Renal & Urology News August 2014 Issue by Haymarket Media

AU G U S T 2014

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VOLUME 13, ISSUE NUMBER 8

ESRD Risk Higher in Living Donors Cardiovascular and all-cause mortality risk also are elevated, study finds

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LIVING KIDNEY DONOR MORTALITY RATES A study of Norwegian living kidney donors found that the risk of ESRD and cardiovascular and all-cause mortality is elevated compared with a control group of individuals eligible for kidney donation. Shown here are proportions of donors and controls who died from any cause and from cardiovascular causes.* 12

All deaths CV deaths

10 8 6

BY JODY A. CHARNOW LIVING kidney donors are at increased risk for end-stage renal disease (ESRD) and cardiovascular and all-cause mortality, according to a new study. Investigators led by Hallvard Holdaas, MD, of Oslo University Hospital in Oslo, Norway, compared 1,901 individuals who donated a kidney from 1963 to 2007 with a control group of 32,621 potentially eligible kidney donors. The median follow-up for the donors and controls was 15.1 and 24.9 years, respectively.

IN THIS ISSUE 3

Warmer temperatures may raise risk of recurrent gout attack

Low serum bicarbonate levels predict renal function decline

Expert Q&A: Using ultrasound to clear kidney stones

Higher uric acid may shorten the time to the start of dialysis

Preop anemia predicts adverse outcomes in CKD patients

Women who have had hypertension for at least 6 years are at increased risk for psoriasis. PAGE 24

Compared with controls, kidney donors had a significant 11.4 times increased risk of ESRD, 1.4 times increased risk of cardiovascular death, and 1.3 times increased risk of death from any cause, after adjusting for potential confounders. ESRD developed in 9 donors (0.47%). The median time from donation was 18.7 years. “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 poten-

CKD Risk Factors May Appear Early RISK FACTORS for chronic kidney disease (CKD) are identifiable 30 years or more before the diagnosis of CKD, according to recently published findings. Researchers led by Caroline S. Fox, MD, of the National Heart, Lung, and Blood Institute’s Framingham Heart Study in Framingham, Mass., conducted a case-control study using data from the Framingham Offspring Study. During follow-up, Dr. Fox and her colleagues identified 441 new cases of CKD and matched these cases to 882 controls without CKD. Compared with controls, participants who eventually continued on page 7

4 2 0

11.8%

3.6%

1,901 donors

7.4%

2.1%

32,621 controls

*Unadjusted data Source: Mjøen G et al. Long-term risks for kidney donors. Kidney Int 2014;86:162-167.

tial increased long-term risks for kidney failure and mortality in kidney donors. However, this has to be put into perspective.” Living donor transplantation, they noted, has been a necessary and essen-

tial part of providing ESRD patients with freedom from dialysis and enabling transplant recipients to enjoy a superior quality of life. “Most potential living donors are willing to accept continued on page 7

Kidney Stones, CKD Linked WOMEN WHO have a history of kidney stones are at increased for chronic kidney disease (CKD), according to a new study. An analysis of data gathered from 5,971 participants in the National Health and Nutrition Examination Survey (NHANES 2007–2010) showed that individuals with a history of kidney stones were 1.5 times more likely have CKD and 2.4 times more likely to receive dialysis treatment than those without a history of kidney stones, researchers led by Brian H. Eisner, MD, co-director of the Kidney Stone Program at Massachusetts General Hospital in Boston, reported

online ahead of print in The Journal of Urology. This increased risk was driven mostly by women, in which a history of kidney stones was associated with a nearly 1.8 times increased risk of CKD and a greater than 3-fold increased risk of receiving dialysis treatment. The researchers found no significant association between kidney stone history and CKD or dialysis treatment in men. Dr. Eisner and his colleagues defined CKD as an estimated glomerular fi ltration rate below 60 mL/min/1.73 m2, a urinary albumin to creatinine ratio greater than 30 mg/g, or both. continued on page 7

EXPERT Q&A

Jonathan Harper, MD, explains how ultrasonic propulsion of kidney stones works. SEE STORY PAGE 11

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VOLUME 13, ISSUE NUMBER 8

Obesity Raises PCa Progression Risk Increased long-term risk observed in a study of men on active surveillance BY JODY A. CHARNOW OBESITY MAY increase the longterm risk of disease progression in men on active surveillance for low-risk prostate cancer (PCa), according to study fi ndings presented at the Canadian Urological Association annual meeting in St. John’s, Newfoundland. Bimal Bhindi, MD, and colleagues at the University of Toronto studied 565 PCa patients on active surveillance for low-risk disease. Patients underwent digital rectal examinations (DRE) and PSA testing every 3 months (6 months

IN THIS ISSUE 8 10

Greater intake of citrus fruit may decrease bladder cancer risk Prostate cancer mortality is linked to age at diagnosis

Expert Q&A: Using ultrasound to clear kidney stones

Men who drink coffee are at lower risk of erectile dysfunction

The Affordable Care Act could lead to better PCa outcomes New research suggests that high consumption of citrus fruit may protect against bladder cancer. PAGE 8

in stable patients). The men had confirmatory biopsies at a median of 1 year. Of the 565 patients, 124 (22%) were obese (body mass index [BMI] of 30 kg/m2 or greater). The cohort had a median follow-up of 48 months. The researchers observed pathologic progression (defined as no longer meeting criteria for low-risk criteria on follow-up biopsy) in 168 men (30%) and therapeutic progression (defined as intent to start active treatment) in 172 men (30%). Obesity was not associated with reclassification risk after confir-

Metformin Has Bladder CA Benefits BY JODY A. CHARNOW METFORMIN therapy is associated with improved oncologic outcomes among diabetic patients undergoing radical cystectomy (RC) for bladder cancer, researchers reported at the Canadian Urological Association annual meeting in St. John’s, Newfoundland. In a retrospective study of 85 diabetic patients who underwent RC for muscle-invasive bladder cancer (MIBC) and high-risk non-muscleinvasive bladder cancer (NMIBC), Madhur Nayan, MD, of the University of Toronto, and colleagues found that those who used metformin had continued on page 7

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BMI AND PROSTATE CANCER PROGRESSION Obese men on active surveillance for prostate cancer are more likely to experience both pathologic and therapeutic progression of disease. Shown here are the numbers of progression events per 1,000 patient-years according to body mass index (BMI). 100

Events per 1,000 patient-years

AU G U S T 2014

Pathologic progression

Therapeutic progression

60 40 20 0

< 25 (normal)

25–30 (overweight) BMI (kg/m2)

≥ 30 (obese)

Source: Bhindi B et al. Obesity is associated with risk of progression for low risk prostate cancers being management expectantly. Data presented in poster format at the Canadian Urological Association annual meeting in St. John’s, Newfoundland.

matory biopsy, but it was associated with an increased risk of progression beyond confirmatory biopsies, according to the investigators. Each 5-unit increment in BMI was associated with a significant 49% increased risk of

pathologic progression and a significant 37% increased risk of therapeutic progression. In a poster presentation, Dr. Bhindi’s group concluded that their findings have implications for risk continued on page 7

EXPERT Q&A

Jonathan Harper, MD, explains how ultrasonic propulsion of kidney stones works. SEE STORY PAGE 11

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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.

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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

Renal & Urology News 3

Gout Attack Risk Linked To Weather HIGHER TEMPERATURES and lower relative humidity are associated with an elevated risk of a recurrent gout attack, according to researchers. Tuhina Neogi, MD, PhD, of the Boston University School of Medicine, and colleagues evaluated the combined association of temperature and relative humidity with the risk of recurrent gout in in 619 individuals who responded to questions on a study website. All had physician-diagnosed gout and had a gout attack within the past 12 months. The study population had a median age of 54 years (range 21–88 years).

Recurrent attacks are more likely with higher temperatures and lower humidity. Compared with a temperature of 50°– 59° F, temperatures of 70°–79° and 80° F and above were associated with a 43% and 40% increased risk of a recurrent gout attack, respectively. Temperatures of 30°–39° F and less than 30° F were associated with a 25% and 40% decreased risk, respectively, Dr. Neogi’s group reported online ahead of print in the American Journal of Epidemiology. Compared with a relative humidity of 60%–74%, a relative humidity of 40%– 49% and less than 40% was associated with a 37% and 55% increased risk of a recurrent gout attack, respectively, according to the investigators. In addition, the researchers found that the risk of a recurrent gout attack was 2-fold greater when the temperature was 70° F or higher and the relative humidity was below 60% compared with when the temperature was 50°–69° F and the relative humidity was 60%–74%. “The biological mechanisms underlying these associations require further exploration and my include volume depletion or behavioral changes in response to the weather that may influence gout attack risk,” the authors concluded. “Patients with gout may be advised that under conditions of hot and/or dry weather, appropriate measures, such as increased water intake, should be considered to minimize the risk of recurrent gout attacks.” n

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4 Renal & Urology News

AUGUST 2014 www.renalandurologynews.com

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Why Not Business-Class Hemodialysis?

hen we book an airline flight, we often have the option of paying extra to upgrade to business or first class. We can choose to use higher levels of comfort and amenities if we can afford them. Many hospitals offer private rooms with additional services to patients who wish to be in a distinct environment. When patients sign up for in-center hemodialysis (HD) treatment in a dialysis clinic, however, there is only one option. Some dialysis centers have isolated rooms, but they are usually used for patients with hepatitis B infection. Historically, with the implementation of end-stage renal disease (ESRD) legislation in 1972, the first exception to the Medicare eligibility threshold age became reality in this country. Patients younger than 65 years would be a Medicare beneficiary when they needed chronic dialysis treatment to survive. Whereas the ESRD program is a proud legacy, and an exceptionally expensive benefit for taxpayers, it has an overarching homogeneity in its format and pattern of services. Dialysis centers have a rather uniform and basic operation, and providers do not offer anything above and beyond what is already offered to everybody. Patients cannot choose to pay for extra services because there are no extra services to buy. Is this highly uniform patient care what we strive for in our quest for excellence in patient care? I would like to pose a provocative question: If the fundamental dialysis care is provided to all ESRD patients, would any heterogeneity in the choice of additional services be unethical or implausible? A dialysis patient should have a choice to pay for extra services, such as accommodation in an isolated area or an executive suite, access to private bathrooms with showers, 5-star level meals prepared by a special cook, watching recently released movies on a large screen, and so on, all of which while receiving HD treatment in a rather distinct environment. Can we not have dialysis centers with 2 or more levels of patient services, including business-class and first-class tiers? In California and some other states, we are fortunate that we can offer maintenance dialysis treatments to illegal immigrants with ESRD. Now that we provide this life-saving treatment to more than 400,000 patients in our country, we should be able to have additional choices for those who wish to have a different experience during their 3-times-a-week visits to dialysis centers. If airlines can offer business-class and first-class seats and if hospitals can offer private rooms, dialysis centers, too, should become more innovative and offer a variety of services and choices. Having the option of paying for additional services does not discriminate against those patients who cannot afford them. It would promote more innovation in the dialysis industry and engender creativity and motivation to work harder. Differences make us strong. Kam Kalantar-Zadeh, MD, MPH, PhD Chief, Division of Nephrology & Hypertension Professor of Medicine, Pediatrics and Public Health University of California Irvine School of Medicine

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Medical Director, Urology

Medical Director, Nephrology

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

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

Nephrologists

Urologists

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 Associate Clinical Professor of Surgery/Urology University of Connecticut School of Medicine, Urology Center New Haven 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 Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center, Detroit

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

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

Renal & Urology News (ISSN 1550-9478) Volume 13, Number 8. Published monthly by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. Periodicals postage paid at New York, NY, and an additional mailing office. The subscription rates for one year are, in the U.S., $75.00; in Canada, $85.00; all other foreign countries, $110.00. Single issues, $20.00. www.renalandurologynews.com. Postmaster: Send address changes to Renal & Urology News, c/o DMD Data Inc., 2340 River Road, Des Plaines, IL 60018. For reprints, contact Wright’s Reprints at 1.877.652.5295. Copyright: All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2014.

