Renal & Urology News June 2014 Issue by Haymarket Media

JU N E 2014

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VOLUME 13, ISSUE NUMBER 6

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www.renalandurologynews.com

High BMI May Lower Transplant Odds Effect of overweight and obesity on the likelihood of getting a kidney transplant differs by sex BMI and Likelihood of Renal Transplantation Among women, increasing body mass index (BMI) was associated with decreasing likelihood of receiving a kidney transplant. Researchers observed a different trend among men. Shown here are the decreases and increases in the odds of receiving a kidney transplant stratified by BMI (kg/m2) and sex. 30 20 10 0 −10 −20 −30 −40 −50 −60 −70 −80

Women 25%

−5%

Men

24%

−2% −11%

−35%

−42% −62%

25.0–29.9

30.0–34.9

35.0–39.9

40+

Body Mass Index (BMI) Source: Gill JS, et al. Differential association of body mass index with access to kidney transplantation in men and women. Clin J Am Soc Nephrol 2014;9:951-959.

BY JODY A. CHARNOW OVERWEIGHT and obesity in patients with end-stage renal disease (ESRD) are associated with a decreased likelihood of receiving a kidney transplant primarily among women, according to researchers. In a study of 702,456 ESRD patients, investigators found that, among women, a body mass index (BMI) of 25.0 kg/m2 or higher (overweight and obese) was associated with a 25% decreased likelihood of receiving a kidney transplant. Among men, investigators observed a decreased likelihood of receiving a transplant mainly in those with a BMI of 40 kg/m2. “Our findings may be useful in ensuring access to transplantation among

Kidney Stone Guidelines Unveiled Kidney Stones BY JODY A. CHARNOW basis of the guidelines, summarized Raise Cardiac ORLANDO, Fla.—The American the recommendations in a presentation Urological Association (AUA) announced at the AUA’s 2014 annual meeting. Disease Risk at its annual meeting the development of In discussing the rationale for the new its first guidelines for the medical management of kidney stones. Margaret S. Pearle, MD, PhD, who chaired the panel that reviewed the available evidence that formed the

guidelines, Dr. Pearle noted that kidney stones are a common problem with a high rate of recurrence, and despite effective and established treatment continued on page 7

END-OF-LIFE DIALYSIS

Placing terminally ill patients on dialysis may not necessarily be in their best interest. SEE STORY PAGE 18

KIDNEY stones are associated with an increased risk of cardiovascular disease, including coronary heart disease (CHD) and stroke, according to a meta-analysis. “Our study suggests that kidney stones might be an important contributor to the risk of vascular events; the potential mechanisms for the findings may be related to metabolic disturbances,” the researchers wrote in a report published online ahead of print in the American Journal of Kidney Diseases. Researchers at the First Affiliated Hospital of Guangxi Medical University in Nanning, Guangxi Zhuang Autonomous Region, China, analyzed data from 49,597 patients with kidney stones and 3.5 million controls who were enrolled in 6 prospective cohort studies. The median duration of follow-up was 8.9 years. Pooled results showed kidney stones were associated with a 19% increased risk of CHD and a 40% increased risk of

women in the current era in which the prevalence of obesity among patients with ESRD is rapidly increasing,” the authors wrote. The study, led by John S. Gill, MD, of the University of British Columbia in Vancouver, British Columbia, found that the odds of women receiving a kidney transplant decreased as BMI increased. Compared with women who had a BMI of 18.5–24.9 kg/m2 (normal weight), those who had a BMI of 25.0–29.9 (overweight), 30.0–34.9 (class I obesity), 35.0– 39.9 (class II obesity), and 40 kg/m2 or higher (class III obesity) had a 5%, 11%, 35%, and 62% decreased likelihood of receiving a transplant, respectively, according to study results published continued on page 7

IN THIS ISSUE 3

Computed tomography with contrast carries minimal CIN risk

ESAs may raise cancer risk in dialysis patients

Risks remain despite recovery from acute kidney injury

Heart failure after starting dialysis raises death risk

Younger patients more likely to undergo parathyroidectomy

Phosphate binder may eliminate IV iron need

Carotid plaque is associated with coronary artery stenosis

Expert Q&A Suzanne T. Ildstad, MD, discusses immunosuppressionfree transplants. PAGE 25

continued on page 7

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JU N E 2014

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VOLUME 13, ISSUE NUMBER 6

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www.renalandurologynews.com

FQR Bacteria Complicate Biopsies Rectal carriage of fluoroquinolone-resistant bacteria ups infection risk after prostate biopsies Post-Prostate Biopsy Infections Fecal cultures positive for fluoroquinolone-resistant (FQR) bacteria are associated with higher infection rates after prostate biopsies, according to a study.

2.6% Overall infection rate 1.6% Men with FQR-negative cultures Men with FQR-positive cultures 6.6% 0

Source: Liss M, et al. Rectal culture prior to prostate biopsy identifies men at risk for infection: A multi-institutional international collaborative study. Data presented in poster format at the American Urological Association 2014 annual meeting.

BY JODY A. CHARNOW ORLANDO, Fla.—Fluoroquinolones are widely accepted as a standard for prophylaxis prior to prostate biopsies, but new studies presented at the American Urological Association 2014 annual meeting suggest that many men experience post-biopsy infections with bacteria resistant to these antibiotics. Data show that rectal carriage of fluoroquinolone-resistant (FQR) bacteria is associated with an increased risk of a post-biopsy infection. In one study, Michael A. Liss, MD, of the University of California San Diego, and colleagues studied 2,673 men with a median age of 66 years who underwent rectal culture prior to prostate biopsy in 2007–2013. The cultures

Kidney Stone Guidelines Unveiled Bladder CA BY JODY A. CHARNOW basis of the guidelines, summarized Treatments ORLANDO, Fla.—The American the recommendations in a presentation Urological Association (AUA) announced at the AUA’s 2014 annual meeting. Underused at its annual meeting the development of In discussing the rationale for the new its first guidelines for the medical management of kidney stones. Margaret S. Pearle, MD, PhD, who chaired the panel that reviewed the available evidence that formed the

guidelines, Dr. Pearle noted that kidney stones are a common problem with a high rate of recurrence, and despite effective and established treatment continued on page 7

END-OF-LIFE DIALYSIS

Placing terminally ill patients on dialysis may not necessarily be in their best interest. SEE STORY PAGE 18

RADICAL cystectomy (RC) and chemoradiation are underused for muscle-invasive bladder cancer (MIBC) even though these treatments offer a survival benefit compared with other therapies or no treatment, new findings suggest. Using the National Cancer Data Base, Angela B. Smith, MD, of the University of North Carolina at Chapel Hill, and colleagues studied 36,469 patients with MIBC. Of these, 27% underwent RC, 10% had chemo-radiation, 61% had other therapies, and 2% received no treatment. The other-therapy group include patients who had partial cystectomy, transurethral resection of bladder tumor alone, chemotherapy alone, or radiation alone. The median follow-up periods for the RC, chemo-radiation, other-therapy, and no-therapy groups were similar: 38 months, 33 months, 39 months, and 39 months, respectively. The median overall survival (OS) for the entire cohort was 25.1 months, Dr. Smith’s

revealed colonization by FQR organisms in 20.5% of patients. Post-biopsy infection occurred in 1.6% of patients who had cultures negative for FQR bacteria compared with 6.6% of those with cultures positive for FQR bacteria. For the entire cohort, an FQRpositive culture was associated with a 4-fold increased overall risk of infection and a 4.8 times increased risk of infection-related hospitalization, after adjusting for bowel preparation and diabetes. Among men who received fluoroquinolone prophylaxis only, positive FQR cultures were associated with a nearly 5-fold increased overall risk of infection and a 5.7 times increased risk of hospitalization for infection. continued on page 7

IN THIS ISSUE 8

Renal ablation found safe, effective for elderly patients

MRI helps detect significant prostate cancer

Pelvic floor exercises may be effective for premature ejaculation

Ejaculatory problems linked to BPH medications

Risks remain despite recovery from acute kidney injury

Statins found to improve erectile function

Prostate cancer upgrading and upstaging does not differ by race

Expert Q&A Suzanne T. Ildstad, MD, discusses immunosuppressionfree transplants. PAGE 25

continued on page 7

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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

Minimal CIN Risk from CT Scans COMPUTED tomography (CT) scans using contrast media are associated with a minimal risk of contrast-induced nephropathy (CIN), researchers reported at the Canadian Society of Nephrology 2014 annual meeting in Vancouver, B.C. Michael Garfinkle, MD, and colleagues at the University of Saskatchewan in Saskatoon, analyzed the incidence of CIN associated with 2,583 CT scans with contrast performed on 2,277 unique patients. They compared the incidence of acute kidney injury (AKI) immediately after contrast administration and then a few days afterward in the same patients. They also corrected for creatinine kinetics by considering an AKI occurring prior to a CT scan and leading to a cre-

CIN incidence is insignificant at all levels of baseline renal function. atinine rise continuing after the CT scan not to be associated with the scan itself. The investigators assumed that the difference between the incidence of the immediate post-scan and delayed postscan AKI was the risk of AKI attributable to the imaging study. Dr. Garfinkle’s group found a statistically insignificant incidence of postcontrast AKI and need for dialysis at all levels of baseline kidney function, according to researchers’ poster presentation. At worst, they noted, the maximum incidence of AKI attributable to CT contrast administration is 1.4%, 5.6%, 11%, and 24% for patients with an estimated glomerular filtration rate below 60, 30–60, 15–30, and less than 15 mL/min/1.73 m2, respectively. “The benefits of enhanced CT may outweigh this small risk [of CIN] in certain patients with renal dysfunction,” the researchers concluded. The authors noted that AKI in hospitalized patients is common, which likely leads to inflated reports of the true incidence of CIN associated with contrast CT. Patients who experienced a creatinine rise of 26.5 μmol/L or more or an increase greater than 150% were considered to have AKI. n

5/28/14 1:29 PM

4 Renal & Urology News

JUNE 2014 www.renalandurologynews.com

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Doc, Did You Check My Cholesterol?

