk From Kidney Cancer Compared with surgery, nonsurgical management of early-stage kidney cancer is associated with an increased risk of death from the cancer among patients aged 75-79 years.

13

Tasquinimod Benefits Men With mCRPC The investigational drug slows disease progression and increases survival, data show.

15

Smoking Should Stop When Starting Sunitinib Active smoking appears to shorten progression-free and overall survival in patients starting the sunitinib treatment for metastatic renal cell carcinoma.

17

High-Dose-Rate Brachytherapy May Be Better for Penile Cancer Results are good and the toxicity is equivalent to that of low-dose-rate treatment.

Nephrologists should consider establishing

alternate types of vascular access more quickly.

See our story on page 17

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Register at

Urology

News Coverage

Genitourinary Cancers Symposium, San Francisco, January 30-February 1.

January 22, 6-9 p.m. EST RenalAndUrologyNews.com/Kidney2014

15

Clinical Quiz

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 November winner: Francis Vasquez, MD

High Furosemide Dosage May Harm Kidneys in HF Patients The glomerular filtration rate increased in heart failure patients with impaired renal function after dosage was reduced.

invites you to Kidney Care Congress 2014, a virtual conference where you can earn CME credit

19

Departments 6

From the Editor Why not a federal medical license?

9

News in Brief Heparin bladder instillations can cut UTI rate

11

Men’s Health Update Testosterone shown to ease Crohn’s disease

14

Expert Q&A Active surveillance for renal masses

16

Renal Nutrition Update Gluten-free diet could benefit type 1 diabetics

19

Legal Issues in Medicine Confusing potassium prescription leads to a death

20

Malpractice News Californians to vote on a malpractice cap increase

12/26/13 11:53 AM

Contents

www.renalandurologynews.com JANUARY 2014

JANUARY 2014

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Renal & Urology News 7

VOLUME 13, ISSUE NUMBER 1

Urology

ONLINE

this month at renalandurologynews.com Expert Q&A

Aydogan Ozcan, PhD, of the University of California Los Angeles, discusses a new albumin self-testing platform he and his team developed.

Clinical Quiz

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 November winner: Francis Vasquez, MD

The Medical Minute

Visit renalandurologynews.com /the-medical-minute/ to hear podcast reports on new studies.

Our latest include: • Investigational Drug May Boost Survival in men with Metastatic PCa • Mortality Risk in Older Men Linked to Testosterone • CTC Counts May Help Predict mCRPC Patient Survival

News Coverage

Genitourinary Cancers Symposium, San Francisco, January 30-February 1.

2 1

NSM Raises Death Risk From Kidney Cancer Compared with surgery, nonsurgical management of early-stage kidney cancer is associated with an increased risk of death from the cancer among patients aged 75-79 years.

13

Tasquinimod Benefits Men With mCRPC The investigational drug slows disease progression and increases survival, data show.

15

Smoking Should Stop When Starting Sunitinib Active smoking appears to shorten progression-free and overall survival in patients starting the sunitinib treatment for metastatic renal cell carcinoma.

17

January 22, 6-9 p.m. EST Register at RenalAndUrologyNews.com/Kidney2014

High-Dose-Rate Brachytherapy May Be Better for Penile Cancer Results are good and the toxicity is equivalent to that of low-dose-rate treatment.

Nephrology 0 1

12

13

15

19

Gum Disease Ups Death Risk in CKD Periodontal disease is associated with increased death risk in patients with chronic kidney disease, new findings suggest.

No Kidney Injury Risk from High-Potency Statins Pooled analysis of data from two large randomized trials show no link patients with acute coronary syndromes.

High Furosemide Dosage May Harm Kidneys in HF Patients The glomerular filtration rate increased in heart failure patients with impaired renal function after dosage was reduced.

Transplanted Kidneys Can Harbor HIV-1 HIV-1 can infect kidney allografts after transplantation despite undetectable viremia, researchers concluded.

Clinicians should consider molecular

characterization of HGPIN as a means to improve risk stratification.

See our story on page 8

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invites you to Kidney Care Congress 2014, a virtual conference where you can earn CME credit

Departments 6

From the Editor Why not a federal medical license?

9

News in Brief Heparin bladder instillations can cut UTI rate

11

Men’s Health Update Testosterone shown to ease Crohn’s disease

14

Expert Q&A Active surveillance for renal masses

16

Renal Nutrition Update Gluten-free diet could benefit type 1 diabetics

19

Legal Issues in Medicine Confusing potassium prescription leads to a death

20

Malpractice News Californians to vote on a malpractice cap increase

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8 Renal & Urology News

JANUARY 2014 www.renalandurologynews.com

Stents and RAS continued from page 1

The 947 patients enrolled in the open-label CORAL study had atherosclerotic RAS (greater than 60% occlusion but less than 100%) and either hypertension that required two or more antihypertensive drugs to control or stage 3 or higher CKD. Investigators randomly assigned patients to receive medical therapy with candesartan— with or without a thiazide diuretic— and amlodipine/atorvastatin, or the same medical therapy plus renal artery stenting.

Mean systolic blood pressure (SBP) on study entry was 150 mm Hg, the

mean estimated glomerular filtration rate was 58 mL/min/1.73 m 2, and the mean percent diameter stenosis was 67%.

The mean percent diameter stenosis in the stented group was reduced to 16% and the mean SBP was reduced by 2.3 mm Hg more in the intervention patients compared with the group randomized to medical therapy alone. Procedural complications were infrequent.

Over a median follow-up of 43 months, the rates of a composite endpoint of cardiovascular or renal death, stroke, myocardial infarction, hospitalization for heart failure, progressive renal insufficiency, or need for renal

replacement therapy occurred in 35.1% of stented patients compared with 35.8% of those on medical therapy alone, a difference that was not statistically significant.

Commenting on the new study, Harold Duerman, MD, Professor of Medicine at the University of Vermont in Burlington, and a CORAL investigator, observed: “This is a trial that complements other trials like ASTRAL [Angioplasty and Stent for Renal Artery Lesions]. We have already seen a reduction in renal artery stenting over the past five years. [CORAL] should have an ongoing effect on a trend that’s already happening in terms of renal revascularization.” n

Obesity May Predict More Rapid eGFR Declines OVERWEIGHT and obese young adults are at elevated risk for declines in renal function.

Researchers led by Vanessa Grubbs, MD, MPH, of the University of California San Francisco, studied 2,839 participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study who had

Microalbuminuria continued from page 1

ing that two different organ beds are involved, were related to development of AF.” Dr. Agarwal and his colleagues analyzed data from the Atherosclerosis Risk in Communities (ARIC) database.

The population-based ARIC study included a biracial cohort of 16,000 middle-aged men and women from four U.S. communities. Participants had retinal examinations and baseline measurement of urine albumin early in the study. After exclusions for missing data, missing potential confounders, and prevalent AF, the authors were left with 10,009 study subjects (56% women, 20% African American), 1,100 of whom developed AF over approximately 15 years of follow-up.

Of those with retinopathy at baseline, AF developed in 17.3%, compared with only 10.4% among those without retinopathy. After adjusting for age, race, sex, diabetes, blood pres-

Stroke and dialysis pts continued from page 1

subjects in the reference cohort (42.4 and 13.0 per 10,000 person-years).

In multivariate analysis, HD and PD were associated with a 2.88 and 3.21 times increased risk of ischemic stroke, respectively, and a 6.83 and 6.15 times increased risk of hemorrhagic stroke, respectively, compared with age- and sex-matched individuals in the reference group.

After adjusting for all potential confounders and competing risks for death and matching of PD and HD patients by propensity scores, researchers found that PD was associated with a signifi-

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sure, other cardiovascular risk factors, and prevalent cardiovascular disease, the risk of AF was increased by 37% with retinopathy at baseline.

“Retinal micro-hemorrhages are very strongly associated with developing AF, irrespective of confounders,” said Dr. Agarwal, a clinical investigator at Johns Hopkins University in Baltimore. “Small hemorrhages showed a 42% higher risk of developing AF independent of any other heart disease that develops. Aneurysms are associated with AF but once adjusted for events during the follow-up, they were no longer associated.”

The study revealed no significant association between other retinal microvascular signs (arteriovenous nicking, focal/generalized narrowing or central retinal arterial equivalent) and incident AF. “There were only 27 people who had both albumin in the urine and retinopathy. Out of them, 45% developed AF,” he said.

The incidence rates of AF were 24.4,

16.8, 8.9, and 5.7 per 1,000 personyears for those with retinopathy and microalbuminuria, microalbuminuria only, retinopathy only, and neither, respectively.

“We know that AF is often hidden [paroxysmal], and people don’t have symptoms, and it’s associated with an almost fivefold risk of stroke. We are able to reduce this risk by more than 60% with use of appropriate therapy,” Dr. Agarwal said. “All of this leads to thinking that if somebody finds retinopathy or microalbuminuria, they should think about whether the patient has AF or might develop AF.” Autonomic nervous system dysfunction may also play a role in AF development, he said. “People who have smallvessel disease may also have damage to their autonomic nervous system, which may increase their risk of AF downstream.”

In a separate analysis of the ARIC database he presented here, chronic kidney disease increased the risk of sudden cardiac death. n

preserved renal function at baseline (estimated glomerular filtration rate [eGFR] above 90 mL/min/1.73 m2 as measured using cystatin C levels).

These subjects were among 5,115 asymptomatic individuals aged 18-30 years recruited from 1985-1986 and who took part in a 10-year follow-up examination in 1995-1996. At baseline, patients had a mean age of 35 years and 24.5% were obese.

After age 30 years, the average eGFR declined progressively with each increment in BMI, after adjusting for baseline age, race, gender, hyperlipidemia, smoking status, and physical activity.

Compared with participants who had a BMI of 18.5-24.9 at baseline, those with a BMI of 25.0-25.9 (overweight), 30.0-39.9 (obese), and 40 or above (extremely obese) at baseline had a 1.5, 2.0, and 2.6 times increased odds of a rapid eGFR decline (greater than 3% per year), respectively, based on cystatin C measurements, researchers reported

cant 25% lower risk of hemorrhagic stroke compared with HD, but the two modalities did not differ significantly with respect to ischemic stroke risk.

The study, which was led by JungDer Wang, MD, ScD, of National Cheng Kung University College of Medicine in Tainan, was published online ahead of print in the American Journal of Kidney Diseases.

“To our knowledge, our study is the first nationwide population-based cohort study to quantify incidence rates of ischemic and hemorrhagic strokes in patients undergoing HD and PD in comparison to a reference cohort drawn from the general population,” the authors observed.

Previous studies in the U.S. and Japan found twofold to 10-fold increased risks of stroke in dialysis patients compared with the general population, Dr. Wang’s group noted.

The investigators acknowledged some study limitations, such as the retrospective design and the absence of data on important variables that might affect stroke risk, such as body mass index, physical activity, and smoking and nutritional status. In addition, the researchers focused their analyses on stroke hospitalization. They might have overlooked patients with minor stroke who sought only ambulatory care, leading to an underestimate of stroke incidence. n

online ahead of print in the American Journal of Kidney Diseases.

The association between elevated BMI and more rapid decline in kidney function was observed for men and women and for blacks and whites, according to the investigators.

“Given the growing epidemic of obesity in adults and children, the long-term impact of these findings could be substantial,” the authors concluded. “Clinicians should vigilantly monitor overweight and obese patients for evidence of early kidney function decline.” n

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Peyronie’s disese continued from page 1

per injection administered into a Peyronie’s plaque. Up to eight injections (four treatment cycles) may be administered in the course of treatment. After each treatment cycle, a penile modeling procedure is recommended to disrupt the plaque. If more than one plaque is present, it should be injected only into the plaque causing the curvature deformity.

Possible adverse effects of Xiaflex treatment include hematoma, swelling at the injection site or along the penis, pain or tenderness at the injection site, along and above the penis, and penis bruising.