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6 Renal & Urology News

AUGUST 2014

www.renalandurologynews.com

Contents

AUGUST

2014

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VOLUME

Nephrology

ONLINE 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 June winner: Haider Lalarukh, MD

Videos

Some of our recent postings include: • Summer Kidney Stones: What to Know • Adding Secondary Insulin Increases Death Risk • Trends in Urologic Research

Drug Showcase

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.

Gout Attack Risk Linked To Weather High temperatures and low humidity may be associated with an elevated risk of a recurrent gout attack.

Decreased Renal Function Tied to High Homocysteine Multivariate analysis demonstrated an inverse association between serum homocysteine and estimated glomerular filtration rate.

Hyponatremia Linked to Hip Fracture Surgery New-onset hyponatremia is common following surgery for hip fractures.

Hypertension Ups Psoriasis Risk The skin disease is 27% more likely to occur in women who have had hypertension for 6 or more years compared with nonhypertensive women.

American Society for Radiation Oncology (ASTRO) San Francisco September 14–17 International Continence Society Annual Meeting Rio de Janeiro October 20–24 Kidney Week Philadelphia November 11–16 Annual Dialysis Conference New Orleans January 31–February 3 Genitourinary Cancers Symposium Orlando, Fla. February 26–28 European Association of Urology Madrid March 20–24

Urology 9

New Data Support Prostate Cancer AS Active surveillance (AS) is a durable management option for favorable-risk prostate cancer, with 64% of patients remaining on AS after 5 years, data show.

Shockwaves May Be Effective for Severe ED A new study showed promising results with low-intensity extracorporeal shockwave therapy.

PCa Mortality Tied to Age at Diagnosis Older age at the time of a prostate cancer diagnosis is associated with a higher risk of cancer-specific mortality, even after adjusting for the risk of death from other causes. Cholesterol Predicts RCC Outcomes High versus low preoperative serum levels are associated with a 43% decreased risk of death.

“Similar to the general population, preoperative anemia is associated with adverse postoperative outcomes in patients with CKD.”

See our story on page 24

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NUMBER

CALENDAR

this month at renalandurologynews.com

13, ISSUE

Departments 4

From the Medical Director Business-class dialysis treatment

News in Brief Citrus fruit may cut bladder cancer risk

Expert Q&A Ultrasonic propulsion of kidney stones

Men’s Health Update Coffee drinking found to lower ED risk

Practice Management Narrowing the gap between the administrative and clinical sides can boost efficiency

7/22/14 12:57 PM

6 Renal & Urology News

AUGUST 2014

www.renalandurologynews.com

Contents

AUGUST

2014

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VOLUME

Urology 9

ONLINE

this month at renalandurologynews.com Clinical Quiz

13, ISSUE

NUMBER

CALENDAR

New Data Support Prostate Cancer AS Active surveillance (AS) is a durable management option for favorable-risk prostate cancer, with 64% of patients remaining on AS after 5 years, data show. Shockwaves May Be Effective for Severe ED A new study showed promising results with low-intensity extracorporeal shockwave therapy. PCa Mortality Tied to Age at Diagnosis Older age at the time of a prostate cancer diagnosis is associated with a higher risk of cancer-specific mortality, even after adjusting for the risk of death from other causes. Cholesterol Predicts RCC Outcomes High versus low preoperative serum levels are associated with a 43% decreased risk of death.

Videos

Some of our recent postings include: • Summer Kidney Stones: What to Know • Adding Secondary Insulin Increases Death Risk • Trends in Urologic Research

Drug Showcase

News Coverage

Visit our website for timely reports from upcoming meetings.

Nephrology 3

Gout Attack Risk Linked to Weather High temperatures and low humidity may be associated with an elevated risk of a recurrent gout attack.

Decreased Renal Function Tied to High Homocysteine Multivariate analysis demonstrated an inverse association between serum homocysteine and estimated glomerular filtration rate.

Hyponatremia Linked to Hip Fracture Surgery New-onset hyponatremia is common following surgery for hip fractures. Hypertension Ups Psoriasis Risk The skin disease is 27% more likely to occur in women who have had hypertension for 6 or more years compared with nonhypertensive women.

“Similar to the general population, preoperative anemia is associated with adverse postoperative outcomes in patients with CKD.”

See our story on page 24

RUN0814_TOC_URO.indd 6

Departments 4

From the Medical Director Business-class dialysis treatment

News in Brief Citrus fruit may cut bladder cancer risk

Expert Q&A Ultrasonic propulsion of kidney stones

Men’s Health Update Coffee drinking found to lower ED risk

Practice Management Narrowing the gap between the administrative and clinical sides can boost efficiency

7/22/14 12:59 PM

www.renalandurologynews.com AUGUST 2014

Kidney donor risk

continued from page 1

a degree of risk when the recipient is a family member of a close friend.” Previous studies have suggested that living kidney donors maintain long-term renal function and have no increase in cardiovascular or all-cause mortality, Dr. Holdaas’ group stated. Most investigations, however, have included control groups that were less healthy than the living donor population and have had relatively short follow-up periods, they pointed out. The researchers said their findings will not change their opinion about promoting live kidney donation. “However,” they pointed out, “poten-

tial donors should be informed of increased risks, although small, associated with donation in short-term and long-term perspective.” A separate study of 96,217 kidney donors led by abdominal transplant surgeon Dorry Segev, MD, PhD, associate professor of surgery 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 (JAMA 2014;311:579-586). However, contrary to the study by Dr. Holdaas’s team, Dr. Segev’s group found no increased risk of death among kidney donors

in a previous study of 80,347 donors (JAMA 2010;303:959-966). Commenting on the new study, Dr. Segev noted that, historically, studies of outcomes in living kidney donors have compared donors to the general population, even though the general population is not nearly as healthy as the donors. “We are now starting to see studies using a more appropriate comparison group, namely individuals who are as healthy as ... living donors but have two kidneys. These studies are showing that donating a kidney does indeed put the donor at some increased risk [of ESRD], which is not surprising given the fact that they are losing half of their nephron mass.” n

Renal & Urology News 7

AKI Timing May Affect Death Risk HOSPITAL-ACQUIRED acute kidney injury (h-AKI) is associated with significantly greater mortality and longer hospital stays than communityacquired AKI (c-AKI), according to a new study. Patients with hospital-acquired AKI who survive, however, are more likely to be independent of renal replacement therapy at discharge and follow-up. In a retrospective study, Ching Ling

CKD risk factors

continued from page 1

developed CKD had a significant 76%, 71%, and 43% greater likelihood of having hypertension, obesity (body mass index 30 kg/m2 or higher), and higher triglyceride levels, respectively, 30 years before their CKD diagnosis, the researchers reported online ahead of print in the Journal of the American Society of Nephrology. Additionally, the CKD patients had a significant 38% and 35% greater likelihood of having hypertension and higher triglyceride levels, respectively, and a significant 2.9 times greater likelihood of having diabetes 20 years before their CKD diagnosis. They were not significantly more likely to have obesity. “Our results suggest that CKD should be considered a life course disease,” the investigators wrote. “Identifying individuals at increased risk of CKD early in life may allow interventions that reduce the risk of CKD. In particular, individuals with

multiple risk factors could be targeted for more aggressive risk factor management.” Dr. Fox’s group noted that up to 15% of adults in the United States are estimated to CKD, which confers an

“Our results suggest that CKD should be considered a life course disease.” increased risk of cardiovascular and all-cause mortality. Risk factors for CKD have been well characterized, they pointed out, but most studies have evaluated risk factor profiles at or near the time of CKD diagnosis. The finding of that obesity did not predict CKD at time points closer to CKD diagnosis supports recent data “suggesting that obesity in early adulthood was more strongly associated with CKD in later life than obesity that developed later. It is possible that the

duration of exposure to this risk factor could play an important role in determining the magnitude of the association with CKD.” The researchers defined CKD as an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 or less. The CKD patients had a mean age of 69.2 years at diagnosis. Their median eGFR at diagnosis was 54.2 mL/ min/1.73 m2. Dr. Fox’s team noted that the extensive phenotyping and long follow-up of the Framingham Offspring Study is a key strength of the current investigation. “The participants were relatively young at the time of entry into the study and were followed for up to 30 years, which allows us to generalize our results across a wide age range.” They also pointed out some study limitations. The cohort was entirely of European ancestry, which may limit the generalizability of results to other ethnic or racial groups, they noted. Further, the observational design of the study prevented them from inferring causality. n

Pang, MD, and colleagues at the Heart of England NHS Foundation Trust, U.K., analyzed data from 306 patients with AKI who received intermittent hemodialysis and had a 6-month follow-up visit. Of the 306 patients, 250 had communityacquired AKI and 56 had hospitalacquired AKI. The survival rates at hospital discharge were significantly lower for the h-AKI group than the c-AKI group (42.9% vs. 72%), the researchers reported online ahead of print in the European Journal of Internal Medicine. The survival rates at 6 months, however, did not differ significantly (82.8% vs. 87.5%). In addition, 35% of the c-AKI group was dialysis dependent at hospital discharge compared with 16.7% of the h-AKI group. At 6 months, 32.2% of patients in the c-AKI group were dialysis dependent at 6 months compared with 12.5% of those in the h-AKI group. The investigators hypothesize that renal survival

Stones, CKD linked continued from page 1

Cover-Jumps_Neph_RUN0814.indd 7

proportion of those needing dialysis was 1.6% and 3.1%, respectively. The differences in the proportions were not statistically significantly. “Our finding of no significant association between nephrolithiasis and CKD in men but an increased risk in women may reflect the different pathophysiology of these disease processes in each gender,” the authors wrote. One plausible explanation may be that the interactions of each risk factor for CKD (hypertension, diabetes, and obesity) and stone disease may be different among men and women, according to the investigators.