ot infrequently, after spending significant amounts of time and effort working up and managing a CKD case and explaining to the patient and his/her family members that the CKD is in an advanced stage and that dialysis initiation is imminent, the patient asks, “What about my cholesterol, doc? Did you check my cholesterol?” I then have to spend extra time to enlighten the concerned patient and family members that transition from advanced CKD to dialysis therapy has little to do with cholesterol levels. Nevertheless, many patients still insist that I need to check and manage their cholesterol. In many CKD patients, the cholesterol obsession is too strong to overcome by a conventional patient-physician conversation. Even during my dialysis rounds, I have to deal with the cholesterol question sporadically. Recently, in the intensive care unit, I conducted a lengthy discussion with the family members of a patient with anuric AKI and multi-organ failure, who was on multiple pressors and continuous renal replacement therapy, and who had a poor prognosis. The family members were asking me why I had not checked the patient’s cholesterol yet. Occasionally, when I try to explain to some of my patients that a high serum cholesterol level accounts for only a small fraction of the burden of cardiovascular disease, they seek second opinion to find a better doctor who can check their cholesterol more frequently. What is the moral of the cholesterol story? First, many lay people, likely under the influence of overzealous efforts by pharmaceutical industry, have become convinced that serum cholesterol level is the most important health metric. Second, nephrologists have a long way to go to increase public education and awareness about the high prevalence and poor outcomes of CKD and AKI. Third—and this is good news—the process of educating the public about the importance of blood levels of a biomarker can be very effective if concerted efforts by both healthcare professionals and the pharmaceutical industry are realigned, as has been the case for cholesterol education. How should the physician react when family members of a patient in critical condition with AKI or CKD in the ICU and a poor prognosis ask that the patient’s cholesterol level be checked? The appropriate approach is to educate the patient and his/her family members that there are many more important clinical and prognostic measures than serum cholesterol level. This approach may be associated with the risk of antagonizing the patient and jeopardizing your reputation or being labeled as uncooperative and unfriendly. The less challenging course of action is to order a cholesterol level and finish rounds faster and more efficiently. Your choice. 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

Web editor

Editorial coordinator

Stephan Cho Candy Iemma

Production editor Kim Daigneau

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 6. 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.

5/28/14 12:20 PM

Urology Pharmacy Service Benefits Doctors and Patients New program helps assure physicians that patients get the brand-name medications they are prescribed, and at the lowest cost.* MOST PHYSICIANS at one time or other have written a prescription for a brand-name medication that they believe is the best option for a patient, only to have a pharmacy substitute a generic or me-too version that the physicians opted not to prescribe. In the majority of states, pharmacists can substitute a generic for a brand-name drug unless the prescriber has instructed otherwise on the prescription with such language as “dispense as written” or “brand medically necessary.” In some of these states, the law even requires pharmacists to substitute a generic. Actavis, Inc., has launched its Urology Pharmacy Service as a way to insure that patients get the Actavis-branded drugs they were prescribed. Actavis has partnered with CompleteCare Pharmacy Champaign® to offer Rapaflo® (silodosin), Enablex ® (darifenacin), Gelnique 3%® (oxybutynin) gel, Androderm® (testosterone transdermal system), and OXYTROL® (oxybutynin transdermal system). Patients who opt to use the Urology Pharmacy Service can get these medications at the lowest cost* without the need to visit a pharmacy.

Benefits Include: ■■ Prescriptions dispensed

as written

■■ Branded drugs at the

lowest monthly cost*

■■ Patient convenience

Marc D. Colton, MD, managing partner of the Morris Urology division of Garden State Urology in Denville, New Jersey, is among the first urologists to try out the new service. He became hooked on it after using it for only several months. “It’s very frustrating for me to write a prescription for a medication and find out that it was substituted with something else,” says Dr. Colton, who noted that he prefers to prescribe brand-name drugs such as Rapaflo®. “The service allows me to prescribe the drug that I want, give the patient the lowest cost for that drug, and give the patient one-stop shopping.” Patients benefit not only from getting the drugs their doctors prescribed, but also from not having to make a

trip to a pharmacy and wait on line to pick up their medications, he says. CompleteCare Pharmacy Champaign® delivers the prescriptions directly to patients in three to five days. U.S. participants in the service benefit from the lowest monthly cost* for the drugs. “Patients get a generic cost for the branded drug,” Dr. Colton says. “The

Urology Pharmacy Service At a Glance ■■ With the Urology Pharmacy Service, commercial patients pay no more than $15 for a 30-day supply and $40 for

a 90-day supply of Rapaflo and pay no more than $30 and $80 for a 30-day and 90-day supply, respectively, of Androderm®, Enablex®, Gelnique®, and OXYTROL®. ■■ Patients with no prescription drug coverage pay $60 for a 30-day supply. ■■ Co-pay savings are handled automatically by the pharmacy; no co-pay card, voucher, or coupon is required. ■■ Medicare patients may fill their prescriptions through CompleteCare Pharmacy Champaign® Specialty Services,

but because of government regulations, may not participate in co-pay reduction programs.

patients end up saving money by using the service.” Even in the short time he has been offering the service to patients, office personnel are spending less time on the telephone seeking prior authorization from third-party payers and haggling with pharmacists to ensure they dispense product as written. “It has enhanced the efficiency of the administrative staff,” Dr. Colton says. Dr. Colton has surveyed patients who have participated in the Urology Pharmacy Service and found a greater satisfaction, with patients saying they would use the service again. He says he plans to expand the use of the service. “As my experience and comfort level grow, I will offer this program to everyone who could benefit from the medications offered through the service,” Dr. Colton says. “That’s my goal.” n

■■ CompleteCare Pharmacy Champaign® receives no incentives to switch prescriptions and therapeutic substitutions

are not offered to patients. ■■ Physicians simply send their prescriptions directly to CompleteCare Pharmacy Champaign® Specialty Services

via their e-prescribing platform or by fax to 1-866-234-3755. Alternatively, patients can mail a written prescription to CompleteCare Pharmacy Champaign® Specialty Services at 6000 Creek Road, Cincinnati, Ohio 45242. ■■ Pharmacy consulting services are available free to patients, including refill reminders and processing.

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*Lowest monthly cost for commercial retail prescriptions filled in the United States, based on commercial retail copay practices.

Disclaimer: The views expressed in this article do not necessarily reflect those of Haymarket Media, Inc., publisher of Renal & Urology News.

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BMI and transplants continued from page 1

in the Clinical Journal of the American Society of Nephrology (2014;9:951-959). Results showed a different trend in the men. Compared with normalweight men, overweight men and those with class I obesity had a 25% and 24% greater likelihood of receiving a transplant. Men with class II and III obesity had a 2% and 42% decreased likelihood of receiving a transplant. The researchers observed similar trends when they looked at the odds of kidney transplantation by donor type (deceased and living). “With regard to

living donor transplantation, it is possible that overweight and obese women may have different perceptions about pursuing living donor transplantation compared with men with a similar BMI,” they noted. “Alternatively, physicians and potential living donors may perceive obesity differently in men versus women.” Obese patients had a higher frequency of being placed on hold, which suggests “the lower likelihood of transplantation after activation to the wait list is in part due to increased comorbid disease burden and medical complications in patients with a high BMI.” In an accompanying editorial, Anne M. Huml, MD, of University Hospitals

Case Medical Center in Cleveland, and Ashwini R. Sehgal, MD, of MetroHealth Medical Center in Cleveland, pointed out that little is known about physician decision making for the study subjects. “Physicians may perceive obese patients as poor surgical candidates or as nonadherent. Surgeons’ perceptions about size

mismatching between smaller deceased donors and obese potential recipients may also be a consideration.” They added, however, that why these factors would differ between the sexes remains unclear. “In the end,” Drs. Huml and Sehgal wrote, “we must realize that obesity is a medical and public health issue, not a character flaw. Unfortunately, obese individuals in our society, especially women, are often subject not only to the health effects of obesity but also to various forms of social stigma and discrimination. We need to make sure that transplant-related decisions are guided by medical considerations and the best interests of patients regardless of their BMI or sex.” n

parathyroid hormone is considered an optional study that should be obtained only if primary hyperparathyroidism is suspected, Dr. Pearle said. In addition, a stone analysis should be performed at least once if a stone is available because knowledge of stone composition can implicate certain underlying etiologies, such as a low urine pH in patients with uric acid stones. Metabolic testing should be performed in high-risk or interested firsttime stone formers as well as in recurrent stone formers, she said. Metabolic

testing should consist of one or preferably two 24-hour urine collections obtained under random diet. These urine collections should be analyzed for total volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine. “The 24-hour urine is then used to guide recommendations regarding dietary measures and medication.” The guidelines also recommend that: • All stone formers should be advised to drink enough fluids to achieve a urine volume of at least 2.5 L daily. • Patients with calcium stones and high urinary calcium should be advised to limit their sodium intake and to consume the recommended daily allowance of calcium of 1,000 to 1,200 mg daily. • Patients with uric acid stones and calcium stones and high urinary uric acid should be advised to limit their intake of non-dairy animal protein. About 30% of urinary uric acid is derived from dietary purine intake, and animal protein accounts for most purine intake, Dr. Pearle noted. • Patients with high urinary calcium and recurrent calcium stones should be offered thiazide diuretics because these medications act directly on the distal renal tubule and indirectly at the proximal renal tubule to promote renal calcium reabsorption.

