Renal & Urology News April 2014 Issue

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Donor Biopsy Role Questioned

BY DELICIA HONEN YARD DECEASED-donor kidneys that could be acceptable for transplantation may be needlessly discarded based on routine procurement biopsies, according to the findings of two studies.

In one investigation, Bertram L. Kasiske, MD, of the Scientific Registry of Transplant Recipients (SRTR) and the Hennepin County Medical Center in Minneapolis, and collaborators examined biopsy reports for 83 kidneys that were discarded in 2010 due to biopsy findings (cases) and compared those with biopsy reports from 83 contralateral transplanted kidneys from

IN THIS ISSUE 8 Contrast-induced AKI raises the risk of poor outcomes

9

Adverse safety events common in CKD patients

9 Hip fracture incidence following

kidney transplantation declining

10

Intravenous to oral vitamin D switch may be beneficial

12 Controversies in BP manage-

ment in hemodialysis patients Expert Q&A Jeremy P. Grummet, MBBS, discusses the merits of transperineal biopsy.

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the same donor (contralateral controls) and 83 deceased donors randomly matched to cases by donor risk profile (randomly matched controls).

Among the biopsies, 69% were wedge biopsies and 94% used frozen tissue. Dr. Kasiske’s group found the biopsy reports to be of low quality, with the reports often not indicating amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis.

A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%). Dr. Kasiske and his colleagues reported a poor correlation between

Lipid Profiles Urged for All CKD Patients

BY JODY A. CHARNOW FULL LIPID profiles are recommended for all patients with chronic kidney disease (CKD) at first presentation, according to a new guideline developed by a work group of the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“No direct evidence indicates that measuring lipid status will lead to better clinical outcomes,” the guideline states. “However, measuring lipid status is noninvasive, inexpensive, and might improve the health of people with secondary dyslipidemia.” In the judgment of the work group, “these continued on page 7

© CMSP / B. SLAVIN

Transplantable kidneys may be discarded

PROCUREMENT KIDNEY BIOPSY reports are often of low quality, data suggest.

first and second procurement biopsies, with only 25% of the variability in glomerulosclerosis explained by biopsies being from the same kidney.

The team also found that the percent-

ages of glomerulosclerosis overlapped substantially among the discarded kidneys, the contralateral controls, and the randomly matched controls, continued on page 7

CKD Cause Predicts ESRD Risk

BY JODY A. CHARNOW PATIENTS with cystic kidney disease are significantly more likely to progress to end-stage renal disease (ESRD) and less likely to die than patients with other causes of chronic kidney disease (CKD), a study found.

The study included 6,245 nondialysis CKD patients in the Study of Heart and Renal Protection (SHARP).

Investigators led by Martin J. Landray, PhD, FRCP, of the University of Oxford in the U.K. categorized patients into four groups according to the baseline cause of kidney disease: cystic kidney disease, diabetic nephropathy, glomerulonephritis,

and other recorded diagnoses, such as hypertension, renovascular disease, and pyelonephritis.

During an average 4.7 years of followup, 2,080 patients progressed to ESRD: 454 with cystic kidney disease (23% per year); 378 with glomerulonephritis (10% per year); 309 with diabetic nephropathy (12% per year); and 939 with other recorded diagnoses (8% per year). Compared with patients who had cystic kidney disease, those with glomerulonephritis, diabetic nephropathy, and other recorded diagnoses had a 72%, 60%, and 71% decreased risk of ESRD after adjusting for confoundcontinued on page 7

OMEGA-3 FATTY ACIDS AND PROSTATE CANCER

What should patients be advised with regard to dietary and supplement intake?

SEE STORY PAGE 13

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Robotics Improve PCa Control

Decreased risk of positive surgical margins found

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Robotic Surgery Cuts Need for Additional Treatment Patients undergoing robot-assisted radical prostatectomy (RARP) were less likely to require additional treatment with androgen deprivation therapy or radiotherapy, according to a study. The relative risk reductions with RARP versus open radical prostatectomy are shown here.

35 30 25

BY JODY A. CHARNOW ROBOT-assisted prostate surgery is associated with improved early cancer control, according to a new study.