The researchers acknowledged some study limitations. For example, the scope of their analysis was restricted by incomplete data collection. “The absence of serum albumin and creatinine values for a subset of responders diminished the number of patients in our final analysis.” Another limitation was the study’s cross-sectional design. The researchers could not ascertain the timing of the development of kidney stones and CKD. “It is therefore possible that CKD itself is a risk factor for nephrolithiasis.” In addition, the study did not distinguish among subsets of patients with nephrolithiasis. n

benefit in the h-AKI group was due to a higher proportion of patients with sepsis and a pre-renal cause of AKI, so survivors had a greater chance to recover renal function. The mean length of stay was 23.9 days for the c-AKI group compared with 48.6 days for the h-AKI group. The researchers noted that their findings are consistent with data from other studies, where mortality associated with AKI requiring renal replacement therapy has been reported to be as high as 70%. n

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PCa progression risk

continued from page 1

assessment and counseling for men currently on active surveillance. Other studies have suggested that obesity might impede PCa detection because of increased prostate size, more difficult DRE, and PSA hemodilution. Studies have also suggested that obesity also might cause biologic abnormalities that promote carcinogenesis, cancer proliferation, and progression, they explained. The

Metformin benefits

continued from page 1

a significant 62% decreased risk of cancer recurrence and a significant 43% decreased risk of cancer-specific mortality compared with non-users in adjusted analyses. Dr. Nayan’s team found no association between metformin use and overall survival. They also found no association between the use of other oral hypoglycemic agents and insulin and any of the previously mentioned outcomes. Of the 85 patients in the study, 39 used metformin and 46 did not. The median follow-up was 50 months. “The present study provides the longest reported follow-up for diabetic patients undergoing RC for MIBC and high risk NMIBC and is the first to demonstrate that metformin use is associated with improved oncologic outcomes in this patient population,”

Stones, CKD linked continued from page 1

Among the women with no history of kidney stones, 13.5% had CKD and 1.5% required dialysis treatment. Among the women with a history of stones, 23.2% had CKD and 5.6% required dialysis treatment. The differences in the proportions between women with and without a history of kidney stones were statistically significant. The proportion of men with CKD was 11.4% among those with no history of kidney stones and 15.2% among those with such a history; the proportion of those needing dialysis was 1.6% and 3.1%, respectively. The differences in the proportions were not statistically significantly. “Our finding of no significant association between nephrolithiasis and CKD in men but an increased risk in women may reflect the different patho-

Cover-jump_URO_CA0814.indd 7

Renal & Urology News 7

new study suggests that in patients on active surveillance, there may be a true biological progression risk rather than merely an issue of misclassification. In an interview with Renal & Urology News, Dr. Bhindi explained that when patients are diagnosed with low-risk PCa and go on active surveillance, there are always 2 questions: was a higher-risk cancer misdiagnosed as low risk and will this cancer progress? “We typically perform a confirmatory biopsy at an average of 6-12 months following the initial diagnosis

to make sure we did not miss a higher risk cancer,” Dr. Bhindi said. “Our study found no association between obesity and risk of re-classification at the time of confirmatory biopsy. The next phase [of the study] was the longer-term monitoring. During this phase, we detected that obesity is associated with an increased risk of progression.” The apparent link between obesity and an increased risk of cancer progression while on active surveillance presents a clinical dilemma,

Dr. Bhindi said. “Obese men are at an increase of dying of other causes such as cardiovascular disease, making them great candidates for active surveillance: They will die of something else before prostate cancer. On the other hand, they are also at an increased risk of cancer progression. This makes decision-making challenging for obese patients with low risk prostate cancer. We feel active surveillance should still be used in obese men, but increased vigilance is required.” n

the authors concluded in a poster presentation. With respect to study limitations, the researchers pointed to the relatively small number of patients and events. In addition, the metformin dose and duration of use prior to surgery was not assessed. The study also did not account for medication changes during follow-up. In an interview with Renal & Urology News, Dr. Nayan noted that metformin has been evaluated for its chemopreventive effects in various malignancies, and randomized, controlled trials are underway looking at starting metformin in non-diabetic patients to improve their cancer treatment outcomes. Limited research is available, however, on the influence of metformin on bladder cancer outcomes. “Our study suggests that metformin use among diabetic patients undergoing radical cystectomy is associated with improved relapse-free survival and blad-

der cancer specific survival,” Dr. Nayan said. “Given that metformin has demonstrated safety among non-diabetics, and given its low cost, further studies are warranted to evaluate potential therapeutic and preventative roles of metformin in patients with bladder cancer.” At the 2014 American Urological Association annual meeting in Orlando, researchers reported on a study showing that diabetic prostate cancer (PCa) patients who took both metformin and a statin may be at lower risk of biochemical recurrence after radical prostatectomy. Matthew Danzig, MD, and collaborators at Columbia University in New York analyzed data from 3,031 patients who underwent RP from 19872010 and who had at least 6 months of follow-up. The overall BCR rate was 23.7%. Diabetics had a rate of 30.5%, which was reduced to 28.3% with metformin use and 23.5% with statin use. Combined use further reduced the

rate to 15%, similar to the 13% rate observed in non-diabetics who were taking statins. A study published online ahead of print in European Urology found that metformin use is associated with a decreased risk of a PCa diagnosis. In a study of 12,226 men diagnosed with PCa and 122,260 population controls, Mark A. Preston, MD, of Massachusetts General Hospital in Boston, and colleagues found that men who used metformin had a significant 16% decreased risk of a PCa diagnosis in adjusted analyses compared with non-users. Among men who had undergone PSA testing in the previous year, metformin use was associated with a significant 34% decreased risk of a PCa diagnosis. Diabetics on no medication or on other oral hypoglycemic agents did have a significant decrease in the risk of a PCa diagnosis, the researchers reported. n

physiology of these disease processes in each gender,” the authors wrote. One plausible explanation may be that the interactions of each risk factor for CKD (hypertension, diabetes, and obesity) and stone disease may be different among men and women, according to the investigators. The researchers acknowledged some study limitations. For example, the scope of their analysis was restricted by incomplete data collection. “The absence of serum albumin and creatinine values for a subset of responders diminished the number of patients in our final analysis.” Another limitation was the study’s cross-sectional design. The researchers could not ascertain the timing of the development of kidney stones and CKD. “It is therefore possible that CKD itself is a risk factor for nephrolithiasis.” In addition, the study did not distinguish among subsets of patients with nephrolithiasis. n

Lithium Treatment Hikes Solid Renal Tumor Risk LITHIUM-TREATED patients are at

Lithium-treated patients had an

increased risk of renal tumors, accord-

incidence of renal tumors 7.5 times

ing to French researchers.

greater than that of the general French

In a retrospective study of 170 lithium-

population, researchers led by Aude

treated patients, renal tumors devel-

Servais, MD, of Hôpital Necker in

oped in 14 (8.2%) over a 16-year period.

Paris, reported in Kidney International

These tumors included 7 malignant and

(2014;86:184-190). Additionally, the

7 benign tumors. The mean duration of

researchers compared lithium-treated

lithium exposure at diagnosis was 21.4

patients with chronic kidney disease

years. The cancers included 3 clear-cell

(CKD) and a group of lithium-free CKD

and 2 papillary renal cell carcinomas,

patients matched for age, sex, and

1 hybrid tumor with chromophobe and

estimated glomerular filtration rate.

oncocytoma characteristics, and 1

The frequency of renal cancer and

clear-cell carcinoma with leiomyomatous

oncocytoma was significantly higher in

stroma. The benign tumors included 4

the lithium-treated group (4.1% vs. 0.3%

oncocytomas, 1 mixed epithelial and

and 2.4% vs. 0%, respectively), accord-

stromal tumor, and 2 angiomyolipomas.

ing to the investigators. n

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8 Renal & Urology News

AUGUST 2014

www.renalandurologynews.com

News in Brief

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

Short Takes Urodynamic Studies On the Upswing

study that included 3,017 type 1 and

The use of urodynamic studies for

ment with Afrezza plus oral anti-diabetic

female Medicare patients increased by

drugs provided a mean reduction in

29% from 2000 to 2010, from 422 to

HbA1c that was significantly greater

543 per 100,000 beneficiaries, accord-

than the reduction observed among

ing to study findings published online

placebo recipients.

type 2 diabetics. At week 24, treat-

ahead of print in Neurourology and art Reynolds, MD, MPH, of Vanderbilt

Reasons for Switching Alpha Blockers Identified

University Medical Center in Nashville,

About one-fifth of patients prescribed

Tenn., examined a 5% sample of U.S.

an alpha blocker for lower urinary

Medicare utilization records. Results

tract symptoms suggestive of benign

showed that the rate of urodynamic

prostatic hyperplasia have their

studies performed by gynecologists

prescription changed to another alpha

increased by 144% over the study

blocker, and lack of efficacy is the

period, whereas that of urologists

main reason for the switch, according

decreased by 3%. In 2010, urologists

to a new study published online ahead

performed 58% of all urodynamic stud-

of print in Urology.

Urodynamics. The study, led by W. Stu-

ies and gynecologists performed 35%.

Tae Nam Kim, MD, of Pusan National University Hospital in Pusan, Korea,

Rapid-Acting Inhaled Insulin Approved

and colleagues studied 3,200 patients

The FDA has approved Afrezza (insulin

ers (doxazosin, alfuzosin, tamsulosin,

human) Inhalation Powder, a rapid-act-

and silodosin). Of these patients, 694

ing inhaled insulin to improve glycemic

(21.7%) had a prescription change

control in adults with diabetes. The

to another alpha blocker after taking

drug is administered at the start of

their first one for a mean 10.8 weeks.

each meal or within 20 minutes after

The main reasons for the change were

starting a meal. The drug’s safety and

lack of efficacy (52.7%) and adverse

efficacy were evaluated in a 24-week

events (33.1%).

who took 1 of 4 different alpha block-

Experience Questioned In a recent online poll, Renal & Urology News asked urologists and nephrologists the following question: “Do you, or would you, feel slighted if a patient asked how often you have done a certain procedure?” Here are the results based on 104 responses:

Not at all: 57.7%

A little: 34.6%

A great deal: 6.57%

RUN0814-NIB.indd 8

Citrus Fruit May Lower Bladder Cancer Risk I

ncreased intake of citrus fruit is associated with a decreased risk of bladder cancer, according to a new meta-analysis published online ahead of print in the International Journal of Food Sciences and Nutrition. The meta-analysis, by Sudong Liang, MD, of Soochow University in Yangzhou Jiangsu, China, and colleagues, included 8 case-control studies and 6 cohort studies totaling 7,372 cases and 935,800 subjects. Pooled data from the 14 studies showed that individuals with the highest intake of citrus fruit had a 15% decreased risk of bladder cancer risk compared with those who had the lowest intake. Analysis of data from the case-control studies showed a significant 23% decreased risk. Investigators found no association between fruit intake and bladder cancer risk in the cohort studies. “Our results suggest that there is limited evidence for a protective association between high citrus fruit intake and bladder cancer risk,” the researchers wrote.