Stanton Honig, MD, of Yale University in New Haven, Conn., a urologist who specializes in male sexual medicine and was involved in phase 2 and 3 trials of Xiaflex, said physicians, especially those specializing in men’s health, “are very excited to be able to offer an FDA approved, nonsurgical treatment option to men who suffer from Peyronie’s disease. We know a significant percent of these patients suffer from depressive symptoms as a result of the sequelae of Peyronie’s disease, which include shortening of the penis, dysmorphic changes in the penis, and curvature.”

In the clinical studies, Xiaflex treatment was associated with a low rate of

major complications, but a significant number of men had local complications, including bruising, swelling, ecchymosis, and hematoma, Dr. Honig said. A few cases of penile fracture occurred, and these were likely related to early sexual activity after treatment. Surgery is associated with greater improvements in curvature than Xiaflex injections, but surgery poses a greater risk of significant complications, including a shorter penis, erectile dysfunction, and changes in penile sensation, Dr. Honig said.

The ideal candidate for Xiaflex treatment would be a man who has had Peyronie’s disease for at least 12 months, has stable disease, and a curvature of 30 degrees or more, he said. n

Protein May Predict PCa Development THE PRESENCE of the ERG protein in biopsied prostate tissue appears to substantially raise the likelihood that prostate cancer (PCa) will develop, according to researchers.

The findings emerged from a post-hoc analysis of data obtained from a phase 3 clinical trial involving 1,590 men with biopsy-diagnosed high-grade prostatic intraepithelial neoplasia (HGPIN). The men had

Urologist shortage continued from page 1

61.8%, and 157.2%, respectively.

Meanwhile, the urology workforce has aged. From 1981-2009, the proportion of urologic surgeons older than 55 years increased from 24.6% to 44% and the proportion older than 70 years increased from 3.4% to 7.4%. Among all surgical specialties, 6.1% of the workforce was aged 70 or older in 2009.

In 2009, the average age of urologists was 52.5 years. Only thoracic surgeons were older, with an average age of 53.6 years. The average age of the surgical workforce overall was 50.9 years.

For the study, Raj S. Pruthi, MD, of the University of North Carolina at Chapel Hill, and colleagues identified surgeons using a combination of American Medical Association primary and secondary self-reported specialties and American Board of Specialties certifications. They published their findings online ahead of print in Urology.

“The aging workforce suggests that the full-time equivalent supply is likely even lower than suggested by simple head counts, as physician work hours tend to peak in the 50-54-year age range, and decline thereafter,” the authors noted. “Aging and subsequently retiring urologists coupled with a reduction in the pipeline of new urologists portray a manpower supply that is contracting in the face of the growing and aging general population, which will require more, not less, urologic health services.”

In 2009, the U.S. had 9,775 actively practicing urologic surgeons, excluding residents in training. Projections from the U.S. Department of Health and Human Services forecast urology as the medical or surgical subspecialty requiring the greatest percentage increase in the coming years, with a projected need of 14,000 urologists by 2015 and 16,000 by 2020, the authors pointed out.

The study also showed that urology continues to be a male dominated specialty, with men accounting for 94.8%

of the urology workforce in 2009. The number of female urologists, however, has increased substantially from 34 in 1981 to 512 in 2009, a relative increase of more than 1,000%, the researchers reported. The study also documented that the urban concentration of urologic surgeons has remained stable from 19812009, with seven urologic surgeons in urban areas for every one urologic surgeon in a rural area.

Dr. Pruthi and his group are working on projection models to estimate the future supply of urologic surgeons, taking into account the aging workforce and including the potential impact of several other factors, including the feminization of the workforce, variable federal graduate medical education funding, the impact of advanced practice providers, and the changing working patterns of the “millennial” generation. Current models by his group (unpublished data) suggest that the U.S. will have fewer than 8,000 urologists by 2020, far short of the HHSprojected need of more than 16,000, according to Dr. Pruthi. n

been randomized to treatment with toremifene or placebo for three years or until a diagnosis of PCa was made on prostate biopsy. As part of the study, a pathologist evaluated biopsies of men with HGPIN at baseline and at 12, 24, and 36 months of follow-up. The tissue was tested for the presence of ERG. ERG expression was detected in 51 of 461 patients (11.1%) with isolated HGPIN. More than one-third of that group (36.9%) group received a diagnosis of PCa at some point during the three-year study period, with 14.7% receiving the diagnosis during the first year. PCa developed in 27 of 51 ERG-positive men (53%) compared with 143 of 410 ERG-negative patients (35%). ERG expression was not associated with age, baseline prostate-specific antigen (PSA) level, Gleason score, or tumor volume.

“This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression,” Mark A.

Blood type continued from page 1

tases compared with those who had blood group O. Of 29 patients with bilateral RCC, 17 (58.6%) had blood group O compared with 193 (36.6%) of 527 patients with unilateral disease.

ABO blood group overall was not associated with RCC prognosis.

Of the 556 patients, 93 died, 61 from RCC. The five-year overall and cancerspecific survival rates were 75% and 83%, respectively, with no significant difference between blood group O and non-O blood group.

The researchers noted that their study did not confirm a previously

RUN0114_Cover_URO.indd 2

reported finding of an association between ABO blood group and overall survival. Last year, researchers published study results in BJU International (2012;110 [11 Pt B]:E641-E646) demonstrating that RCC patients with a non-O blood type had a significant 68% increased death risk compared with those who had blood type O. The patient groups did not differ significantly with respect to cancer-specific survival.

Dr. Klatte’s group noted that their study may have been underpowered to detect a significant difference in overall survival.

“Since the study population and inclusion criteria differed considerably,

the two studies should be interpreted as complementary, not oppositional,” they wrote.

“The mechanisms through which blood group may influence cancer risk and progression are largely unknown,” the authors pointed out. Blood group antigens may affect cell adhesion, membrane signaling, and immune surveillance, the investigators stated, and this in turn may influence cancer development and progression.

Dr. Klatte and his colleagues acknowledged some study limitations, including the retrospective design and the relatively small number of patients and short follow-up, pointing to the need for additional research. n

Rubin, MD, Profesor of Urology at Weill Cornell Medical College and New York–Presbyterian Hospital in New York, and colleagues concluded in the Journal of Clinical Oncology.

“Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification.”

Dr. Rubin noted that their study is the largest ever conducted looking at the relationship between HGPIN and ERG in a systematic way. When confirmed in larger studies, testing for ERG in these HGPIN may change clinical practice and lead to early cancer detection, he said. n

12/26/13 11:50 AM

www.renalandurologynews.com JANUARY 2014

Renal & Urology News 9

News in Brief

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

Short Takes Bladder Instillations of Heparin Curb UTIs

Sindhu Chandran, MBBS, of the

Bladder instillations of heparin

and colleagues studied 143 living

decreased the rate of urinary tract

kidney donors who had impaired fasting

infection (UTI) in a pilot study of 18

glucose (IFG) prior to donation. At a

women with a history of recurrent UTI,

mean follow-up of 10.4 years, 57.8%

researchers reported in Therapeutic

of these donors had reverted to normal

Advances in Urology (2013;5:303-309).

fasting glucose. The researchers also

University of California San Francisco,

compared 45 of the IFG donors with

The women, whose UTIs were resistant to standard therapy, received

45 matched controls who had normal

intravesical instillations consisting of

predonation fasting glucose and found

heparin 40,000 U, 2% lidocaine 8

no difference in estimated glomerular

mL, and sodium bicarbonate 4 mL

filtration rate and albumin excretion.

once weekly for six weeks. Of the therapy, that is, had a greater than

AKI During MI Hospital Stay Worsens Outcomes

50% reduction in UTI rate, Tova

A study of U.S. veterans found that

Ablove, MD, and colleagues at the

those who develop acute kidney

University of Wisconsin in Madison re-

injury (AKI) during hospitalization for

ported. UTI infection rates decreased

myocardial infarction (MI) have

from 4.4 infections in the six months

worse long-term renal and cardiovas-

before therapy to 1.1 infections in the

cular outcomes than those with AKI or

six months after treatment.

MI alone, according to a report in the

18 women, 13 (78%) responded to

Clinical Journal of the American Society

Prediabetes Need Not Stop Kidney Donation

of Nephrology.

Carefully screened prediabetic living

36,980 patients with a mean age of

kidney donors have preserved kidney

66.8 years, showed that veterans

function 10 years after nephrectomy,

with AKI alone have worse outcomes

researchers reported online ahead of

than those diagnosed with an MI in the

print in Transplantation.

absence of AKI.

In addition, the study, which included

Most Favor Federal Licensure In a recent online poll, Renal & Urology News asked readers, “Should there be a federal medical license?” Here are the results based on 392 responses.

Yes: 72.19%

No: 25.26%

Do not know: 2.55%

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Early Salvage Radiotherapy Yields Excellent Outcomes E

arly salvage radiotherapy (eSRT) after biochemical recurrence of prostate cancer following radical prostatectomy (RP) leads to excellent cancer control, researchers reported online ahead of print in European Urology. Alberto Briganti, MD, of Vita Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy, and colleagues studied 472 node-negative patients who experienced biochemical recurrence (BCR) after RP. All patients underwent eSRT, defined as local radiation to the prostate and seminal vesicle bed delivered when PSA levels were 0.5 ng/mL or lower. BCR after eSRT was defined as two consecutive PSA values of 0.2 ng/mL or higher. The mean and median follow-up was 58 and 48 months, respectively. The overall five-year BCR-free survival rate after eSRT was 73.4%. In multivariable analysis, pathologic stage, Gleason score, positive surgical margins, and pre-eSRT PSA level were significantly associated with BCR after eSRT.

Mind-Body Activity May Help Fatigued PCa Patients A

12-week intervention involving the mind-body activity Qigong improved levels of fatigue and distress among prostate cancer (PCa) patients in a small randomized controlled trial.

Qigong, which combines slow, flowing movements, coordinated deep breathing, and meditative exercises, is performed at a slow pace and can even be done while sitting. Anita Y. Kinney, PhD, of the University of New Mexico Cancer Center in Albuquerque, and colleagues enrolled 40 fatigued PCa patients (median age 72 years, range 58–93 years). The men were randomized to 12 weeks of Qigong or stretching classes. The Qigong group had significantly higher class attendance and significantly greater improvements in measures of fatigue and distress than did the stretching group, the investigators report online ahead of print in the Journal of Cancer Survivorship.

Heredity Influences Gout Risk, New Study Confirms A

population-based study confirms that gout aggregates within families, according to a report in Annals of the Rheumatic Diseases.

Chang-Fu Kuo, MD, of the University of Nottingham, Nottingham, U.K., and colleagues evaluated data from 1,045,059 patients with physician-diagnosed gout, obtained from a national health research data base in Taiwan. Subjects with a first-degree relative with gout had twofold increased risk for developing the condition compared with the general population. The risk increased with the number of first-degree relatives affected. Men and women whose second-degree relatives suffered from gout had a 27% and 40% increased risk of gout, respectively, compared with the general population.

Individuals with a twin affected by gout had an eightfold increased risk and those with an affected sibling had a 2.6 times increased risk. Individuals with an affected son or daughter and those with an affected parent had a twofold increased risk. Those with an affected grandchild had a 48% increased risk and individuals with an affected niece or nephew had a 40% increased risk.

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10 Renal & Urology News

■ Kidney Week 2013

JANUARY 2014 www.renalandurologynews.com

Reports below are from the American Society of Nephrology’s Kidney Week 2013 in Atlanta.

Gum Disease Ups Death Risk in CKD The presence of both periodontal disease and chronic kidney disease hiked risk by nearly 2.3-fold NEW FINDINGS from separate studies may help to define the relationship between periodontal disease and mortality among patients with kidney disease. One study showed that periodontal disease is associated with increased death risk in patients with chronic kidney disease (CKD) and another study found unclear associations between periodontal disease and all-cause and cardiovascular mortality in hemodialysis (HD) patients.