In a retrospective population-based study of patients with prostate cancer (PCa), Jim C. Hu, MD, MPH, of the University of California Los Angeles (UCLA), and Maxine Sun, PhD, of the University of Montreal Health Center, used Surveillance Epidemiology and End Results (SEER)-Medicare linked data to study 5,556 men who underwent robot-assisted radical prostatectomy (RARP) and 7,878 who underwent open radical prostatectomy (ORP). In

IN THIS ISSUE 8 Percutaneous nephrolithotomy may raise diabetes risk

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Greater use of transperineal prostate biopsy recommended

10 Prostate cancer is linked to metabolic syndrome

18 Blood transfusions may increase RCC patient mortality risk

21 Dancing may help ease urinary incontinence

Expert Q&A Jeremy P. Grummet, MBBS, discusses the merits of transperineal biopsy.

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propensity-adjusted analyses, RARP was associated with a significant 34% and 30% decreased likelihood of positive surgical margins (PSMs) compared with ORP among men with intermediate- and high-risk cancer, respectively.

Additionally, results showed that RARP was associated with a 25%, 27%, and 33% decreased likelihood of requiring additional cancer treatment (androgen deprivation and radiation) within 6, 12, and 24 months, respectively.

Previous research has demonstrated that PSMs are independently associated with higher PCa-specific mortal-

PSA Can Predict Bone Scan Results PSA levels and kinetics may be used as selection criteria for ordering bone scans for prostate cancer (PCa) patients who experience biochemical recurrence following radical prostatectomy, whether or not they have received androgen-deprivation therapy, according to researchers.

Daniel M. Moreira, MD, of the Arthur Smith Institute for Urology at North Shore Long Island Jewish Health System in New Hyde Park, N.Y., and colleagues analyzed 380 bone scans of 301 hormone-naïve PCa patients and 214 bone scans of 137 PCa patients after receiving androcontinued on page 7

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25%

27%

33%

6

12

24

10 5 0

Months after surgery Source: Hu JC et al. Comparative effectiveness of robot-assisted versus open radical prostatectomy cancer control Eur Urol (published online ahead of print).

ity and with an increased risk of biochemical recurrence, local recurrence, and use of salvage therapy.

The researchers, who published findings online ahead of print in European

Urology, concluded that their findings “are particularly policy relevant, as there is greater consensus toward the appropriateness of active surveillance continued on page 7

Donor Biopsy Role Questioned DECEASED-donor kidneys that could be acceptable for transplantation may be needlessly discarded based on routine procurement biopsies, according to the findings of two studies.

In one investigation, Bertram L. Kasiske, MD, of the Scientific Registry of Transplant Recipients (SRTR) and the Hennepin County Medical Center in Minneapolis, and collaborators examined biopsy reports for 83 kidneys that were discarded in 2010 due to biopsy findings (cases) and compared those with biopsy reports from 83 contralateral transplanted kidneys from the same donor (contralateral controls) and 83 deceased donors randomly

matched to cases by donor risk profile (randomly matched controls).

Among the biopsies, 69% were wedge biopsies and 94% used frozen tissue. Dr. Kasiske’s group found the biopsy reports to be of low quality, with the reports often not indicating amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis.

A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%). Dr. Kasiske and his colleagues reported a poor correlation between first and second procurement biopsies, with only 25% of the variability continued on page 7

OMEGA-3 FATTY ACIDS AND PROSTATE CANCER

What should patients be advised with regard to dietary and supplement intake?

SEE STORY PAGE 13

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Renal & Urology News 3

FROM THE EDITOR EDITORIAL ADVISORY BOARD

Nutrition Advice Challenged—Again

H

uman beings are unique in the animal kingdom when it comes to nutrition.

Besides being the only creatures that cook food, we are the only ones that make conscious decisions about what to eat. The world’s animals—herbivores, carnivores, and omnivores— just seem to know instinctively what plants or prey to devour. Female monarch butterflies cannot be taught to lay their eggs in the milkweed plants upon which the larvae feed and ingest toxic cardiac glycosides as a defense against predators. But they do it. The fantastic diversity and success of animal life affirm that nature has found ways to ensure proper nutrition.

Human beings also know what plants and animals to eat—and avoid—perhaps through observation and trial and error over millennia. Eventually, we came to realize that too much or too little of some types of foods results in medical problems, and that a “balanced diet” is necessary for good health.