Decreased Renal Function Tied to High Homocysteine E

levated serum homocysteine (Hcy) levels are associated with decreased renal function, but not with serum uric acid levels, according to a new study. Researchers at Chung-Ang University College of Medicine in Seoul compared 91 men with gout and 97 age-matched healthy male controls. Serum uric acid levels did not differ significantly between the two groups, possibly because most of the gout patients enrolled in the study were treated with uric-acid lowering medications, the investigators, led by Jung-Soo Song, MD, reported in the Journal of Korean Medical Science (2014;29:788-792). Serum Hcy levels, however, were significantly higher in the gout patients compared with controls (13.96 vs. 12.67 μM/L). In the gout group, patients with stage 1-2 chronic kidney disease (CKD) had significantly lower serum Hcy than those with stage 3-5 CKD (13.15 vs. 17.45 μM/L). Multivariate analysis demonstrated an inverse association between serum Hcy and estimated glomerular filtration rate.

NSS Suitable for Tumors in Transplanted Kidneys N

ephron sparing surgery (NSS) is safe and appropriate for small renal cell carcinomas that develop in transplanted kidneys, according to researchers who concluded that the surgery is associated with good long-term functional and oncologic outcomes. Xavier Tillou, MD, of CHU de Caen, France, and colleagues studied 43 patients who underwent NSS for de novo tumors in a renal allograft. Most of the tumors were clear cell (34.9%) and papillary carcinomas (52.1%), the investigators reported online ahead of print in the American Journal of Transplantation. Nine patients experienced postoperative complications. At last follow-up, 41 patients had a functional renal allograft and did not require dialysis. They had no long-term complications. The mean time between transplantation and tumor diagnosis was 142.6 months. The mean age of the transplanted kidneys at the time of diagnosis was 47.5 years.

7/22/14 12:52 PM

www.renalandurologynews.com AUGUST 2014

Renal & Urology News 9

New Data Support Prostate Cancer AS Study provides real-world data on adherence to active surveillance outside of a specific protocol ACTIVE surveillance (AS) is a durable management option for favorable-risk prostate cancer (PCa), with 64% of patients remaining on AS after 5 years, according to a population-based study of Swedish men. Stacy Loeb, MD, of New York University, along with Pär Stattin, MD, PhD, and colleagues from the National Prostate Cancer Register of Sweden, looked at data from 11,726 men aged 70 years or younger in this comprehensive Swedish registry. The men were diagnosed with very low-risk to intermediate-risk PCa from 2003 to 2007 and had completed a 5-year follow-up. By year 5, 36% of the men had discontinued AS, Dr. Loeb’s group reported online ahead of print in European Urology. Among men with very lowrisk, low-risk, and intermediate-risk disease, the discontinuation rate by year 5 was 35%, 33%, and 41%, respectively. “In a population-based setting outside clinical trials, we demonstrate that AS is a feasible and durable management strategy to reduce PCa overtreatment while at the same time maintaining the chances of detection of

Active Surveillance Discontinuation A Swedish study found that 36% of men on active surveillance (AS) for favorable-risk prostate cancer discontinued AS by year 5. The discontinuation rates varied according to risk, as shown here.

41% 40

35%

33%

Source: Loeb S et al. Five-year nationwide follow-up study of active surveillance for prostate cancer. Eur Urol 2014; published online ahead of print.

Very low risk

high-risk PCa,” Dr. Loeb and her colleagues concluded. Of 614 men who discontinued AS during follow-up, data on the reasons for discontinuation were available for 530 (86%). The reason was patient preference for 108 men (20%), PSA progression for 276 (52%), biopsy progression for 129 (24%), and other reasons for 17 (3%). For the men who discontinued AS for nonbiologic reasons, “there is a need for support and counseling for men to continue AS in the absence of signs of

Low risk

Intermediate risk

progression to improve adherence to AS and decrease overtreatment.” In the subset of men who discontinued AS because of PSA progression, the median PSA level was 6.3 ng/mL at diagnosis and 9.8 ng/mL at discontinuation. Of the men who discontinued AS, 68% underwent radical prostatectomy and 32% received radiation therapy. The study also examined predictors of AS discontinuation. In multivariable analysis, compared with men younger than 60, men aged 65–70 years

Low Bicarbonate Predicts eGFR Decline LOWER serum bicarbonate levels are independently associated with rapid renal function decline in communitydwelling individuals with an estimated glomerular filtration rate (eGFR) above 60 mL/min/1.73 m2, according to a new study. The study included 5,810 participants in the Multi-Ethnic Study of Atherosclerosis. Of these, 1,730 (33%) had a rapid kidney function decline, defined as an eGFR decline of more than 5% per year. Each 1 standard deviation lower baseline serum bicarbonate level

was associated with a 12% increased risk of rapid kidney function decline and an 11% increased risk of incident reduced eGFR in adjusted analyses, Todd H. Driver, MD, of the University of California San Francisco, and colleagues reported online ahead of print in the American Journal of Kidney Diseases. Compared with a bicarbonate level of 23–24 mEq/L, a level below 21 mEq/L was associated with a 35% increased risk of rapid kidney function decline and a 16% increased risk of incident reduced eGFR.

The association of low bicarbonate level with both renal outcomes was strongest among black subjects, the researchers observed. “Our findings ultimately may have clinical implications,” the authors wrote, noting that “serum bicarbonate is an inexpensive laboratory test that is present on standard clinical chemistry panels; it may have the potential to identify persons at risk of developing CKD, perhaps in combination with other biomarkers, which could inform more aggressive management of kidney disease risk factors.” n

were 31% less likely to discontinue AS. The likelihood of discontinuing AS increased by 1% with each 0.1 ng/ mL increment in PSA and decreased by 14% with each 1-unit increment in Charlson score. Men with T2 disease were 63% more likely to discontinue AS than those with T1 disease. A high level of education was associated with a 45% increased likelihood of discontinuing AS compared with a low level of education. “From a public health perspective,” the authors wrote, “it is critical to understand the underlying reasons for discontinuing AS,” Dr. Loeb’s group observed. The researchers noted that their “evaluation provides real-world data on the adherence to AS outside the confines of a specific protocol and on whether discontinuation was for biologic or nonbiologic reasons.” With respect to study limitations, they noted that they did not measure cancer-related anxiety, which prior investigations found to be a critical factor in AS adherence. In addition, data from Swedish men may not be generalizable to other populations with different healthcare systems and cultural backgrounds. n

High CRP Is a CKD Risk Factor C-REACTIVE protein (CRP) is an independent risk factor the development of chronic kidney disease (CKD), researchers have concluded. In a study of 4,345 patients attending a screening center in Israel, CKD developed in 42 (1%) during a mean follow-up of 7.6 years. After controlling for established renal risk factors, elevated CRP levels were associated

Shockwaves May Be Effective for Severe ED LOW-INTENSITY extracorporeal shockwave therapy may benefit men with severe erectile dysfunction, researchers reported online ahead of print in the International Journal of Urology. Chi-Hang Yee, MD, and colleagues at The Chinese University of Hong Kong studied 58 men with ED who received

News1_RUN0814.indd 9

either low-intensity shockwave therapy (30 patients) or a sham treatment (28 patients). The two groups did not differ significantly in baseline International Index of Erectile Function-Erectile Function (IIEF-EF) domain score and Erection Hardness Score. At week 13, the mean IIEF-EF domain score in the

shockwave therapy and sham arms was 17.8 and 15.8, respectively. The mean Erection Hardness Score was 2.7 and 2.4. These differences were not statistically significant. Shockwave therapy, however, was superior to sham treatment in men with severe ED (mean IIEF-EF domain score 10.1 vs. 3.2). n

with a 5.4 times increased likelihood of CKD, Eitan Kugler, MD, of Rabin Medical Center in Petah Tikva, Israel, and colleagues reported online in the Journal of Nephrology. CRP’s predictive value is enhanced in patients with diabetes, hypertension, or baseline estimated glomerular filtration rate of 60–90 mL/min/1.73 m2, they noted. n

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High-Risk PCa Most Likely in Blacks New study characterizes the presentation and treatment of localized prostate cancer in the U.S. NON-WHITE RACE, older age, and living in more impoverished counties predict a greater likelihood of being diagnosed with high-risk prostate cancer (PCa) and a decreased likelihood of receiving local PCa treatment, according to a new study. The study, led by Usama Mahmood, MD, of the University of Texas MD Anderson Cancer Center in Houston, also showed that PCa patients with intermediate-risk tumors are more likely to receive local treatment than those with high- or low-risk malignancies, according to a new study. Using the Surveillance, Epidemiology, and End Results (SEER) registry, Dr. Mahmood’s team identified 42,403 men diagnosed with localized PCa in 2010 and who were assigned National Comprehensive Cancer Network (NCCN) risk based on clinical factors. The SEER registry recently released Gleason score at the time of biopsy or transuretheral resection of the prostate, which for the first time allows accurate assessment of the presentation and treatment of PCa according to clinical factors at diagnosis, the researchers pointed out.

Allopurinol Offers No CV Benefit ALLOPURINOL therapy is not associated with beneficial cardiovascular outcomes in gout patients, according to a study of 4,966 patients with newly diagnosed gout. Of these, 2,483 were on allopurinol and 2,483 were not. Subjects were matched for age, gender, diabetes, hypertension, hyperlipidemia, and atrial fibrillation.

Of the 42,403 men, 38%, 40%, and 22% had low-, intermediate-, and high-risk disease, respectively. Among 38,634 patients for whom PCa was the first malignancy, 23% received no local treatment, 40% underwent radical prostatectomy (RP), 36% had radiation treatment, and 1% had local tumor destruction (mostly cryotherapy). Results showed that blacks, Hispanics, and Asian/Pacific Islanders had a significant 42%, 23%, and 35% increased odds of having high-risk PCa at presentation, respectively, compared with whites. Each 1-year increase in age was associated with a significant 6% increased risk. In addition, compared with patients in the lowest quartile of county poverty rate, those in the highest quartile had a significant 13% increased odds, Dr. Mahmood’s group reported online ahead of print in The Journal of Urology. In addition, blacks were more likely to undergo radiation therapy than whites (42.5% vs. 34.7%) and less likely to undergo RP (33.7% vs. 42.3%). With increasing age, the use of radiation therapy increased and the use of RP decreased. Radiation use increased

High-Risk Prostate Cancer by Race and Ethnic Group

Researchers who examined trends in the clinical presentation and treatment of localized prostate cancer (PCa) in the U.S., found that non-whites were more likely than whites to present with highrisk PCa. Shown here are the increased odds of high-risk PCa at diagnosis according to race/ethnicity compared with whites.