In a study of 10,755 participants in the Third National Health and Nutrition Examination Survey (NHANES III), Ambarish Athavale, MD, of the University of Illinois in Chicago and collaborators demonstrated that participants with moderate or severe periodontal disease (MSPD) but no CKD had a significant 42% increased risk of death compared with those who had neither CKD nor MSPD. Subjects with CKD but no MSPD had a 63% increased risk and

Binder May Cut IV Iron, ESA Use FERRIC CITRATE (FC), a novel phosphate binder, reduces intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) use.

Kausik Umanath, MD, of Henry Ford Hospital in Detroit, and colleagues conducted a 52-week randomized trial that enrolled more

those with both CKD and MSPD had a nearly 2.3 times increased risk. A total of 1,773 deaths occurred during a follow-up of 14 years.

Dr. Athavale’s group defined MSPD as a loss of attachment of 6 mm or greater in at least two mesial sites and greater than 5 mm pocket depth in at least one mesial site (severe PD) or loss of attachment of 4 mm or greater in at least two mesial sites or at least two mesial sites with 5 mm pocket depth not on the same tooth (moderate PD).

MSPD was more common in subjects with CKD than in those without CKD (9.2% vs. 4.8%).

In the other study (Oral-D), Suetonia Palmer, PhD, of the University of Otago in Christchurch, New Zealand, and colleagues concluded in a poster presentation that “uncertain associations” exist between periodontal disease and all-cause and cardiovascular mortality in hemodialysis (HD) patients. In

the study, 3,340 dentate HD patients received a complete evaluation for periodontitis and completed followup. A total of 3,036 patients (91%) had periodontitis and 344 (10%) died during a median follow-up of eight months. Periodontitis was associated

In hemodialysis patients, the link with mortality is less clear. with an increased risk of all-cause and cardiovascular mortality in unadjusted analyses, but not in adjusted analyses, the researchers reported.

The findings were presented before Oral-D was completed.

In a previous study published in Kidney International (2009;75:746751), HD patients with moderate

to severe periodontal disease were five times more likely to die from cardiovascular disease (CVD) compared with those who had mild or no periodontal disease, according to researchers.

The findings were based on a retrospective study of 168 HD patients conducted by Abhijit V. Kshirsagar, MD, of the University of North Carolina Kidney Center in Chapel Hill, and colleagues.

Of the 168 patients, 100 had mild or no periodontal disease and 68 had moderate to severe disease, defined as two or more teeth with at least 6 mm of inter-proximal attachment loss.

Twenty-two deaths—14 from CVD— occurred during an 18-month followup period, the investigators reported in Of the 14-CVD-related deaths, 11 occurred in the moderate-to-severe periodontal disease group and three occurred in the mild or no periodontal disease group. n

Folic Acid May Benefit PD Patients ORAL FOLIC acid therapy may be a cost-effective addition to anemia management in patients on peritoneal dialysis (PD).

Subir K. Paul, MD, and colleagues at Shoals Kidney and Hypertension Center in Florence, Ala., studied the effect of folic acid treatment on plasma hemoglobin concentration in 16 PD patients (mean age 47.8 years) with plasma Hb levels below 11 g/ dL, a folic acid level of 5 ng/mL or less, and iron saturation more than

20%. Patients were treated with 3-5 mg of oral folic acid daily. All patients had normal vitamin 12 levels. The researchers evaluated serum folic acid levels and plasma Hb at four weeks prior to initiation of therapy, at initiation, and four weeks after initiation.

Maintenance therapy with intravenous iron and epoetin alfa were continued according to standard protocol.

At four weeks prior to initiation and at initiation, patients’ mean folic acid level was 3.93 and 3.96 ng/mL,

respectively. Following therapy with folic acid, mean folic acid level rose from 3.96 to 19.26 ng/dL. During the pretreatment phase, mean plasma Hb level remained unchanged at 10.42 and 10.29 g/dL (four weeks prior to therapy and at initiation of therapy).

Following folic acid therapy, mean plasma Hb level improved significantly from 10.29 to 11.30 g/dL and mean epoetin alfa dose decreased significantly from 14,875 units to 10,437 units every two weeks. n

than 400 dialysis patients randomly assigned to receive either FC or active control (sevelamer carbonate, calcium acetate, or both). At 52 weeks, the FC group received less elemental IV iron than the active control group (median 1.85 vs. 3.84 mg/day) and less ESA (median 758 vs. 993 U/day), according to the investigators.

Hemoglobin levels were maintained safely throughout the trial. n

RUN0114_KidneyWk.indd 10

Carotid Plaques Predict Progression to Dialysis CAROTID plaques predict rapid decline in renal function and progression to dialysis among patients with stage 3 and 4 chronic kidney disease (CKD), new findings suggest.

Jwa-Kyung Kim, MD, of Hallym University Sacred Heart Hospital in Anyang, South Korea, enrolled 411 stage 3 and 4 CKD patients. All underwent

carotid ultrasonography at the time of CKD diagnosis. Subjects had a baseline estimated glomerular filtration rate of 44.5 mL/min/1.73 m2. Carotid plaques were found in 282 patients (68.6%).

These patients had significantly faster rates of renal function decline than those without carotid plaques (-3.64 vs.

-1.20 mL/min/1.73 m2 per year.

During 2.5 years of follow-up, 47 patients (11.4%) started dialysis. Subjects with carotid plaques had a 3.3 times greater likelihood of progressing to dialysis than those without carotid plaques.

Detecting carotid plaque may help identify patients at high risk for progression of renal dysfunction, the authors concluded. n

12/26/13 11:56 AM

www.renalandurologynews.com JANUARY 2014

Renal & Urology News 11

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

Children of Older Dads More Likely to Die Before Age 5 Children born to fathers aged 40 year or older are at increased risk of dying before age 5 years compared with those born to younger fathers, according to the results of a Danish study published online ahead of print in Human Reproduction. In a population-based register study of more than 1.5 million live born children from 1978 to 2004, researchers found that, compared with children born to fathers aged 30-34 years, those born to fathers aged 40-44 and 45 or older were 10% and 16% more likely to die before age 5 years. When only considering children aged 1-5 years, children born to fathers aged 40-44 and 45 and older had a 24% and 65% increased risk of death. “The results suggest that the elevated risk for children of fathers aged 40 years or more was primarily attributed to an elevated risk of dying from congenital malformations, malignancies and external causes,” the authors wrote.

Optimal Testosterone Levels Associated with Better Survival Optimal testosterone levels are a biomarker for better survival in older men, according to a new study.

The study included 3,690 community-dwelling men aged 70-89 years. Of these, 974 (26.4%) died, including 325 who died from ischemic heart disease (IHD). After controlling for other risk factors, men in the second and third quartiles of total testosterone had a significant 18% and 22% decreased risk of death from any cause, respectively, compared with those in the first quartile, Bu Beng Yeap, MBBS, PhD, of Fremantle Hospital in Fremantle, Western Australia, and colleagues reported online ahead of print in The Journal of Clinical Endocrinology & Metabolism. Men in the third quartile of dihydrotestosterone (DHT) had a significant 24% decreased risk of death from any cause compared with men in the first quartile. Men in the third or fourth quartiles of DHT had a significant 42% and 31% decreased risk of death from IHD, respectively, compared with men in the first quartile.

Preterm Birth Predicts Low Exercise Capacity in Young Men Being born preterm or small for gestational age predicts low exercise capacity in otherwise healthy young men, a Swedish study found. Jenny Svedenkrans, MD, of Karolinska

Testosterone Therapy May Ease Crohn’s Disease A

RLINGTON, Va.—Normalization of testosterone (T) levels improved Crohn’s disease in hypogonadal men in a prospective, observational registry study, researchers reported at the 2013 Men’s Health World Congress.

The study included 71 hypogonadal men with Crohn’s disease and two with colitis ulcerosa. The patients received treatment with parenteral testosterone undecanoate on day 1, after six weeks, and every 12 weeks thereafter for up to 75 months.

Twelve hypogonadal men of similar age with Crohn’s disease who did not receive testosterone served as an untreated control group. T levels at baseline were 9.37 and 10.75 nmol/L in the T group and control group, respectively. During treatment, T increased to 15.72 nmol/L and declined slightly in the control group. The Crohn’s Disease Activity Index improved from 231 to 75 in the testosterone-treated group but worsened from 196 to 210 in the control arm. Scores below and above 150 are considered to reflect inactive and active disease, respectively. © THINKSTOCK

Short Takes

Post-RP Penile Shortening Temporary, Study Finds P

rostate cancer (PCa) patients undergoing radical prostatectomy (RP) may experience a small early loss of penile length after surgery, but this recovers by six months post-operatively, according to new findings.

In a study that included 118 men at baseline, a single evaluator measured stretched flaccid penile length (SFPL) before RP and again at two and six months after RP. At two and six months, 76 and 63 men, respectively, were evaluated. At two months post-surgery, patients had a mean 2.4 mm decrease in SFPL, but at six months, they observed no significant difference in SFPL from baseline overall, researchers led by John P. Mulhall, MD, of Memorial Sloan-Kettering Cancer Center in New York, reported online ahead of print in BJU International.

At six months, men who took a daily phosphodiesterase-5 inhibitor (PDE5i) had no SFPL loss, whereas those who did not take a PDE5i consistently had a significant mean 4.4 mm SFPL loss compared with baseline.

Institutet in Stockholm, and colleagues conducted a population-based study of 218,820 males entering military service the results in watts (W) from a maximal exercise test (Wmax) that a conscript could manage on a cycle ergometer.

Preterm birth predicted low Wmax in a dose-response related pattern, with a 25 W reduction in Wmax for the lowest gestational ages (those born after 27 weeks’ gestation or less, the researchers reported in PLoS One (2013;8(12):e80869). Low birth weight for gestational age also independently predicted low Wmax compared with normal and high birth weight (32 W reduction for those with a birth weight standard deviation score below 2).

RUN0114_MensHealth.indd 1

MEDISTAT

in 1993-2001 and born in Sweden from 1973-1983. The primary outcome was

40 PERCENT

The percentage of men aged 70 and older who reported chronic knee pain in an Australian longitudinal cohort study.

Source: Fransen M et al. A longitudinal study of knee pain in older men: Concord Health and Ageing in Men Project. Age Ageing 2013; published online ahead of print.

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12 Renal & Urology News

JANUARY 2014 www.renalandurologynews.com

No Kidney Injury Risk from High-Potency Statins Pooled analysis of two trials show absence of a link in ACS patients day (intensive strategy) or placebo for four months followed by simvastatin 20 mg/day (conservative strategy). Patients with baseline serum creatinine levels of 2.0 mg/dL or higher in either trial were excluded from the pooled analysis.

Baseline characteristics were similar in the two studies, including levels of serum creatinine (1.03 mg/dL in PROVE IT-TIMI 22 vs. 1.14 mg/dL in A to Z). The mean follow-up in both trials was two years.

Kidney injury was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) classification

© CMSP / ERIC HERZOG

BY WAYNE KUZNAR DALLAS—A pooled analysis of two large randomized clinical trials found no increased risk of kidney injury with the use of high-potency statins compared with moderate-potency statins in patients with acute coronary syndromes (ACS). The analysis was presented by Amy A. Sarma, MD, at the American Heart Association’s Scientific Sessions 2013.

Earlier this year, caution was urged in prescribing high-potency statins when examination of a large administrative database found that newly

Kidney injury-related adverse event risks in patients with acute coronary syndromes did not differ by statin potency, a study found.

treated patients who were prescribed high-potency statins—defined as 10 mg or more of rosuvastatin, 20 mg or more of atorvastatin, or 40 mg or more of simvastatin—was associated with an increased rate of hospital admission for acute kidney injury compared with lower potency statins. The increased risk of admission occurred early, within 120 days after statin treatment and remained elevated for at least two years.