• Patients with recurrent calcium stones and low urinary citrate should be offered potassium citrate because this medication provides an alkali load that promotes a citraturic response and increases urinary inhibitory activity. • Patients with recurrent calcium stones and who have hyperuricosuria should be offered allopurinol. • Thiazide diuretics and/or potassium citrate should be offered to patients with recurrent calcium stones in whom no metabolic abnormality is identified or in whom appropriate metabolic abnormalities have been addressed but stone formation persists. • Allopurinol should not routinely be offered as first-line therapy to patients with uric acid stones. Uric acid nephrolithiasis is primarily a disease of urinary acidification, and at a pH greater than 6 to 6.5, most uric acid will be found in its soluble or undissociated form, and even high amounts of uric acid at these higher urinary pHs will be fully solublized, Dr. Pearle explained. Dr. Pearle concluded her talk by mentioning the importance of followup. “Success is gauged by improvement in urinary stone risk factors and ultimately by reduction in stone formation,” she said. Serial urine collections must be obtained to address changes in urinary risk factors. n

15% increased risk. “The evidence for increased risk of MI in female but not male patients is suggestive but not conclusive,” the authors noted. “We cannot explicitly test for this difference using metaregression analysis to claim a definite conclusion because of the limited number of studies. In addition, the difference between male and female cohorts in our analyses was unexpected and difficult to explain.” Previous studies have demonstrated an

association between kidney stones and metabolic syndromes, such as obesity, insulin resistance, hyperglycemia, hypercholesterolemia, and hypertension, the investigators stated. “These abnormalities may contribute to a higher risk of uric acid and calcium stone formation.” In their discussion of study strengths, the researchers noted their study is the first meta-analysis and systematic review of the relationship between kidney stones and risk of cardiovascular dis-

eases. In addition, their meta-analysis only included studies with a prospective cohort design, which should decrease selection and recall biases, they pointed out. Study limitations included the use of observational studies, which precludes drawing conclusions about causality. In addition, the researchers said they were unable to exclude residual confounding by imprecisely measured cardiovascular risk factors or unmeasured confounding factors. n

Stone guidelines

Stones and CVD continued from page 1

stroke compared with controls, investigators led by Xue Qin, MD, PhD, reported. Specifically, kidney stones are associated with a 29% increased risk for myocardial infarction (MI) and a 31% increased risk of coronary revascularization. Female patients had a significant 49% increased risk for MI whereas male patients had a non-significant

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continued from page 1

regimens for medical management, evidence suggests that medical management is underused. Additionally, she said, management of patients with recurrent stones lacks uniformity. The guidelines contain 27 statements that fall broadly into the categories of evaluation, diet therapies, pharmacologic therapies, and follow-up. All patients diagnosed with a stone should have a screening evaluation that consists of dietary intake, medical therapies, serum chemistries, urinalysis, and urine culture, said Dr. Pearle, professor of urology and internal medicine at the University of Texas Southwestern Medical Center in Dallas. The evaluation is aimed at identifying medical conditions associated with stone formation, such as primary hyperparathyroidism or type 2 diabetes, dietary aberrations, such as low or high calcium intake or excessive intake of animal protein, or medications such as topiramate, she told listeners. Serum chemistries should be obtained to define underlying conditions that may be associated with recurrent stones, such as primary hyperparathyroidism or distal renal tubule acidosis. Measuring serum

Renal & Urology News 7

A stone analysis should be performed at least once if a stone is available.

Obese patients may be perceived as poor surgical candidates or as nonadherent.

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FQR bacteria continued from page 1

“The study is the largest to date to investigate the natural history of prostate biopsy infectious complications analyzing the association of fecal carriage of FQR organisms,” Dr. Liss told Renal & Urology News. “We show that FQR is a very significant, independent predictor of infection and subsequent hospitalization from transrectal prostate biopsy. Infections were most noticeable when only a fluoroquinolone was used for prophylaxis in men who had a positive FQR rectal culture, which indicates an alternative prophylaxis regimen would be

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group reported online ahead of print in BJU International. RC patients had the longest median OS (47.7 months). The median OS was 27.7 months for the chemo-radiation group, 19.7 months for the other-therapy group, and 5.3 months for the no-treatment group. In adjusted analyses, RC and chemoradiation were associated with similar overall survival. Compared with patients who had RC, those who received other therapies and no therapy had a significant

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indicated in these men instead of treating all men with additional antibiotics.” In another study, Jason Cohen, MD, and collaborators at Johns Hopkins University in Baltimore, looked at 354 prostate cancer patients undergoing prostate biopsy as part of an active surveillance protocol. Of these, 85 had FQR bacteria on at least 1 rectal swab. Men with diabetes were 2.4 times more likely to carry FQR organisms than those without diabetes. A third study demonstrated that screening for FQR Escherichia coli prior to a prostate biopsy may enable targeted antibiotic prophylaxis that can decrease the risk of post-biopsy sepsis.

Michael Holmes, MD, of Waikato Hospital in Hamilton, New Zealand, and colleagues identified 3,338 men who underwent prostate biopsy from 2006–2013. In 2012, the hospital began a policy of culturing rectal swabs on ciprofloxacin-impregnated agar plates prior to biopsy. Positive cultures are re-plated to assess antibiotic resistance patterns. Prophylactic antibiotics are altered to ceftriaxone or ertapenem depending on culture findings. Rectal swabs prior to biopsy were obtained in 248 men in 2013. FQR E. coli was identified in 20 men (12.4%). Seventeen isolates were multidrugresistant but ceftriaxone sensitive; 3 had

extended beta-lactamase activity. Sepsis rates rose from 0.25% in 2006 to 1.9% in 2011 before falling to 0.28% in 2013, the researchers reported. The investigators defined sepsis as presentation to a regional hospital within 14 days of biopsy with a temperature of 38° C or higher. Lastly, Paul Womble, MD, of the University of Michigan in Ann Arbor, and collaborators analyzed data from the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry and found that nearly 1% of men who have undergone transrectal prostate biopsy are treated for infectionrelated hospitalizations. Most cultures identified FQR bacteria as the cause. n

recurrent stones, such as primary hyperparathyroidism or distal renal tubule acidosis. Measuring serum parathyroid hormone is considered an optional study that should be obtained only if primary hyperparathyroidism is suspected, Dr. Pearle said.

In addition, a stone analysis should be performed at least once if a stone is available because knowledge of stone composition can implicate certain underlying etiologies, such as a low urine pH in patients with uric acid stones. Metabolic testing should be performed in high-risk or interested firsttime stone formers as well as in recurrent stone formers, she said. Metabolic testing should consist of one or preferably two 24-hour urine collections obtained under random diet. These urine collections should be analyzed for total volume, pH, calcium, oxalate, uric

acid, citrate, sodium, potassium, and creatinine. “The 24-hour urine is then used to guide recommendations regarding dietary measures and medication.” The guidelines also recommend that: • All stone formers should be advised to drink enough fluids to achieve a urine volume of at least 2.5 L daily. • Patients with calcium stones and high urinary calcium should be advised to limit their sodium intake and to consume the recommended daily allowance of calcium of 1,000 to 1,200 mg daily. • Patients with uric acid stones and calcium stones and high urinary uric acid should be advised to limit their intake of non-dairy animal protein. About 30% of urinary uric acid is derived from dietary purine intake, and animal protein accounts for most purine intake, Dr. Pearle noted. • Patients with high urinary calcium and recurrent calcium stones should be offered thiazide diuretics because these medications act directly on the distal renal tubule and indirectly at the proximal renal tubule to promote renal calcium reabsorption. • Patients with recurrent calcium stones and low urinary citrate should be offered potassium citrate because this

medication provides an alkali load that promotes a citraturic response and increases urinary inhibitory activity. • Patients with recurrent calcium stones and who have hyperuricosuria should be offered allopurinol. • Thiazide diuretics and/or potassium citrate should be offered to patients with recurrent calcium stones in whom no metabolic abnormality is identified or in whom appropriate metabolic abnormalities have been addressed but stone formation persists. • Allopurinol should not routinely be offered as first-line therapy to patients with uric acid stones. Uric acid nephrolithiasis is primarily a disease of urinary acidification, and at a pH greater than 6 to 6.5, most uric acid will be found in its soluble or undissociated form, and even high amounts of uric acid at these higher urinary pHs will be fully solublized, Dr. Pearle explained. Dr. Pearle concluded her talk by mentioning the importance of followup. “Success is gauged by improvement in urinary stone risk factors and ultimately by reduction in stone formation,” she said. Serial urine collections must be obtained to address changes in urinary risk factors. n

42% and 2.4-fold increased risk of death. “An important novel contribution of this study is the observation that chemo-radiation, another guidelinesrecommended treatment for MIBC, offers similar OS times to those of radical cystectomy, suggesting a method to address barriers to access to extirpative surgery,” the authors wrote. The authors acknowledged limitations of their study, including the absence of granular data on patient or provider preference, “which can greatly contribute to patterns of care and thus affect survival times.”

In addition, the researchers were not able to investigate the dosage of radiation or choice of specific radiotherapy. “This may be especially important for patients receiving chemo-radiation, for whom carboplatin does not have proven efficacy but, based on our clinical experience, is commonly used as an alternative to cisplatin; therefore, nuances in treatment might increase or decrease OS estimates for this group.” The new findings are consistent with those of a previous study published in the Journal of the National Cancer Institute (2010;102:802-811). The study,

by John L. Gore, MD, of the University of Washington School of Medicine in Seattle, and colleagues, looked at a cohort of 3,262 Medicare beneficiaries aged 66 years or older at diagnosis with stage 2 MIBC. Of these, 21% underwent RC. The authors concluded that guideline-recommended care with RC is underused for patients with MIBC. Older age at diagnosis and greater comorbidity burden were associated with a decreased likelihood of having RC. OS was better for patients who underwent RC compared with those who had alternative treatments. n

Stone formers should drink enough fluid to achieve a urine volume of 2.5 L daily.

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8 Renal & Urology News

JUNE 2014

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News in Brief

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

Short Takes Unplanned Visits After Stone Treatment Defined

the Children’s Hospital of Pittsburgh,

Researchers have found that,

randomized study of 607 children

overall, 1 in 7 patients who undergo

with VUR diagnosed after a first or

a procedure to treat urinary stones

second febrile or symptomatic UTI.

make unplanned, high-acuity, follow-up

Recurrent UTI occurred in 39 of 302

visits, defined as presentation to an

children who received prophylaxis

emergency department or a hospi-

with trimethoprim-sulfamethoxazole

tal admission within 30 days of the

(TMP-SMX) compared with 72 of 305

procedure. Charles D. Scales, MD, of

children who received placebo, which

Duke University in Durham, N.C., and

translated into a 50% decreased risk

colleagues identified 93,523 initial pro-

of recurrence in the TMP-SMX group.

and colleagues conducted a 2-year

cedures to fragment or remove urinary frequently after shock wave lithotripsy

Hip Fracture Risk Greater with Hemodialysis

(12% of cases) and occurred with

Hemodialysis (HD) is associated with

similar frequency after ureteroscopy

a higher risk of hip fracture than

and percutaneous nephrostolithotomy

peritoneal dialysis (PD), data show.