35% Asian/Pacific Islanders

42% Blacks

23% Hispanics

Source: Mahmood U, et al. Current Clinical Presentation and Treatment of Localized Prostate Cancer in the United States. J Urol 2014; published online ahead of print.

from 18.1% of patients younger than 55 years to 27.5% of patients aged 55 and older but younger than 65, 42.6% of those aged 65 and older but younger than 75, and 49.1% of men older than 75. In these respective age groups, RP use decreased from 67.2% to 53.7%, 33.9%, and 5.7%, respectively. Patients with intermediate-risk disease were more likely to receive local treatment than those with high-risk disease (84.4% vs. 75.2%), which Dr. Mahmood said he considers to be the most surprising of the study’s findings.

Patients with intermediate-risk disease also were less likely to receive no treatment than men with low-risk disease (15.6% vs. 24.9%). Among patients with low-risk disease, 70.7% received local therapy and 29.3% received no treatment. The authors noted that other studies have demonstrated differences in local treatment according to patient demographics and geography, but their study is unique in that they were able to demonstrate the variability in local treatment according to NCCN risk determined at clinical presentation. n

PCa Mortality Tied to Age at Diagnosis OLDER AGE at the time of a prostate cancer (PCa) diagnosis is associated with a higher risk of cancer-specific mortality (CSM), even after adjusting for the risk of death from other causes, researchers reported at the Canadian Urological Association annual meeting in St. John’s, Newfoundland. Vincent Trudeau, MD, of the University of Montreal Health Center, and collaborators studied 205,551 men with clinically localized PCa who underwent radical prostatectomy from 1988 to 2009. The researchers stratified subjects

by age group: age 50 or younger; 51–60; 61–70; and 71 and older. Compared with men aged 50 and younger (the reference group), those aged 61–70 and 71 and older had a significant 28% and 49% increased risk of CSM, respectively, in a multivariable competing-risks regression model. CSM risk did not differ significantly among men aged 51–60. Among men with more aggressive disease, such as those with Gleason scores of 8–10 and pT3b tumors, age at diagnosis did not independently predict CSM.

“Those findings could fuel further research on the biological characteristics of PCa in older individuals,” Dr. Trudeau said. Moreover, the study showed that the risk of dying of PCa in patients with high grade/stage disease was significant. Specifically, the 15-year CSM rates of patients with Gleason 8–10 and pT3b disease were approximately 13% and 20%, respectively. “Those findings highlight the need for improved therapies for aggressive PCa, whatever the age of the patient at diagnosis,” he said. n

After a median follow-up of 5.2 years, the allopurinol group had a modest 20% increase in cardiovascular risk compared with the non-allopurinol group, Victor C. Kok, MD, of Kuang Tien General Hospital, Shalu, Taichung, Taiwan, and colleagues reported online in PLoS One (9:e99102). This increased to 25% after adjusting for chronic kidney disease, uremia, and gastric ulcers. n

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Hyponatremia Linked to Hip Fracture Surgery NEW-ONSET hyponatremia is common following surgery for hip fractures, according to British researchers. James Edward Rudge, MB, and Daniel Kim, MB, of City Hospital, Sandwell and West Birmingham Hospitals NHS Trust - Postgraduate Centre, Birmingham, UK, retrospec-

tively studied 254 patients who underwent hip surgery in 2012. The incidence of moderate (less than 135 mmol/L) and severe (less than 130 mmol/L) post-operative hyponatremia was 27% and 9%, respectively, the researchers reported online ahead of print in Age and Ageing. Patients with moderate

hyponatremia had a significantly longer hospital stay than normonatremic patients (30 vs. 21 days). Post-operative hyponatremia also was significantly associated with proton pump inhibitor use, selective serotonin re-uptake inhibitor use, and increasing number of medications. n

7/22/14 1:09 PM

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AUGUST 2014

Renal & Urology News 11

Ultrasonic Propulsion of Stones Imagine a noninvasive treatment for renal calculi that does not shatter the stones but instead employs low-intensity, ultrasound-generated pulses to move them to and through the ureter. Clinical trials principal investigator Jonathan Harper, MD, associate professor in the Department of Urology at the University of Washington (UW) School of Medicine in Seattle, explains to Renal & Urology News how he and his collaborators are turning their “Rolling Stones” concept into a feasible office procedure. BY DELICIA HONEN YARD What do you call the low-power ultrasound device you are using in your studies?

Dr. Harper: We call the procedure ultrasonic propulsion. In the FDA application we called the device Propulse 1. Casually around UW, we refer to our work and our group as Rolling Stones. If this becomes a startup company, we like the name Sonomotion. How does the device/intervention work?

Dr. Harper: Generally, sound waves are focused on the stone and they transfer momentum to the stone, which makes it move. Specifically, it looks like a diagnostic ultrasound machine with an ultrasound image. The user puts the probe against the skin and visualizes the stone and kidney, touches the image of the stone on the screen, and watches the stone move. Touching the screen sends the focused wave to the stone without interrupting imaging. What inspired you and your team to develop this process and device?

Dr. Harper: [Senior principal engineer and adjunct assistant professor of urology] Michael Bailey and others in the UW Applied Physics Laboratory have worked on shock wave lithotripsy (SWL) for a long time. Stones are fragmented with SWL, but often these pieces remain in areas of the kidney and do not pass. Many have wanted to

On The Web RUN0714_QA.indd 11

find a way to help those pieces pass. We knew ultrasound could be used to create a pushing force, and so applied that to this problem. Ultrasound engineers use the force to calibrate instruments. In our case we tried to use focused ultrasound to break stones like lithotripsy, but ended up moving the stones and had to chase them around a water tank.

to drive the stone through a maze. [The group will be demonstrating the procedure again at the May 2014 AUA annual meeting in Orlando, Florida.—Eds.] What advantages does low-power ultrasound have over extracorporeal SWL and such other treatments for kidney stones as flexible ureteroscopy and percutaneous nephrolithotomy?

Dr. Harper: Ultrasonic propulsion serves a different purpose. Most stones are small enough to pass naturally; however, many of them ultimately require surgery. Any of the above-mentioned surgeries breaks the stone into fragments that either pass naturally or remain in the kidney. These fragments may slowly grow and ultimately require another surgery. The goal of our technology is to help the small stones or residual fragments pass by moving them out of the calyx and closer to the UPJ [ureteropelvic junction] or ureter. In turn, we would expect to avoid some surgeries and improve the outcomes of others. There are other possible scenarios of moving a stone that would be of

Why do you think ultrasonic propulsion could be successful?

Dr. Harper: It is a practical solution to a real problem. The design and operation are pretty simple and elegant. We know the forces we can generate and have a good feel for the forces that are required. The outputs to achieve these forces have been shown to be safe and not cause pain. We have had success in multiple preliminary studies and are now performing the first clinical trial. There also has been enthusiasm from many expert endourologists throughout the country, which is encouraging. In addition, we have had many patients contact us with questions and [express] interest in volunteering as subjects. Approximately 300 urologists visited the hands-on demonstration [conducted at the 2013 annual meeting of the American Urological Association (AUA)], and all survey respondents marked [that they would be] “likely” or “very likely” to use the technology. They had the chance to use the system to reposition stones in a mannequin or

‘The design and operation are pretty simple and elegant.’ —Jonathan Harper, MD

benefit, such as dislodging a large stone obstructing the UPJ. This could not only relieve a patient’s pain and obstruction, but also could avoid an urgent procedure and allow for scheduling an elective surgery. Moving a stone before or during surgery could facilitate access to a hard-to-reach stone. Other uses are [related to] diagnostic feedback—for example, by inducing movement, one might be able to tell that two stones next to each other are in fact two stones and not one. What are the disadvantages of lowpower ultrasound?

Dr. Harper: The unanswered questions are: How well does it work in humans? Is it useful? Will urologists perform it? It certainly has worked in preclinical studies and initial results in the clinical trial are encouraging. In a collapsed collecting system it may be harder to displace a stone than within a wellhydrated one. American urologists do not often perform kidney ultrasound, although the AUA is offering certification courses in kidney imaging. Our group published a training study that indicated urologists could learn to use our system. As for utility, there are some urologists and patients who fear moving a stone to the ureter since that could result in obstruction or pain. However, others state that the standard of care is to allow a trial of passage for ureteral stones anyway, and any stone patient has the risk of pain and obstruction at any time. We envision the greatest utility in two areas. One is expelling small recurrent stones or fragments before they enlarge to a size too big to pass. Many of these patients may like the predictability of facilitated stone passage with ultrasonic propulsion and concurrent medical expulsive therapy [MET] to aid passage. The second theoretical use is moving the large obstructing UPJ stone back into the kidney in the ER [emergency room] or clinic setting. How would MET work with ultrasonic propulsion?

Dr. Harper: There is potential for synergy with MET and ultrasonic

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

7/22/14 1:13 PM

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Protocol Cuts Risk of Contrast AKI

Novel approach, based on left ventricular end-diastolic pressure, reduced the relative risk by 59% BY JILL STEIN AMSTERDAM—A fluid protocol based on left ventricular (LV) end-diastolic pressure may prevent contrast-induced acute kidney injury (AKI) in patients with stable renal insufficiency undergoing cardiac catheterization, researchers reported at the 51st Congress of the European Renal Association- European Dialysis and Transplant Association. “The hydration regimen is very easy to adopt into clinical practice and does not interrupt the flow of the procedure,” said principal investigator Somjot Brar, MD, director of vascular medicine at Kaiser Permanente Los Angeles. “It is also inexpensive since patients do not have to be admitted 12 hours before the procedure or remain hospitalized for 12 hours afterwards. What’s more, it can be used in patients undergoing outpatient or in-hospital cardiac catheterization.” He emphasized, however, that the protocol is not suitable in patients with

decompensated heart failure as well as patients with severe valvular heart disease. Dr. Brar and his colleagues randomized 396 patients to LV end-diastolic pressure-guided volume expansion or to a standard fluid administration protocol as part of the phase 3 Prevention of Contrast Renal Injury with Different

Harper

continued from page 11

propulsion. MET applies to stones in the ureter, not in the kidney. Our goal is to move stones from the kidney to the ureter, at which time MET may help them pass. The process can ideally be scheduled and coordinated. We do not yet know if ultrasonic propulsion can reposition stones within the ureter, which might further augment stone clearance. Who is the ideal patient for low-power ultrasound?

