Renal & Urology News October 2014 Issue

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Gout Risk Linked to Body Mass Index Each 5-unit increment in BMI is associated with a 55% increased relative risk, meta-analysis shows

The Effect of BMI on Gout Risk A new meta-analysis shows that the relative risk of gout increases with increasing body mass index (BMI). Shown here are the numbers of times by which the relative risk of gout increases with each 5-unit increment in BMI compared with a BMI of 20 kg/m2.

Source: Aune D et al. Body mass index and the risk of gout: a systematic review and dose– response meta-analysis of prospective studies. Eur J Nutr (published online ahead of print).

Risk Increased by 1.8 × BMI

25

2.7 × 30

3.6 × 35

4.6 × 40

Body mass index (kg/m2)

Calciphylaxis Incidence Rising CALCIPHYLAXIS, a rare and potentially fatal disorder seen predominantly among patients with end-stage renal disease, has been increasing significantly in incidence, according to researchers who developed a novel algorithm to characterize the disorder’s epidemiology.

The study, published online in the Journal of General Internal Medicine

Living kidney donor transplantation has been declining since 2004.

(JGIM), also showed that chronic hemodialysis (HD) patients with calciphylaxis have mortality rates 2.5 to 3.0 times higher than their counterparts without calciphylaxis.

“To the best of our knowledge, ours is the first study to systematically investigate the incidence and mortality of continued on page 7

THE LIVING KIDNEY DONOR DILEMMA

Many people who want to donate a kidney cannot because of various barriers.

SEE STORY PAGE 12

BY JODY A. CHARNOW AS AN INDIVIDUAL’S body mass index increases, so does his or her risk of gout, according to a new study.

In a systematic review and metaanalysis of 10 prospective studies involving a total of 27,944 cases among 215,739 participants, researchers found that each 5-unit increment in BMI was associated with a 55% increased relative risk of gout, with a non-significant difference in relative risk between men and women (62% vs. 49%, respectively).

In addition, compared with individuals who had a BMI of 20 kg/m2, those with a BMI of 25, 30, 35, and 40 kg/m2 had a 1.8, 2.7, 3.6, and 4.6 times increased relative risk of gout, Dagfinn Aune, a PhD student in nutrition at the Norwegian

CKD Predicts AKI Following Nephrectomy PREOPERATIVE chronic kidney disease (CKD) stage 2 and 3, a history of neurovascular disease, and obesity are among the factors that independently predict development of acute kidney injury (AKI) within 30 days of undergoing radical (RN) or partial (PN) nephrectomy, according to researchers.

Marianne Schmid, MD, of Brigham and Women’s Hospital, Harvard Medical School in Boston, and University Medical Center HamburgEppendorf, Hamburg, Germany, and colleagues studied 3,320 patients who underwent surgery for renal cell carcinoma (RCC), including 1,944 patients (58.6%) and 1,376 (41.4%) patients who underwent RN or PN, respectively. Patients with an estimated glomerular filtration rate less than 30 mL/ min/1.73 m2 were excluded from the analyses.

AKI—defi ned as a greater than 2 mg/dL rise in serum creatinine above baseline or the need for dialysis within

University of Science and Technology in Trondheim, Norway, and colleagues reported online ahead of print in the European Journal of Nutrition.

Of the 10 studies, 2 reported on BMI in younger adulthood (aged 21–25 years), waist-to-hip ratio (WHR), and weight gain in relation to gout. The study totaled 836 cases among 53,413 participants. In early adulthood (age 21–25 years), each 5-unit increment in BMI was associated with a 57% increased relative risk of gout. Each 0.1-unit increment in WHR was associated with an 82% increased relative risk of gout. Each 5-kg of weight gain from age 21–25 to baseline was associated with a 28% increased risk of gout. continued on page 7

IN THIS ISSUE 5

RARP outcomes similar in obese and non-obese patients

10

Most cases of erectile dysfunction go untreated

12

Feature: Why living donor kidney transplantation is in decline

18

LUTS found to progress in a high proportion of men

18

FDA approves a lab test for predicting acute kidney injury

19

Sitting may ease urination problems in male LUTS sufferers

25

Microscopic hematuria shown to increase bladder cancer risk Experts offer advice on how to negotiate payer contracts.

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Radical Prostatectomy Rates Rising Utilization rates jumped by double digits across prostate cancer risk groups from 2004 to 2011 SURGERY PREDOMINATES AS PCa TREATMENT

RISK

A study of 823,977 men diagnosed Low with localized prostate cancer from 2004 to 2011 showed a significant increase in the use of radical prostatectomy and a significant decline in the use of radiotherapy. Intermediate Shown here are the rates of RP use in 2004 and 2011 according to disease risk group.

40.3% 54.4%

48.1% 58.5%

30.6%

2004

2011

High

41.3%

Source: Gray PJ et al. Recent trends in the management of localized prostate cancer: Results from the National Cancer Data Base. Presented at the ASTRO 2014 annual meeting in San Francisco. Poster 2553.

Advice First Urged for IC/BPS PATIENTS WITH moderate to severe interstitial cystitis/bladder pain syndrome (IC/BPS) experience significant improvement after receiving only advice and support, according to the findings of a proof-of-concept study.

Consequently, physicians should review standard advice with all IC/ BPS patients before starting medical

Living kidney donor transplantation has been declining since 2004.

treatment, stated investigator Philip C. Bosch, MD, of Palomar Medical Center in Escondido, Calif.

Dr. Bosch conducted a double-blind, placebo-controlled study enrolling 43 patients with moderate to severe IC/ BPS. Patients were randomly assigned to receive subcutaneous adalimumab continued on page 7

THE LIVING KIDNEY DONOR DILEMMA

Many people who want to donate a kidney cannot because of various barriers.

SEE STORY PAGE 12

BY JODY A. CHARNOW USE OF RADICAL prostatectomy (RP) for localized prostate cancer (PCa) increased significantly from 2004 to 2011, whereas the use of radiotherapy decreased during that period, according to study findings presented at the 56th annual meeting of the American Society for Radiation Oncology in San Francisco.

Using the National Cancer Data Base, Phillip J. Gray, MD, of Massachusetts General Hospital in Boston, and colleagues identified 823,977 patients diagnosed with PCa from 2004 to 2011. Of these, 38.5%, 42.7%, and 18.9% had low-, intermediate-, and high-risk disease, respectively, according to National Comprehensive Cancer Network guidelines.

PCa Treatment Lowers Mental Illness Risk

BY JODY A. CHARNOW MENTAL HEALTH issues (MHI) develop in one-fi fth of elderly men with localized prostate cancer (PCa), with those who undergo radical prostatectomy or radiotherapy at lower risk for MHI than those on watchful waiting, according to a new study.

The study, by Praful Ravi, MBBChir, of Imperial College Healthcare NHS Trust, London, and colleagues, included 50,856 men aged 65 years or older with localized PCa diagnosed from 1992 to 2005 and without a mental illness diagnosis at baseline. MHI developed in 10,389 patients (20.4%) during the study period, the investigators reported online ahead of print in Urologic Oncology.

Compared with men aged 65–69 years, those aged 75 years or older had a significant 29% increased risk of MHI, such as anxiety, major depressive disorder, and neurotic depression. Compared with patients who had a Charlson comorbidity index of 0, those with an index of 1, 2,

In low-risk patients, active surveillance rates increased from 12.4% to 18.5% from 2004 to 2011 and the RP rates rose from 40.3% to 54.4%.

During the same period, brachytherapy rates decreased from 24.4% to 11.4% and the rates of external beam radiotherapy (EBRT) alone decreased from 18.2% to 13.4%.

Among patients with intermediaterisk disease, active surveillance rates increased from 6.1% to 7.3% and RP rates increased from 48.1% to 58.5%, whereas brachytherapy rates dropped from 12.1% to 6.4%. Rates of combined therapy with EBRT and androgen deprivation therapy (ADT) declined from 14.7% to 8.7%. continued on page 7

IN THIS ISSUE 5

RARP outcomes similar in obese and non-obese patients

10

Most cases of erectile dysfunction go untreated

12

Feature: Why living donor kidney transplantation is in decline

18

LUTS found to progress in a high proportion of men

18

FDA approves a lab test for predicting acute kidney injury

19

Sitting may ease urination problems in male LUTS sufferers

25

Microscopic hematuria shown to increase bladder cancer risk Experts offer advice on how to negotiate payer contracts.

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continued on page 7

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www.renalandurologynews.com OCTOBER 2014

Brief Summary: Please see Full Prescribing Information for additional information

Labor and Delivery No Velphoro treatment-related effects on labor and delivery were seen in animal studies with doses up to 16 times the maximum recommended clinical dose on a body weight basis. The effects of Velphoro on labor and delivery in humans are not known.

Nursing Mothers Since the absorption of iron from Velphoro is minimal, excretion of Velphoro in breast milk is unlikely.

INDICATIONS AND USAGE Velphoro (sucroferric oxyhydroxide) is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis.

DOSAGE AND ADMINISTRATION Velphoro tablets must be chewed and not swallowed whole. To aid with chewing and swallowing, tablets may be crushed.

The recommended starting dose of Velphoro is 3 tablets (1,500 mg) per day, administered as 1 tablet (500 mg) 3 times daily with meals.

Adjust by 1 tablet per day as needed until an acceptable serum phosphorus level (less than or equal to 5.5 mg/dL) is reached, with regular monitoring afterwards. Titrate as often as weekly.

DOSAGE FORMS AND STRENGTHS Velphoro (sucroferric oxyhydroxide) chewable tablet 500 mg.

CONTRAINDICATIONS None.

WARNINGS AND PRECAUTIONS Patients with peritonitis during peritoneal dialysis, significant gastric or hepatic disorders, following major gastrointestinal surgery, or with a history of hemochromatosis or other diseases with iron accumulation have not been included in clinical studies with Velphoro. Monitor effect and iron homeostasis in such patients.

ADVERSE REACTIONS In a parallel design, fixed-dose study of 6 weeks duration, the most common adverse drug reactions to Velphoro chewable tablets in hemodialysis patients included discolored feces (12%) and diarrhea (6%).

To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Medical Care North America at 1-800-323-5188 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS Velphoro can be administered concomitantly with ciprofloxacin, digoxin, enalapril, furosemide, HMG-CoA reductase inhibitors, hydrochlorothiazide, losartan, metformin, metoprolol, nifedipine, omeprazole, quinidine and warfarin.

Take alendronate and doxycycline at least 1 hour before Velphoro.