A balanced diet consists of the “right” proportions of this or that food item. Generally, this has come to mean, among other things, a diet emphasizing fruits, vegetables, and whole grains; increased intake of fish; and decreased consumption of red meat and foods high in saturated fat. Medical societies recommend higher or lower intake of various foods based largely on scientific evidence showing what appears to be beneficial, harmful, or not helpful. The effort is commendable, but everybody needs to keep in mind that, any day, a new study can challenge the notion of what may or may not be good for you.

For example, the American Heart Association recommends eating fish at least twice a week, and cites recent research demonstrating that eating oily fish containing omega-3 fatty acids, such as salmon and herring, may help reduce the risk of death from coronary artery disease. A study published recently in Journal of the National Cancer Institute, however, confirmed a previously reported association between high blood levels of long-chain omega-3 fatty acids and increased prostate cancer risk. [See our feature article on page 13.]

In addition, a meta-analysis published recently in Annals of Internal Medicine (2014;160:398-406) found no significant evidence to support eating a diet high in polyunsaturated fatty acids and low in saturated fats to lower the risk of coronary disease. “Current evidence does not clearly support guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats,” the study authors concluded.

What constitutes healthy eating, as ascertained in studies, is always in flux, but that should not stop people from aspiring to good nutrition. Moderation in the amounts of food consumed would be a good beginning.

Jody A. Charnow Editor

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Medical Director, Urology

Medical Director, Nephrology

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

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

Nephrologists

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

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

Renal & Urology News Staff

Editor

Senior editor

Web editor

Editorial coordinator

Art director

Group art director, Haymarket Medical VP, audience development and operations

Production manager

Production director

Product manager, digital products

Circulation manager

National accounts manager

Editorial director

Publisher VP medical magazines and digital products

CEO, Haymarket Media Inc.

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

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

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Contents

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Nephrology

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ONLINE

this month at renalandurologynews.com Expert Q&A Lance Dworkin, MD, who chaired the CORAL study, discusses the study’s finding that renal stenting did not improve outcomes in patients with renal artery stenosis.

9

9

10

Clinical Quiz Take our latest quiz at renalandurologynews.com /clinical-quiz/. Answer correctly and you will be entered to win a $50 American Express gift card.

Congratulations to our February winner: David Paul, MD

Drug Showcase Read up on recently approved pharmaceuticals. Our latest include: • Farxiga (dapagliflozin), for type 2 diabetes • Fortesta (testosterone gel), for hypogonadism • Invokana (canagliflozin), for type 2 diabetes

News Coverage Visit our website for timely reports from upcoming meetings.

N U M B E R

High HDL May Raise HD Patient Death Risk The inverse association is opposite of what is observed in the general population.

European Association of Urology 2014 Congress Stockholm, Sweden April 11-15

Adverse Safety Events Common in CKD Impaired renal function, altered drug clearance, and comorbid conditions are contributing factors

National Kidney Foundation 2014 Spring Clinical Meetings Las Vegas April 22-26

Post-Tx Hip Fracture Rate Declining Patients who received a kidney transplant in 2010 had a 44% decreased risk of hip fracture compared with those who received a transplant in 1997.

IV to Oral Vitamin D Switch Beneficial Oral activated vitamin D may offer similar control of secondary hyperparathyroidism in patients on hemodialysis with lower doses of the drug required.

6

D'Amico PCa Criteria Questioned In a study, D’Amico criteria incorrectly classified 37.5% of patients as having low-risk disease.

9

Use Transperineal Biopsy More, Researchers Say The transperineal approach is associated with a lower risk of sepsis than the more commonly used TRUS-guided biopsy, data show.

10

PCa Linked to Metabolic Syndrome Metabolic syndrome is independently associated with a 54% increased likelihood of a prostate cancer diagnosis.

Sildenafil Benefits Men After PCa Radiotherapy Sildenafil taken daily during and after radiotherapy for localized prostate cancer may improve post-treatment erectile function compared with placebo.

Taking a supplement to make up for deficiencies

in one of the behaviors that can actually help you doesn’t work.