Two large double-blind trials in which patients with ACS were randomized to high- or moderate-potency statins were examined: PROVE IT-TIMI 22 and A to Z. In PROVE-IT TIMI, 4,162 patients were randomized to receive either pravastatin 40 mg/day or atorvastatin 80 mg/day. In the “Z” phase of the A to Z trial, 4,497 ACS patients were randomly assigned to simvastatin 20 mg/day or 40 mg/day for one month, followed by simvastatin 80 mg/

RUN0114_AHA1.indd 12

with serum creatinine as the referent.

Kidney function was assessed at 1, 4, 8, and 12 months in each trial.

The odds of a 1.5-fold or greater increase and a twofold or greater increase in serum creatinine levels were not significantly different between the high-potency regimens and the moderate-potency regimens in either study, said Dr. Sarma, a resident physician in internal medicine at Brigham and Women’s Hospital in Boston.

Compared with moderate-potency statins, high-potency statins were associated with a non-significant 16% increased odds of a 1.5-fold or greater increase in serum creatinine in PROVE-IT TIMI and a non-significant 9% decreased odds in A to Z. Compared with moderate-potency statins, high-potency statins were associated with a non-significant twofold or greater increase in serum creatinine in

PROVE IT-TIMI and a non-significant 25% increased odds in A to Z. When the trials were pooled, the risk of kidney injury-related adverse events was not significantly different between the moderate- and high-potency regimens, both within the first four months and later trial periods.

During the first four months of treatment, when previous studies showed that kidney injury from statin therapy was most likely, there was no difference in the change in creatinine level between the high-potency and moderate-potency regimens. This was also the case over the long term.

The rates of kidney injury were also not significantly different between the two groups in the subgroup of patients with baseline estimated glomerular filtration rate (eGFR) below 60 mL/ min/1.73m2.

Tara I. Chang, MD, MS, an instructor of medicine at Stanford University in Palo Alto, Calif., said the results of the pooled analysis may have been affected by patient demographics. Those enrolled in PROVE IT-TIMI 22 and A to Z were younger than the general population with myocardial infarction, were less often female, and fewer had diabetes. “Age, sex, and diabetes are strong risk factors for subsequent kidney injury,” she said.

In addition, the percentage with an eGFR below 60 was only 14% in PROVE IT-TIMI 22 and 60% in A to A. She also questioned the ability of the pooled analysis to detect a safety signal, with only about 8,600 participants combined in the two trials, whereas recent observational studies finding a link between high-dose statins and kidney injury included more than four million. In fact, the point estimates for acute kidney injury and kidney injury over the long term in the pooled analysis were consistent with those of the observational studies, but because the pooled analysis had fewer enrollees and fewer events, the confidence intervals were wide and crossed 1.0.

Finally, the definition of “high potency” varied between studies, which could have affected outcomes, Dr. Chang said. n

NSM Raises Kidney Ca Death Risk NONSURGICAL management (NSM) of early-stage kidney cancer is associated with an increased risk of death from the cancer among patients aged 75-79 years compared with surgical treatment, researchers reported.

Hiten D. Patel, MD, MPH, of the James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, and colleagues studied 7,177 Medicare beneficiaries aged 65 and older diagnosed with localized T1a kidney cancer. Of these, 754 (10.5%) underwent NSM, 1,849 (25.8%) underwent partial nephrectomy (PN), and 4,574 (63.7%) underwent radical nephrectomy (RN).

At a median follow-up of 56 months, 436 NSM patients (57.8%), 389 PN patients (21%), and 1,598 RN patients (34.9%) died. PN and RN were associated with a 60% and 50% decreased risk of all-cause mortality and a 58% and 38% decreased risk of cancer-specific mortality compared with NSM, the researchers reported online ahead of print in Urology. Among patients younger than 75, results showed no difference in cancer-specific survival between any two treatment groups, “indicating that these patients are well selected for treatment,” the authors stated. Among patients aged 75-79, PN and RN were associated with a significant 73% and 60% decreased risk of cancer-related mortality compared with NSM. Among patients aged 80 and older, PN was associated with a significant 59% decreased risk of cancer-related death. RN was associated with a nonsignificant 32% decreased risk.

Dr. Patel’s group noted that it is important to consider the influence of confounding by indication. “The best candidates for NSM might be older individuals with multiple comorbidities, which imposes an inherent bias for comparative effectiveness as these patients experience significant all-cause mortality,” they wrote.

“However, these competing risks of death might be necessary to reduce the proportion of deaths because of kidney cancer.”

They also noted: “Improved riskstratification might be needed for patients aged 75 years or older, as a significant proportion might still die of kidney cancer.” n

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www.renalandurologynews.com JANUARY 2014

High Furosemide Dosage May Harm Kidneys in HF Patients GFR rose in patients with impaired renal function after dosage was reduced

Renal & Urology News 13

Tasquinimod Benefits Men With mCRPC AN INVESTIGATIONAL drug has been

BY WAYNE KUZNAR DALLAS—Halving the dosage of furosemide in patients with stable class II/III systolic heart failure and impaired renal function may improve glomerular filtration rate (GFR), according to data from a pilot study presented at the 2013 Scientific Sessions of the American Heart Association (AHA).

Furosemide and other loop diuretics are mainstays in the medical management of heart failure. Although they have a class I indication in the AHA/ American College of Cardiology guidelines, the level of evidence is C, suggesting that loop diuretics have not been extensively studied, said Paul McKie, MD, the study’s lead investigator. “Preliminary data have shown that aggressive loop diuretics may adversely activate neurohumoral pathways and ultimately impair renal blood flow and decrease GFR,” he said. GFR is an important prognostic marker for cardiovascular morbidity and mortality in heart failure.

Thirty-two patients were enrolled in the National Heart Lung and Blood

Institute sponsored study, 19 with normal GFR (above 60 mL/min/1.72 m2) and 13 with reduced GFR (60 mL/ min/1.72 m2 or below).

Patients were monitored for at least three weeks prior to enrollment to ensure clinical stability on a stable dosage of furosemide. After three weeks, they underwent a comprehensive baseline assessment that included measurements of GFR and renal plasma flow, hemodynamic assessments, and assessment of functional capacity. After baseline assessment, individuals decreased their furosemide dosage by half. After three weeks they underwent the same assessments as at baseline.

Compared with patients who had normal renal function, those with reduced GFR were older (mean age 76 vs. 68 years), were taking higher doses of furosemide (119 vs.

103 mg/day), used ACE inhibitors/ angiotensin receptor blockers less often (68% vs. 92%), and had greater use of nitrates and hydralazine (37% vs. 15%), consistent with underlying renal insufficiency.

The mean daily furosemide dosage at baseline was 119 and 103 mg in the reduced and normal renal function cohorts, respectively. During the three weeks of reduced furosemide, dosing the mean daily dose was 66 and 57 mg in reduced and normal renal function cohorts, respectively.

“There is a differential renal response to furosemide reduction according to baseline GFR,” said Dr. McKie, a cardiologist at the Mayo Clinic in Rochester, Minn.

Following three weeks of reduced furosemide dosing, the researchers noted that GFR increased significantly from 42 to 51 mL/min/1.72 m2 in the reduced renal function cohort, with a trend toward an increase in renal plasma flow. GFR and renal plasma flow were not changed in the normal renal function cohort. A significant increase in the level of atrial natriuretic peptide and a strong trend toward an increase in cyclic guanosine monophosphate also occurred after halving the furosemide dose in the reduced GFR group but not in the group with normal renal function. n

shown to slow the progression of disease and increase survival among men with minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).

An oral immunomodulatory, antiangiogenic, and antimetastatic agent, tasquinimod appears to affect the function of myeloid-derived suppressor cells, which are found in increased numbers in cancer patients.

Tasquinimod had already demonstrated an ability to delay progression of metastatic castration-resistant prostate cancer (mCRPC) in a randomized, placebo-controlled phase 2 trial funded by developer Active Biotech and reported in Journal of Clinical Oncology in October 2011. Now, Andrew J. Armstrong, MD, ScM, of the Duke Cancer Institute at Duke University Medical Center in Durham, N.C., and fellow investigators are sharing data on long-term survival among those patients, and publishing their findings online ahead of print in Clinical Cancer Research.

In the study, 134 men with mCRPC

FSGS May Respond to Arthritis Drug A STUDY of five patients with focal segmental glomerulosclerosis (FSGS) showed that the drug abatacept (Orencia), already approved as a treatment for rheumatoid arthritis, induced partial or complete remission of proteinuria in persons with the ­kidney disease.

“We identified abatacept as the first personalized, targeted treatment for kidney disease and specifically for FSGS, a devastating and largely untreatable disease,” affirmed Peter Mundel, MD, of the Division of Nephrology at Massachusetts General Hospital in Boston, in a statement issued by the facility. “We also identified a biomarker that helps us discern which patients are most likely to benefit from therapy with abatacept.”

Dr. Mundel was the senior author of The New England Journal of Medicine report describing the abatacept findings.

As he and his team explained, this immunomodulator is an inhibitor of the T-cell co-stimulatory molecule B7-1 (CD80).

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Podocyte B7-1 expression is found in patients with certain glomerular diseases, but not in healthy human kidneys.

FSGS—characterized by the formation of scar tissue in the glomeruli—affects millions of patients worldwide and often leads to end-stage renal disease (ESRD).

“In particular, primary FSGS as well as recurrent FSGS after kidney transplantation remain largely untreatable, leading to ESRD and, after transplantation, to allograft loss,” Dr. Mundel and colleagues wrote.

After observing B7-1 immunostaining in 13 of 21 randomly selected biopsy specimens from patients with proteinuric kidney disease and in every biopsy specimen from patients with recurrent FSGS, Dr. Mundel’s group treated five FSGS patients with abatacept. Four of the patients had rituximab-resistant recurrent FSGS after transplantation, and one had glucocorticoid-resistant primary FSGS.

Abatacept therapy induced remission of FSGS-caused proteinuria in all five patients. At the time the study findings were released, two of the patients with recurrent disease had been in remission for three and four years after receiving a single dose of the drug. The other two patients with recurrent disease had been in remission for 10 and 12 months, after receiving a second dose of abatacept when proteinuria reappeared a few weeks after administration of the first dose.

The patient with primary FSGS receives monthly doses of abatacept, has been in remission for a year, and no longer needs high-dose steroids and immunosuppressive drugs.

“Our clinical and in vitro data, taken together, indicate that podocyte B7-1 induction in primary and recurrent FSGS offers a rationale for using abatacept to treat a subgroup of patients with proteinuric kidney diseases,” Dr. Mundel and co-investigators concluded. n

were randomized to tasquinimod therapy. Of the 67 men randomized to placebo, 41 crossed over to tasquinimod. A total of 136 participants had bone metastases.

During a median follow-up of 37 months, 111 deaths occurred.

Median overall survival was 33.4 months for tasquinimod versus 30.4 months for placebo overall, and 34.2 months with tasquinimod versus 27.1 months with placebo among men with bone metastases.

Time to symptomatic progression also was improved with tasquinimod, particularly among those with bone metastases: Overall, men taking the drug experienced no cancer progression for 7.6 months, compared with 3.3 months for placebo. Men with bone metastases remained progression-free for 8.8 months with tasquinomod, compared with 3.4 months with placebo. n

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14 Renal & Urology News

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Active Surveillance of Renal Masses The use of active surveillance as ­primary management for small renal tumors is increasing, but data on patient outcomes remain limited, wrote Paul L. Crispen, MD, in a “News and Views” piece for the May 2013 issue of Nature Reviews Urology (2013;10:255-256). In an interview with Renal & Urology News, Dr. Crispen, Assistant Professor of Urology at the University of Florida in Gainesville, highlights the advantages and challenges of active surveillance for small renal masses.