Velphoro should not be prescribed with oral levothyroxine and oral vitamin D analogs.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B: Reproduction studies have been performed in rats and rabbits at doses up to 16 and 4 times, respectively, the human maximum recommended clinical dose on a body weight basis, and have not revealed evidence of impaired fertility or harm to the fetus due to Velphoro. However, Velphoro at a dose up to 16 times the maximum clinical dose was associated with an increase in post-implantation loss in pregnant rats. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

There are no adequate and well-controlled studies in pregnant women.

News003_RUN1014.indd 3

Pediatric Use The safety and efficacy of Velphoro have not been established in pediatric patients.

Geriatric Use Of the total number of subjects in two active-controlled clinical studies of Velphoro (N=835), 29.7% (n=248) were 65 and over.

No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

OVERDOSAGE There are no reports of overdosage with Velphoro in patients. Since the absorption of iron from Velphoro is low, the risk of systemic iron toxicity is negligible. Hypophosphatemia should be treated by standard clinical practice.

Velphoro has been studied in doses up to 3,000 mg per day.

HOW SUPPLIED/STORAGE AND HANDLING Velphoro are chewable tablets supplied as brown, circular, bi-planar tablets, embossed with “PA 500” on 1 side. Each tablet of Velphoro contains 500 mg iron as sucroferric oxyhydroxide. Velphoro tablets are packaged as follows: NDC 49230-645-51 Bottle of 90 chewable tablets Storage Store in the original package and keep the bottle tightly closed in order to protect from moisture.

Store at 25°C (77°F) with excursions permitted to 15 to 30°C (59 to 86°F).

PATIENT COUNSELING INFORMATION Dosing Recommendations Inform patients that Velphoro tablets must be chewed and not swallowed whole. To aid with chewing and swallowing, the tablets may be crushed [see Dosage and Administration].

Velphoro should be taken with meals.

Some drugs need to be given at least one hour before Velphoro [see Drug Interactions].

Adverse Reactions Velphoro can cause discolored (black) stool. Discolored (black) stool may mask GI bleeding. Velphoro does not affect guaiac based (Hämocult) or immunological based (iColo Rectal, and Hexagon Opti) fecal occult blood tests.

Distributed by: Fresenius Medical Care North America 920 Winter Street Waltham, MA 02451

US Patent Nos. 6174442 and pending, comparable and/or related patents. © 2014 Fresenius Medical Care North America. All rights reserved.

Renal & Urology News 3

Early ESRD Predictors Identified SWEDISH RESEARCHERS have identified risk factors present in adolescence that independently predict the risk of end-stage renal disease (ESRD) in middle-aged men, according to a recent report.

These factors include proteinuria, erythrocyte sedimentation rate (ESR), blood pressure, and body mass index (BMI).

Proteinuria in adolescence predicted a significant 7.7 times increased adjusted odds of developing ESRD in middle age compared with the absence of proteinuria, researchers reported online ahead of print in the American Journal of Kidney Diseases. An ESR of

Results support the concept that CKD often can be traced back into childhood.

11 mm per hour or higher was associated with a significant 2-fold increased likelihood of ESRD versus an ESR of 1 mm per hour. Grade 2-3 hypertension (systolic BP 160 mm Hg or higher and diastolic BP 100 mm Hg or higher) was associated with a significant 4-fold increased likelihood of ESRD compared with normal blood pressure (systolic BP 120-129 mm Hg and diastolic BP 80-84 mm Hg). Compared with a BMI of at least 18.5 but less than 25 kg/m 2, men with a BMI of 30 kg/m 2 or greater as adolescents had 3.5 times increased likelihood, according to the investigators.

For the study, Per-Ola Sundin, MD,of Örebro University Hospital in Örebro, Sweden, and colleagues used a cohort of Swedish male residents born from 1952 through 1956 who attended mandatory military conscription examinations in late adolescence. From January 1, 1895 through December 31, 2009, the researchers identified 534 ESRD cases and 5,127 controls matched by birth year, county, and vital status.

“Our results support the concept that CKD [chronic kidney disease] often can be traced back into childhood much in parallel to the evidence supporting the onset of atherosclerosis early in life,” the investigators wrote. n

9/25/14 10:59 AM

4 Renal & Urology News

OCTOBER 2014 www.renalandurologynews.com

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

The Medical-Industrial Complex and Physicians

I

n his farewell address to the nation, President Dwight D. Eisenhower warned Americans to beware of the “military-industrial complex” as it can overwhelm us.

He noted a “formidable union” between politicians, the armed forces, and defense contractors implying that soldiers were not central players in an “iron triangle” between Congress, special interests, and bureaucracy.

It is no surprise to practicing physicians that an American medical industrial complex has evolved. Physicians are increasingly commoditized and corporatized, ill equipped due to our training and/or nature to battle the forces of change brought about by the “iron triangle” of politics, economics, and the ever-growing bureaucracy of healthcare.

In 2012, healthcare spending accounted for more than 17% of our gross domestic product (GDP). In 2013, national healthcare spending increased 3.6% to $2.89 trillion (compared with a 3.4% increase of the overall GDP). This marks the fifth consecutive year that medical spending increases were less than 4%. While economists debate how much is attributable to the Affordable Care Act, the most likely explanation is that bending of the curve is largely a product of a sluggish economy and a trend toward medical consumer cost sharing. Not surprisingly, spending on prescription drugs showed the greatest increase while spending on physician services showed the greatest decrease—down nearly 30% from 2012 to 2013.

American medicine is undergoing vast changes, placing the status of physicians in the medical industrial complex at risk. Most physicians feel overwhelmed by increasing bureaucratic mandates from insurers, hospitals, and government. At the same time, physicians are the front line employees of healthcare and assume the majority of the risk for patient care. This has left many in the profession with increasing disillusionment.

So while there is no simple solution for the mounting frustration within the profession, the long hours, and years of post-graduate training, remember that all ecosystems swing into and out of balance.

Medicine is no different. Physician empowerment in the medical complex comes from the realization that we are indispensable, especially when we are engaged.

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

Stevens CW, Glatstein E. Beware the Medical-Industrial Complex. Oncologist. 1996;1:IV-V. 2 Armour S. Health Spending Grew 3.6% in 2013, Projections Show. The Wall Street Journal. Sept 3, 2014.

3 Jauhar S. Why Doctors are Sick of Their Profession. The Wall Street Journal. Aug 29, 2014.

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

Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, N.C.

Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City

Suphamai Bunnapradist, MD Director of Research Department of Nephrology Kidney Transplant Research Center The David Geffen School of Medicine at UCLA

R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD, FACS Vice President Regional Medical Operations Professor & Horvitz/Miller Distinguished Chair in Urological Oncology Cleveland Clinic Regional Hospitals Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California Irvine

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.

James M. McKiernan, MD Assistant Professor of Urology Columbia University College of Physicians and Surgeons New York City

Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto

Kenneth Pace, MD, MSc, FRCSC Assistant Professor Division of Urology St. Michael’s Hospital 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.

Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Lynda Anne Szczech, MD, MSCE Medical Director, Pharmacovigilence and Global Product Development, PPD, Inc. Morrisville, N.C.

Renal & Urology News Staff

Editor Jody A. Charnow Production editor Kim Daigneau Web editor

Stephan Cho

Group art director, Haymarket Medical Jennifer Dvoretz

Production manager Krassi Varbanov

Production director Kathleen Millea Grinder Circulation manager Paul Silver National accounts manager William Canning Publisher Dominic Barone Editorial director

Jeff Forster

Senior VP, medical journals & digital products

Jim Burke, RPh

Senior VP, clinical communications group

John Pal

CEO, Haymarket Media Inc.

Lee Maniscalco

1

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Renal & Urology News (ISSN 1550-9478) Volume 13, Number 10. 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.

9/25/14 11:31 AM

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OCTOBER 2014

Renal & Urology News 5

News in Brief

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

Short Takes RARP Outcomes Similar for Obese, Non-Obese

In a press release issued by the drug’s

Perioperative outcomes of robot-

lead investigator Julia Lewis, MD, a

assisted radical prostatectomy (RARP)

nephrologist and professor of medicine

in obese patients are mostly compa-

at Vanderbilt University Medical Center

rable to those of non-obese patients,

in Nashville, said she believes the drug

researchers reported online ahead of

“offers clear benefits to patients and

print in the Journal of Endourology.

represents a new way for physicians to

maker, Keryx Biopharmaceuticals, Inc.,

manage hyperphosphatemia.”

Tianyuan Xu, MD, and colleagues at Shanghai Jiaotong University School analyzed data from 13 observational

Study: AKI Common in Surgical ICU Patients

studies that included a total of 1,821

Acute kidney injury (AKI) is common in

obese patients and 4,801 non-obese

critically ill surgical patients and is as-

patients. Pooled odds ratios showed

sociated with worse survival, research-

no significant difference in complica-

ers reported online ahead of print in the

tions, hospital length of stay, and

Journal of Critical Care.

of Medicine in Shagnhai, China,

positive surgical margin rates. Operat-

In a retrospective study of 624 gen-

ing time and estimated blood loss,

eral surgical intensive care unit patients,

however, were significantly greater in

Donald G. Harris, MD, and colleagues

the obese compared with non-obese

at the University of Maryland School of

patients. Obese patients were more

Medicine in Baltimore found that AKI

likely to have urinary incontinence and

developed in 296 (47%), with 42% of

erectile dysfunction at 1 year.

the AKI events present upon admission and 36% occurring postoperatively.

Ferric Citrate Okayed for Phosphorus Control

Patients with AKI had significantly worse

The FDA has approved ferric citrate

and 1-year mortality. AKI starting before

(formerly known as Zerenex) for the

admission was associated with worse

control of serum phosphorus levels in

renal dysfunction and greater renal

patients with chronic kidney disease.

morbidity than de novo inpatient AKI.

outcomes, including increased inpatient

U.S. Readiness for Ebola In a recent online poll, Renal & Urology News asked readers, “Do you think the U.S. is prepared to contain an Ebola outbreak should it occur?”

Here are the results based on 165 responses.

Yes: 22.42%

No: 65.45%

Do not know: 12.12%

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10

20

30

40

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Prior Cancer Ups Death Risk After a Kidney Transplant A

pre-transplant history of malignancy is associated with 22% increased risk in 10-year mortality among adult kidney transplant recipients, according to a new study presented at the 2014 World Transplant Congress in San Francisco.