See our story on page 13

RUN0414_TOC_Nephrology.indd 4

I S S U E

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CALENDAR

Urology

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1 3 ,

American Urological Association Annual Meeting Orlando, Fla. May 16-22 American Society of Hypertension Annual Meeting New York May 17-20 American Society of Clinical Oncology Annual Meeting Chicago May 30-June 3 European Renal Association-European Dialysis and Transplant Association Annual Meeting Amsterdam, The Netherlands May 30-June 3

17

Departments 3

From the Editor Nutrition advice challenged again

8

News in Brief PCNL for stones may increase diabetes risk

17

Expert Q&A Transperineal prostate biopsy should be used more

19

Practice Management How to cut down on no-shows

3/25/14 10:01 AM

4 Renal & Urology News

APRIL 2014 www.renalandurologynews.com

Contents

A P R I L

2 0 1 4

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VO L U M E

Urology

ONLINE

this month at renalandurologynews.com Expert Q&A Lance Dworkin, MD, who chaired the CORAL study, discusses the study’s finding that renal stenting did not improve outcomes in patients with renal artery stenosis.

Take our latest quiz at renalandurologynews.com /clinical-quiz/. Answer correctly and you will be entered to win a $50 American Express gift card.

Congratulations to our February winner: David Paul, MD

D'Amico PCa Criteria Questioned In a study, D’Amico criteria incorrectly classified 37.5% of patients as having low-risk disease.

9

Use Transperineal Biopsy More, Researchers Say The transperineal approach is associated with a lower risk of sepsis than the more commonly used TRUS-guided biopsy, data show.

10

PCa Linked to Metabolic Syndrome Metabolic syndrome is independently associated with a 54% increased likelihood of a prostate cancer diagnosis.

11

Sildenafil Benefits Men After PCa Radiotherapy Sildenafil taken daily during and after radiotherapy for localized prostate cancer may improve post-treatment erectile function compared with placebo.

Drug Showcase Read up on recently approved pharmaceuticals. Our latest include: • Farxiga (dapagliflozin), for type 2 diabetes • Fortesta (testosterone gel), for hypogonadism • Invokana (canagliflozin), for type 2 diabetes

News Coverage Visit our website for timely reports from upcoming meetings.

Nephrology

7

Adverse Safety Events Common in CKD Impaired renal function, altered drug clearance, and comorbid conditions are contributing factors

9

Post-Tx Hip Fracture Rate Declining Patients who received a kidney transplant in 2010 had a 44% decreased risk of hip fracture compared with those who received a transplant in 1997.

IV to Oral Vitamin D Switch Beneficial Oral activated vitamin D may offer similar control of secondary hyperparathyroidism in patients on hemodialysis with lower doses of the drug required.

Taking a supplement to make up for deficiencies

in one of the behaviors that can actually help you doesn’t work.

See our story on page 13

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N U M B E R

4

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

High HDL May Raise HD Patient Death Risk The inverse association is opposite of what is observed in the general population.

9

10

I S S U E

CALENDAR

6

Clinical Quiz

1 3 ,

17

Departments 3

From the Editor Nutrition advice challenged again

8

News in Brief PCNL for stones may increase diabetes risk

17

Expert Q&A Transperineal prostate biopsy should be used more

19

Practice Management How to cut down on no-shows

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6 Renal & Urology News

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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

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

D’Amico PCa Criteria Questioned D’AMICO criteria alone may incorrectly classify more than one third of prostate cancer (PCa) patients as having low-risk disease, according to new findings.

Daimantas Milonas, MD, of the Department of Urology, Medical Academy, Lithuanian University of Health Sciences in Kaunas, Lithuania, and colleagues studied 248 men who had biopsy-detected low-risk PCa based on D’Amico criteria (biopsy Gleason score of 6 or less, PSA level of 10 ng/mL or less, and clinical stage T1c- T2a) and underwent radical prostatectomy (RP). Of the 248 men, 32 (12.9%) had pT3a tumors and three (1.2%) had pT3b tumors found after

Underestimates of aggressive cancer may occur in up to 37.5% of patients.

RP. Tumors were upgraded after surgery in 32.7% of cases. Overall, after RP, the investigators found unfavorable PCa in 37.5% of patients who originally were identified by D’Amico criteria as having low-risk cancer, Dr. Milonas’s team reported online ahead of print in the Scandinavian Journal of Urology. The researchers defined unfavorable disease as non-organ-confined cancer (T3) and/or Gleason score of 7 or higher with any cancer stage.