(15%), the investigators reported in

Zhe-Zhong Lin, MD, and colleagues at

Surgery (2014;155:769-775).

Chi-Mei Medical Center in Tainan, Tai-

stones. Unplanned visits occur less

wan, analyzed the records of 51,473

VUR Antimicrobial Prophylaxis Beneficial

patients who initiated dialysis from

Antimicrobial prophylaxis for children

4.1 years, during which 1,903 patients

with vesicoureteral reflux (VUR) after

suffered a hip fracture. HD patients had

a febrile urinary tract infection (UTI)

a 31% higher risk of hip fracture than

decreases the risk of recurrent UTI,

those on PD, the researchers reported

but not renal scarring, according to

online ahead of print in Bone. The risk

a report published online ahead of

of hip fracture was 13 times greater

print in The New England Journal of

among patients aged 65 years or more

Medicine. Alejandro Hoberman, MD, of

than among those aged 18–44 years.

1999 to 2005. The mean follow-up was

Many Docs Drop Bad Payers In a recent online poll, Renal & Urology News asked urologists and nephrologists, “Have you ever stopped accepting private insurance that reimburses poorly?” Here are the results based on 177 responses.

Yes: 60.45%

No: 25.42%

I plan to: 14.12%

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ESAs May Raise Cancer Risk in Dialysis Patients E

rythropoiesis-stimulating agents (ESAs) may increase the risk of cancer in chronic dialysis patients, researchers reported at the Canadian Society of Nephrology annual meeting in Vancouver, B.C. Hind Harrak, MS, of Maisonneuve-Rosemont Hospital Research Center in Montreal, and colleagues studied 4,574 patients starting chronic dialysis from January 1, 2001 to December 31, 2007 in Quebec. The researchers excluded patients with a prior cancer diagnosis. Exposure to ESAs was evaluated from 6-9 months prior to the first cancer diagnosis. Mean exposure to ESAs was categorized as low dose (less than 30 μg/week), moderate dose (30–70 μg per week), and high dose (more than 70 μg per week). The investigators identified 319 cases of cancer and 3,895 matched controls during the study period. Compared with patients not exposed to ESAs, patients in the high-dose group had a 77% increased risk of a cancer diagnosis.

Renal Ablation Found Safe, Effective for Elderly Patients P

ercutaneous ablation provides a safe and effective way to manage small renal tumors in elderly patients, researchers reported at the Society for Interventional Radiology annual meeting in San Diego. Andrew Miller, MD, and collaborators at Mayo Clinic in Rochester, Minn., examined the outcomes of 104 percutaneous ablation procedures performed for T1a renal tumors in patients aged 80 years or older (mean age 84 years). These included 62 cryoablation procedures and 42 radiofrequency ablation (RFA) procedures. Patients had a mean tumor size of 2.7 cm. The estimated overall survival rates at 1, 3, and 5 years was 94%, 78%, and 53%, respectively, following cryoablation, and 100%, 80%, and 58%, respectively, following RFA. The estimated recurrence-free survival rates at 1, 3, and 5 years were 99%, 97%, and 91%, respectively, following cryoablation, and 97%, 94%, and 94%, respectively, following RFA. Patients had a mean hospital stay of 1.2 nights. Five procedures (4.6%) resulted in major complications: 4 after cryoablation and 1 after RFA. None resulted in death.

Lowering LDL Cholesterol Fails to Halt CKD Advance L

owering LDL cholesterol by 1 mmol/L does not slow progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), researchers reported online ahead of print in the Journal of the American Society of Nephrology. Richard Haynes, MD, at the University of Oxford in the U.K., and colleagues randomly assigned 6,245 non-dialysis CKD patients to receive simvastatin 20 mg plus ezetimibe 10 mg daily or matching placebo. During a median 4.8 years of follow-up, the simvastatin-ezetimibe group had an average LDL cholesterol difference of 0.96 mmol/L compared with the placebo arm. The incidence of ESRD— the main study outcome—decreased by a non-significant 3% in the lipid-lowering arm. The researchers defined ESRD as the initiation of dialysis or kidney transplantation. In addition, the researchers observed no significant effect of simvastatin-ezetimibe on the rate of change in estimated glomerular filtration rate.

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■ EAU 2014, Stockholm

JUNE 2014

Renal & Urology News 9

Reports below are from the European Association of Urology’s 29th Annual Congress in Stockholm

MRI Helps Detect Significant PCa BY JODY A. CHARNOW SEPARATE STUDIES confirm the utility of magnetic resonance imaging (MRI) in detecting significant prostate cancer (PCa) and suggest that MRI can improve surgical margins in PCa patients with non-palpable tumors. In one study, a team led by Urs E. Studer, MD, professor and chairman, department of urology, University of Bern, Switzerland, showed that diffusion-weighted MRI (DW-MRI) detects significant PCa with a high probability using no contrast media or endorectal coil. The prospective study included 111 men with primary prostate cancer and/ or bladder cancer undergoing 3 Tesla DW-MRI of the pelvis without endorectal coil prior to radical prostatectomy (78 patients) or cystoprostatectomy (33 patients). Three independent readers (A, B, and C) blinded to clinical and pathological data graded the MRI scans. The reference standard was final pathology of prostates with and without cancer. The investigators defined significant PCa as a tumor with a maximum diameter of 1 cm or larger, extraprostatic extension, or a Gleason score of 7 or higher. The sensitivity and specificity for the detection of significant PCa were 89% and 77%, 90% and 81%, and 91% and 77%, for readers A, B, and C, respectively, the researchers reported in a poster presentation. The median DW-MRI reading times were 13 minutes, 17 minutes, and 18 minutes, respectively. “This

technology should be further investigated as a possible tool for prostate cancer screening,” the authors concluded. Previous studies have shown that DW-MRI enables detection of significant PCa, but Dr. Studer told Renal & Urology News that the study by his team differs from others in at least two important ways. First, in all other studies, MRI examinations were performed in patients who were known or very likely to harbor PCa, and biopsy was used to confirm the diagnosis. With this approach, it is likely that a positive MRI finding also results

It is possible to find 90% of significant prostate tumors, lead investigator says. in a positive biopsy, Dr. Studer said. It would not be known in how many cases the MRI finding would be falsely negative because in most institutions no biopsies are performed in men without a positive MRI. “In our study, however, we also included men who had no prostate cancer, but in whom the prostate was removed in the frame of a radical cystoprostatectomy,” he said. “Thus, for the first time, there were negative controls included in the study.” The second important way in which the new study differs from previous

It also may lower the risk of positive surgical margins in men with non-palpable tumors

A prostate tumor on a T2-weighted MRI scan.

The same tumor on a DW-MRI scan.

investigations is that tbe study showed it is possible to find, with high sensitivity and specificity, approximately 90% of significant prostate tumors with 2 MRI sequences only: T2-weighted and DW-MRI. “This allows for a fast and cost-effective examination, in contrast to all the other multi-parametric MRI studies with many sequences, use of contrast medium [gadolinium], additional washout studies, spectroscopy, and eventually the use of rectal coils,” Dr. Studer stated. “In that case, of course, the examination is extremely costly and could never serve as a screening tool in view of the healthcare costs. The technique we propose, however, is affordable, namely when compared to repetitive, useless serum PSA determinations, ‘blinded’ ultrasound-guided prostate biopsies, and repeat biopsies.” In the study looking at surgical margins, Erik Rud, MD, of Oslo University Hospital, Aker, and colleagues randomly assigned 413 PCa patients to have or not

have preoperative MRI scans prior to radical prostatectomy. Among patients with non-palpable (cT1) tumors, those who had preoperative MRI scans had a significant 46% decreased risk of positive surgical margins (PSM) compared with those who did not have the scans. These patients constituted the largest patient subgroup (54% of the overall cohort). For the cohort overall, the risk of PSM was 17% lower for the MRI group, but this decrease was not statistically significant. The researchers observed a trend toward lower PSM rates in other patient subgroups, but this, too, was not statistically significant. Nevertheless, Dr. Rud noted that his group believes these declines are clinically significant. The cohort had a mean age of 63 years. The overall prevalence of pT3 disease was 53%. In addition, 26%, 49%, and 25% of patients had low-, intermediate-, and high-risk disease based on D’Amico criteria. The investigators defined PSM as extension of tumor into the cut surface. ■

Pelvic Floor Exercises May Be Effective for Premature Ejaculation BY JODY A. CHARNOW PELVIC FLOOR exercises may be an effective treatment for hard-to-treat premature ejaculation (PE), researchers reported. Antonio Pastore, MD, of Sapienza University of Rome, and colleagues studied 40 men (aged 19–46 years) who had lifelong PE and had tried various therapies without significant improvement. The researchers trained them to exercise their pelvic floor muscles over a 12-week period. At the start of the trial, the average ejaculation time was 31.7 seconds. After 12 weeks of pelvic floor exercises,

RUN0614-EAU.indd 9

this time increased to 146 seconds, a greater than 4-fold increase. Of the 40 men, 33 improved within 12 weeks. Five men showed no significant improvement and 2 had dropped out of the trial early after showing improvement. Results also showed that 13 of the 33 patients continued the trial up to the 6-month mark and they reported maintaining their extended ejaculation time. Additionally, the fact that the men were able to improve their sex lives through their own efforts boosted their self-confidence. “This is a small study, so the effects need to be verified in a bigger trial,” Dr.