Alfonso Santos, MD, of the University of Florida, Gainesville, and his colleagues examined patient and graft survival rates in 1,128 adult kidney transplant recipients with history of malignancy before transplant. The patient and graft survival rates were compared to the rates occurring in 5,635 kidney recipients with no history of malignancy. Recipients with prior malignancies were more likely to have delayed graft function (18.7% vs. 14.1% in the no-malignancy group). The rejection rates were similar (16.1% vs. 15.7% for the no-malignancy group). The patients with prior malignancies had worse 5- and 10-year survival rates post-transplant than the no-malignancy group (75% vs. 81% and 53% vs. 60%, respectively).

Kidney Stone Burden Found To Predict Risk of CKD K

idney stone formers with a cumulative stone size less than 20 mm are at increased risk for chronic kidney disease (CKD), Iranian investigators reported online ahead of print in the International Journal of Urology.

Farrokhlagha Ahmadi, MD, of the Tehran University of Medical Sciences, and colleagues studied 97 stone formers who were candidates for extracorporeal shockwave lithotripsy. Among patients with a cumulative stone size (the sum of diameters of all stones) less than 20 mm, the estimated glomerular filtration rate (eGFR) decreased significantly from the first measurement (75.5 mL/min/1.73 m2) to the fourth (56.4 mL/min/1.73 m2). Each 1 mm increment in cumulative stone size was associated with a 20% increased risk of CKD. The investigators observed no association between cumulative stone size and CKD among patients with a cumulative stone size 20 mm or greater.

Stroke May Be More Likely After Recovery from AKI H

ospitalized patients who recover from acute kidney injury (AKI) requiring dialysis are at increased risk of stroke and death compared with those who did not have AKI, a new study suggests.

Vin-Cent Wu, MD, PhD, of National Taiwan University Hospital in Taipei, and colleagues enrolled 4,315 patients who recovered from dialysis-requiring AKI and compared them with a matched group of 4,315 control patients without AKI or stroke.

After a median follow-up of 3.36 years, the rate of incident stroke was 15.6 per 1,000 person-years. Compared with controls, the AKI-recovery group had a significant 25% increased risk of stroke as well as an increased severity of stroke events in adjusted analyses, the researchers reported online ahead of print in the Journal of the American Heart Association. After hospital discharge, the rate of incident stroke was statistically similar in patients with diabetes alone (without AKI) and in those with AKI alone (without diabetes), the researchers noted. In addition, the AKI-recovery group had a significant 2.4 times increased risk of death compared with the control group.

9/25/14 12:51 PM

6 Renal & Urology News

OCTOBER 2014

www.renalandurologynews.com

Contents

OCTOBER 2014

■

VOLUME 13, ISSUE NUMBER 10

Nephrology 3

ONLINE

5

this month at renalandurologynews.com

Videos

Early ESRD Predictors Identified The risk of ESRD in middle-aged men is linked to proteinuria, erythrocyte sedimentation rate, BP, and BMI in adolescence.

Kidney Week Philadelphia November 11–16

Prior Cancer Ups Death Risk After a Kidney Transplant A pre-transplant history of malignancy is associated with a 22% increased risk in 10-year mortality.

Genitourinary Cancers Symposium Orlando, Fla. February 26–28

10

Bone, Mineral Parameters in ESRD Vary

By Time of Day Patients with end-stage renal disease exhibit circadian variation in blood levels of phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D.

18

AIN Causes Differ in the Elderly Acute interstitial nephritis due to drugs is significantly more common in the elderly than in younger individuals.

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 August winner: Michael Berard, MD

CALENDAR

Some of our recent postings include: • Multidisciplinary Approach to mCRPC • Kidney Cancer: Evolving Role of Genomic Testing • Alternative Doses for Renal Cell Carcinoma Agents

Urology 10

Study: Most ED Cases Not Treated Despite a high prevalence of erectile dysfunction, only a quarter of men with the condition receive treatment for it.

Drug Showcase

11

Palpable Tumors Plus Low PSA May Increase PCSM Among men with normal-range PSA levels at diagnosis, the risk of cancer-related death increases as PSA levels decrease.

18

High Rate of LUTS Progression Found In a study, 41% of men who reported mild or no LUTS at baseline had moderate or severe LUTS at 4 years.

Read up on recently-approved pharmaceuticals. Our latest include: • Adempas (riociguat), for chronic hypertension • Farxiga (dapagliflozin), for type 2 diabetes • Fortesta (testosterone gel), for hypogonadism

News Coverage

Visit our website for timely reports from upcoming meetings.

19

Active Surveillance May Be Okay for Testicular Cancer This approach is associated with excellent outcomes in men with clinical stage I testicular cancer, researchers reported.

“Putatively, the most common reason

for under-reporting of ED is patient embarrassment or decreased bother/severity.

See our story on page 10

006_Neph_RUN1014.indd 6

Annual Dialysis Conference New Orleans January 31–February 3

European Association of Urology Madrid March 20–24 National Kidney Foundation 2015 Spring Clinical Meetings Dallas March 25–29

Feature 12

Living Donor Dilemma: Willing But Unable to Give a Kidney A decline in living donor kidney donation may be due in part to a growing prevalence of disqualifying medical conditions.

19

Departments 4

From the Medical Director The medical-industrial complex and physicians

5

News in Brief Stroke risk possibly higher after AKI recovery

19

Men’s Health Update Active surveillance for testicular cancer

24

Practice Management Tips for negotiating new payer contracts

9/25/14 12:13 PM

www.renalandurologynews.com OCTOBER 2014

Prostatectomy rates continued from page 1

In the high-risk group, active surveillance rates and EBRT monotherapy rates remained stable over the study period (about 8% and 10%, respectively), whereas radical surgery rates rose from 30.6% to 41.3%, the researchers reported. The rates of combined EBRT plus ADT declined from 30.4% to 28.0% and brachytherapy rates fell from 8.7% to 4.1%. Rates of primary ADT dropped from 7.2% to 5.8%.

On multivariable analysis, the researchers found that black men were 48% less likely than whites to undergo RP versus radiotherapy. Individuals without insurance and those covered

by Medicaid were 34% and 50% less likely, respectively, than those with pri-

Mental illness risk continued from page 1

or 3 or more had a significant 23%, 39%, and 63% increased risk, respectively.

Men who underwent radical prostatectomy (RP) and radiotherapy (RT) had a significant 21% and 15% lower risk of MHI, respectively, compared with patients who underwent watchful waiting (WW).

“This is, to our knowledge, the first comparison of the diagnosed rates of mental illness across treatment modalities for prostate cancer, and these find-

Advice first for IC/BPS

continued from page 1

(21 patients) or subcutaneous placebo (22 patients). At the onset of the study all patients received standard advice and support. Overall, patients in the placebo arm had a statistically significant improvement in the Interstitial Cystitis Symptom Index (ICSI) at week 12 compared with baseline, as reported by Dr. Bosch in Urology. The ICSI outcome data showed that 11 placebo recipients (50%) had a statistically significant improvement.

“Patients who received placebo and statistically improved were surprised that they had not received the study drug adalimumab,” he observed.

Not a placebo effect Most of the improved placebo patients reported that this was due to following physician behavior modification advice and less stress while in the study rather than a placebo effect, Dr. Bosch added.

“The greatest improvement was seen in patients who were stricter about their

Cover_URO_RUN1014.indd 7

vate insurance to have RP rather than radiotherapy. Patients living in lowincome areas also were less likely to undergo RP versus radiotherapy.

“I think one of the most surprising trends that we didn’t expect to find was that, over the study period, the use of RP for patients went up by double digits across all risk groups,” Dr. Gray told Renal & Urology News.

“This was particularly striking for lowrisk patients. While active surveillance increased slightly for patients with lowrisk disease, the absolute number of patients on active surveillance was low, and, during this time, rates of surgery were increasing. This suggests that it is primarily the patients that would typically be treated with radiotherapy who are being placed on surveillance, not the patients who are primarily discuss-

Renal & Urology News 7

ing active surveillance versus RP with their urologist.”

The trend for increased use of surgery in high-risk disease is concerning, Dr.

Gray added. “Many patients with highrisk disease who are undergoing surgery have indications for post-operative radiotherapy and perhaps hormonal therapy, and are therefore potentially being subjected to multiple treatments that can additively affect quality of life.”

As for why black patients are less likely than whites to undergo RP, the reasons are unclear. “One hypothesis is that the majority of RPs are occurring at large academic centers,” Dr. Gray said. “There are ample data to suggest that racial minorities lack access to high-quality medical care. Additionally, minorities who live in rural areas may not have the resources that would allow them to travel to a center which could offer RP. Other socioeconomic factors may also be at play given the correlation between higher income and the receipt of RP.” n

ings are especially pertinent in the abence of any randomized data in this field,” the authors wrote.

Urinary incontinence was associated with a significant 47% increased risk of MHI, where erectile dysfunction was associated with a significant 10% decreased risk.

The median time to development of MHI was significantly greater in men who had RP than in those who underwent RT (not reached vs. 182 months) or WW (not reached vs. 180 months).

MHI rates at 10 years were 29.7%, 29.0%, and 22.6% among patients under-

going WW, RT, and RP, respectively.

“We feel that watchful waiting was associated with a higher risk of mental health issues because patients may feel their cancer is not being definitively managed,” Dr. Ravi told Renal & Urology News. “This could again explain why median time to development of MHI was greater for RP compared to WW. Additionally, the later development of toxicity with RT may also explain why median time to development of MHI was longer for RP compared to RT.” Previous research has documented elevated risks for depression, anxiety,

and suicide among men diagnosed with PCa. For example, a Swedish study found that men diagnosed with PCa had a 29%, 42%, and 61% increased risk of psychiatric hospitalization due to depression, anxiety, and post-traumatic stress disorder, respectively, compared with men who did not have PCa, according to a report in the European Journal of Cancer (2011;47:2195-2201).

In addition, the PCa patients were 65% more likely to use antidepressants. The study included 72,613 men with PCa and 217,839 age-matched controls without PCa. n

diet and used stress reduction techniques while in the study,” Dr. Bosch said. Stress was the most significant flare factor for IC/BPS patients.

patients, all of whom had received a standardized education and behavior modification program at the beginning of the study. The rate of response of participants reporting either moderately or markedly improved from baseline was 55% and 45% in the amitriptyline and placebo groups respectively, a difference that was not statistically significant.

Physicians should give advice and support before medical treatment.

In a previous study comparing adalimumab and placebo for IC/BPS, Dr. Bosch found that 50% of the placebo recipients had a 50% or greater overall improvement in global response assessment (GRA), according to his report in The Journal of Urology (2014;191:77-82).

These results were comparable to those found in a study by Harris E. Foster, Jr., and colleagues, which was published in the same journal (2010;183:1853-1858).