How did the topic of active surveillance for renal masses capture your interest?

Dr. Crispen: I first became interested in this during my urology residency. At the time our experience was quite limited, with the majority of data merely focusing on growth rates of renal masses.

There was little information on predictors of growth rates, tumor histology, or the potential impact of a period of active surveillance on eventual therapy.

For these reasons we began evaluating the relationship between tumor histology and observed tumor growth and changes in management strategy based upon length of delay between diagnosis and treatment. Through our work and that being done at other institutions we began to appreciate the indolent nature of most small renal tumors. While most of our initial experience was based upon patients who were too high-risk for surgery or those refusing treatment, we realized that active surveillance had the potential to be utilized in other select patient populations presenting with small renal masses.

Why is active surveillance for renal masses gaining attention as a nontreatment strategy now?

Dr. Crispen: Through active surveillance series we have learned that the majority of small renal masses will grow slowly over time and are associated with a low risk of metastatic progression. Active

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surveillance may provide select patients with a means of avoiding treatmentrelated morbidity including surgical complications and decreased renal function.

Is there anything about the specific mechanics of the kidney or kidney cancer that make active surveillance for this disease either a particularly effective or challenging option?

What motivated you to write the Nature Reviews Urology article?

Dr. Crispen: There are still large knowledge gaps regarding the active surveillance of renal masses. The reviewed article by Parker et al. (Eur Urol 2013;63:1122-1127) is one of the first to evaluate the impact of active surveillance on quality-of-life measures. I feel that this is a critical area of investigation because we employ active surveillance as a potential method of avoiding treatment-related side effects of surgical intervention. The article provides us with very useful information that can be used for patient counseling and may help us to design and implement measures to improve the quality of life in patients who undergo active surveillance of their renal mass.

Are any of these quality-of-life issues unique to renal patients?

Dr. Crispen: The quality-of-life issues evaluated are applicable to the majority of persons with cancer. However, in the study by Parker et al, as well as many other series evaluating the active surveillance of renal masses, tumor histology is unknown in the majority of patients.

Dr. Crispen: The greatest challenge in recommending a patient to undergo active surveillance is the potential for metastatic progression. At present, there are no established guidelines for who should initiate a period of active surveillance or when active surveillance should be terminated and definitive therapy be performed.

This is an important factor as up to 30% of patients with small renal masses will have benign tumor histology. Thus, we do not know which patients that we are following actually have cancer.

Obviously, the uncertainty of knowing whether they have cancer or not may be very unsettling to patients. Furthermore, it would be interesting to evaluate how tumor-related anxiety in this population of patients compares to patients undergoing active surveillance for other malignancies.

What reservations do you have about active surveillance over more aggressive treatment?

Dr. Crispen: The greatest reservation is the potential for metastatic progression.

With the active surveillance of renal masses we may be allowing a curable malignancy to progress to a lethal disease. The reported rate of progression during active surveillance is approximately 1% to 2%. However, this rate of progression is based on limited followup, with most series following patients for less than three years. Additional risks for active surveillance include increased radiation exposure from repeated CT scans, which may be avoided with the use of MRI or ultrasound during follow-up examinations.

The known risks of active surveillance are important considerations given further improvements in nephronsparing procedures and other measures implemented to decrease treatmentrelated morbidity.

Are you planning more work in this area?

Which patients (or lesions) are best suited to active surveillance?

Dr. Crispen: When selecting a patient for active surveillance it is important to consider both tumor- and patientrelated features. Small—less than 3 cm—asymptomatic masses are likely the best candidates for this. Limited data exist on renal masses greater than 4 cm and I would only advise this approach in patients who are not surgical candidates or have a known benign histology.

Life expectancy, renal function, performance status, and overall surgical candidacy are important factors that should be considered.

At present, there are no established guidelines for active surveillance. ­—Paul L. Crispen, MD

Dr. Crispen: Ongoing work continues in an attempt to improve our knowledge of small-renal-mass biology and the efficacy of active surveillance. I am still interested in evaluating the biology of renal tumors to potentially identify predictors of aggressive disease. As part of this I feel that renal-mass biopsy may become standard practice in the evaluation of small renal masses and will help guide treatment decisions. With the known limitations of renal-mass biopsy and standard histologic predictors of malignant potential, the discovery and use of additional molecular markers will likely enhance treatment decisions. 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.

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Renal & Urology News 15

Smoking Should Stop When Starting Sunitinib PATIENTS STARTING sunitinib (Sutent) treatment for metastatic renal cell carcinoma (mRCC) should be advised to quit smoking, as active smoking appears to negatively affect progression-free and overall survival in such patients, according to findings published online ahead of print in The Oncologist.

The study, by Michael A. Carducii, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltirmore, and colleagues, focused on 278 patients (median age 63 years) with mRCC who underwent sunitinib therapy from 2004 to 2013.

Among the participants, 67 were obese, 73 had diabetes, and 165 had pretreatment hypertension. Approximately half the patients were never-smokers, more than 20% were active smokers, and

the remaining subjects had smoked at some point.

After a median follow-up period of 55 months, a complete response was noted in 3% of patients, a partial response in 36%, stable disease in 39%, and progression in 22%.

Ultimately, nearly 90% of patients had progressed and 73% had died. Active smokers had significantly worse overall survival (11 vs. 25 months). The association between smoking and survival remained strong in additional analyses, one of which indicated that never-

smokers and past smokers had a dramatically lower risk of showing progression on follow-up and had more than double the rate of progression-free and overall survival when compared with active smokers matched on age, gender, and a number of clinical characteristics. n

WE’RE

CHANGING THE WAY

Transplanted Kidneys Can Harbor HIV-1

PROSTATE CANCER PATIENTS ARE TREATED EVEN WHEN THEY’RE NOT BEING TREATED

HIV-1 can infect kidney allografts after transplantation despite

When it comes to treating prostate cancer, we do not believe

undetectable viremia, researchers

in a one-size-fits-all approach. That’s why doctors at UPMC are

concluded in a report published

experts in both traditional methods of urologic surgery and in

online ahead of print in the Journal of

cutting-edge robotic surgery. But our doctors also recognize

the American Society of Nephrology.

when the best management is not an operation, but careful

Guillaume Canaud, MD, of Institut

observation. We believe it is important to be well versed in

National de la Santé et de la

all options to ensure patients receive the right treatment at

Recherche Médicale (INSERM) in

the right time. Because our job is not only to save lives, but

Paris, and colleagues noted that

to preserve the quality of life of every patient we treat. Learn

reports have documented unex-

more at UPMCPhysicianResources.com/ProstateCancer.

plained decreased allograft survival in patients infected with HIV-1. The researchers hypothesized that unrecognized infection of the transplanted kidney by HIV-1 can compromise long-term allograft function.

Dr. Canaud’s group used electron microscopy and molecular biology to examined protocol renal transplant biopsies from 19 kidney recipients with HIV-1 who did not have detectable levels of plasma HIV-1 RNA at transplantation. In 68% of these patients, HIV-1 infected the allograft. “Notably, HIV-1 infection was detected in either podocytes predominately (38% of recipients) or UPMC is affiliated with the University of Pittsburgh School of Medicine.

tubular cells only (62% of recipients),” the authors wrote. n 2145_UPMC_Urology_7x10.indd 1

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Renal Nutrition Update T

ype 1 diabetes has a strong correlation with gluten intolerance.

Because of this association, gluten-intolerant individuals may have increased risk for microvascular complications, including retinopathy, neuropathy, and nephropathy. Prior studies have demonstrated the deleterious effects of gluten intolerance on neuropathy (Lancet 1998;352(9140):15821585; J Neurol Neurosurg Psychiatry 2003;74:490-494). Interestingly, type 1 diabetes patients with celiac disease (CD) often have reduced rates of albumin excretion when compared to non-CD diabetics (Pediatr Diabetes 2013;14:455-458). Researchers have questioned whether a gluten-free diet is protective in this manner.

Beneficial effects A prior study did not find increased risk of CD in type 1 diabetic patients who also exhibited nephropathy (Diabetologia 2005;48:1416-1417), but diabetic CD patients compliant with gluten-free diets have been shown to have reduced albumin to creatinine ratios and reduced advanced glycation end-products (AGEs) compared with non-CD dia-

ratio, triglycerides, and urinary albumin to creatinine ratio. Advanced nephropathy appeared to improve, but due to a small sample size, statistical significance was not achieved.

Retinopathy improved after one year of gluten-free diet intervention.

Similarly, another study failed to find an association between risk rates in type 1 diabetics with or without CD and nephropathy, but CD patients following a gluten-free diet had reduced rates of retinopathy (Acta Diabetol 2013;50:319-324).

Furthermore, a recent study found that CD patients who did not comply with a gluten-free diet had significantly higher albumin excretion rates compared with non-compliant individual (Diabet Med 2013; published online ahead of print).

Pediatric populations Several of these studies have focused on pediatric patient populations, and thus nephropathy may not have been able to manifest in such a short time. Thus, the appearance of increased proteinuria is more indicative that potential renal damage is occurring.

A trial of a gluten-free diet presents no inherent risk for patients starting to exhibit microvascular damage. betics (Diabetologia 2009;52:798-800).

Another study found improvements in newly diagnosed CD patients after one year of gluten-free diet adherence (Diabetes Care 2011;34:2158-2163).

These improvements included an increase in high-density lipoprotein (HDL) cholesterol and a decrease in hemoglobin A1c, cholesterol to HDL

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Gluten exposure in CD patients induces an inflammatory response that can have a wide range of downstream effects, including reduced insulin sensitivity. It is worth questioning whether the protective effect of a gluten-free diet experienced by these patients are strictly due to reducing their overall gut inflam-

© THINKSTOCK

Adherence to a gluten-free diet may help to prevent nephropathy in patients with type 1 diabetes BY GRISSIM CLARK CONNERY, MS, RD, LD

Type 1 diabetics with celiac disease on a gluten-free diet had reduced rates of retinopathy.

mation or if a more complex mechanism exists. Interestingly, anti-gliadin antibodies may have an association with IgA nephropathy (Ups J Med Sci 2006;111:339-352).

Case reports have found a glutenfree diet in CD patients to resolve nephrotic syndrome (Pediatr Nephrol 2009;24:1247-1250; Nephrol Dial Transplant 2009;24:3545-3548).

In a cohort of IgA nephropathy patients, one study reviewed rectal mucosal reaction to gluten using through nitric oxide production as well as myeloperoxidase and eosinophil cationic protein (Nephrol Dial Transplant 2009;24:2476-2481).

Additionally, they reviewed serum IgG antigliadin antibodies as well as multiple IgA antibodies.

One third of the patients demonstrated gluten sensitivity via the rectal measurements, but interestingly this did not correlate with serum measurements. This presentation of gluten sensitivity without the classical serum markers is now being referred to as

non-celiac gluten sensitivity (NCGS).

This affliction has been a growing area of interest due to the increasing awareness that intolerance of wheat products can present without small intestinal destruction or wheat allergy (Nutrients 2013;5:3839-3853).

Adherence to a gluten-free diet in CD individuals is critical for an array of health parameters. Although nephropathy does not appear to be as common as retinopathy or neuropathy in gluten-intolerant individuals, these disease processes are closely related.

For patients beginning to exhibit microvascular damage, a trial of a gluten-free diet presents no inherent risk. Because NCGS is only now being truly recognized, a temporary elimination diet may be the most appropriate approach to test for food intolerance until adequate standardized diagnostic criteria can assess NCGS. n Mr. Connery is Research Coordinator at Case Western Reserve University in Cleveland.

We’ve got more on our website highlighting effective diets for delaying CKD progression and ­helping patients manage sodium and phosphorus intake. See us at www.renalandurologynews.com/nutrition.