Pastore said. “Nevertheless, the results are very positive. The rehabilitation exercises are easy to perform, with no reported adverse effects.” Previously, the men in the trial had tried, with little success, treatments that included creams, behavioral therapy, selective serotonin reuptake inhibitors, and psychological treatments. “This technique seems to offer significant benefits over many existing techniques, including cost-savings and lack of side-effects,” Dr. Pastore said. “Although the exact exercises are still to be standardized, the results obtained

in our patients with lifelong PE suggest that it may be considered as a therapeutic option for patients with premature ejaculation.” “This is an interesting study,” said Carlo Bettocchi, MD, of the University of Bari in Bari, Italy, speaking on behalf of the EAU. “Premature ejaculation is a real problem for many men, and any way which we can find to help this condition is welcome. This method particularly welcome because it is the sufferers themselves who overcome the problem through their own efforts — which will have additional psychological benefits.” ■

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10 Renal & Urology News

JUNE 2014 www.renalandurologynews.com

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

Short Takes ED Drugs Used Improperly A new Spanish study has demonstrated that many patients who fail treatment of erectile dysfunction (ED) with phosphodiesterase-5 inhibitors (PDE5is) are using the medications improperly. The study, by Javier Romero Otero, MD, of 12 de Octubre University Hospital in Madrid, and colleagues evaluated 250 patients who failed to respond to PDE5is as primary ED treatment. A staggering 69% (172 patients) of patients had at least 1 deviation from ideal proper usage of the medication. In fact, 42%, 28%, and 7% had 2, 3, or more than 3 deviations, respectively, according to findings published online ahead of print in Urology. Frequent errors included failure to try the medication at least 6 different days, failure to reach maximum dose, failure to try at least 2 medications, and failure to take the medication on an empty stomach (if required).

Female Intuition and Testosterone Exposure to prenatal testosterone accounts for many of the differences between men and women, particularly in the brain. Researchers from Spain and London demonstrated that intuition itself is driven by testosterone, or a lack thereof, according to a report published online ahead of print in Psychoneuroendocrinology. The study, by Antoni Bosch-Demenech, PhD, of Universitat Pompeu Fabra and Barcelona Graduate School of Economics in Barcelona, and colleagues, used an established method of determining prenatal testosterone exposure by calculating the ratio of the 2nd digit to the 4th digit on the hands of the participants (2D:4D). A lower 2D:4D reflects a higher prenatal exposure to testosterone. A total of 623 subjects whose digit ratios were calculated then took a cognitive reflection test (CRT). The test penalizes quick, intuitive thinking. Higher scores on the test reveal a more reflexive or ‘controlled’ way of thinking rather than intuitive or ‘automatic’ thought. After controlling for sex, the researchers observed that increased testosterone exposure was significantly associated with a higher number of correct answers on the CRT. The effect appeared stronger in females.

‘Baby Blues’ for Dads While the “baby blues” are well documented in peri-partum women, little is known or understood about depression in men undergoing the transition to fatherhood.

BY JAIME LANDMAN, MD, and ADAM KAPLAN, MD, of the University

of California Irvine, Department of Urology

Ejaculatory Problems Linked to BPH Medications M

edications used to treat benign prostatic hyperplasia (BPH) may increase the risk of ejaculatory dysfunction (EjD), according to study findings presented at the European Association of Urology 29th annual congress in Stockholm. Mauro Gacci, MD, of the University of Florence in Italy, and colleagues conducted a systematic review and meta-analysis of data from 30,000 patients enrolled in randomized controlled trials showing that alpha blockers increased the risk of EjD nearly 6-fold compared with placebo. Silodosin and tamsulosin were associated with a 32.5 times and 8.6 times increased risk versus placebo, whereas doxazosin and terazosin did not differ significantly from placebo. Results also showed that use of 5-alpha reductase inhibitors (5ARIs) was associated with a significant 2.7 times increased risk of EjD compared with placebo. Finasteride and dutasteride were associated with similar EjD risk. The risk of EjD did not differ significantly between alpha blockers and 5ARIs. Combination therapy with both alpha blockers and 5ARIs was associated with a 3-fold increased risk compared with either drug class alone.

Sperm Functionality Declines After Age 35, Study Shows S

perm function may have an upper age limit, according to researchers at the Dokkyo Medical University in Koshigaya, Japan. They found that infertility in older couples may have an important male factor that eludes common semen analysis. In an abstract presented at the Men’s Health World Congress, Hiroshi Okada, MD, and colleagues evaluated sperm’s ability to activate an egg. The study included men with normal semen analyses, including normal sperm concentration, sperm motility and form. Using intracytoplasmic sperm injection (ICSI), their sperm were instilled in mouse oocytes. The activation rates ranged from 68% and 90% in all age groups (ages 20–60 years) but declined significantly after 35 years of age. While previous studies have shown a decrease in sperm motility with aging, this study shows a potential new factor to consider in the workup of older infertile couples.

New research from McGill University in Montreal shows that dads get sad, too.

the first prenatal year using validated self-reported questionnaires. The results showed that 13% of expectant fathers exhibited depressive symptoms. This was associated with some independent factors, including unemployment, poorer sleep quality, lower perceived social support, greater financial stressors and increased depression in their partners. Paternal depression can have detrimental effects on children’s early behavior and emotional development. Fathers at risk for depression will require strategies to promote better sleep, manage stress and mobilize social support.

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MEDISTAT

collaborators prospectively evaluated 469 men for depressive symptoms during

60.2 Source: National Center for Health Statistics 2012 data.

The proportion of men aged 18 years and older in the United States reporting current regular alcohol consumption. © TOP AND BOTTOM: THINKSTOCK

In an abstract at the Men’s Health World Congress, Deborah Da Costa, PhD, and

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Renal & Urology News 11

Risks Remain Despite AKI Recovery Higher risk of health problems found in patients who recover from acute kidney injury requiring RRT PATIENTS with acute kidney injury (AKI) requiring renal replacement therapy (RRT) face a long-term increased risk of coronary events, malignancy, and death, according to the findings of three recent studies. One study, by Vin-Cent Wu, MD, PhD, of National Taiwan University Hospital in Taipei City, Taiwan, and colleagues, included hospitalized patients who recovered from dialysis-requiring AKI. Among 17,106 acute dialysis patients who were discharged, 4,869 recovered from dialysis-requiring AKI, the researchers reported in the Journal of the American Society of Nephrology (2014;25:595-605). Upon matching these individuals with 4,869 patients without AKI, the researchers found that incidence rates of coronary events were 19.8 per 1,000 person-years in the AKIrecovery group versus 10.3 per 1,000 person-years in the non-AKI group. Compared with the non-AKI group, patients who recovered from AKI had a 67% greater risk of experiencing coro-

nary events or of dying during the study period, independent of the effects of subsequent progression to chronic kidney disease and end-stage renal disease. The post-discharge risk of coronary events in patients with AKI was similar to that seen in patients with diabetes, suggesting that dialysis-requiring AKI with subsequent recovery should be considered a risk category for cardiovascular disease. “Follow-up care after discharge among patients experiencing dialysisrequiring AKI and subsequent recovery are necessary to enhance secondary prevention,” the authors noted.

Increased malignancy risk In a second study, Dr. Wu and colleagues found that dialysis-requiring AKI increases the long-term risk of malignancy. The study, published in the Journal of Cancer Research and Clinical Oncology (2014;130:613-621), included 625 patients with a mean age of 63.3 years who recovered

from dialysis-requiring AKI. These patients were compared with matched groups of 625 AKI patients who did not recover and 625 individuals without AKI. The mean follow-up was 3.7 years. In adjusted analyses, the recovery group had a significant 44% increased risk of new-onset malignancy compared with the non-AKI group. The non-recovery group had a significant 34% decreased risk. The third study was a follow-up analysis of data from the RENAL (Randomised Evaluation of Normal vs Augmented Levels of RRT) trial. Martin Gallagher, MBBS, MPH, Senior Director of the Renal and Metabolic Division at the George Institute for Global Health in Sydney, Australia, and colleagues prospectively examined the long-term outcomes and effects of RRT dosing in intensive care unit (ICU) patients with AKI, extending the follow-up of 1,464 RENAL participants (97%) from 90 days to four years after randomization. The subjects,

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all aged 18 years or older, had been randomized to receive 25 mL/kg/h (lower intensity) or 40 mL/kg/h (higher intensity) of continuous hemodiafiltration. At a median 43.9 months’ postrandomization, 468 of the 743 lowerintensity patients (63%) and 444 of the 721 higher-intensity patients (62%) had died, Dr. Gallagher and colleagues reported in PLoS Medicine (2014;11:e1001601). However, only 21 of the 411 survivors to day 90 (5.1%) in the lower-intensity group and only 23 of the 399 survivors to day 90 (5.8%) in the higher-intensity group required maintenance dialysis. Albuminuria was common in both groups, afflicting 40% of the lowerintensity survivors and 44% of the higher-intensity survivors, according to the investigators. Quality of life did not differ between the two treatment groups. “These findings support the view that survivors of AKI are at increased risk and that closer surveillance may be justified,” the authors concluded. ■

Update on mCRPC 2014: Urology Perspective

Judd W. Moul, MD, FACS Division Chief, Urology Director, Duke Prostate Center Professor of Surgery Duke University Medical Center Durham, N.C.

2014 State of the Art Review of Peyronie’s Disease

Stanton C. Honig, MD Clinical Professor of Urology University of Connecticut School of Medicine Yale University Department of Urology New Haven, Conn.

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12 Renal & Urology News

■ ACC 2014

JUNE 2014 www.renalandurologynews.com

American College of Cardiology 2014 Annual Meeting, Washington, D.C.