That study compared amitriptyline and placebo in a randomized doubleblind trial which included 271 IC/BPS

Phillip J. Gray, MD

Better than some drugs “This significant improvement with only advice and support is higher than many commonly used medications for the treatment of IC/BPS,” Dr. Bosch emphasized.

Based on American Urological Association guidelines and his own experience, Dr. Bosch developed a practical IC/BPS standard advice checklist to guide patient management.

According to the checklist, clinicians should validate to the patient that they have IC/BPS, explain that IC/BPS is a chronic disease requiring a long-term healthcare plan, encourage water hydration, recommend a bowel program, explain dietary restrictions, discuss

Philip C. Bosch, MD

sexual therapy, explain stress reduction, and discuss support resources.

“Validation of the disease is important to patients, as many have lived with IC/BPS symptoms for years,” Dr. Bosch stated. “Patients are reassured to know that they are not alone with these symptoms, and they are part of a well-described syndrome, which is not life-threatening.” n

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8 Renal & Urology News

OCTOBER 2014

www.renalandurologynews.com

Twice-Weekly HD May Preserve Residual Kidney Function Better Reduced session frequency did not adversely affect hemodialysis adequacy

ESA Response May Be Linked To Fat Tissue HIGHER PERCENTAGES of fat tissue are associated with a better

TWICE-WEEKLY hemodialysis (HD) during the first year of dialysis treatment is associated with better preservation of residual kidney function (RKF) compared with thrice-weekly HD, according to a new study.

RKF has consistently been a predictor of greater survival in patients on maintenance hemodialysis (MHD), but the relationship between HD treatment frequency and RKF preservation has not been well characterized. Jing Chen, MD, PhD, of Huashan Hospital, Fudan University, Shanghai, China, and colleagues, in collaboration with Kamyar Kalantar-Zadeh, MD, PhD, of the University of California Irvine, conducted a 2-part study. In the first part, they examined an historical cohort of 85 MHD patients with a urine output of at least 500 mL per day. In this main cohort study, 30 patients were started with twice-weekly HD for 6 months or longer and 55 were started and maintained on thrice-weekly HD treatment.

In the second part, the researchers examined a subcohort of the 48 incident MHD patients (32 from the main cohort and 16 new patients) to assess the independent risk factors responsible for RKF decline during the first year on HD therapy. The patients had a baseline

Twice-Weekly vs. Thrice Weekly HD In a study, the proportion of patients who lost residual kidney function was lower with twice-weekly than thriceweekly hemodialysis.

100 80 60 40 20 0

60%

82%

Twice-weekly Thrice-weekly Hemodialysis frequency

Source: Chen J, et al. Association of initial twice-weekly hemodialysis treatment with preservation of residual kidney function in ESRD patients. Am J Nephrol 2014;40:140-150.

urine output of at least 500 mL per day and an HD vintage less than 12 months.

The main cohort study showed that the clinical outcomes were almost the same between the 2 groups, but the proportion of patients with RKF loss—defined as a urine volume less than 200 mL per day—was significantly lower in the twiceweekly group compared with the thriceweekly group (60% vs. 82%), Dr. Chen and colleagues reported in the American Journal of Nephrology (2014;40:140-150).

In the 48 incident MHD patients, the investigators observed no significant differences between the 2 groups except for variations in HD frequency.

Patients in both groups had comparable HD adequacy.

On multivariate analysis, male gender, HD frequency, urea reduction ratio (URR), and intradialytic hypotension episodes were associated with RKF loss, the researchers reported. In the first year of treatment, an increase of 1 HD session per week or 1 episode of intradialytic hypotension was associated with a significant 7.2 times and 2.51 times increased risk of RKF loss respectively. Male gender was associated with a 92% decreased risk of RKF loss and each 1% increment in URR was associated with a 15% decreased risk, according to the investigators.

The researchers pointed out that KDOQI [Kidney Disease Outcomes Quality Initiative] guidelines recommend thrice-weekly HD as the standard of care for achieving an adequate HD dose in patients with end-stage renal disease, but twice-weekly HD is widely used as the initial treatment in China, India, and many other developing countries for various clinical and economic reasons. ■

response to erythropoiesis-stimulating agents (ESAs) in hemodialysis (HD) patients, according to a recent study.

In a cross-sectional observational study, Almudena Vega, MD, PhD, of Hospital General Universitario Gregorio Marañón, Madrid, Spain, and colleagues analyzed erythropoietin resistance index (ERI) in relation to body composition in 218 HD and peritoneal dialysis (PD) patients.

They calculated ERI by dividing the weekly weight-adjusted dose of ESA by the hemoglobin (Hb) level. They also calculated the fat tissue index (FTI) and lean tissue index (LTI), defined, respectively, as fat tissue and lean tissue adjusted for body surface area.

The study, published online ahead of print in Renal Failure, revealed a direct linear correlation between BMI and FTI and a significant inverse correlation between ERI and BMI and FTI in HD patients, but not in PD patients. They observed no association between ERI and LTI. The authors said they assumed that the protective effects of BMI on ERI may

Sclerostin Declines After Kidney Transplantation

be due to a higher percentage of fat

MARKEDLY ELEVATED blood levels of sclerostin in patients with end-stage renal disease (ESRD) decrease rapidly to normal or subnormal values after renal transplantation, a new study suggests.

Sclerostin is a glycoprotein secreted by osteocytes that inhibits bone formation and contributes to the development of osteoporosis. Sclerostin levels are elevated in patients with chronic kidney disease and ESRD. A team led by Rudolf P. Wüthrich, MD, measured sclerostin levels by ELISA in 42 consecutive renal transplant recipients before and at defined intervals in the first year following transplantation. The recipients had a mean age of 49 years; 90% of them had hypertension and 14% had diabetes. Pre-transplant levels were elevated in all subjects, who had a mean level of 61.8 pmol/L (20-30 pmol/L is the normal range).

association between fat tissue and

News-B_RUN1014.indd 8

Within 15 days after transplantation—and correlating with improvement in renal function—sclerostin levels dropped to 21 pmol/L and then increased to 23.8 and 28.0 after 6 and 12 months, respectively, Dr. Wüthrich and his colleagues reported in Kidney & Blood Pressure Research (2014;39:230-239).

The researchers stated that this rise was not influenced by estimated glomerular filtration rate, but paralleled the reduction of parathyroid hormone and normalization of calcium, phosphate, and vitamin D. “The inhibition of sclerostin might be a promising therapeutic strategy for the preservation of bone mass,” the researchers concluded.

Antibodies targeting sclerostin are being developed for the treatment post-menopausal osteoporosis, showing increased bone growth in preclinical studies, they noted. For example, a

phase 1 study found that a single dose of romosozumab, an anti-sclerostin antibody, increased bone density in the hips and spines of healthy men and postmenopausal women (J Bone Miner Res 2011;26:19-26). In another study, multiple doses of the drug in healthy men and postmenopausal women led to an increase in bone mineral density at the lumbar spine (J Clin Pharmacol 2014;54:168-178).

One possible explanation for the decline in sclerostin after transplantation is improvement in renal function that leads to better clearance of sclerostin, the researchers stated. In addition, the authors pointed out that mechanical stress on the skeleton is known to decrease production of sclerostin, and this could contribute to higher sclerostin levels in patients on dialysis, who often have decreased physical activity. ■

tissue.

Although the data show an ESA response, the researchers acknowledged that they cannot offer a causal explanation. They suggest, however, an association between the hydration state and fat tissue. “As fat tissue presents a lower percentage of water, it is possible that a decreased distribution volume of hemoglobin in patients with a higher percentage of fat may influence ESA response,” they wrote.

Alternatively, fat tissue may autonomously modulate ESA response via autocrine regulation, the researchers stated. They noted that leptin, which occurs at higher levels in overweight patients, has been shown to stimulate erythropoiesis. ■

9/25/14 11:37 AM

10 Renal & Urology News

OCTOBER 2014 www.renalandurologynews.com

Low Bicarbonate, Reduced BMD Linked The association is stronger in women, especially those who are postmenopausal, a study found greater lumber BMD and a significant 0.018 g/cm2 greater total BMD compared with the reference group.

Additionally, compared to the reference group, women with a bicarbonate level of 27 mEq/L or higher had a 32% reduced odds of having low total bone mass, which was defined as 1.0 standard deviation below the mean value of young women in the cohort.

In a subgroup analysis of 2,805 preand post-menopausal women, the researchers found a significant association between bicarbonate levels and total BMD only in postmenopausal women.

In this group, those with a bicarbonate level of 27 mEq/L or higher had 0.024 g/ cm2 greater total BMD than those with a level below 24 mEq/L. Among men, each 2.2 mEq/L increment in bicarbonate level was associated with a significant 0.008 g/cm2 increase in lumbar BMD and a non-significant 0.004 g/cm2 increase in total BMD. Compared to the reference group (bicarbonate level

Bone, Mineral Parameters In ESRD Vary By Time of Day PATIENTS WITH end-stage renal

­discontinued. For 5 days thereafter,

disease (ESRD) exhibit circadian varia-

participants consumed a diet controlled

tion in mineral and bone parameters,

in calcium (1,200 mg per day) and

according to a new study.

phosphorus (1,000 mg per day). On

“Our results suggest that random

day 6, which was a non-dialysis day for

testing of bone mineral parameters in

the ESRD patients, subjects underwent

ESRD, and treatment decisions based

12 2-hour blood draws for phosphate,

on such results, should consider the

ionized calcium, parathyroid hormone,

circadian pattern particularly when

total 25-hydroxyvitamin D, and fibro-

values are close to the boundaries of

blast growth factor-23 (FGF-23).

the desired range,” researchers stated

In the ESRD patients, plasma

in a report published online ahead of

phosphate demonstrated significant cir-

print in the Journal of Nephrology. In

cadian variation, with a peak occurring

addition, guidelines for managing bone

around 3:30 a.m. and nadir occurring

mineral parameters in ESRD patients

around 11:00 a.m. The peak and nadir

need to consider circadian changes in

for ionized calcium was around 12:15

the recommendations, they noted.

p.m. and 8:00 p.m., respectively. The

Hariprasad Trivedi, MD, of the

peak and nadir for PTH were 5:45

Medical College of Wisconsin in

p.m. and 10:15 a.m., respectively. For

Madison, and collaborators studied 17

25-hydroxyvitamin D, they were 9:45

ESRD patients on long-term hemodi-

a.m. and 4:00 p.m. The researchers

alysis and 8 volunteers without kidney

observed no circadian variation in

disease who served as a control

levels of FGF-23. In the control group,

group. Phosphate binders, vitamin D

only phosphate and PTH levels demon-

analogues, and calcimimetics were

strated circadian variation. n

News-G_RUN1014.indd 10

Bone mineral density is linked to serum bicarbonate levels, a study found.

below 24mEq/L), men with a bicarbonate level of 27 mEq/L or greater had a significant 0.019 g/cm2 greater lumbar BMD and a non-significant 0.012 g/cm2 greater total BMD compared with the reference group.