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Renal & Urology News 17

Renal Denervation Results Promising Treatment shown to benefit patients with stage 3 or 4 CKD and treatment-resistant hypertension

BY WAYNE KUZNAR DALLAS—Data from a small pilot study reveal that renal denervation “slows or even halts the decline of renal function in treatment-resistant hypertensive patients” with stage 3 or 4 chronic kidney disease (CKD). The 15-patient study was presented at a poster session during the American Heart Association’s Scientific Sessions 2013.

The study was conducted in patients with stage 3 or 4 CKD who had a mean age of 66 years and an office blood pressure (BP) of 140/90 mm Hg or higher despite treatment with at least three antihypertensive agents and a 24-hour ambulatory BP of 130/80 mm Hg. All underwent renal denervation using the Medtronic Symplicity Flex catheter system. Renal function was evaluated up to three years prior to and up to one year after renal denervation. The estimated glomerular filtration rate (eGFR), calculated using the

Study: CVCs Implicated in Bacteremias

BY JOHN SCHIESZER SAN FRANCISCO—Central venous catheters are associated with the development of vascular-access-related bloodstream infections (VABSI) in outpatient hemodialysis (HD) patients, according to a study presented at IDWeek 2013.

The findings suggest that improved infection surveillance by HD providers according to vascular access type may be needed, researchers reported. In addition, laboratories should provide ongoing notification and review of blood culture results for timely detection and response to VABSIs in HD patients.

“During the investigative period, outpatients with central venous catheters were 13 times more likely to develop VABSI than outpatients without central venous catheters,” said investigator Kavita Trivedi, MD, with the Healthcare Associated Infections Program in the California Department of Public Health in Richmond.

She and her colleagues noted that there has been a concerted national effort to increase the use of arteriovenous fistulas

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Modification of Diet in Renal Disease (MDRD) study formula, was 47.0 mL/ min/1.73 m2 at baseline. Other baseline characteristics were a mean office BP of 157/78 mm Hg, a mean 24-hour ambulatory BP of 157/80 mm Hg, a mean aortic systolic BP of 150.0 mm Hg, and a mean heart rate of 66 bpm.

Seventy-five percent of patients had diabetes. Patients were on a mean of 5.8 antihypertensive agents at entry.

One year following renal denervation, office BP was reduced by a mean of 26/6 mm Hg and 24-hour ambulatory BP was reduced by 13/6 mm Hg, reported lead investigator Roland E. Schmieder, MD, from the department of nephrology, University Hospital of Erlangen, Germany. Aortic systolic BP declined by 24 mm Hg. Before renal denervation, the mean decline in eGFR was 5.6 mL/min/ 1.73 m2. After renal denervation, eGFR remained stable (47.0 mL/min/1.73m2 at baseline vs. 49.2 mL/min/1.73m 2

(AVFs) and arteriovenous grafts (AVGs) and decrease the use of central venous catheters (CVCs). CVCs remain the most common form of access in outpatient HD centers in the U.S., however.

A Health Maintenance Organization in October 2011 noted a cluster of 11 outpatients who developed VABSIs associated with one HD provider in two counties in California during a four-month period.

Patients were analyzed based on access type and blood culture data where the cluster of cases occurred. For comparison, researchers also looked at non-HMO patients at the same dialysis centers. They compared the VABSI rates from baseline (January to June rates) to the investigative period (July to October rates). Nine HD centers were involved in this study; infection control audits were conducted at three centers. The VABSI rates for the HD centers overall were low compared with national rates. A rise in VABSI rates was revealed during the investigative period, and associated with patients who had CVCs. No CVC breaches were observed. “Nephrologists should consider establishing alternate types of vascular access more quickly,” Dr. Trivedi told Renal & Urology News. “Additionally, nephrologists should assist outpatient hemodialysis centers in improving infection surveillance for timely detection and response to VABSI.” n

at one year). The difference in eGFR change per year pre- and post-renal denervation was significant.

None of the 15 patients had a doubling of serum creatinine or required dialysis after renal denervation at any point.

Researchers from the First

Two small studies reveal improvements in renal function and cardiac parameters Cardiology Clinic at the University of Athens, Greece, presented their own findings on renal denervation (using the EnligHTN) in 20 patients with drug-resistant hypertension who were followed for six months. Cardiac parameters were assessed using transthoracic echocardiography and blood measurement of

N-terminal B-type natriuretic peptide (NT-proBNP). The mean age of the cohort was 57 years; patients were on a mean of 4.5 antihypertensive drugs at baseline.

Both office BP and 24-hour ambulatory BP decreased significantly from baseline to month 6. The effects on BP were accompanied by favorable cardiac remodeling and attenuation of neurohormal overdrive as reflected by decreased NT proBNP levels.

Significant improvements from baseline in left atrial diameter, left ventricular mass index, and diastolic function were observed six months after renal denervation. Intervernicular septum in diastole decreased significantly from 12.1 mm at baseline to 11.6 mm at six months, and the mitral valve E’/A’ ratio increased significantly from 0.62 to 0.82. NT-proBNP fell from 85.0 pg/mL at baseline to 58.6 pg/mL at month 6). n

High-Dose-Rate Brachytherapy May Be Better for Penile Cancer

BY JOHN SCHIESZER ATLANTA—Low-dose-rate interstitial brachytherapy is commonly used for conservative treatment of penile carcinoma, but high-dose-rate interstitial brachytherapy (HIB) may be a better option, French researchers reported at the American Society for Radiation Oncology’s 55th annual meeting.

“The results were good and the toxicity was equivalent to the toxicity observed with the previous technique of low-dose rate. Of course, we have short follow-up but we obtained promising results,” said study investigator Yohann Rouscoff, MD, a urologist at Centre Antoine Lacassagne, Nice.

Dr. Rouscoff and his colleagues analyzed clinical outcome and dosimetric data for 12 men with histologically proven T1-T2 (less than 4 cm) penile carcinoma treated with highdose rate interstitial brachytherapy (HIB). For 11 patients, HIB was the sole therapy following biopsy; one patient

had HIB performed in an adjuvant setting after conservative surgical resection. Among the 12 patients, 11 patients were had T1 disease (eight patients with T1a and three patients with T1b disease), and one patient had T2 disease, according to the UICC TNM classification 2009. None of these patients presented with inguinal lymph node involvement.

The median age of the patients was 77 years (range 47-84 years) and the median follow-up was 20.5 months (range 5.1-83 months). The median tumor size was 25 mm (range 9-32 mm).

The median delivered dose was 38.5 Gy. “We found that the patients did very well in terms of erectile dysfunction,” said study co-investigator Jean-Michel Hannoun-Levi, MD, Professor of Radiation Oncology, University of NiceSophia-Antipolis, Nice. “There were no complications after the procedure compared to baseline. Sexual function was unaffected.” n

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18 Renal & Urology News

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Donor Criteria Consensus Sought

The goal is to eliminate the need for donors to travel to recipients’ transplant centers for nephrectomy

BY ROSEMARY FREI, MSc MONTREAL—A team is hammering out consensus criteria across Canada for assessment and acceptance of donors involved in the Living Donor Paired Exchange (LDPE) registry run

by Canadian Blood Services.

An important objective of these criteria is to streamline donor assessment so that donors who live far from recipients do not have to be assessed twice: once at the center closest to their home and again at the center where the recipient will undergo transplantation. This is a common dilemma in the LDPE, which pairs unrelated donors and recipients across the country.

The hope is that once the standards are set for the LDPE they will be applied to everyone who seeks to be a kidney donor in Canada. This is the first time such a consensus has been sought anywhere in the world. If a consensus is reached, centers in Canada would be able to ship donor kidneys to the recipients’ transplant center.

“Right now there’s a moratorium

on shipping kidneys because Health Canada requires uniform assessment and acceptance criteria for the centers at which the donor is worked up and donating, and that’s not necessarily a great situation for donors,” David Landsberg, MD, Chair of the Living Donor Advisory Committee (LDAC) that is spearheading the project, told attendees of the Canadian Society of Nephrology’s 2013 annual meeting.

“But as soon as we have national standards and everybody does the same assessment, we can start to ship the kidneys.”

National standards should also reduce the number of chains that collapse because donors do not meet the acceptance criteria of the center at which they were to donate, he pointed out. Between 2009 when the LDPE was created and April 3, 2013, 39 chains collapsed, only six of which were repaired, contributing to a total of 16 completed chains. In most of the cases the chain collapses were due to the recipient’s center declining the donor.

The first phase in the harmonization process is arriving at a consensus for assessment and acceptance of living donors for the LDPE. Then they will adjust their consensus donor assessment and acceptance criteria based on the evidence included in the KDIGO (Kidney Disease – Improving Global Outcomes) guidelines for donor assessment and acceptance, which are slated to be completed in 2014, Dr. Landsberg said.

There are five working groups within LDAC, covering all of the areas of donor assessment and acceptance. All members of LDAC met in Toronto on April 11-12.

“We had a pretty dynamic engagement of differing opinions at that meeting,” Dr. Landsberg said. “The central areas in which there are currently disparate donor-acceptance criteria are impaired fasting glucose, future diabetes risk, hypertension, glomerular filtration rate (GFR) cutoffs, body mass index, and the cardiac and microscopic hematuria workups.

Among the areas in which the LDAC

members have come to a consensus is that donors over age 50 who have hypertension that is well-controlled on one blood pressure medication and no evidence of target organ damage are acceptable donors. In addition, they agreed that having a body mass index over 35 is a contraindication to donation, with heavily muscled men being a possible exception. The GFR cutoffs they set as being acceptable for donation are greater than 90 mL/min/ 1.73 m2 for donors aged 18-30 years, greater than 85 for those aged 3140 years, greater than 80 for those aged 41-65 years, and greater than 75 for anyone over 65.

“We’ll now package our recommendations, bring them to each transplant center, and get feedback and buy-in from the centers,” Dr. Landsberg said.

“We’ll be influenced and guided by the American guidelines when they come out, but we want to achieve consensus before that. I think that in three years the harmonization will be completed and we’ll be shipping kidneys.” n

IR Placement of Fiducial Markers Safe, Study Finds

BY JOHN SCHIESZER NEW ORLEANS—Transrectal ultrasound (TRUS)-guided prostate fiducial marker placement appears to be a safe and reliable technique that may be performed by an interventional radiologist for subsequent prostate localization during radiotherapy, according to a new study presented at the Society of Interventional Radiology’s 38th Annual Scientific Meeting.

Lead investigator Amy Deipolyi, MD, PhD, a research fellow at Massachusetts General Hospital in Boston, noted that the procedure traditionally has been done in urologists’ offices, “so we wanted to show that it could be safely done in interventional radiology.”

“The primary issue is that we see is a misplaced marker,” Dr. Deipolyi said.

“Sometimes, one of the markers goes to a place we don’t want it to.” This is always corrected easily on the day of the procedure, however, with placements of addi-

tional markers if necessary, she added.

Dr. Deipolyi and her colleagues conducted a study with 111 patients who underwent TRUS-guided prostate fiducial marker placement from January, 2011 to August, 2012. In this series of patients, three gold markers were placed, one each in the right and left prostate base as well as right apex. Post-procedure frontal and lateral radiographs confirmed placement.

An additional marker was placed if malposition was noted.

The 111 men had a mean age of 69 years (range 52-90 years), a mean PSA level of 11 ng/mL (range 1-106 ng/mL), and mean prostate volume of 31.5 mL (range 2-130 mL). The mean Gleason score was 7 (range 6-9). Clinical stages ranged from T1c-T3b. Six patients (5.4%) previously had undergone transurethral resection of the prostate and one patient (0.9%) previously had received cryotherapy.

In 60 men (54%), 1% lidocaine was injected into the neurovascular bundle;

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Amy Deipolyi, MD

the remaining 51 men (46%) received no lidocaine. Moderate sedation was used to allay anxiety on one patient and general anesthesia was used because of anal canal stenosis in another patient.