Dr. Harper: In what we have tested, we are thinking an ideal patient will have small recurrent stones or fragments and will want to pass those stones. Such a patient with residual fragments following surgery might be the most ideal since the patient has already either elected or required some type of intervention for various reasons. The stone is also less likely to be attached to the underlying urothelium. A recurrent stone-former is likely to understand the symptoms and may have been able to pass stones previously. A larger skin-to-stone distance in larger patients makes any imaging

RUN0714_QA.indd 12

cornerstone treatment for the prevention of contrast-induced AKI, there is scant information on the optimal rate and duration of fluid administration,” Dr. Brar said. “Available guidelines generally recommend hydration and usually with normal saline; however, there have been no head-to-head comparisons of volume expansion with saline at varying rates or durations in populations at risk including patients undergoing coronary catheterization.” About 15%-25% of patients with an eGFR of 60 or less undergoing cardiac catheterization—the study’s target population—are at risk of AKI, he added. Dr. Brar explained that the LV enddiastolic pressure was selected for evaluation because it is a hemodynamic parameter routinely obtained during cardiac catheterization and is a measure of intravascular volume status. “The rationale is that the pressure itself corresponds ‘fairly reliably’ with intravascular volume and that the pressure value can be used to identify

patients who are candidates for much more aggressive hydration.” The primary endpoint was a greater than 25% or 0.5 mg/dL increase in serum creatinine concentration. Contrast-induced AKI occurred in 6.7% of patients randomized to hemodynamic guided-fluid administration who were followed for up to 6 months after their procedure compared with 16.3% of control patients, with a significant 59% relative risk reduction in the primary endpoint with the novel hydration regimen and a significant 9.5% absolute risk reduction. The 6-month rate of major adverse clinical events was 3.1% and 9.5% in the two groups, respectively. Dr. Brar noted that his institution now routinely uses the hydration protocol tested in this study. It is important that the pressure measurement be obtained at the start of the procedure to allow fluids “to be set” prior to administration of the contrast agent, he said. n

or treatment more challenging but as the ultrasound probe is pressed against the skin and perhaps under the ribs, an estimate of skin-to-stone distance on CT [computed tomography] might not correlate to the distance in the ultrasound therapy. As stated above, we think there are other applications as well and as such, other “ideal” candidates: e.g., a patient with a difficult-to-access lower pole stone during ureteroscopy, a patient for whom the CT is questionable as to whether the stone is one stone or a cluster of more than one stone, or an ER patient with obstructing UPJ stone.

How long will these patients have been followed by study’s end?

or will the technology be prohibitively costly or complicated for widespread use?

What are the objectives of your current 15-person study?

Dr. Harper: We are learning about the subtleties and differences in patients. We have had the patients pass stones following the procedure, and it does not cause pain in the clinical setting. The procedure is also helpful in distinguishing a collection of small stones from a single larger one. We are very encouraged so far but feel it is too early to make any conclusions at this point.

Hydration regimen is very easy to adopt into clinical practice, researcher says. Hydration Strategies (POSEIDON) study. Study participants had an estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m2 or less and at least one of several contrast nephropathy risk factors. “Even though the administration of intravenous fluid remains a

Dr. Harper: The objective is to determine if we can reposition stones in the human kidney. We will obtain feedback on discomfort of the procedure and adverse effects, if any. Secondarily, we may be able to measure clearance of small stones, reduction in pain medication caused by movement, and capability to move larger stones that might obstruct. We are learning about probe size, output levels, image quality, and urologist comfort with the procedure.

Dr. Harper: Research staff will contact the patients by telephone each week for three weeks and review their charts each week for 90 days to assess for acute renal colic events, stone passage, and/or additional intervention. Subjects will be asked to record the date of any stone passage since the investigational study. Pain medication taken by the participant will be recorded. Participants will also receive imaging four weeks after the procedure. Can you tell us anything about the findings to date?

Could this device become the standard of care for kidney stone treatment,

Dr. Harper: As mentioned, ultrasonic propulsion would not replace lithotripsy procedures, but there is potentially significant benefit to a large number of patients with low additional risk. We expect an office procedure that would not require anesthetic. Our research group has received a great deal of commercialization advice and can see two paths: [In one approach, we] envision a dedicated unit for imaging and repositioning stones. Although an early estimate, this could be sold for $50,000 to $80,000 per unit. This unit would have capability to better image stones with ultrasound and more accurately determine their size. With further advancements it could grow to have other ultrasound imaging or lithotripsy capabilities. The other option is to add the ability to reposition stones to existing ultrasound imagers. In this model there would be a button to switch to reposition a stone or to switch to a specific imaging mode. As of yet there is no reimbursement code for repositioning kidney stones, so we cannot comment on this. n

7/23/14 3:41 PM

www.renalandurologynews.com AUGUST 2014

Renal & Urology News 13

High Phosphorus May Up Death Risk HIGH SERUM phosphorus levels after fasting 12 or more hours are associated with an increased risk of all-cause and cardiovascular mortality, according to a new study. Among individuals fasting for 12 or more hours, those in the highest quartile of serum phosphorus had a significant 74% increased risk of allcause mortality and a significant twofold increased risk of cardiovascular mortality compared with those in the lowest quartile, investigators reported online ahead of print in the American Journal of Kidney Diseases. Serum phosphorus was not associated with all-cause or cardiovascular mortality among individuals fasting less than 12 hours. Furthermore, at serum phosphorus levels above 3.5 mg/dL, each 1 mg/dL increment was associated with a 35% increased risk of all-cause mortality and 45% increased risk of cardiovascular death in adjusted analyses; at

HCV Found To Increase ESRD Risk HEPATITIS C virus (HCV) infection is associated with an increased risk of endstage renal disease (ESRD) in patients with chronic kidney disease, data show. Jia-Jung Lee, MD, Kaohsiung Medical University, Kaohsiung, Taiwan, and colleagues enrolled a prospective cohort of 4,185 patients with chronic kidney disease (CKD). Of these, 317 had HCV infection and 3,868 did not. The prevalence of HCV infection was 7.6% and it increased with CKD stage. During a follow-up of 9,101 person-years of follow-up, 446 patients died and 1,205 progressed to ESRD. The rates of ESRD and death (per 100 patient-years) were 13.2% and 4.9%, respectively. In a death-adjusted competing risk analysis, the estimated 5-year cumulative incidence rate of ESRD among patients with and without HCV infection were 52.6% and 38.4%, respectively. In multivariable analysis, HCV infection was associated with a 32% increased risk of ESRD compared with the absence of HCV infection,

News3_RUN0814.indd 13

levels below 3.5 mg/dL, each 1 mg/dL increment was associated with a 19% increased risk of all-cause mortality and 38% increased risk of cardiovascular death. Investigators Alex R. Chang, MD, MS, of Geisinger Health System in Danville, Pa., and Morgan E. Grams, MD, PhD, of Johns Hopkins University in Baltimore, said the much stronger association between serum phosphorus levels and mortality among individuals with longer fasting duration suggests that risk prediction may be enhanced with the use of fasting phosphorus levels. Drs. Chang and Grams noted that serum phosphorus levels exhibit a diurnal variation, with a midmorning trough, an early afternoon peak followed by a plateau, and a higher peak in the early morning hours. “Diet may amplify this variation: higher phosphorus intake results in higher mean 24-hour serum phosphorus levels, with the early afternoon increase particu-

the investigators reported in PLoS One (2014;e100790). The study revealed no significant association between hepatitis B infection and ESRD risk. Results also showed that HCV infected patients were significantly older than non-infected patients (mean 64.5 vs. 61.7 years). The HCV infected group also had a significantly higher proportion of women (52.4% vs. 40.6%). In a previous meta-analysis published in the Clinical Journal of the American Society of Nephrology (2012;7:549-557), Fabrizio Fabrizi, MD, of Maggiore Policlinico in Milan, Italy, and collaborators demonstrated that HCV is independently associated with proteinuria but not decreased glomerular filtration rate in the general population. In a report published in BMC Nephrology (2013;14:187), Yi-Chun Chen, MD, of Tzu Chi University, Hualien, Taiwan, and colleagues concluded that HCV is a causal risk factor for CKD beyond traditional risk factors. They based their conclusion on a 6-year cohort study that included 3,182 individuals with newly diagnosed HCV infection and no traditional CKD risk factors and 12,728 randomly selected matched controls without HCV infection. In multivariate analysis, the HCV-infected group had a significant 75% increased risk of CKD compared with the HCV-uninfected group. n

Association seen among individuals with serum levels measured after fasting for 12 or more hours

Phosphorus levels exhibit a diurnal variation.

larly exaggerated by dietary phosphorus intake and diminished by phosphorus restriction,” the researchers explained. As dietary phosphorus intake may introduce random variability in serum phosphorus levels, the researchers

said they hypothesized that the association between serum phosphorus and mortality would be stronger with longer fasting duration among participants in the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994). For their study, Drs. Chang and Grams analyzed data from 12,984 NHANES III participants aged 20 years and older. Of these, 6,351 had a fasting duration less than 12 hours and 6,633 had a fasting duration of 12 hours or more. Patients who had a less than 12 hour fasting duration had a significantly higher mean age than those who had a fasting duration of 12 hours or more (45.1 vs. 43.6 years). They also had a higher proportion of individuals with an estimated glomerular filtration rate below 60 mL/min/1.73 m2 (5.3% vs. 3.5%). Higher serum phosphorus levels might increase death risk by promoting vascular calcification or endothelial dysfunction, the researchers noted. n

Study Challenges Purported Resveratrol Health Benefits RESVERATROL, a substance found in

markers C-reactive protein, interleukin

grapes, red wine, and chocolate that is

(IL)-6, IL-1β, and tumor necrosis factor,

thought to have antioxidant, anti-inflam-

nor were they associated with prevalent

matory, and anti-cancer properties, has

or incident CVD or with cancer.

no significant effect on all-cause mortal-

“Resveratrol levels achieved with the

ity inflammatory markers, cardiovascular

diet do not show any apparent protective

disease (CVD), or cancer, a study found.

association with disease and markers of

The prospective cohort study, which

disease in humans and are not associ-

was led by Richard D. Semba, MD, MPH,

ated with lifespan,” the authors wrote.

of The Johns Hopkins School of Medicine

Last year, researchers in Denmark

in Baltimore, included 783 community-

published the results of a small study

dwelling men and women aged 65 years

showing that high-dose resveratrol

and older. The investigators measured

supplementation had no effect on insulin

24-hour urinary resveratrol metabo-

sensitivity and certain other metabolic

lites. During 9 years of follow-up, 268

parameters in obese men, despite prom-

subjects (34.3%) died. From the lowest

ising findings from some animal studies.

to the highest quartile of resveratrol

Morten M. Poulsen, MD, of Aarhus

urinary metabolite concentrations, the

University Hospital, and colleagues ran-

proportion of participants who died from

domized 24 obese but otherwise healthy

any cause was 34.4%, 31.6%, 33.5%,

men to receive 4 weeks of resveratrol or

and 37.4%, respectively, Dr. Semba’s

placebo. “Insulin sensitivity, the primary

group reported online ahead of print

outcome measure in the study, dete-

in JAMA Internal Medicine. Resveratrol

riorated insignificantly in both groups,”

levels were not significantly associated

the researchers reported in Diabetes

with serum levels of the inflammatory

(2013;62:1186-1195). n

7/22/14 1:30 PM

18 Renal & Urology News

AUGUST 2014 www.renalandurologynews.com

Men’s Health Update Short Takes Testosterone Therapy Does Not Raise MI Risk Older men treated with intramuscular testosterone therapy found. In fact, the treatment may be protective against MI in men at higher MI risk. Jacques Baillargeon, PhD, and colleagues at the

are not at elevated risk of myocardial infarction (MI), a study

University of Texas Medical Branch in Galveston studied 6,355 Medicare beneficiaries who received at least 1 injection of testosterone from January 1 1997 to December 31, 2005. These men were matched to 19,065 men not treated with testosterone based on a composite MI prognostic score. For men in the highest quartile of the MI prognostic score, testosterone therapy was associated with a 31% decreased risk of MI, the researchers reported online ahead of print in Annals of Pharmacology. The researchers found no difference in MI risk among men in the 1st, 2nd, and 3rd quartiles.