Study: Most Cases of ED Not Treated DESPITE a high prevalence of erectile dysfunction (ED), only a quarter of men with the condition receive treatment for it, according to a recently published study.

A team led by Kevin T. McVary, MD, of Southern Illinois University School of Medicine in Springfield used a commercial insurance database to identify 6.2 million men diagnosed with ED during a 12 month period ending June 2011. Men who filled a prescription for a phosphodiesterase type 5 (PDE5) inhibitor, injection or urethral prostaglandins, or androgen replacement therapy (ART) were considered treated and those who received an ED diagnosis but did not fill a prescription were considered untreated. Only 25.4% of the cohort was treated during the study period, Dr. McVary and his colleagues reported online ahead of print in The Journal of Sexual Medicine.

Among the treated men, the most commonly prescribed medical therapies

Dr. Chen’s group noted that, for patients with chronic kidney disease, the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines suggest supplementation with alkali salts to maintain serum bicarbonate levels at 22 mEq/L or higher because bicarbonate supplements have been shown to improve skeletal metabolism in clinical studies. Despite evidence for the beneficial effects of alkali therapy on bone health, alkali therapy still is not given routinely to individuals without kidney disease in the clinical setting to maintain bone mass, the authors stated. “Our study demonstrates that within a relatively normal range of serum bicarbonate levels, having higher serum bicarbonate levels is associated with higher BMD in the general population without advanced CKD,” the authors wrote.

“These data give more support to providing alkali therapy in the general population for improvement of bone health. n”

were PDE5 inhibitors (75.2%), followed by ART either as monotherapy or in combination therapy (30.6%).

Men older than 60 years were significantly less likely to be treated than men aged 50–59 years. Treatment frequency did not vary as a function of the number of co-morbidities, according to the researchers.

To the investigators’ knowledge, this study is the first to report the frequency of associated ED medical therapies in a relatively large patient population.

“It has previously been assumed that a significant percentage of men suffer from ED and remain undiagnosed unless specifically questioned about this problem,” the researchers wrote.

“Putatively, the most common reason for under-reporting of ED is patient embarrassment or decreased bother/ severity. However, it has been shown that once the topic is initiated, patients become willing to discuss their potency issues.”

The authors noted that although it is well known that the frequency of ED increases with advancing age, their results show that treatment rates do not follow the same trend. “The lack of therapy in older men may reflect the fact that the percentage of men motivated to receive treatment remains constant,” they wrote. n

© LOOKATSCIENCES / PHOTOTAKE

LOW SERUM bicarbonate levels are associated with decreased bone mineral density (BMD) in U.S. adults, particularly postmenopausal women, according to findings published online ahead of print in the American Journal of Kidney Diseases.

Wei Chen, MD, of the University of Rochester School of Medicine and Dentistry in Rochester, N.Y., and colleagues at the Albert Einstein College of Medicine, Bronx, N.Y., studied 9,724 adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999–2004.

Among women, each 2.2 mEq/L increment in serum bicarbonate level was associated with a significant 0.007 g/cm2 greater lumbar BMD and significant 0.005 g/cm2 greater total BMD. Using a bicarbonate level below 24 mEq/L as a reference value, women with bicarbonate levels of 27 mEq/L or higher had a significant 0.019 g/cm2

9/25/14 11:53 AM

www.renalandurologynews.com OCTOBER 2014

Renal & Urology News 11

Palpable Tumors Plus Low PSA May Increase PCSM

BY JODY A. CHARNOW AMONG MEN with palpable prostate cancer (PCa) and normal-range PSA level at diagnosis, the risk of cancerrelated death increases as PSA level decreases, a new study suggests.

The finding suggests the existence of clinically detectable, low-PSA-secreting disease with an elevated risk of PCSM and highlights the importance of the digital rectal examination in men with PCa and normal-range diagnostic PSA, Itai Pashtan, MD, of Brigham and Women’s Hospital in Boston, and colleagues concluded in an online report in Cancer Epidemiology.

The study included 9,081 men with non-metastatic PCa and a diagnostic

PSA level below 2.5 ng/mL. Of these, 1,710 had non-palpable tumors (clinical stage T1c) and 7,371 men had palpable tumors (clinical stage T2–T4). The groups had a median PSA level at diagnosis of 1.3 and 1.4 ng/mL, respectively.

After a median follow-up of 2.8 years, 548 men died, 118 (21.5%) from PCa.

In men with non-palpable tumors and a Gleason score of 7–10, each 1-point increment in PSA was associated with a significant 2-fold increased risk of PCSM, after adjusting for confounders.

Among the men with palpable tumors and any Gleason score, each 1-point increment in PSA was associated with a

significant 34% decreased risk of PCSM. The researchers analyzed 2004– 2007 data from the Surveillance, Epidemiology and End Results (SEER) database. The 9,081 men represented 5.5% of all men (163,982) diagnosed with non-metastatic PCa during that time period. n

Risk Factors for Post-Tx RCC ID’d patient: MARK SMITH

SAN FRANCISCO—Ultrasound surveillance for renal tumors should be

PSA 6.2

performed on native and graft kidneys from 3 years after kidney transplantation, Australian researchers reported at the 2014 World Transplant Congress.

Gleason Score

6

Oncotype DX® GPS

8

A study led by Alexandra Hockings, MBBS, and presented by Cristian

IDENTIFIED FOR

ACTIVE SURVEILLANCE

Udovicich, MD, looked at factors that predispose renal transplant recipients to an increased risk for renal cell carcinoma (RCC). The investigators, who are from St. Vincent’s Hospital in Melbourne, examined data from the Australian and New Zealand Dialysis and Transplant Registry. They identified 11,922 patients who received their transplant from 1992 to 2011.

The incidence of RCC after renal transplantation was 1.25%. The

The Oncotype DX Genomic Prostate Score (GPS) improves risk stratification to help guide initial treatment decisions. The test is for newly diagnosed men with very-low, low, and low-intermediate (low volume 3+4) risk prostate cancer.

researchers found that 72% of RCCs occurred only in the native kidney, 25% only in the graft kidney, and 3% in both native and graft kidneys. Male gender, Caucasian ethnicity, and history of prior RCC were all signifi-

Review the development and validation data published in European Urology www.OncotypeDX.com/EUP

cantly associated with an increased risk of RCC diagnosis following renal transplantation.

Recipients with the identified risk

Genomic Health and Oncotype DX are registered trademarks of Genomic Health, Inc. © 2014 Genomic Health, Inc. All rights reserved. GHI40033_0714

factors should be targeted for more vigorous surveillance, according to the investigators. n GENP-13869_ProstateAd_Renal&UrologyNews_Oct2014_1-0.indd 1

News011_RUN1014.indd 11

8/14/14 11:20 AM

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12 Renal & Urology News

october 2014 www.renalandurologynews.com

n feature

Living Donor Dilemma: Willing But Unable to Give a Kidney Medical exclusions cited as one reason why living donor kidney transplantation is declining

By JODY A. CHARNOW

‘13

Living Kidney Transplants Declining Data from the Organ Procurement and Transplantation Network shows that the number of living kidney donor transplantation rose steadily until peaking in 2004, followed by a steady decline. The numbers of these transplants for selected years are shown here.

5,733

‘10 6,278

‘07 6,043

‘04 6,647

‘01 6,045 additional barriers to living donation or a new steady state is yet unclear.”

Medical exclusions Michelle A. Josephson, MD, professor of nephrology at the University of Chicago and chair of TAG, said the LKD decline may be due in part to a growing prevalence of obesity, diabetes, and hypertension in the U.S. As a result, increasing numbers of potential donors may have these medical conditions, which are common reasons for medically ruling out individuals as donors, Dr. Josephson said.

Research findings document that medical conditions are a major reason for donor exclusion. In a study of 484 prospective living kidney donors at Stanford’s transplant center, Dr. Tan and colleagues found that 229 individuals were excluded from donation.

Of these, 150 were excluded for medi-

cal reasons, mainly obesity, hypertension, abnormal glucose tolerance, and nephrolithiasis, according to results published in Clinical Transplantation (2011;25:697-704).

In a study presented at this year’s World Transplant Congress in San Francisco, Uday S. Nori, MD, and colleagues at The Ohio State University Wexner Medical Center in Columbus found that hypertension, glucose intolerance, and high body mass index accounted for 60% of all medical deferrals.

At last year’s American Transplant Congress in Seattle, Zoe A. Stewart, MD, PhD, of the University of Iowa Hospitals and Clinics in Iowa City, presented findings of a study involving 450 living kidney donor candidates, of whom 398 were rejected for donation and 52 were approved. Rejected candidates had a mean BMI of 28.9 kg/ m2, which was significantly higher than the mean 25.9 kg/m2 for the approved

group. Of candidates approved for donation, only 11.5% were obese (BMI above 30) and 88.5% were non-obese (BMI below 30).

Heidi M. Schaefer, MD, a nephrologist and an associate professor of medicine at Vanderbilt University School of Medicine in Nashville, Tenn., noted that her institution’s transplant center turns down about 40% of potential living kidney donors for medical reasons.

“We have become more stringent over the past 10 years, in particular with 24-hour urine protein cutoffs and blood glucose cutoffs,” said Dr. Schaefer, who also is a TAG member. In addition, the center is seeing larger numbers of older and marginal donors. “Both factors are probably contributing to our inability to increase our living donor pool at our institution,” Dr. Schaefer said.

Financial consequences Another potential barrier to LKD is concern about the financial consequences of donation. It takes weeks or months to recuperate from a nephrectomy, and this may mean lost wages for employed individuals who would have to take time off from their jobs.