The researchers observed excellent primary placement in 105 patients (94.5%).

Malposition of one marker was recognized on ultrasound in four cases (3.6%) and on radiograph in two cases (1.8%).

These malpositions required additional fiducial placement. In all cases, the fiducials were still used during radiotherapy.

As a result of poor visualization of the fiducial markers, three patients (2.7%) required additional prostate localization using B-mode acquisition and targeting ultrasound at the time of radiotherapy.

All the patients later underwent radiotherapy. Forty patients underwent proton beam radiotherapy and 71 underwent intensity-modulated radiation therapy.

All the patients received ciprofloxacin 500 mg twice a day for three days periprocedurally and gentamycin 80 mg at the time of procedure. Post-procedure, a urinary tract infection requiring oral antibiotics occurred in one patient (0.9%) and urosepsis requiring hospital admission and intravenous antibiotics occurred in one patient (0.9%). n

For upcoming news visit renalandurologynews.com for coverage of the International Continence

Society annual meeting in Barcelona, Aug. 26-30, and ASTRO’s 55th annual meeting in Atlanta, Sept 22-25.

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Renal & Urology News 19

Legal Issues in Medicine D

r. F, 58, was a nephrologist with a busy practice in a large city. One of his patients was a 72-year-old woman, Mrs. D, who was on dialysis. Mrs. D’s condition was poor and she was admitted to the hospital for a foot amputation. While visiting her in the hospital, Dr. F began writing a prescription for 10 mmol of potassium for the patient. He was interrupted while he was writing, and when he went back to it afterwards, he rethought the dosage and decided to make it 20 mmol instead. However, rather than start with a fresh prescription, or cross out what was already written, Dr. F attempted to write a number “2” over the “1.”

After he left the hospital, the nurse and pharmacist misread the prescription, believing that it read 120 mmol rather than 20. The prescription was filled for 120 mmol of potassium.

Within 12 hours, Mrs. D was dead.

When Dr. F was notified about his patient’s death, and the circumstances surrounding it, he was flabbergasted.

He was called into the hospital as part of the administration’s investigation into Mrs. D’s death. “I may have been a little messy when I wrote the prescription,” he admitted, “but it went through a pharmacist and a nurse before the patient received it. How could the nurse and pharmacist not have realized that a 120 mmol dose of potassium is fatal?”

Doctor refuses to settle Within a few months, both the hospital (as the employer of the nurse and pharmacist) and Dr. F were sued for malpractice by Mrs. D’s family. The hospital settled out of court for an unspecified amount, but Dr. F did not want to settle.

“Even if I was a little sloppy in writing the script,” he told his defense attorney, “there were at least two other healthcare

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professionals who should have caught it before it ever reached the patient. And if they couldn’t read what I’d written, why didn’t they call me?”

At trial, the plaintiffs (the three adult daughters of Mrs. D) testified about the anguish that their mother’s untimely death had caused them. Their attorney presented witnesses who testified that despite her health conditions, Mrs. D might have lived six or more years. In his closing argument, the attorney urged the jury to punish Dr. F, saying “these errors are happening on a daily basis, but are a dirty secret that often gets swept under the rug. You the jury, with your verdict, can suppress or encourage this type of behavior.”

The plaintiffs asked for $1.25 million for loss of companionship and mental anguish, $250,000 for Mrs. D’s pain and suffering, and $19,000 for funeral expenses.

The defense introduced experts who estimated that due to Mrs. D’s poor health, she would only have lived six months to a year at most. Other experts testifying for the defense explained the roles of the pharmacist and nurse, and how the hospital employees should have had safeguards in place to ensure such an error did not happen. Dr. F testified that although he was very sorry for the outcome, he could not in his wildest imagination have thought that a dosage that high would be taken seriously by trained professionals. The defense attorney argued that the dosage was so outside of the norm that the pharmacist and nurse had a duty to call the physician before filling it.

The jury deliberated for two days before finding Dr. F negligent. The jury awarded the family a total of $380,000: $250,000 for Mrs. D’s pain and suffering, $110,000 for loss of companionship, and $20,000 for funeral expenses. The jury, however, also

© THINKSTOCK

A doctor’s confusing potassium prescription and careless hospital staff result in a patient’s death BY ANN W. LATNER, JD

A pharmacist and nurse failed to realize a patient was prescribed a fatal dose of potassium.

determined that the hospital was 90% at fault and Dr. F was only 10% at fault.

Legal background If someone is injured by the acts of more than one party, the jury is often asked to apportion the percentage of responsibility to each defendant, and then the monetary damages would be paid proportionally by the defendants (although there are exceptions in different jurisdictions). In some cases, another party’s actions (for example, the pharmacist, if she did not heed an out-of-range dosage warning on her computer) might negate the original negligence (Dr. F’s bad writing), and result in Dr. F facing no liability at all. But in this case, Dr. F ended up being responsible for 10% of the jury’s verdict.

Protecting yourself The topic of physicians’ handwriting is something of a joke. In fact, one national pharmacy publication runs a monthly “Can You Read This Prescription”

column, where pharmacists send in illegible prescriptions for their contemporaries to guess at. Hopefully, e-prescribing will help to avoid errors in the future, but until then it is important to make sure all prescriptions are legible. Taking an extra moment to neatly print an order can make all the difference in the world – and not just to the patient. A great deal of time is spent by pharmacists trying to decipher illegible prescriptions. While the nurse and pharmacist were certainly at fault here – they should have called Dr. F if they couldn’t read or didn’t understand the prescription – the simple act by Dr. F of writing neatly could have avoided anguish on all sides. n Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y. Cases presented are based on actual occurrences. Names of participants and details have been changed. Cases are informational only; no specific legal advice is intended.

What do you think? Did the jury make the right decision in this case? We want to know your thoughts. Leave us a comment at the end of this article—or any article—at www.renalandurologynews.com/legal.

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20 Renal & Urology News

JANUARY 2014 www.renalandurologynews.com

Malpractice News

© CMSP / B. SLAVEN

It took 10 years for the case to be resolved, but an Alabama jury has awarded $6.7 million to a man injured when a hernia surgery went awry. The plaintiff and his wife sued a surgeon and his practice in 2003 alleging that the surgeon had perforated the patient’s small intestine and failed to repair the injury during a four-hour hernia operation in 2002.

The surgeon noted that he had punctured the outer layer of the plaintiff’s intestine during surgery but didn’t think it was deep enough to cause a problem. The night after the operation, the patient began to suffer excruciating abdominal pain. By the next day, the patient had a fever and elevated pulse, and his white blood cell count and urinary output had dropped. Two days after the surgery, his organs began to fail and he required a ventilator to breathe.

Despite the fact that the patient’s condition worsened after the surgery, the surgeon did not discover the perforation until four days later, when another physician suggested the surgeon determine whether the patient had an intestinal infection. A needle aspiration revealed the intestinal leak. Although surgery was performed that day to correct the prob-

A surgeon discovered a perforation four days after hernia repair surgery

On The Web RUN0114_MalPractice.indd 20

lem, the infection had already spread.

The patient required three more surgeries and then developed severe bed sores resulting in permanent disability. The patient, who was 57 at the time of surgery, was no longer able to work, and his wife had to quit her job to become his caretaker. The jury awarded the patient $5.2 million, and his wife $1.5 million.

ping prescription drug addict whose medications were not being monitored by his various physicians. One of the measures called for in the ballot initiative is mandatory use of the electronic CURES database, which tracks prescriptions dispensed in California in order to identify drug-seekers.

The initiative needs about 750,000 valid signatures to make it onto next year’s ballot.

Study Highlights Complexity Of Medical Malpractice Cases A recent study of the trial court workload in Tennessee has revealed that even if fewer medical malpractice cases are filed, they still use up more time than any other type of case. The study detailed how state judges in Tennessee spend their time, and was a 2013 update to a 2007 study.

The report reveled that in fiscal year 2013, 385 medical malpractice cases were filed in Tennessee courts.

This number represents an extremely small percentage of total cases filed in Tennessee. A mere 0.18% of all Tennessee court filings—both criminal and civil—were medical malpractice cases. However, despite the small number of cases, they account for a much higher proportion of a judge’s time. Judges spent 3.83% of their time on medical malpractice cases; the greatest portion of that (2.45%) was for trial work. The report also showed that pre-trial work took up about a third of judges’ time in medical malpractice cases, but that post-trial issues barely used any time.

In terms of actual hours spent, each malpractice case took about 22 hours of a judge’s time. This number is higher than any other type of case, including first-degree murder, which only took about 13 hours of a judge’s time.

California Clears Initiative To Raise Malpractice Caps In 1975, California became the first state to enact caps on non-economic damages (such as pain and suffering)

VA Paid Out Over $800 million To Settle Claims in Past Decade © THINKSTOCK

Alabama Couple Awarded $6.7 Million in Malpractice Case

BY ANN W. LATNER, JD

In 2014, California voters will decide on an increase in malpractice award cap.

in medical malpractice cases. While the idea was progressive and became a template for other states, the law has faced increasing scrutiny over the last few years. The cap is set at $250,000, which in 1975 was a lot more than what it is worth today ($58,000).

A new ballot initiative, slated for 2014, is intended to remedy that by raising the cap to $1.1 million. The ballot initiative is already causing a commotion.

The California Medical Association has spent $5 million to defeat the measure so far, and more than $31 million has already been raised to oppose the measure.

The increase in malpractice caps is only one part of the initiative. The measure also aims to reduce harm caused by physicians under the influence of drugs or alcohol, and requires random drug and alcohol testing for physicians, as well as mandatory testing after an unexpected death or injury to a patient.

The ballot measure—called the Troy and Alana Pack Patient Safety Act of 2014—was authored by Bob Pack whose seven-year-old daughter and 10-year-old son were killed by a drugged driver who fell asleep at the wheel and ran over the children. The driver turned out to be a doctor-shop-

A recent analysis has revealed that the U.S. Department of Veterans Affairs has paid out about $845 million for medical malpractice cases since 2003. The high point in payouts came in 2012, when the VA settled 454 cases, totaling $98.3 million in settlements. The largest number of payouts occurred in 2008—a total of 462 for that year.

How does this compare to the civilian sector? A New England Journal of Medicine study found that private health systems pay out on about 20% of medical malpractice claims. The VA’s percentage of claims paid is about 25%.

During this same 10-year period, the VA has faced increasing scrutiny for paying bonuses and raises to healthcare practitioners who were providing substandard care.

A government accountability study revealed that in 2011, the VA gave $160 million in bonuses and performance awards to providers without equating better performance with the extra pay. VA officials, however, have pointed out that they manage one of the country’s largest medical networks, and that they only receive a relatively low number of claims. For example, in 2012, the year with the highest payout, 6.3 million veterans were treated by the VA, and only 1,544 claims were filed. n Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

Looking for more malpractice news? Visit us at renalandurologynews.com/malpractice to see noteworthy jury verdicts, recent trends in legislation, and surprising settlements!

12/26/13 12:30 PM

www.renalandurologynews.com JANUARY 2014

Renal & Urology News 21

Cutting Abdominal Fat May Halt CKD

BY DELICIA HONEN YARD REDUCTIONS in waist circumference and 24-hour urine phosphorus excretion may prevent chronic kidney disease (CKD) or slow its progression, according to study findings published in the American Journal of Kidney Diseases (2013;62:900-907).

A team led by Alex Chang, MD, MS, formerly with Johns Hopkins University in Baltimore but now affiliated with Geisinger Health System in Danville, Pa., studied urinary albumin excretion (UAE) in 481 patients with normal kidney function who had participated in the PREMIER blood pressure–lowering trial. That study focused on weight loss, healthful diet, and exercise among mostly overweight or obese individuals with prehypertension or stage I hypertension.