The median follow-up period was 60 months. The overall biochemical relapse rate was 14.1%, according to the investigators.

The eight-year biochemical progression-free survival rate was 83.3% for low-risk PCa and 68.2% for unfavorable PCa. Positive surgical margins and post-operative Gleason score were the most significant predictors of biochemical relapse, the investigators found.

“In conclusion, the D’Amico criteria may underestimate aggressive prostate cancer in up to 37.5% of patients,” the authors wrote. “Consequently, caution is recommended when the decision concerning treatment is based on D’Amico criteria alone.” n

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Kidney Donor Biopsy continued from page 1

at 17.1%, 9%, and 5%, respectively.

Glomerulosclerosis of more than 20% was the only biopsy result that independently correlated with discard, suggesting that this biopsy finding was the only one used in acceptance decisions.

One-year graft survival was 79.5% in contralateral controls and 90.7% in randomly matched controls, compared with 91.6% among all deceased-donor transplants in the SRTR,” the researchers reported online ahead of print in the Clinical Journal of the American Society of Nephrology (CJASN).

“If the discarded kidneys had been transplanted with the same graft survival as the transplanted kidneys from the opposite side, many patients may have benefited,” Dr. Kasiske pointed out in an accompanying statement from the American Society of Nephrology (ASN). “All together, these results question whether routine procurement biopsies result in discarding kidneys that could be acceptable for many of the patients who die waiting for a kidney transplant.”

In the other study, which also was reported online ahead of print in

CKD Cause continued from page 1

ing factors. After adjusting for differences in prognostic factors, cystic kidney disease was associated with a 3-fold high risk of ESRD compared with the other causes of kidney disease, the investigators reported online ahead of print in the American Journal of Kidney Diseases.

Patients with cystic kidney disease had the lowest risk of death before ESRD compared with those who had glomerulonephritis, diabetic nephropathy, and other recorded diagnoses (1% vs. 3%, 8%, and 4%, respectively), the investigators reported. Patients with diabetic nephropathy had a 2.35 times increased risk of death compared with patients who had cystic kidney disease.

Dr. Landray and his colleagues also examined the effect of micro- and macroalbuminia and estimated glomerular filtration rate (eGFR) on progression to ESRD. Micro- and macroalbuminuria were not associated with a significantly increased ESRD risk among patients with cystic kidney disease, but macroalbuminuria was associated with a significantly increased ESRD risk among patients in the other categories. In all

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CJASN, Chirag R. Parikh, MD, PhD, associate professor medicine (nephrology) at Yale University School of Medicine in New Haven, Conn., and associates evaluated relationships between deceased-donor biopsy reports of acute tubular necrosis

Procurement biopsy reports are often of low quality, researchers found.

(ATN) and delayed graft function (DGF) in a multicenter study.

Among 651 kidneys from 369 donors and four organ-procurement organizations that had been biopsied and then transplanted between March 2010 and April 2012, ATN was reported in 110 (17%). A total of 262 recipients (40%) experienced DGF, and 38 (6%) experienced graft failure.

DGF occurred in nearly half (45%) of the kidneys with reported ATN, compared with 39% of the kidneys without ATN. No significant difference existed in graft failure for kidneys with reported ATN and without ATN (8%

categories of primary kidney disease, eGFR was a highly significant predictor of ESRD risk, according to the researchers. Compared with an eGFR of 30 mL/min/1.73 m2 or higher, an eGFR below 15 mL/min/1.73 m 2 was associated with a 13.1 times, 20.4 times, 20.6 times, and 23.6 times increased risk of ESRD among patients

Diabetic nephropathy was associated with the highest risk of pre-ESRD death. with cystic kidney disease, glomerulonephritis, diabetic nephropathy, and other recorded diagnoses, respectively, study results showed.

The researchers pointed out that the SHARP study population consisted of willing participants selected for inclusion in a randomized trial.

“Consequently, they are not likely to be representative of the CKD population as a whole,” the authors wrote.

In addition, nearly all SHARP participants had CKD stage 3b or worse, so results may not be generalizable to less severe CKD stages, they noted. n

vs. 5%), according to the investigators.

Other than finding a modest association between DGF and kidneys donated after cardiac death, the study revealed no significant associations overall between pre-implant biopsyreported ATN and the outcomes of DGF or graft failure, Dr. Parikh and coauthors reported.