James R. Rodrigue, PhD, of Beth Israel Deaconess Medical Center in Boston, and colleagues surveyed recipients of kidneys from deceased and live donors and patients on a waiting list for a kidney transplant and found that almost half of respondents reported not asking potential living kidney donor about considering donation because of concern about the impact of lost income on the donors or their families. In addition, 36% reported being told by a family member or friend that they were willing to donate but were concerned

© thinkstock

D

espite public awareness campaigns and innovative approaches such as kidney paired donation, living kidney donation (LKD) in the U.S. has been declining. Data from the Organ Procurement and Transplantation Network (OPTN) show that the number of living donor transplants increased from 1,817 in 1988 to a peak of 6,647 in 2004, and then dipped to 6,573 in 2005. In 2013, 5,735 LKDs took place. The decline in living donor transplants has occurred mainly among blood relatives, OPTN data show. The number of recipients receiving a kidney from a living blood relative (such as a parent, child, or sibling) decreased from 4,340 in 2004 to 2,886 in 2013 (a 33.5% drop), whereas the number of recipients of a kidney from a living donor who is not a blood relative (such as a spouse or an anonymous donor or an unrelated individual participating in a paired donation) actually increased during that period from 2,307 to 2,847 (a 23.4% increase).

Nephrologist Jane C. Tan, MD, an associate professor of medicine at Stanford University in Palo Alto, Calif., pointed out that living donation may have spiked in the early to mid 2000’s due to multiple reasons, including increased public awareness, greater use of donor chains, and desensitization protocols, and this “gave a transient bump in living donation.”

“This would be the ‘low hanging fruit’ phenomenon,” said Dr. Tan, who is a member of the American Society of Nephrology’s Transplant Advisory Group (TAG). “Those who were eligible and very ready to donate did so during that era. To what extent the recent downward trend represents

www.renalandurologynews.com october 2014

about potential lost income. Wait-listed patients and recipients of a deceased donor kidney transplant (DDKT) were more likely than recipients of a live donor kidney transplant (LDKT) not to talk to others about living kidney donation (51% and 61% vs. 31%) and more likely to have others not pursue LKD evaluation. Lower income and African-American patients were significantly more likely to report not having talked to someone about LKD and to have someone not pursue LKD because of financial concerns.

Many patients, especially those on a waiting list and those who received a DDKT after years on a waiting list, may decide not to pursue LDKT due to concerns about the financial impact on the donor, Dr. Rodrigue and his colleagues stated in a poster presented at this year’s World Transplant Congress.

In addition, two-thirds of potential living kidney donors who expressed financial concern to the patient did not initiate evaluation.

“These findings highlight that potential lost income following LKD may be a more significant barrier to LDKT than previously thought, especially for low income and Black patients,” they wrote. “Removing this disincentive may attenuate the national decline in LDKT.”

Insurance concerns Potential donors also might be reluctant to donate a kidney because they are worried about how this would affect their ability to obtain and keep health and life insurance. In a study recently published online ahead of print in the American Journal of Transplantation, a team at Johns Hopkins University in Baltimore led by Dorry Segev, MD, PhD, demonstrated the potential negative impact of LKD on the ability to change or initiate health and life insurance following donation. They surveyed 1,046 individuals who donated a kidney at their institution from 1970 to 2011.

Among 395 donors who changed or initiated health insurance after donation, 27 (7%) reported difficulty. Of these, 15 were denied altogether, 12 were charged a higher premium, and 8 were told they had a pre-existing condition because they were kidney donors.

Among 186 donors who changed or initiated life insurance after donation, 46 (25%) reported difficulty. Of these, 23 were denied altogether, 27 were charged a higher premium, and 17 were told they had a pre-existing condition because they were kidney donors.

“These practices by insurers create unnecessary burden and stress for

those choosing to donate and could negatively impact the likelihood of live kidney donation among those considering donation,” the authors concluded.

The subjects in the study had donated a kidney prior to January 1, 2014, when discrimination in the provision of health insurance based on pre-existing conditions became illegal under the Patients Protection and Affordable Care Act (ACA), the authors noted, “so insurance companies can no longer refuse health insurance to live kidney donors or charge them a higher insurance rate. However, numerous attempts have been made to repeal the law. If protections for live kidney donors are repealed in the future, the difficulties we report here will likely resurface.”

Furthermore, Dr. Segev’s team pointed out that ACA does not apply to life insurance, “which was more commonly a source of difficulty for live kidney donors in our study than was health insurance.”

With lower death rates than the general population, Dr. Segev and his colleagues stated, kidney donors represent excellent candidates for health and life insurance. “Failure to provide insurance to donors harms those who have willingly undergone an invasive procedure on behalf of an ESRD patient; it also makes poor financial sense for insurance companies.”

“It is incumbent upon the transplant community to provide accurate and comprehensive information about the health status of live donors in order to inform insurance companies of donors’ excellent insurability,” they concluded. “Additionally, regulation may be required to prevent discrimination against live kidney donors.”

Congressional initiative Such legislation already is being considered by the U.S. House of Representatives. Rep. Jerrold Nadler (D-NY) and Rep. Michael Burgess (R-TX) in July introduced the Living Donor Protection Act to promote organ donation and protect the rights of living donors. “Organ donation saves Medicare millions of dollars every year,” Nadler noted in a press release.

“It cuts health care costs by as much as two-thirds by reducing the need for dialysis and other expensive medical interventions to treat chronic illnesses.

Yet, after taking this heroic step to save a life, living organ donors may unfortunately face discrimination when they try to take medical leave or buy insurance—our bill would address that injustice.” n

Renal & Urology News 13

New Studies May Help Quantify the Risks of Living Kidney Donation Amid a decline in living kidney donation (LKD) nationally in the U.S., emerging evidence suggests that LKD may be associated with greater risks than previously thought.

For example, a study led by Hallvard Holdaas, MD, of Oslo University Hospital in Oslo, Norway, found that living kidney donors had an 11.4 times increased risk of end-stage renal disease (ESRD), a 40% increased risk of cardiovascular death, and a 30% increased risk of death from any cause compared with a control group of potentially eligible kidney donors. The median follow-up times for the donors and controls were 15.1 years and 24.9 years, respectively.

“Our findings raise some medical and ethical considerations regarding livekidney donation,” the authors wrote in Kidney International (2014;86:162-167).

“The present study indicates potential increased long-term risks for kidney failure and mortality in kidney donors.”

The researchers noted, however, that this must be put into perspective.

Living donor transplantation has been a necessary and essential part of providing ESRD patients with freedom from dialysis and enabling transplant recipients to enjoy a superior quality of life, Dr. Holdaas and his colleagues pointed out. “Most potential living donors are willing to accept a degree of risk when the recipient is a family member of a close friend,” they stated.

A separate study of 96,217 living kidney donors led by Dorry Segev, MD, PhD, an abdominal transplant surgeon at Johns Hopkins University in Baltimore, found that the incidence rate of ESRD was 30.8 per 10,000 among living donors compared with 3.9 per 10,000 among healthy matched controls, but still much lower than individuals in the general population, according to a report published in the Journal of the American Medical Association (JAMA 2014;311:579-586).

“Compared with matched healthy nondonors, kidney donors had an increased risk of ESRD over a median of 7.6 years; however, the magnitude of the absolute risk increase was small,” Dr. Segev and his colleagues concluded. “These findings may help inform discussions with persons considering live kidney donation.”

Contrary to the study by Dr. Holdaas’ team, Dr. Segev’s group found no increased risk of death among living kidney donors in a prior study of 80,247 donors, which also was published in JAMA (2010;303:959-966).

“I definitely think the findings [of these studies] need to be made part of informed consent discussions,” Dr. Segev said, “but I think the findings are actually quite reassuring, given the extremely low risk of ESRD in kidney donors, and I have not found in my own clinical practice that donors are surprised or dissuaded by this information. Rather, they seem to appreciate the careful work that has gone into making sure donating a kidney is safe.”

At the 2014 World Transplant Congress in San Francisco, researchers presented the findings of a study showing that LKD is associated with a modestly increased long-term risk of gout. A team led by Ngan N. Lam, MD, of the London Health Sciences Centre in London, Ontario, studied 1,988 living kidney donors and 19,880 matched healthy non-donors who were followed for a median of 8.4 years, with a maximum follow-up of 20.8 years. The median age at the index date of the donors and matched controls was 43 years, and the median time to a first gout diagnosis was 5.7 years. Gout developed in significantly more donors than non-donors (3.4% vs. 2.0%), a difference that translated into a 60% increased risk of gout among living donors, according to a poster presentation. In addition, significantly more donors than non-donors received prescriptions of the gout medicines allopurinol or colchicine (3.8% vs. 1.3%), which translated into a 3.2 times increased likelihood of a gout medication prescription.

18 Renal & Urology News

OCTOBER 2014 www.renalandurologynews.com

High Rate of LUTS Progression Found Vast majority of men who progress to moderate or severe lower urinary tract symptoms go untreated A LARGE PERCENTAGE of men experience progression from mild or no lower urinary tract symptoms (LUTS) to moderate or severe LUTS, and only about 1 in 10 of these men receive pharmacologic or minimally invasive or surgical treatment, a study found.

The study, led by Lauren P. Wallner, PhD, MPH, of the University of Michigan in Ann Arbor, included 19,505 men enrolled in the Southern California Kaiser Permanente Health Plan. The men had answered survey questionnaires in 2002–2003 and 2006–2007 and at baseline did not have a diagnosis of benign prostatic hyperplasia (BPH) and were not on medication for LUTS at baseline.

Of the 9,640 men who reported no or mild LUTS at baseline, 3,993 (41%) reported moderate or severe symptoms after 4 years of follow-up, having experienced at least a 4-point increase in American Urological Association Symptom Index (AUASI) score. Of these patients, 351 (8.8%) had received a pharmacologic treatment and 8 (0.2%) had undergone a minimally invasive or surgical procedure, Dr. Wallner and her

Heart Failure Ups ESRD Risk in CKD RECURRENT INTERIM heart failure is associated with a stepwise increase in the risk of end-stage renal disease (ESRD) and death before ESRD in patients with chronic kidney disease (CKD), researchers reported online ahead of print in the Journal of the American Society of Nephrology.

In a retrospective study of 2,887 CKD patients, David Naimark, MD, of the University of Toronto, and colleagues found that compared with patients with no heart failure hospitalizations, those who had 1, 2, or 3 or more heart failure hospitalizations had a 4.9-, 10-, and 14-fold increased risk of ESRD, respectively, and a 3.3-, 4.2-, and 6.9-fold increased risk of death before ESRD, respectively, in adjusted analyses. n

News-C_RUN1014.indd 18

colleagues reported online ahead of print in BJU International.

Among individuals who had severe LUTS at baseline, 51.8% experienced at least a 4-point decrease in AUASI score.

Additionally, study results showed that the 165 men who progressed to severe symptoms (AUASI score of 20 or higher) were 8.0 times more likely to be

“The present results support the notion that LUTS is a dynamic condition.” on medication for BPH, 4.7 times more likely to have a BPH diagnosis, and 2.5 times more likely to have seen a urologist than men who did not progress to severe symptoms (AUASI score less than 20).