Neglected Side Effects of Radical Prostatectomy A questionnaire-based study distributed to men 3–36 months after undergoing radical prostatectomy revealed significant side effects that are not commonly discussed with patients. Common side effects included diminished intensity (60%) or delayed (57%) orgasm and subjective loss of 1 cm or more of penile length (47%), Anders Frey and colleagues reported online ahead of print in the Journal of Sexual Medicine. Orgasm-associated problems and changes in the physiology and anatomy of the penis are common and should be discussed with patients in the pre-operative setting.

Obesity Diminishes Sexual Function in Young Men Obesity can lead to a deterioration of erectile function in young men as a result of reduced testosterone levels, according to a report in Endokrynologia Polska (2014;65:203-209). In a study of 136 men aged 20–49 years, researchers found a significant decrease in total testosterone in obese 30-year-olds compared with men who had a normal body mass index (BMI). In obese 40-year-olds, the researchers also observed decreased luteinizing hormone and sex hormone binding globulin. Erectile function and morning erections were adversely affected by higher BMI and waist-to-hip ratio, and positively correlated with free testosterone index, according to the investigators.

BY JAIME LANDMAN, MD

University of California, Irvine, Department of Urology

Caffeine May Decrease Erectile Dysfunction Risk D

rinking caffeinated beverages may be associated with a lower likelihood of erectile dysfunction (ED), according to study findings presented at the American Urological Association 2014 annual meeting in Orlando, Fla. David S. Lopez, DrPH, MPH, MS, of the University of Texas Medical School in Houston, and colleagues analyzed data from 3,724 men aged 20 years and older who participated in the National Health and Nutrition Examination Survey (2001– 2004), a cross-sectional survey of the general U.S. population. The researchers looked at 24-hour dietary recall to estimate intake of caffeine and caffeinated beverages. Overall, men in the 3rd quintile of total caffeine intake (85–170 mg/day) and the 4th quintile (171–303 mg/day) were less likely to report ED compared with men in the first (reference) quintile (0–7 mg/day). Among overweight and obese men and those with hypertension, the researchers found a significantly decreased likelihood of reported ED among men in the 2nd, 3rd, 4th, and 5th quintiles compared with the reference quartile, after adjusting for multiple variables. The authors concluded that total caffeine intake equivalent to about 2–3 cups of coffee (250–375 mg/day) is associated with a significantly lower risk of reported ED. © THINKSTOCK

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

CP/CPPS May Impair Fertility C

hronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has a significant negative effect on sperm concentration and other semen parameters, according to a recent systematic review and meta-analysis published online in PLoS One (2014;9:e94991). Weihua Fu, MD, of the Third Military Medical University, Chongqing, People’s Republic of China, and colleagues analyzed data from 12 case-control studies that included 999 cases and 455 controls. The meta-analysis showed that sperm concentration and the percentage of progressively motile sperm and morphologically normal sperm from patients with CP/CPPS were significantly lower than in controls. Semen volume, however, was greater in the CP/CPPS patients than controls. Results also demonstrated no significant difference between the group with regard to total sperm count, sperm total motility, and sperm vitality.

Sugary Beverages Reduce Semen Quality

may support the case against these sugary treats. A recent study of young (aged 18–22 years) men demonstrated that sugar-sweetened beverage consumption adversely affected

sperm motility. Men who consumed more than 1.3 servings per day had a 9.8% reduction in sperm motility compared with those who consumed less than 0.2 servings per day, according to a report published online ahead of print in Human Reproduction. This effect was most pronounced among men with a normal body mass index.

MH_RUN0814.indd 18

MEDISTAT

versy, particularly as they pertain to obesity. A recent study

58.9

The percentage of community-dwelling men older than 50 years who suffer from nocturia.

Source: Miranda ED et al. Nocturia is the lower urinary tract symptom with the greatest impact on quality of life of men from a community setting. Int Neurourol J 2014;18:86-89.

Sugar-sweetened beverages have engendered much contro-

7/23/14 12:24 PM

www.renalandurologynews.com AUGUST 2014

Renal & Urology News 19

Cholesterol Predicts RCC Outcomes HIGH PREOPERATIVE serum levels of cholesterol are associated with better cancer-specific survival following surgery for renal cell carcinoma (RCC), according to a new study. The retrospective investigation, led by Tobias Klatte, MD, of the Medical University of Vienna, included 867 patients who underwent partial or radical nephrectomy. Patients with high cholesterol—defined as a level of 161.5 mg/dL or greater—had a 43% decreased risk of death from RCC compared with patients who had low cholesterol (less than 161.5 mg/dL) in multivariable analysis. Each 10 mg/ dL increment in cholesterol was associated with a 6% decreased risk of death from RCC, after adjusting for the effect of known prognostic factors, the researchers reported in a paper published online ahead of print in BJU International. In a subgroup of 750 patients with clinically localized disease, who were

ACA May Improve PCa Outcomes PROSTATE cancer (PCa) patients with health insurance are less likely to present with metastatic disease or die from the cancer than those without health insurance, according to a new study. The findings suggest that expanding health coverage under the Affordable Care Act (ACA) may improve outcomes among PCa patients who are not yet eligible for Medicare, researchers reported online ahead of print in Prostate Cancer and Prostatic Diseases. Investigators led by Paul L. Nguyen, MD, of the Department of Radiation Oncology at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, examined the association between health insurance status and PCa outcomes. Using the Surveillance, Epidemiology and End Results (SEER) database, they analyzed data from 85,203 men younger than 65 years diagnosed with PCa from 2007 to 2010. Results showed that uninsured patients were more likely to be non-

News4_RUN0814.indd 19

considered disease free following complete surgical resection, patients with high cholesterol preoperatively had a 75% decreased risk of death from RCC compared with those who had low cholesterol, the researchers reported. Each 10 mg/dL increment in cholesterol was associated with a 12% decreased risk of death from RCC. Additionally, cholesterol was a prognostic factor in the subgroups of patients with clear cell RCC and papillary RCC, as well as in those with clinically localized disease. Further, Dr. Klatte and his colleagues noted that use of preoperative cholesterol levels increases the discrimination of established prognostic factors.“The present study confirms that cholesterol is an independent prognostic factor for [RCC] patients treated with surgery, with lower levels being associated with worse survival. … As this is a broadly available routine marker, its use may provide a meaningful adjunct in clinical practice,” the authors concluded.

white and come from rural areas and places with lower median household income and lower education level, Dr. Nguyen’s group reported. After adjusting for potential confounders, insured men were 77% less likely to present with metastatic disease, 44% less likely to die from PCa, and 40% less likely to die from any cause compared with uninsured men. In addition, among patients with high-risk disease, insured men were more than twice as likely to receive definitive treatment. All of the risk differences between insured and uninsured men were statistically significant. The authors stated that their results “suggest that insurance coverage improves access to cancer care, likely leading to earlier diagnosis of disease at a non-metastatic stage and more appropriate receipt of potentially curable therapies, and in turn, better overall and cancer-specific survival.” In their discussion of study limitations, the investigators noted that the SEER database does not provide information about insurance coverage periods or the details of patients’ insurance plans, so they analyzed insurance coverage as a binary variable. Consequently, they could not capture the influence of specific policies on PCa outcomes. n

Each 10 mg/dL increment in cholesterol prior to surgery was associated with a 6% decreased risk of RCC death.

The study population had a median age of 64 years. The median postoperative follow-up for living patients was 52 months. Of the 867 patients, 116 (13.3%) died from RCC.

The findings of the new study are consistent with those of a study published recently in Urology (2014;83:154158) by Yoshio Ohno, MD, and colleagues at Tokyo Medical University. The researchers reviewed the records of 364 patients with clear cell RCC who underwent nephrectomy and, like Dr. Klatte’s team, found that preoperative cholesterol was an independent predictor of CSS, with low levels associated with a worse prognosis. In a separate study published in BJU International (2014;113:E75-E81), Chinese researchers found that abnormal elevation of low-density lipoprotein (LDL) significantly more prevalent among RCC patients than controls. Patients with LDL levels of 160 mg/ dL or higher had a 4.7 times increased odds of RCC compared with those who had a normal LDL profile, according Ding-Wei Ye, MD, and Yao Zhu, MD, of Fudan University Shanghai Cancer Center in Shanghai, and colleagues. n

High preoperative levels are associated with a 43% decreased risk of cancer death versus low levels

Earlier Dialysis Initiation Linked to Higher Uric Acid Levels HIGHER URIC acid (UA) levels in incident

mL/min/1.73 m2 decline in estimated

pre-dialysis patients are associated

glomerular filtration rate (eGFR) per

with a shorter time to the start of

year. The change in eGFR decline with

dialysis but not an accelerated decline

each 1 mg/dL increment in baseline

in renal function, a new study suggests.