Gastric Bypass for Diabetes Superior More obese patients achieved glycemic control with bariatric surgery than intensive medical therapy

BARIATRIC surgery is a highly effective long-term treatment for type 2 diabetes in obese patients, according to study findings presented at the annual meeting of the American College of Cardiology in Washington, D.C. and published online in The New England Journal of Medicine (NEJM). The study, led by Philip R. Schauer, MD, director of the Cleveland Clinic’s Bariatric and Metabolic Institute, included 150 obese patients with uncontrolled type 2 diabetes. Subjects were participants in the STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently) trial. Patients underwent either intensive medical therapy alone or intensive medical therapy with surgery (gastric bypass or sleeve gastrectomy). The primary endpoint was a glycated hemoglobin level of 6.0% or less. At 36 months, a significantly higher proportion of patients in the gastric bypass group (38%) met the primary

CVD Linked to Troponin T in ESRD Pts HIGHER serum levels of cardiac troponin T (cTnT), which are associated with cardiovascular disease (CVD) in the general population, are associated with the presence of CVD in patients with end-stage renal disease, a study found. The study, which included 145 dialysis patients with a median cTNT of 0.04 μg/L, found that compared with patients with a cTnT level below 0.014 μg/L, those with a higher level had a significantly higher left ventricular mass index (132 vs. 108 g/m2) and lower left ventricular ejection fraction (52% vs. 56%). They also had a 68% increased odds of having coronary artery disease after adjusting for residual kidney function. n

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endpoint compared with the sleevegastrectomy group (24%) or medical therapy group (5%). In addition, use of insulin and other glucose-lowering medications was lower in both surgical groups than in the medical therapy group. Weight reduction compared with baseline was greater in the surgical groups compared to medical therapy, and qualityof-life was reportedly improved as well, according to the investigators. More than 90% of the patients who underwent bariatric surgery lost 25% of their body weight and controlled their diabetes without the use of insulin and multiple diabetes drugs, the study found. The 3-year data “confirm that bariatric surgery maintains its superiority over medical therapy for the treatment of type 2 diabetes in severely obese patients,” Dr. Schauer said in a press release issued by Cleveland Clinic. “Moreover, data show that bar-

iatric surgery is as effective in treating type 2 diabetes in patients with mild obesity.” The researchers observed no significant changes in patients at 36 months in blood pressure and LDL cholesterol levels among the three groups, although they did note a reduction in the number of required medications to treat hyperlipidemia and hypertension in both surgery groups.

More than 90% of bariatric surgery patients lost 25% of their body weight. Among patients with kidney disease, the researchers observed an improvement in albuminuria in the surgery groups despite a reduction in the use of renin-angiotensin system blockers, with

a significant reduction in the albuminto-creatinine ratio from baseline in both surgery groups compared with the therapy alone group. “Cumulatively, our data should be considered to be hypothesis-generating and suggest the need for further longterm studies examining the effects of bariatric surgery on renal function in diabetes,” the authors wrote in their NEJM report. The researchers acknowledged some important study limitations, including an inadequate sample size and duration to detect differences in the incidence of diabetes complications. “Despite these limitations,” they observed, “we concluded that bariatric surgery represents a potentially useful strategy for the management of type 2 diabetes, allowing many patients to reach and maintain therapeutic targets of glycemic control that otherwise could not be achievable with intensive medical therapy alone.” n

Statins May Improve Erectile Function STATINS are associated with significant improvement in erectile function in men with both high cholesterol and erectile dysfunction (ED), according to a new meta-analysis. The meta-analysis, by John B. Kostis, MD, and Jeanne M. Dobrzynski, of Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J., included 11 randomized, controlled trials in which the International Inventory of Erectile Function (IIEF) questionnaire was used to measure erectile function. The questionnaire

has 5 questions, each scored on 5-point scale and then totaled. Lower scores indicate worse erectile function. Overall, statin use was associated with a significant 3.4-point increase in IIEF score compared with controls. The increase in IIEF with statins was about one-third to one-half of that previously found with phosphodiesterase type 5 inhibitors and larger than the effect of life-style modification or testosterone. Presentation of the results coincided with the online publication of the find-

ings in The Journal of Sexual Medicine. The results of this meta-analysis are consistent with those of a systematic review and meta-analysis published online ahead of print in the Asian Journal of Andrology by Kun-Jie Wang, MD, of Sichuan University, Chengdu, China, and colleagues. Their study focused on five randomized, placebocontrolled trials looking at statins as a treatment for ED. Results showed that statin treatment was associated with a significant 3.27 point improvement in IIEF score. n

HF After Dialysis Start Ups Death Risk PATIENTS who develop heart failure (HF) after starting hemodialysis (HD) are at elevated risk of death compared with those who do not, data suggest. Abel E. Moreyra, MD, and colleagues at the Robert Wood Johnson Medical School in New Brunswick, N.J., studied 4,727 patients hospitalized for HF after

HD initiation and 7,258 on HD who did not experience HF. The investigators matched patients for duration of dialysis up to the time of HF admission. Patients had up to 18 years of follow-up. Compared with HD patients who did not develop HF, those who developed HF within 1 year of HD initia-

tion had a 22% increased risk of death, after adjusting for demographics, health insurance, and etiology of renal failure. Patients who experienced HF 1–2 years, 2–3 years, 3–4 years, 4–5 years, and more than 5 years after starting HD had a 42%, 34%, 34%, 35%, and 26% increased risk of death, respectively. n

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■ NKF 2014, Las Vegas

Renal & Urology News 13

National Kidney Foundation 2014 Spring Clinical Meetings, Las Vegas.

Parathyroidectomy Predictors ID’d Younger age and black race are associated with a greater likelihood of having the operation. YOUNGER AGE, black race, and longer dialysis vintage are among the factors that increase a hemodialysis (HD) patient’s likelihood of undergoing a parathyroidectomy for secondary hyperparathyroidism (SHPT), according to a new study. James B. Wetmore, MD, MS, of the Chronic Disease Research Group, Minneapolis Medical Research Foundation, compared 4,435 adult HD patients who underwent a parathyroidectomy and 315,312 who did not. HD patients aged 19–44 years were twice as likely to have a parathyroidectomy as those aged 45–64 years (reference). Black patients were 29% more likely than whites (reference) to have the surgery. Compared with patients who had a dialysis vintage of at least 1 year but less than 3 years (reference), those with a dialysis vintage of 5 years or more had a greater than 3-fold increased odds

Protocol May Improve ESA Use IMPLEMENTATION OF a pharmacy-managed prescribing protocol for erythropoiesis stimulating agents (ESAs) may promote more prudent use of the agents and decrease medication costs in the hospital setting, according to study findings presented at the National Kidney Foundation’s 2014 Spring Clinical Meetings in Las Vegas. Methodist University Hospital in Memphis, Tenn., developed a protocol requiring ESA prescribers to specify the FDA-approved indication and to verify the following: adequate iron indices (transferrin saturation above 20% and serum ferritin level above 100 ng/mL for non-dialysis chronic kidney disease patients, above 200 ng/mL for hemodialysis patients, and above 800 ng/mL for cancer patients); hospital length of stay of at least 3 days; and no contraindications, including uncontrolled hypertension with blood pressure above 185/110 mm Hg, a hemoglobin level above 12 g/dL or, in a cancer patient, a hemoglobin level of 10 g/dL

RUN0614_NKFnews.indd 13

of undergoing a parathyroidectomy. Patients with a dialysis vintage of at least 3 years but less than 5 years had an approximately 2-fold increased likelihood of having the operation. The study showed that the surgery was more likely to be performed on patients with a higher body mass index and atherosclerotic and other heart disease. Additionally, the researchers found a roughly 2-fold difference in the use of parathyroidectomy by end-stage renal disease network, even after adjusting for other factors. “Thus, some regions of the country seem much more likely to offer parathyroidectomy than others,” Dr. Wetmore told Renal & Urology News. “We cannot, at this time, say which approach is optimal for patients, but this fairly wide range in parathyroidectomy rates suggests there are differences in the nephrology community

or higher, active bleeding, or curative cancer. Pharmacists verified compliance with the prescribing criteria before dispensing an ESA. The study, led by Joanna Q. Hudson, PharmD, of the University of Tennessee Health Science Center in Memphis, compared epoetin alfa use before and after initiation of the protocol (February/March 2010 vs. February/ March 2011) among 43 inpatients. These patients included 35 (81%) on dialysis, 3 (7%) with chronic kidney disease not on dialysis, 2 (5%) with cancer, and 3 (7%) with other indications. The number of epoetin doses decreased from 983 pre-protocol to 289 post-protocol, a 71% decrease, Dr. Hudson’s group reported. The number of epoetin alfa units used dropped from 10.6 million to 3.2 million, a 69% decrease. The cost of treatment decreased from $95,413 to $29,379, a 69% decrease. Dr. Hudson and her colleagues found that prescribers generally complied with the ordering process, but the study revealed areas where additional education was warranted, such as the need for adequate iron indices prior to ESA initiation. Of the 70 instances of noncompliance, 38 (54%) involved a ferritin level below the defined threshold and 15 (21%) involved a transferrin saturation below 20%. n

James B. Wetmore, MD, MS

about its role in the care of secondary hyperparathyroidism.” With respect to study limitations, Dr. Wetmore’s group noted that they did

not have information on laboratory values and medication use, both of which would be expected to influence the likelihood of parathyroidectomy. Guidelines recommend parathyroidectomy for dialysis patients with severe SHPT who fail to respond to medical therapy. In a recently published study in Clinical Endocrinology (2014:80:508515), investigators in Taiwan found that parathyroidectomy is associated with improved cardiovascular outcomes in non-diabetic dialysis patients with severe SHPT. The study included 53 patients. During a mean follow-up of 72 months, 23 patients received only medical treatment for SHPT and 30 underwent parathyroidectomy in addition to medical treatment. The parathyroidectomy group had a significantly decreased incidence of major cardiovascular events. n

Phosphate Binder May Eliminate IV Iron Need FERRIC CITRATE, an oral phosphate

absorbed from ferric citrate increased

binder, may eliminate the need for intra-

iron stores and sustained hemoglobin

venous (IV) iron in dialysis patients.

levels. At 52 weeks, the IV-iron and

Mohammed Sika, MD, of Vanderbilt

no-IV-iron groups showed no significant

University in Nashville, Tenn., and col-

differences in ferritin levels (911 and

leagues analyzed data from 281 dialysis

863 ng/mL, respectively), iron stores

patients who took oral ferric citrate to

(85 and 97 μg/dL), transferrin satura-

control phosphorus. These patients had

tion (38% and 43%), and hemoglobin

participated in a 52-week randomized trial

levels (11.3 and 11.7 g/dL).

in which they were compared with patients

In a separate study presented at the

(active controls) who took either calcium

meeting, Roger Rodby, MD, of Rush

acetate and/or sevelamer carbonate. The

University in Chicago, and colleagues

trial showed that ferric citrate effectively

found that patients with end-stage

bound phosphate, increased iron stores,

renal disease (ESRD) who used ferric

and decreased the use of IV iron and eryth-

citrate for phosphate control had fewer

ropoiesis stimulating agents. In the study, IV

hospitalizations and reduced hospitaliza-

iron use was allowed if serum ferritin levels

tion costs than those who used calcium

were below 1,000 ng/mL and transferrin

acetate or sevelamer carbonate. The

saturation (TSAT) was below 30%. In the

study was a secondary analysis of a

last 6 months of the study, 58% of the ferric

phase 3 trial that included 441 patients

citrate recipients and 24% of the active

with ESRD. Results showed that 34.6%

controls received no IV iron.

of patients taking ferric citrate were

Of the 281 patients, 207 received

hospitalized at least once during the trial

IV iron and 74 did not over 52 weeks.

versus 45.6% of patients taking calcium

In the 74 no-IV-iron patients, iron

acetate or sevelamer carbonate. n

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18 Renal & Urology News

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n FEATURE

The Challenge of Dialysis at the End of Life Dialysis may not benefit all patients in the final phase of life, clinicians and ethicists say BY TAMMY WORTH

Offer a choice The trajectories of end-stage renal disease (ESRD) and cancer are similar. With certain other conditions, patients experience a wave of alternating exacerbations and stabilization. With ESRD and cancer, however, terminal patients follow a horizontal line and then drop off a cliff.