“The present results support the notion that LUTS is a dynamic condition,” the authors wrote. “While a significant proportion of men experienced worsening symptoms during follow-up,

a subset of men in the present study saw improvement in their symptoms over the 4-year follow-up.”

Dr. Wallner’s group commented that their study suggests that a sizeable population of men experience newonset moderate to severe LUTS within 4 years and therefore may be appropriate candidates for a self-management program to manage their symptoms, to prolong the start of drug or surgical treatment, or both.

The researchers cited a study published in the British Medical Journal (2007;334:25) in which researchers in London concluded that a self-management program has the potential to be an ideal first-line treatment for men with uncomplicated LUTS. The study included 140 men referred by general practitioners to outpatient urology departments. Researchers randomized 67 patients to receive standard care alone and 73 to receive standard care and to take part in a self-management program. The self-management group participated in 3 small group sessions that incorporated education, lifestyle advice, and training in problem solving

and goal setting skills. At 12 months, 31% of the self-management group experienced treatment failure—the primary outcome measure of the study— compared with 79% of the standard care only group.

Dr. Wallner’s group noted that while their study used a uniquely prospectively followed, multi-ethnic cohort of men, potential limitations exist. For example, the presence of participation bias cannot be excluded, as 40% of the men who completed the baseline questionnaire did not complete the followup questionnaire. “It is possible that those with more significant symptoms were more likely to complete both and to be included in the present analysis,” the authors pointed out. “This bias may have resulted in inflated estimates of LUTS progression over 4 years, but the present results are similar to those reported in previous large populationbased cohorts.”

They also noted that data on LUTSrelated bother were not available in their study cohort. These data may have influenced the clinical management of men who were experiencing symptoms. n

AIN Causes Differ in Elderly Individuals DRUG-INDUCED acute interstitial nephritis (AIN), primarily from the use of proton-pump inhibitors and antibiotics, is significantly more common in the elderly than in younger individuals, according to a new study. The elderly, however, are less likely to have AIN from autoimmune or systemic causes.

Angela K. Muriithi, MD, of Mayo Clinic in Rochester, Minn., and colleagues examined the characteristics, causes, and outcomes of AIN—an important cause of acute kidney injury (AKI)—in 45 patients aged 65 years and older and 88 younger patients (aged 18–64 years). Drug-induced AIN

Older patients are more likely to have drug-induced acute interstitial nephritis. occurred in 87% of the elderly patients compared with 64% of the younger patients, according to an online report in Kidney International. AIN due to proton pump inhibitors occurred in 18% of the elderly patients versus 6% of the younger patients. AIN due to auto-

immune or systemic causes was present in 7% of the elderly patients compared with 27% of the younger group. The 2 most common culprit drugs in the elderly were penicillin and omeprazole, Dr. Muriithi’s group reported.

AIN caused by proton pump inhibitors was associated with less severe AKI compared with antibiotic-induced AIN. The elderly had a higher prevalence of chronic kidney disease at baseline, higher peak creatinine, and greater need for dialysis compared with the younger patients. Among the elderly, 86% showed partial or complete recovery within 6 months. n

FDA Clears Laboratory Test for Predicting AKI THE FDA has cleared for marketing the NephroCheck test, a first-of-a-kind laboratory test to identify critically ill hospitalized patients at risk of developing moderate to severe acute kidney injury (AKI) in the 12 hours following administration of the test.

Within 20 minutes, the test provides a score based on the amount of the proteins present that correlates to the patient’s risk of developing AKI within 12 hours of the test being performed. No other tests currently on the market are FDA-approved or cleared to assess the

risk of developing AKI in at-risk patients.

NephroCheck detects the presence of insulin-like growth-factor binding protein 7 and tissue inhibitor of metalloproteinases in the urine, which are associated with AKI, according to a press release issued by the agency. n

9/25/14 12:26 PM

www.renalandurologynews.com OCTOBER 2014

Renal & Urology News 19

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

ences. Men focus on hard metrics like release and orgasm, according to a study published online ahead of print in The Journal of Sexual Medicine. In contrast, women focus on emotional outcomes that include closeness and intimacy. The study, which surveyed 203 men and 203 women, found that couples with more compatible outcome measures experienced more improved mutual desire. As such, establishing mutually compatible sexual goals will likely result in superior long-term sexual relationships, Kristen Mark, PhD, MPH, of the University of Kentucky in Lexington, and colleagues reported.

Working Out? Drinking Coffee May Help Caffeine is often maligned, but objective evaluation of the

feine during multiple days of exercise experienced superior performance, investigators reported online ahead of print in Medicine and Science in Sports and Exercise (2014;46:1787-1796). The differences increased as testing continued despite higher pain and creatinine kinase in the caffeinated group.

ED in Middle-Aged Men Linked to Depressive Symptoms When it comes to erectile dysfunction (ED) in middle-aged men, testosterone may not be a key factor, according to a recent study of 614 Finnish men born in 1945. Kadri Suija, MD, of the University of Oulu in Oulu, Finland, and colleagues found a strong association between depressive symptoms and ED, but no association between free and total testosterone levels and ED, according to a paper published online ahead of print in the Scandinavian Journal of Public Health.

“Depressive symptoms rather than testosterone levels should be taken into consideration while treating middle-aged men with erectile problems at the community level,” Dr. Suija’s group concluded.

Low Levels of a Peptide May Explain Some Male Infertility Low levels of human β-defensin 1 (DEFB1) in sperm may © THINKSTOCK

explain some of the common causes of male infertility, according to findings published in Science Translational Medicine (2014;6:249ra108).

© THINKSTOCK

methyl xanthines and their effects often shows advantage to

en with urination problems as a result of an enlarged prostate may be better off sitting rather than standing to urinate.

Ype de Jong, MD, and colleagues at Leiden University Medical Center in Leiden, The Netherlands, analyzed data from 11 studies that included healthy men and those with lower urinary tract symptoms (LUTS). Among men with LUTS, a sitting position during urination was associated with a significantly lower post-void residual volume (PVR) compared with standing, the researchers reported in PLoS One (2014;9:e101320). Maximum urinary flow rate was increased and voiding time was decreased in the sitting position compared with standing, but these differences were not statistically significant. Among healthy men, urination position had no significant effect on urodynamic parameters.

“In patients with LUTS, an improved urodynamic profile approaching the effect of alpha-blockers is found in the sitting position,” the authors concluded. “Incorporating the positive effect of this voiding position in the management of LUTS could have a synergistic effect on improvement of urodynamics in this group of patients.”

Active Surveillance May Be Okay for Testicular Cancer A

ctive surveillance (AS) for clinical stage I (CSI) testicular cancer is associated with excellent outcomes, according to a study published online ahead of print in the Journal of Clinical Oncology.

Christian Kollmannsberger, MD, from the University of British Columbia in Vancouver, and colleagues retrospectively studied data from 2,483 CSI patients: 1,139 CSI nonseminoma and 1,344 CSI seminoma managed with AS. Relapse occurred in 221 (19%) CSI-nonseminoma and 173 (13%) CSI-seminoma patients. For lymphovascular invasion-positive CSI nonseminoma, the median time to relapse was 4 months; it was 8 months for lymphovascular invasion-negative CSI nonseminoma and 14 months for CSI seminoma. The CSI nonseminoma group had 3 disease-related deaths; 1 patient with CSI seminoma and 2 with CSI nonseminoma died from treatmentrelated events. Both early- and late-relapse patients had advanced disease. Standard therapy cured all late recurrences. The 5-year disease-specific survival rate was 99.7%.

Ruiying Diao, of the First Affiliated Hospital of Shenzhen University in China, and

DEFB1 in sperm from men with infertility caused by either asthenozoospermia or leukocytospermia, both of which are associated with reduced motility and bactericidal activity in sperm. The same defects in sperm were observed when there was interference with DEFB1 function.

Treatment with recombinant DEFB1 markedly restores DEFB1 expression, bactericidal activity, sperm quality, and egg-penetrating ability in sperm from men with asthenozoospermia or leukocytospermia, the authors noted.

MH_RUN1014.indd 19

MEDISTAT

colleagues studied sperm and DEFB1 levels in men diagnosed with infertility caused by asthenozoospermia or leukocytospermia. The researchers found low levels of

© ISTOCK

When it comes to sexual desire, men and women manifest significant differ-

24.6 Source: American Heart Association.

This is the proportion of adult men who, in 2012, met the 2008 Federal Physical Activity Guideline.

© THINKSTOCK

Understanding Desire May Optimize Sexual Relationships

that compared with placebo-tested controls, those given caf-

­University of California, Irvine, Department of Urology

Sitting May Ease Urination Problems in Men with LUTS M

Short Takes

caffeine consumption. Evaluation of male athletes revealed

BY JAIME LANDMAN, MD

9/25/14 12:32 PM

24 Renal & Urology News

OCTOBER 2014 www.renalandurologynews.com

Practice Management Get an early start when negotiating a new payer contract because it can take weeks to connect with an insurance company representative BY TAMMY WORTH

Go in prepared Preparation is the first step in negotiating better payer contracts, asserts Steve Selbst, CEO of Healthcents, Inc. About 50% of the entire negotiation process should be focused here. This step can begin with a matrix that shows when your contracts are up for renewal or termination. It would be a good idea to “ping” someone on the staff when it is time to start the negotiation process, which is about 6 months before the termination or renewal date.

It is important to start early because this is not a quick process. Just getting in touch with someone at an insurance company can take weeks or months.

Also, some evergreen contracts require

An exception, Brown said, is ancillary procedures. Things like blood draws may not be money makers, but they bring additional business by keeping patients in the office. Those may be worth losing some money or breaking even on, and could stay off the negotiating table.

Offering a proposal The next step is putting together a proposal letter. Selbst said this should be no longer than 1½ pages or it will not be read. It should begin with stating why the letter is being written (for example, you want an increase in the fee schedule). You then can make the case for the request.

It is best to avoid saying “I provide quality service.” In reality, that means nothing to a payer. Providers have to remember that the goal of the insurance company is to make a profit, Brown points out.

Physicians have to prove they can save money or are more efficient than other providers. They should demonstrate that they have a relative low rate of unnecessary testing and hospital readmissions and that their patients adhere to therapeutic regimens. Much of these information should be readily accessible in the billing system.

Finally, any correspondence should have expected response dates. Selbst

Once contact has been made with a payer and negotiations are moving forward, it is important to be persistent, but realistic. a 90-day notice (before the renewal date) or the terms are automatically continued.