UA was a non-significant −0.14 after

“This may indicate that patients with

adjusting for demographic factors,

higher UA levels should be referred

comorbidities, diet, body mass index,

earlier to pre-dialysis care in order

blood pressure, and other poten-

to guarantee appropriate prepara-

tial confounders, the researchers

tion for start of dialysis,” researchers

reported. Each 1 mg/dL increment in

concluded in an online report in BMC

baseline UA was associated with a sig-

Nephrology (2014;15:91).

nificant 26% increased risk of starting

Hakan Nacak, MD, of Leiden University Medical Center in Leiden, The Netherlands, and colleagues

dialysis, after adjusting for the same potential confounders. “Since UA was not associated with

analyzed data from 131 patients in the

decline in renal function in our cohort,”

PREPARE-2 study, an observational pro-

the investigators noted, “this associa-

spective cohort study that includes inci-

tion [between UA and dialysis initia-

dent pre-dialysis patients with chronic

tion] might be explained by clinical

kidney disease stages 4–5. The median

symptoms such as gout that relate

follow-up was 14.9 months until the

to UA accumulation. … Painful and

start of dialysis, kidney transplantation,

disabling symptoms of gout arthritis

death, or censoring.

could have contributed to the decision

The patients had a mean baseline UA level of 8.0 mg/dL and a mean 1.61

of the nephrologist and patient to start dialysis.” n

7/23/14 3:15 PM

AUGUST 2014 www.renalandurologynews.com

Low Preop Hb Raises Death Risk ANEMIA PRIOR to cardiac surgery is associated with adverse outcomes among patients with chronic kidney disease (CKD), new findings suggest. In a study of 788 CKD patients undergoing open heart surgery, each 1 g/dL decrement in preoperative hemoglobin was associated with a 38%, 31%, 31%, and 38% increased risk of death, sepsis, cerebrovascular accident (CVA), and acute kidney injury (AKI) requiring hemodialysis, respectively. The study, led by Linda Shavit, MD, of Shaare Zedek Medical Center in Jerusalem, Israel, also showed that, compared with a preoperative hemoglobin level above 14 g/dL, levels below 12 g/dL were independently associated with a significant 2.5 times increased risk of death. Preoperative hemoglobin levels below 11 g/dL were independently associated with a significant 3.8 times increased risk of sepsis. Preoperative hemoglobin levels below 12, 11, and 10 g/dL were independently associated with a 2.7, 4.5, and 4.7 times increased risk of kidney failure.

Hypertension Ups Psoriasis Risk Women with hypertension for at least 6 years are at 27% higher risk WOMEN WHO have hypertension for 6 or more years are at increased risk of psoriasis, according to a new study. The study, which examined data from 77,728 women in the Nurses’ Health Study, found that women who had hypertension for 6 years or more had a significant 27% increased risk of psoriasis compared with those who did not have hypertension, after adjusting for multiple potential confounders. Hypertensive women who did not take antihypertensive medications had a significant 49% increased risk of psoriasis and hypertensive women who currently used antihypertensive medications had a significant 31% increased risk compared with women who did not have hypertension and were not on antihypertensive medication. Additionally, compared with women who never used beta blockers, those who regularly used this class of drugs for 6 years or more had a 39% increased risk of psoriasis in multivariate analysis. The investigation, led by Abrar A. Qureshi, MD, MPH, of Brown University in Providence, RI, found no association between use of other individual antihypertensive drugs and psoriasis risk. The researchers reported their findings online in JAMA Dermatology,

24 Renal & Urology News

Psoriasis screening may be warranted for patients with long-standing hypertension.

where they concluded: “These findings provide novel insights into the association among hypertension, antihypertensive medications, and psoriasis.” As a result of the study findings, the researchers stated that “special attention on psoriasis screening may be needed for patients with long-term duration of hypertension and related antihypertensive medication use in clinical practices.” Dr. Qureshi’s team noted that previous studies have shown that i ndividuals

with psoriasis are at higher risk of hypertension, and antihypertensive medications, particularly beta blockers, have been linked to the development of psoriasis. Psoriasis, the researchers explained, is characterized by T-cell-mediated hyperproliferation of keratinocytes and inflammatory processes. Hypertension is characterized by increased oxidative stress and inflammation, and immune mechanisms reportedly are involved in the development of hypertension. In addition, population-based studies have found that chronic inflammation is associated with an increased risk of hypertension. “Therefore, hypertension may be associated with psoriasis development because of the shared inflammatory pathways.” The study found no increased risk of psoriasis among women who had hypertension for less than 6 years, the authors noted, a finding that is consistent with the concept that psoriasis is associated with a chronic inflammatory state. “Hypertensive participants with longer disease durations may have a greater possibility of developing psoriasis later because of the long-lasting increased levels of systemic oxidative stress and inflammation.” n

“Similar to the general population, preoperative anemia is associated with adverse postoperative outcomes in patients with CKD,” the investigators wrote in a paper published online ahead of print in the Clinical Journal of the American Society of Nephrology. Whether outcomes could be improved by therapeutically targeting higher preoperative hemoglobin levels before cardiac surgery in patients with underlying CKD remains to be determined.” Of the 788 patients in the study, 22.5% had preoperative hemoglobin in the normal range (men: 14–18 g/ dL; women: 12–16 g/dL). Dr. Shavit’s group noted that their study was limited by the use of observational data, so they could not entirely rule out known or unknown confounding factors in explaining their results. In addition, data on the preoperative use and dose of erythropoiesis-stimulating agents were not recorded consistently and could not be analyzed. n

024_RUN0814.indd 24

ESRD, Death Risks Equal in CKD Stage 4 Patients PATIENTS WITH chronic kidney disease (CKD) stage 4 are as likely to progress to end-stage renal disease (ESRD) as they are to die prior to ESRD, and certain variables could help to distinguish between the two, researchers reported. The equal likelihood of ESRD and death prior to ESRD is particularly problematic for decisions on the optimal time to begin preparation for renal replacement therapy (RRT), according to investigators led by Maneesh Sud, MD, and David M. Naimark ,MD, MSc, of the University of Toronto. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend starting RRT education and planning when patients’ glomerular filtration rate decreases to below 30 mL/min/1.73 m2, the researchers noted in a paper published in the American Journal of Kidney Diseases (2014;63:928-936). “Our work suggests that if the latter guidelines were

applied to all stage 4 patients, the inconvenience, risk, and cost of RRT preparations would not benefit a substantial proportion of that group,” they wrote. If RRT planning were started only when patients reached CKD stage 5, many patients would not be adequately prepared, the researchers observed. For patients who choose a hemodialysisbased modality, many would initiate dialysis without a functioning arteriovenous access. “Thus, identification of patients with CKD stage 4 at higher risk of progression to ESRD would allow for earlier preparation for RRT and prevention of unplanned initiation of RRT and its associated risks, whereas for patients at higher risk of death prior to ESRD, measures focused on risk reductions, particularly for cardiovascular events, could the main focus of care,” the authors wrote. The researchers studied 3,273 patients with CKD stages 3–5. ESRD developed

in 459 patients (14%), and 540 (16%) died over a median follow-up of 2.98 years. The rates of ESRD and death prior to ESRD, per 100 patient-years, were 7.7 and 8.0 for CKD stage 4, a difference that was not statistically significant. The rates of ESRD and death prior to ESRD were significantly different in other CKD stages. The rates, respectively, were 0.6 versus 2.2 for stage 3A, 1.4 versus 4.4 for stage 3B, and 41.4 versus 9.4 for stage 5. Additionally, in patients with CKD stage 4, each 10-year increment in age was associated with a 22% decreased risk of ESRD and a nearly twofold increased risk of death prior to ESRD, the investigators found. Patients with diabetes had a 59% increased risk of ESRD and a 21% decreased risk of death prior to ESRD. Those with heart failure had a 32% decreased risk of ESRD and a 2.2 times increased risk of death prior to ESRD. n

7/23/14 3:52 PM

www.renalandurologynews.com AUGUST 2014

Renal & Urology News 25

Practice Management Narrowing the divide between the clinical and the administrative sides of a practice can improve efficiency and patient care. BY TAMMY WORTH

A team approach Palmer said the key to making practices work moving forward is to create a physician and practice administrator team model. Because of the move to a value-based system, quality metrics, patient satisfaction, and cost will be tied together. The job of the practice administrator will be to connect the clinical and data-driven sides. For instance, patient satisfaction will be linked to more than whether or not he or she liked the doctor. They may look at things like how soon phone messages were returned, how long it takes to speak with an actual person in the office, if the office hours are sufficient, and how long it takes to get an appointment. “Some of these things start out clinical but become operational,” Palmer said. “We have to understand them as a whole instead of looking at them separately.”

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Health reform changes Palmer said it will be incumbent on the administrative staff to understand insurance changes that are occurring with healthcare reform. There are a large number of high-deductible plans on the market, so the practice manager has to ensure the office staff is communicating well with patients. In urology and nephrology, many of the pharmacy expenses are high and many patients have long-term treatment needs. Staff may have to work with patients differently to ensure they are receiving the treatment they need and paying their bills. Staff has to be able to know what treatments will cost and what patients’ liability will be. Population health Caring for patients within a population health model is also something that can fall under the purview of the practice administrator. Offices can now take on the task of tracking how often patients are seen in the emergency room to see if they could use help from social workers or home healthcare. “We are having to see how we can work with community resources and look at the total lifestyle and social services available with patients,” Palmer said. “It impacts how often they are in the office and how we manage chronic disease.” An office manager can help practices become involved in patient education and support groups. Instead of leaving it up to caregivers and patients to find assistance like home health providers or case management, an office manager can be a liaison to facilitate services. Care coordination Care coordination is a major focus of healthcare change. Much of what has historically been done in a piecemeal manner can now be taken on by a practice manager or delegated to other office staff. One possibility is an insurance coordinator who

istorically, there has been an invisible line separating the clinical and administrative sides of healthcare practices. But as we move to a more comprehensive model of treatment, it may make sense to diminish that separation. One way to help a practice evolve is to look to the practice manager. Modifying the role and responsibilities of a practice manager can be an important factor in the success of an office. Laura Palmer, senior industry analyst of professional development for the Medical Group Management Association, has tips on what a practice manager should be doing and how to make some of those changes. “We will be looking at a broader way of bridging clinical and administrative functions,” Palmer said. “We should be trying to design systems that work across the board from technology, human interaction with staff, and the exchange of information with patients and their whole support system.”

Modifying the role and responsibilities of a practice manager may be crucial to success.

helps understand how insurance networks function. A referral specialist can provide summaries to specialists when a patient is referred. He or she can ensure that necessary labs or other diagnostics are completed before the visit and that a report is sent back to the primary care provider after the specialist has seen the patient.

The value of technology Technology will have the biggest impact on practice administration, Palmer said. Technology can be used by a practice administrator to negotiate contracts with insurers. If a group is working with bundled payments, they can use data to extrapolate what the cost will be to treat a group of patients with renal disease or prostate cancer and negotiate a fee. If a group has a high rate of surgical interventions for certain patients with chronic conditions, data can be used to identify high-risk patients for earlier intervention. Palmer recommends starting small instead of overhauling the entire job of the practice manager. It may be a good

idea to choose 3 or 4 things that can be taken on and start there. For instance, a practice manager might try improving the way an office communicates with patients. A patient portal can be set up with auto alerts to help patients remember to refill prescriptions, track weight loss, monitor glucose levels or provide educational resources. Another opportunity is staffing changes. A nurse practitioner could treat urgent, acute care patients. To improve coordination and population healthcare, a patient care coordinator, dietitian, social worker, or referral specialist might be a good addition. A final task could be monitoring patients with chronic disease. Aside from tracking numbers with technology, an office administrator can manage and monitor patients by making sure they always have good access to the clinic; that timely follow ups are performed; and that prescriptions are filled or samples are provided so there are no lapses or delays in treatment. n Tammy Worth is a freelance medical journalist based out of Blue Springs, MO.

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