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The conversation

irst used in the 1940s, dialysis was intended to be a lifesaving treatment. Focused on young patients with acute renal failure, it helped them until their kidneys were strong enough to function without the therapy. But times have changed. The average patient undergoing treatment is aged 65 years. Dialysis is now used as a maintenance treatment as frequently as for acute episodes, but a shift has occurred in the manner and frequency with which it is offered to different patient populations. “Many of these patients don’t realize they are in the final phase of life because no one has talked forthrightly with them,” said Mildred Z. Solomon, EdD, president of The Hastings Center, an independent, New York-based bioethics research institute. “Many people are being put on dialysis as a rite of passage before they die.” There is a simmering movement by physicians and ethicists who are concerned with the role dialysis has played near the end of life. It is time, they say, to begin having difficult discussions, including advising patients about the likely trajectory of their illness and their prognosis, as well as discussing whether dialysis is something they want to start and letting them know it can be stopped.

Many dialysis patients do not realize they are in the final phase of life.

One difference between cancer and ESRD, though, is the numbers of patients receiving palliative care. Nationally, 37% of patients admitted to hospice for palliative care services in 2011 had a cancer diagnosis. That same year, only 2.7% were admitted for kidney failure, according to the report, Hospice Care in America, by the National Hospice and Palliative Care Organization. “We haven’t had a grown-up conversation that this is a stage of life patients are in and death may not be that far away,” Dr. Solomon said. “People want to have that sort of conversation and are expecting it from their doctors, but physicians aren’t initiating it.” Studies have borne this out. A recent review published in the Journal of General Internal Medicine (2013;28:1511-1516) found that many patients with ESRD reported they did

not know their prognosis and did not recall being offered alternatives to dialysis. Patients reported feeling rushed and pressured into treatment. A study published in the Clinical Journal of the American Society of Nephrology (2010;5:195-204) found that fewer than 10% of the 584 patients with stage 4 or 5 chronic kidney disease presenting for dialysis, transplantation, or predialysis clinics had a discussion about end-of-life care issues with their nephrologist. According to a report in Medical Anthropology Quarterly (2005;24:297-324), researchers who spoke with patients at two Californian dialysis clinics found that only 4 said they initiated dialysis treatments by choice. “Research shows that people don’t make a decision to go on or get off dialysis,” Dr. Solomon said. “It’s more like they are on a conveyer belt.”

Nephrologists have to learn to have “the conversation”—a discussion about how patients want to end their lives— said Lewis Cohen, MD, professor of psychiatry at Tufts School of Medicine in Boston. “Everything we know about patients suggests that most of them want to have the conversation,” Dr. Cohen said. “And patients want doctors to be the ones to broach the subject.” Nephrologists need to be able to tell patients that they are, unfortunately, near the end of their lives, he said. The good news is that they do not have to do it alone. Nephrologists can pull from their team, social workers, hospice, and palliative care specialists to help initiate and continue the discussion. Dr. Cohen recommends talking about the preferences patients have for end of life, what kind of medical care they want, what their goals are, and who should speak for them if they are unable to communicate. The first thing nephrologists need to ascertain is if the patient is willing to hear about their options. The best way to do that is to ask. Dr. Cohen recommends telling them they are facing a life-limiting situation, and then asking if they feel comfortable talking about it or having family present during the discussion. Next, work from what the person knows about their situation. More often than not, Dr. Cohen said, patients know they are on the downward slope and are facing death. They often feel relief to get the issue out in the open so it can be dealt with. Three main points should be included in this conversation. One is to provide as much information to patients as possible, including the downsides of treat-

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Renal & Urology News 19

What the Experts Say Mildred Z. Solomon, EdD The Hastings Center, Garrison, NY

Lewis Cohen, MD Tufts School of Medicine, Boston, Mass.

Michael J. Germain, MD, Baystate Medical Center, Springfield, Mass.

“Many of these patients don’t realize they are in the final phase of life because no one has talked forthrightly with them.”

“Everything we know about patients suggests that most of them want to have the conversation.”

“Often [patients] want to know what you think and that is something that is often missing … we give them choices, but don’t give recommendations.”

ment. The second is a patient-specific estimate of prognosis. The third is the patient’s specific goals for treatment. For instance, a patient with ESRD and cancer may want to forgo dialysis because it will prolong pain and suffering. Another patient with the same conditions may have a granddaughter getting married in 6 months and they want to see the wedding. “You need to explore with them and see what their thoughts are,” said Michael J. Germain, MD, a transplant nephrologist at Baystate Medical Center in Springfield, Mass. “Often they want to know what you think and that is something that is often missing … we give them choices, but don’t give recommendations.” Patients will be the expert in their values and goals and the nephrologist is the expert in the prognosis and treatment options. Both of these things should be considered as part of the process. Patients should hear about their options, including available dialysis treatments and transplantation; not initiating dialysis but continue to receive medical management; a time-limited dialysis trial; and stopping dialysis and receiving end-of-life care. Alvin H. Moss, MD, a nephrologist and professor of medicine at West Virginia University School of Medicine in Morgantown, stresses an “ask, tell, ask” approach during the conversation. Ask what the patient understands about the condition, impart missing information, and ask again what the patient has understood about the discussion and any questions that remain.

RUN0614_Feature_EndofLife.indd 19

Dealing with family One of Dr. Moss’ patients had ESRD, circulatory problems, was a heavy smoker, and had lung disease. When she found out she needed dialysis, she did not want to begin treatment. Her daughters begged her to and she relented. For the first 2 months, she did well, but then quickly went downhill. She came to Dr. Moss and told him she wanted to quit. To help her, he had a series of meetings with the patient and her daughters so they could understand the situation. After a couple of months, she ended treatment and her daughters understood her decision. Kelli Collins, the national kidney patient services director for the National Kidney Foundation, said many of the calls they receive requesting information on dialysis options are from patients’ family members. “We get quite a few calls from families who are having a hard time understanding why their loved one doesn’t want to start or wants to stop dialysis,” she said. “Some people want to know if it’s possible to make them stay on it.” Family members often think the person is giving up and they are resistant to lose him or her, Collins said. Her organization helps patients talk with family members and make educated decisions. “You have better outcomes when you have the support of the family,” she said. “The family might not be happy with it, but they can come around and let the person die with dignity and on their own terms.”

Alvin H. Moss, MD West Virginia University School of Medicine, Morgantown “Before ending treatment, doctors have to make sure there isn’t something they can do to help.”

It was in the late 1990s that nephrology leadership decided that one of the most pressing issues in the specialty was the appropriate initiation and discontinuation of dialysis. Dr. Moss was the editor of the first edition of the guideline addressing this issue, Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis, published in 2000. In 2010, the guide was updated because research showed that older patients with comorbidities are likely to do poorly on dialysis and that dialysis does not necessarily extend their lives. A wealth of research bears this out. A study published in the New England Journal of Medicine (2009;261:15391547) looked at 3,702 patients in nursing homes on dialysis. One year after starting dialysis, 58% had died and only 13% had maintained the same functional status during the period. Researchers from Johns Hopkins Hospital in Baltimore followed a group of 146 elderly patients through hemo-

Daniel P. Sulmasy, MD, PhD University of Chicago, Chicago “It is always hard for physicians, who are trained to help, to sit back and not do something.”

dialysis. Half of the patients aged 65 years and older were considered frail and 35% of the patients younger than 65 years were frail. The 3-year mortality rate for frail patients was 40% versus 16% for non-frail patients. The frail patients also had much higher hospitalization rates. According to the guideline Dr. Moss edited, the following patients are those for whom dialysis should be withheld or withdrawn: patients who refuse treatment; patients without full decision-making capacity who indicated in written or oral form or through a guardian that they do not want dialysis; and patients without awareness of their selves and environment. Other categories for whom strong consideration should be given to not starting or stopping dialysis include patients who are unable to cooperate (for instance, one with dementia who pulls out the dialysis needles); those with terminal illnesses other than continued on page 24

When to withhold According to the guideline Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis, 2nd edition, published by the Renal Physicians Association, dialysis should be withheld or withdrawn from patients: • who refuse treatment • without full decision-making capacity who indicated in writing or oral form or through a guardian they do not want dialysis • who have irreversible, profound neurologic impairment such that they lack awareness of self and environment, signs of thought, sensation, and purposeful behavior.

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24 Renal & Urology News

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Challenge of dialysis continued from page 19

ESRD; and patients older than 75 years with stage 5 chronic kidney disease who are also significantly impaired from multiple comorbid conditions and/or severe chronic malnutrition. Dr. Moss said a nephrologist can ask the “surprise” question for much of this population—“Would I be surprised if

rounds, the patient told him that he remembered their conversation, and it was time to stop. The man’s wife was surprised, but respected his wishes. The patient was moved to a bed in the front room of his house and hospice was called in. Dr. Germain visited him one day and the men were talking about World War II. Dr. Germain held his hand while he rested and he felt it go limp.

The decision to stop dialysis needs to be normalized by providing patients with ‘permission’ to end treatment. this patient died in the next year?” If not, patients should be informed that dialysis may not increase their survival advantage and the burdens may only serve to reduce quality of life.