Basic benchmarking is the fundamental purpose of the preparation phase. Selbst said a practice has to know which 20% of their CPT codes are driving 80% of their revenue.

Look up the Medicare rates for the office’s locality and find out where you are being paid on that spectrum for those codes. If a payer is reimbursing at 132% of Medicare and others are at 160%, then focus on that payer.

PM_RUN1014.indd 24

r­ecommends giving payers a 3-week period to hear back. After 1 week, call them to make sure they received the note and find out who will be working on your contract. Selbst said to ensure you are not just being sent to provider relations or you may get lost in a black hole.

Once contact has been made and negotiations are moving forward, it is important to be persistent, but realistic. Expect some back and forth and be prepared to continue to do analyses and make counter offers, Selbst said.

© THINKSTOCK

N

ancy Brown, CFO and partner in Think Big Health Care Solutions in Wellington, Fla., said she has been to physicians’ practices that have not negotiated new payer contracts in almost a decade.

If you have ever received a fee schedule from a payer and thought, “I can’t work with that,” then it is time to negotiate, she said. These contracts can be changed, and there are measures providers can take to negotiate favorable new payer contracts.

A consultant recommends trying to negotiate a handful of contracts at once.

He also recommends working your way up the ladder if things stall. A contracts manager may not have the authority to change a contract, so find the person who can.

The brick wall If negotiations for a fee-for-service rate increase are unsuccessful, Selbst recommends thinking outside of the box. One option might be try to build in valuebased rewards. Payers may be willing to offer incentives such as payments of 1% above the fee schedule if you use an electronic medical record system, increase the number of prescriptions of generic medications, or follow a set of best practices.

Particularly for small businesses, the fight to change a contract may be futile, Brown said. Without a lot of negotiating power, it can be difficult to demand change. But that does not necessarily mean they should not try. Even if you get nowhere with negotiations, payers may send a new contract.

If all negotiations fail, providers may want to determine whether or not they would fare better going out of network, Selbst said. They would have to look at how much billed charges are discounted, what they might collect, and how many patients might switch

practices if they changed. Providers also have to take into account their demographics (wealthier patients may stay, poorer ones may not) and how many alternatives patients have (more in the city than in a very rural place).

Selbst estimates that his success rate when negotiating contracts for providers is about 75%, with an average increase of 5%–25% per contract. The negotiating process can be done in-house or with outside help. A group may pay $10,000 to have a contractor complete the process for an organization, but if they do, they should be able to expect twice that back in reimbursements the first year, Selbst said. He recommends trying to negotiate a handful of contracts at once instead of just looking at your 1 or 2 highest payers.

“It’s kind of like investing in stocks,” he said. “If you put all of your money on 1 major stock it’s a high-risk, highreward scenario. It’s better to try to negotiate 4 agreements at once.”

Finally, Selbst said it is important to monitor the contracts when changes are made. Groups need to sample at least some contracts on a monthly basis to ensure they are getting paid correctly. n Tammy Worth is a freelance medical journalist based out of Blue Springs, MO.

9/25/14 12:41 PM

www.renalandurologynews.com OCTOBER 2014

Non-Visible Hematuria Ups Bladder CA Risk VISIBLE (GROSS) hematuria is a wellknown risk marker for bladder cancer, but the relative risk of non-visible (or microscopic) hematuria at the population level is more poorly understood.

A new British study may help to clarify this risk, according to a recent report.

Investigators compared 4,915 patients aged 40 years or older diagnosed with bladder cancer and 21,718 age- and sexmatched controls and found that nonvisible hematuria was independently associated with a 20-fold increased risk of bladder cancer.

The positive predictive value (PPV) of non-visible hematuria for bladder cancer was 1.6% among individuals aged 60 years and older and 0.8% among those aged 40-59 years, the researchers reported online ahead of print in the British Journal of General Practice.

These PPVs “support looking for nonmalignant diagnoses initially, with urinary tract infection being the likely main cause,” the researchers wrote.

For the study, the researchers, led

by William T. Hamilton, MD, of the University of Exeter Medical School in Exeter, U.K., examined both coded and uncoded data in electronic records.

Uncoded data included “free-text” notes recorded by general practitioners, Dr. Hamilton’s team explained.

Investigators requested extracts of uncoded records of cases and controls for the year immediately preceding the patient’s diagnosis of bladder cancer.

Each extract contained the expression “haematuria” or “blood in urine,” plus up to 3 words on either side to give context, such as “no haematuria.”

These uncoded entries were categorized according to the type of hematuria described (visible or non-visible) and whether hematuria was present or absent at the time of consultation.

Marc C. Smaldone, MD, MSHP, assistant professor of urologic oncology, Fox Chase Cancer Center-Temple University Health System, Philadelphia, said he believes the new findings are an important contribution to the medical literature.

“This is a large study using electronic health records to demonstrate the prevalence of microscopic and macroscopic hematuria in an unscreened population, as well as their respective associations with a bladder cancer diagnosis,” Dr. Smaldone told Renal & Urology News. “These findings support existing guidelines that recommend urologic evaluation for patients with microscopic hematuria stratified by age.”

What sets this study apart from other population-based studies reliant on claims data is that the authors used uncoded or clinical chart review by multiple abstractors to increase reliability of their hematuria diagnoses, Dr. Smaldone explained. “This increases the face validity of their findings, and also addresses coding discrepancies which is a major limitation of secondary data studies.” n

Induction Protocols Offer Similar Long-Term Survival SAN FRANCISCO – Single-dose alem-

transplant recipients. All patients

tuzumab and multiple-dose rabbit anti-

received tacrolimus and mycopheno-

thymocyte globulin (rATG) induction are

late mofetil. The median follow-up was

associated with similar overall long-term

84 months.

patient and graft survival in kidney and

The 7-year patient and graft survival

kidney/pancreas transplant patients,

rates were 75% and 62%, respectively,

according to a new study presented at

in the alemtuzumab group and 72% and

the 2014 World Transplant Congress.

60%, respectively, in the rATG group.

Jeffrey Rogers, MD, from Wake

Alemtuzumab induction was less

Forest Baptist Health in Winston Salem,

commonly associated with biopsy-

NC, and his colleagues conducted a

proven acute kidney rejection (BPAR)

prospective randomized study compar-

than rATG. This difference did not

ing single-dose alemtuzumab (30 mg)

translate into less chronic allograft

to alternate day rATG induction in 218

nephropathy or graft loss at a median

kidney transplant or kidney/pancreas

follow-up of 7 years. n

News_025_RUN1014.indd 25

treatment with XTANDI. Animal Data In an embryo-fetal developmental toxicity study in mice, enzalutamide caused developmental toxicity when administered at oral doses of 10 or 30 mg/kg/day throughout the period of organogenesis (gestational days 6-15). Findings included embryo-fetal lethality (increased post-implantation loss and resorptions) and decreased anogenital distance at ≥ 10 mg/kg/day,and cleft palate and absent palatine bone at 30 mg/kg/ day. Doses of 30 mg/kg/day caused maternal toxicity.

The doses tested in mice (1, 10 and 30 mg/kg/day) resulted in systemic exposures (AUC) approximately 0.04, 0.4 and 1.1 times, respectively, the exposures in patients. Enzalutamide did not cause developmental toxicity in rabbits when administered throughout the period of organogenesis (gestational days 6-18) at dose levels up to 10 mg/kg/day (approximately 0.4 times the exposures in patients based on AUC).

Nursing Mothers XTANDI is not indicated for use in women. It is not known if enzalutamide is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from XTANDI, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use Safety and effectiveness of XTANDI in pediatric patients have not been established.

Geriatric Use Of 1671 patients who received XTANDI in the two randomized clinical trials, 75% were 65 and over, while 31% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Renal Impairment A dedicated renal impairment trial for XTANDI has not been conducted.

Based on the population pharmacokinetic analysis using data from clinical trials in patients with metastatic CRPC and healthy volunteers, no significant difference in enzalutamide clearance was observed in patients with pre-existing mild to moderate renal impairment (30 mL/min ≤ creatinine clearance [CrCL] ≤ 89 mL/min) compared to patients and volunteers with baseline normal renal function (CrCL ≥ 90 mL/min). No initial dosage adjustment is necessary for patients with mild to moderate renal impairment. Severe renal impairment (CrCL < 30 mL/min) and end-stage renal disease have not been assessed [see Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment A dedicated hepatic impairment trial compared the composite systemic exposure of enzalutamide plus N-desmethyl enzalutamide in volunteers with baseline mild or moderate hepatic impairment (Child-Pugh Class A and B, respectively) versus healthy controls with normal hepatic function. The composite AUC of enzalutamide plus N-desmethyl enzalutamide was similar in volunteers with mild or moderate baseline hepatic impairment compared to volunteers with normal hepatic function. No initial dosage adjustment is necessary for patients with baseline mild or moderate hepatic impairment. Baseline severe hepatic impairment (Child-Pugh Class C) has not been assessed [see Clinical Pharmacology (12.3)].

OVERDOSAGE In the event of an overdose, stop treatment with XTANDI and initiate general supportive measures taking into consideration the half-life of 5.8 days. In a dose escalation study, no seizures were reported at < 240 mg daily, whereas 3 seizures were reported, 1 each at 360 mg, 480 mg, and 600 mg daily.

Patients may be at increased risk of seizure following an overdose.

NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been conducted to evaluate the carcinogenic potential of enzalutamide.

Enzalutamide did not induce mutations in the bacterial reverse mutation (Ames) assay and was not genotoxic in either the in vitro mouse lymphoma thymidine kinase (Tk) gene mutation assay or the in vivo mouse micronucleus assay.

Based on nonclinical findings in repeat-dose toxicology studies, which were consistent with the pharmacological activity of enzalutamide, male fertility may be impaired by treatment with XTANDI. In a 26-week study in rats, atrophy of the prostate and seminal vesicles was observed at ≥ 30 mg/kg/day (equal to the human exposure based on AUC).

In 4-, 13-, and 39-week studies in dogs, hypospermatogenesis and atrophy of the prostate and epididymides were observed at ≥ 4 mg/kg/day

Renal & Urology News 25

(0.3 times the human exposure based on AUC).

Manufactured by: Catalent Pharma Solutions, LLC, St. Petersburg, FL 33716 Manufactured for and Distributed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Marketed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Medivation, Inc., San Francisco, CA 94105 Revised: September 2014 14B006-XTA-BRFS Rx Only © 2014 Astellas Pharma US, Inc. XTANDI® is a registered trademark of Astellas Pharma Inc.

076-0516-PM

9/25/14 12:49 PM