For their observational analysis of the PREMIER participants, Dr. Chang and his colleagues examined 24-hour urine specimens collected at baseline and

PCa Risk Lower in Statin Users PROLONGED statin use is associated with a decreased risk of prostate cancer (PCa), but the extent of this protective effect varies by duration of use time and type of statin, according to a new study.

A team led by Arnon D. Cohen, MD, MPH, PhD, of Clalit Health Services in Tel Aviv, Israel, conducted a population-based cohort study of 66,741 men aged 45-85 years. The mean age at cohort entry was 58 years.

During follow-up, 1,813 PCa cases were diagnosed and 11,245 men died.

A total of 37,645 subjects (56%) had filled at least one prescription for a statin and 26,061 (39%) had filled prescriptions for statins for at least 12 months.

The longer statins were used, the greater the reduction in PCa risk.

In a fully adjusted model, men who used statins for five years or more had a 78% decreased risk of a PCa diagnosis compared with non-users.

Men who used statins for one to five years had a 45% decreased risk and

RUN0114_SIU2.indd 21

at six months. The researchers found that after six months, the proportion of subjects with UAE of 10 mg/day or more fell from 18.7% to 12.7%.

Mean waist circumference decreased by 4.2 cm, mean 24-hour excretion of sodium dropped by 28.2 mmol/ day, mean potassium increased by 8.4 mmol/day, mean phosphorus decreased by 27.7 mg/day, and mean protein intake was reduced by 1.7 g/day.

After adjustment for relevant covariates, the investigators found that decreases in waist circumference, 24-hour urine phosphorus excretion, and protein intake were significantly associated with UAE reduction in separate models.

Ultimately, the first two factors, but not protein intake, remained significantly associated with UAE reduction, even after adjusting for changes in blood pressure and insulin resistance.

In addition, participants with higher UAE and baseline metabolic syndrome

those who used statins for three to 12 months had a 32% decreased risk, the researchers reported online ahead of print in Prostate Cancer and Prostatic Disease.

Risk reductions also varied by cumulative statin use. Compared with men who did not take statins, those who had a cumulative defined daily dose of 1-5,000, 5,001-10,000, 10,001-20,000, and 20,001 mg or higher had an 18%, 36%, 65%, and 76% decreased risk, respectively, in a fully adjusted model.

Moreover, the reduction in risk varied by type of statin. Compared with no statin use, men who used rosuvastatin for at least six months had an 80% decreased risk of PCa in a fully adjusted model. Men who used simvastatin or atorvastatin for at least six months had a 52% and 55% decreased risk. The risk was increased by 34% and 29% for men who used lovastatin or fluvastatin, respectively.

In a separate study published in the same journal (2013;16:254-259), researchers led by Stephen J. Freedland, MD, of the Duke University School of Medicine in Durham, N.C., found no association between statin use and PCa or high-risk PCa among men with a negative baseline prostate biopsy and follow-up biopsies largely independent of PSA. n

© THINKSTOCK

New study also shows that kidney disease may be prevented by decreasing phosphorus intake

Encourage patients to avoid high-fat foods.

experienced greater reductions in UAE from decreases in waist circumference.

“The significant association we observed between changes in 24-hour urine phosphorus and UAE is novel

and needs to be confirmed in other studies,” Dr. Chang’s group stated.

“These findings could reflect changes in total phosphorus intake, the sources of phosphorus being consumed, or less likely, changes in gut absorption or bone metabolism.”

“Other studies have suggested that once [a person is] diagnosed with kidney disease, weight loss may slow kidney disease progression, but this is the first research study to support losing belly fat and limiting phosphorus consumption as a possible way to prevent kidney disease from developing,” noted Joseph Vassalotti, MD, Chief Medical Officer of the National Kidney Foundation.

He added, “A good rule of thumb is that if the food comes in a package, it’s likely to be high in phosphorus. This study suggests limiting the amount of processed foods in [the] diet may be an easy way to reduce [the] risk of developing kidney disease.” n

Hyperuricemia Possibly Linked to Hematospermia

BY ROSEMARY FREI, MSc

remaining patients had other causes of

VANCOUVER— Patients with hemato-

hematospermia.

spermia may have hyperuricemia as

The 22 hyperuricemia patients’ mean

the underlying cause, according to

age at presentation was 32 years (range

study findings presented at presented

20-48) and they had between five and

at the 33rd Congress of the Societé

12 hematospermia attacks over two to

Internationale d’Urologie

six months before going to the hospital.

The study, by Adel Kurkar, MD, of

Their mean serum uric acid level at

Assiut University Hospital in Assiut,

the initial assessment was 9.2 mg/dL.

Egypt, and colleagues, included 143

Fourteen (63.6%) of the hyperuricemia

patients who presented with refractory

patients also had lower urinary tract

hematospermia for more than three

symptoms, 15 had painful ejaculation,

months at the hospital’s urology clinic.

12 had arthralgia, 10 had urate crystals

Treatment was administered and the

in their urine, seven had urate crystals in

patients’ semen was subsequently ana-

their semen. In five patients, transrectal

lyzed once a month until the symptoms

ultrasonography revealed dotted pros-

resolved; thereafter, the semen was ana-

tate calcifications.

lyzed every three months for one year.

All the hyperuricemia patients were

Twenty-two (15.38%) patients had

treated with allopurinol 300 mg tablets

hyperuricemia, making it the second

twice daily for eight weeks, followed by

most common comorbidity with

300 mg daily until the condition was no

hematospermia. Schistosomiasis was

longer present. Complete resolution

present in 31 patients, 21 had idiopathic

of hyperuricemia and hematospermia

hematospermia, 12 each had tubercu-

occurred within an average of two

losis and chronic prostatitis, and the

months (range one to four months). n

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22 Renal & Urology News

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New Scoring System Predicts NSS The Zonal NePhRO system more accurately alerts doctors to possible perioperative complication risks

BY ROSEMARY FREI, MSc RESEARCHERS have developed a new renal scoring system to help physicians determine whether patients are candidates for nephron-sparing surgery (NSS).

The Zonal NePhRO scoring system takes into account four parameters of small renal masses that collectively indicate whether a patient’s tumor should be removed. These are the extent of the tumor (‘Ne’ – nearness to cortex, medulla and collecting system), whether it includes the collecting system (‘Ph’ – physical zones), the tumor’s radius (‘R’), and whether the mass is largely exophytic or endophytic (‘O’ – organization). Each patient is assigned a score of 1, 2, or 3 for each parameter, with low risk for malignancy being scores of 4-6 points, intermediate risk being scores of 7-9 points and high risk being scores of 10-12.

Lead investigator Philippe E. Spiess, MD, and his collaborators from the Department of Genitourinary Oncology at the Moffitt Cancer Center, Tampa, Fla., created the NePhRO system. They compared it in this study to the older but established and validated R.E.N.A.L. nephrometry scoring system. Dr. Spiess and colleagues

determined that the NePhRO scoring system is simpler to complete and more accurately predicts the risk of perioperative complications.

“The zonal NePhRO has unique properties which make it advantageous versus other scoring systems for renal cancer surgery such as ease of use, low inter-observer variability, and ability to better discriminate risk of perioperative complications,” said Dr. Spiess, Associate Professor of Genitourinary Oncology, after his team presented the results at the 2013 annual meeting of the Societé Internationale d’Urologie.

The team retrospectively reviewed the scores and outcomes from patients with stage T1a or T1b renal masses who underwent NSS at Moffitt. None of the patients had solitary kidneys or received any other procedures.

The review covered 200 patients who were treated between 2008 and 2011. Their average age was 59.81 years (range 29-85 years), their average tumor size was 3.06 cm (0.8-6.5 cm) , their mean estimated blood loss during the nephrectomy was 293.7 cc (25-2,500 cm) and the mean clamp time was 19.31 minutes (0-57).

Their mean NePhRO score was 8.62 and their mean R.E.N.A.L. neph-

Philipe E. Spiesse, MD

rometry score was 7.21. The investigators invited other urologists to score each patient; those physicians’ mean time to determine the NePhRO score was 15.19 seconds, where it took them an average of 21.15 seconds to determine patients’ R.E.N.A.L. scores.

A total of 37 patients were determined to have a low risk on the NePhRO scoring system, while 84 had intermediate-risk masses and 79 had high-risk masses. There was significantly more estimated blood loss with increasing risk level (163.6 cc, 263

cc and 344.3 cc, for low, intermediate and high risk, respectively). None of the low-risk-lesion patients developed a urine leak, whereas four of the intermediate-risk-lesion and six of the highrisk-lesion patients did so. Twenty-five (67.6%) of the low-risk lesions were found to be renal cell carcinoma compared with 57 (67.9%) in the intermediate-risk category and 60 (75.9%) in the high-risk category.

A total of 39 perioperative complications occurred. NePhRO predicted these on both univariate and multivariate analyses. However, the scoring system did not predict urinary leaks, tumor pathological stage, or maximum tumor diameter on multivariate analysis.

“We believe the zonal NePhRO takes into account tumor size in the designation of a given complexity score, and that this is why this endpoint did not come out as predictive in our multivariate model,” Dr. Spiess explained. “We are developing other predictive tools as they pertain to the characteristics of the tumor which may help predict tumor biology and potentially risk of urinary fistulae, and these will likely be integrated in our scoring system in the months to come.” n

Sacral Neuromodulation Eases Stubborn OAB

BY JILL STEIN BARCELONA—Sacral neuromodulation (SNM) with Interstim Therapy is significantly better than an additional trial of standard medical treatment (SMT) for patients with refractory overactive bladder (OAB) who have not exhausted all possible medication options, investigators reported at the 43rd Annual Meeting of the International Continence Society (ICS).

In their study, improvements in efficacy and quality of life have been shown to last at least six months.

Tomas L. Griebling, MD, MPH, who is the John P. Wolf 33rd-Degree Masonic Distinguished Professor of Urology at the University of Kansas in Kansas City, presented six-month outcomes of a study comparing SNM with InterStim therapy versus SMT for the treatment of OAB. Interstim therapy uses a small implanted pulse generator connected

RUN0114_SIU_1.indd 22

to a quadripolar lead that transmits a low-level electrical impulse to the third sacral nerve root. The resultant neurostimulation decreases bothersome urinary symptoms without interfering with normal urination.

Improvements in efficacy, quality of life last at least six months.

The ongoing InSite OAB Trial includes patients with bothersome symptoms of idiopathic OAB including urinary urge incontinence (OAB wet) or urge frequency (OAB dry) who have failed or are unable to tolerate at least one anticholinergic or antimuscarinic medication and have at least one anticholinergic or antimuscarinic medica-

tion that they have not yet tried.

This group represents a less severe segment of SNM-eligible patients than has been previously studied, Dr. Griebling said.

Patients stopped their OAB medications prior to and during baseline assessment and were randomized to SNM or SMT. Individuals in the SNM arm underwent test stimulation and were implanted with SNM if successfully tested, while those assigned to the SMT arm resumed treatment with their prior OAB medication or started the next recommended medication.

Therapeutic success was defined as a 50% or greater reduction in the average number of leaks per day or a 50% or greater reduction improvement in voids per day or a return to normal voiding frequency (fewer than eight voids per day).

The analysis included 51 implanted SNM patients and 77 SMT patients.

Most study participants were women, with a mean age of 58.7 years.

In the intent-to-treat (ITT) population, the therapeutic success rate was 61% for the SNM patients versus 42% for the SMT patients, according to the researchers. The ITT population included all randomized subjects, including 19 subjects who were randomized but not implanted.

In the as-treated population, the therapeutic success rates were 76% and 49% for the two treatment arms, respectively. The as-treated population included subjects with diary data at baseline and six months.

The SNM group also had statistically significant improvements in quality of life measured by the widely validated, disease-specific International Consultation on Incontinence Modular Quality of Life Questionnaire. The two groups did not differ significantly with respect to adverse events. n

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