Doing nothing may be best One patient Dr. Germain remembers well is a man in his 80s who fit criteria for poor dialysis outcomes. Dr. Germain talked with him and the patient decided to do a trial run of dialysis. He underwent treatment for 3 years without any major events. One day, when Dr. Germain was doing

“I turned to his wife and daughter and told them he was gone,” he said. “It was a very touching moment.” Dr. Solomon said the decision to stop dialysis needs to be normalized by providing patients “permission” to end treatment. Dialysis should be framed as a trial instead of never-ending maintenance. “Things start off on a very positive note about all of the good that this is going to do for you,” Dr. Cohen said. “It is difficult to slip in the beginning that they don’t have to do this and they aren’t going to get eternal life as a result of it.” Daniel P. Sulmasy, MD, PhD, professor of medicine and ethics at the

Carotid Plaque May Predict Coronary Artery Stenosis MAXIMAL carotid artery plaque height (MCAH) may predict coronary artery stenosis in patients with and without chronic kidney disease (CKD), researchers reported at the Canadian Society of Nephrology annual meeting in Vancouver, B.C. The researchers, led by Jocelyn Garland, MD, of Queen’s University in Kingston, Ont., noted that coronary angiography, which is used to diagnose occlusive coronary disease, can be nephrotoxic. MCAH quantification is an emerging surrogate for coronary intimal atherosclerosis and has been correlated with coronary events in the general population, they stated in a poster presentation. Dr. Garland’s group studied 266 outpatients referred for coronary angiography and had data available for estimating kidney function. MCAH and carotid intimal media thickness (CIMT) were measured using carotid

RUN0614_Feature_EndofLife.indd 24

ultrasound. Coronary artery disease was defined as at least 1 coronary artery with greater than 50% stenosis demonstrated by angiography. Patients who had coronary stenoses had significantly increased MCAH compared with patients who did not (2.64 mm vs. 1.81 mm). CIMT was not significantly different between the groups. In multivariable analysis, increased MCAH was associated with a 3-fold increased likelihood of coronary artery stenosis greater than 50%. In patients with CKD (estimated glomerular filtration rate below 60 mL/min/1.73 m2), it was associated with a significant 4.5 times increased likelihood. “Carotid ultrasound with plaque quantification may aid the selection of patients who would benefit from coronary angiography and these results appear to be generalizable to the CKD population,” the authors concluded. n

University of Chicago, said this concept is merely relearning the teachings of Hippocrates who counseled that when a patient is overridden with disease, it may be time to understand that medicine can be powerless. “When I was chief resident, my chief of medicine used to say, ‘Don’t just do something, Dan, stand there,’” he said. “It is always hard for physicians, who are trained to help, to sit back and not do something.” Tools are available to help nephrologists gauge which patients might not do as well on dialysis. Touchcalc is a tool available online (http://touchcalc. com/calculators/sq) and as an app. The calculator asks a set of questions and prognosticates patient mortality on dialysis after 6 months, 1 year, and 18 months. Dr. Moss said the calculator can predict with about 85% accuracy how the patient will fare on treatment.

Not the death of dialysis Dr. Moss had a patient on dialysis who came to him saying she was too sick, had no quality of life and had suffered enough. She was ready to end treatment. She had heart and lung disease, lived alone, and rarely saw her only son. Dr. Moss sympathized with her, and told her he understood her situation. He was surprised when she became furious with him, asking why he did not

try to talk her out of stopping treatment. She was just reaching out for help. Dr. Moss called her son and told him what had happened and that she needed time with him. After that, the patient smiled more and was content. She spent time with her son and lived another 9 months before having a major stroke. “Before ending treatment, doctors have to make sure there isn’t something they can do to help,” he said. “She just wanted a better relationship with her son.” Dr. Moss contends that taking more patients off of dialysis and recommending fewer initiate it will not be the death of the treatment. “For most people, if you say, ‘This may or may not extend your life,’ they are going to hear the ‘may,’” he said. “I still think the vast majority of patients will start, but they will have a better understanding of the issues.” Dr, Moss said it will give patients the permission they may need to end dialysis if they decide their quality of life is not what they expected. Some patients may choose home dialysis and still others may remain on treatment if conversations with physicians make them more aware of ways to alleviate side effects. “It will be good for dialysis patients overall,” Dr. Moss said. “Dialysis has a bright future as it becomes more patient-centered.” n

PCa Upgrading, Upstaging Does Not Differ by Race RESEARCHERS have found no sig-

respectively, and these rates did not

nificant racial variation in the rates

differ significantly by racial group, the

of prostate cancer (PCa) upstaging

investigators reported online ahead of

and upgrading at the time of radical

print in European Urology. The upgrad-

prostatectomy among men with low-risk

ing rates were 33%, 34%, and 33% for

disease, according to a recent report.

Caucasians, African Americans, and

African Americans, however, are signifi-

other races, respectively. The upstag-

cantly more likely than other races to

ing rates were 13%, 13%, and 16%,

have positive surgical margins (PSM).

respectively. The PSM rate was 31%

A team at the University of California

for African Americans versus 21% and

San Francisco led by Matthew R.

20% for Caucasians and other races. In

Cooperberg, MD, studied 4,231 patients

multivariate analysis, African Americans

with low-risk PCa based on initial biopsy

were 63% and 41% more likely than

findings. All had undergone with RP

Caucasians and other races to have PSM.

within 1 year of diagnosis. The group

Additionally, African-American

included 3,771 Caucasians, 273 African

patients were significantly younger than

Americans, and 187 patients of other

Caucasians and other races (mean 58.7

races.

years vs. 60.0 and 60.5 years) and more

The overall rate of pathologic upgrading and upstaging was 34% and 13%,

likely to have comorbidities such as hypertension and diabetes. n

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Renal & Urology News 25

Immunosuppression-Free Transplants Immunologic mismatch may no longer be a barrier between living kidney donors and recipients, thanks to work being done by Suzanne T. Ildstad, MD, director of the Institute for Cellular Therapeutics at the University of Louisville in Louisville, KY, and colleagues. The group has overseen complete immunosuppression withdrawal at the 1-year mark in a handful of kidney-transplant recipients after employing a pretransplant strategy for building donor-specific tolerance (Transplantation 2013;95[1]:169-176). (Dr. Ildstad is also the founding scientist of biotechnology company Regenerex, LLC, which is involved in this research.) Dr. Ildstad described the process to Renal & Urology News. BY DELICIA HONEN YARD How is donor-specific tolerance achieved?

Dr. Ildstad: Normally, transplanted organs are seen as “foreign” by the host immune system, and high levels of immunosuppression are needed to prevent rejection of the transplant. Tolerance is when the host immune system no longer recognizes the transplant as “foreign” but instead sees it as “self” and no longer attempts to reject it. In our approach, peripheral blood mononuclear cells are mobilized by granulocyte colony-stimulating factor [GCSF; a glycoprotein that stimulates bone marrow to produce and release blood cells, including stem cells]. That is, the recipient undergoes treatment with growth factors that cause the stem cells to be released into the blood, where they can be collected in a manner similar to that for blood donation. Once collected from the donor, the GCSFmobilized blood cells are processed to

On The Web RUN0514_QA.indd 25

of immunosuppression (hypertension, diabetes, infections). Moreover, the same immunosuppressive agents that are critical to preventing rejection directly damage the kidneys. As a result, the induction of tolerance with elimination of the need for these agents has remained the Holy Grail of organ transplantation.

Dr. Ildstad: We are currently experiencing tolerance and successful elimination of immunosuppression for kidney transplants in the clinic with approximately 86% success.

Why does the review article highlight the concept of chimerism?

Dr. Ildstad: Hopefully, we can avoid immunosuppression completely after 1 year post-transplant and avoid all of the associated toxicities.

Dr. Ildstad: Chimerism refers to the coexistence of more than one genetically disparate component in one recipient. The most common chimeras are those mythological figures on temples and cathedrals worldwide. The chimerism we use is bone marrow chimerism (the donor hematopoietic stem cell coexists peacefully in the recipient). How soon might we see a drastic reduction in the need for posttransplant immunosuppression?

Dr. Ildstad: Currently, renal transplant recipients must take approximately 25 pills per day to prevent graft rejection and to control the complications associated with the use

Are there any concerns regarding or disadvantages to the achievement of donor-specific tolerance and the elimination of post-transplant immunosuppressive therapy?

Dr. Ildstad: No. What changes would be needed in the renal-transplant process for donorspecific tolerance to be achieved?

Dr. Ildstad: The subject would undergo conditioning to make space for the donor bone marrow. This has been managed to date as an outpatient procedure. The donor is treated with GCSF to expand facilitating cells and stem cells and cause their egress into the peripheral blood, and the mobilized hematopoietic product is collected by apheresis.

remove “bad” GVHD [graft-versus-host disease]-causing cells but to retain stem cells and facilitating cells. The product is frozen and shipped back to the site for transplantation. The recipient is then “conditioned” [with low-intensity chemotherapy and radiotherapy] to accept the facilitating cell-based hematopoietic stem cell product to promote tolerance one day after the living-donor kidney transplant is performed. In your review article for Clinical & Cellular Immunology (2012;S9; available at http://www.omicsonline. org/chimerism-and-tolerance-in-solidorgan-transplantation-2155-9899. S9-003.pdf), you and your coauthors stated that donor-specific tolerance has been referred to as the Holy Grail of organ transplantation. Why is this?

Today, kidney-transplant recipients can expect to be on lifelong immunosuppressive therapy. How do you see this scenario changing?

How prominent a role does kidney transplantation have in donor-specific tolerance research?

Tolerance has been achieved in approximately 86% of cases. —Suzanne T. Ildstad, MD

Dr. Ildstad: The advantage of kidney transplantation for a phase I study is that living-donor kidney transplants are electively scheduled and do not rely upon the unpredictable availability of deceased donors. What is the next step needed to advance the goal toward donor-specific tolerance?

Dr. Ildstad: More advanced clinical trials are being planned to confirm our early results. Ultimately, pivotal clinical trials will be performed and eventually submitted to FDA and other health authorities. ■

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

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