“Biopsies are listed as the primary reasons for discarding deceased-donor kidneys; however, as currently related to reported acute kidney injury, [procurement biopsies] provide little utility for determining the overall risk of delayed organ function or even premature organ failure,” Dr. Parikh said in the ASN statement.

Commenting on the new findings, Dorry L. Segev, MD, PhD, an abdominal transplant surgeon and associate professor of surgery at Johns Hopkins University in Baltimore, asserted that biopsy definitely has a place in organ evaluation. “However, to be useful, biopsy needs to be performed in a selective manner by experienced persons, reviewed expeditiously by experienced pathologists as well as the physician evaluating the organ offer, and considered in light of all available clinical information,” Dr. Segev said. n

High HDL May Raise HD Patient Death Risk ELEVATED high-density lipoprotein (HDL) cholesterol protects against cardiovascular disease in the general population, but it may increase the risk of cardiovascular and all-cause mortality in hemodialysis patients, according to researchers.

In a study of 33,109 HD patients followed for up to 3 years, patients with HDL concentrations of 60 mg/dL or higher had a significant 8% and 5% increased risk of cardiovascular and all-cause mortality compared with patients with HDL concentrations of 30 mg/dL or higher but less than 60 mg/dL, Kamyar Kalantar-Zadeh, MD, PhD, of the University of California Irvine and colleagues reported online ahead of print in Nephrology Dialysis Transplantation.

In addition, HDL levels below 30 mg/ dL were associated with a significant 8% and 28% increased risk of all-cause and cardiovascular mortality. n

Renal & Urology News 7

Lipid Profiles continued from page 1

considerations justify a strong recommendation despite the low quality of the supporting evidence.”

In addition, the guideline recommends that patients aged 50 years and older with an estimated glomerular filtration rate (eGFR) below 60 mL/ min/1.73 m2 —but not treated with chronic dialysis or kidney transplantation—be treated with a statin alone or in combination with ezetimibe. Statin treatment is rcommended for patients aged 50 years and older with CKD and an eGFR of 60 or higher.

For adults aged 18-49 years with CKD not treated with dialysis or kidney transplantation, the guideline recommends statin treatment if one or more of the following are present: known coronary disease, diabetes mellitus, prior ischemic stroke, or a greater than 10% estimated 10-year incidence of coronary death or non-fatal myocardial infarction.

The work group, led by Christoph Wanner, MD, of University Hospital Wurzburg in Wurzburg, Germany, suggests that statins alone or in combination with ezetimibe not be initiated in adult dialysis patients. They pointed out that three large trials have failed to show a conclusive benefit of statin treatment among prevalent dialysis patients, “raising the hypothesis that inadequate statistical power was responsible for the apparent lack of benefit. Nonetheless, it is clear that even if statins do prevent cardiovascular events in prevalent dialysis patients, the magnitude of any relative reduction in risk is substantially smaller than in early stages of CKD.” The guideline, which was published online ahead of print in Kidney International, suggests that patients already receiving statins or a statin/ ezetimibe combination at the time of dialysis initiation should continue to receive these agents.

In adults with CKD, including those treated with chronic dialysis or kidney transplantation, follow-up measurement of lipid levels is not required for most patients. Follow-up measurement of lipid levels should be reserved for instances in which results would alter management, such as assessment of adherence to statin treatment, a change in renal replacement therapy modality, concern about the presence of a new secondary cause of dyslipidemia, or to assess the 10-year cardiovascular risk in patients younger than 50 years and not currently receiving a statin. n

3/24/14 10:50 AM

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Robotics and PCa continued from page 1

for men who have low-risk PCa, with a resultant shift of RP toward intermediate- and high-risk disease.”

In an interview with Renal & Urology News, Dr. Hu said the study is the first population-based investigation to demonstrate improved cancer control with robotic prostatectomy. One of the study strengths was that it included community settings and academic centers across the United States with complete follow-up data, he said.

“Open surgeons assert that the absence of tactile feedback during robotics leads to worse cancer control,” said Dr. Hu, director of UCLA’s Robotic and Minimally Invasive Surgery Program. “In other words, they claim that during open surgery, the sense of feel allows them to cut wider in areas of suspicion by touch and therefore avoid positive margins and achieve better cancer control. Our observational study does not support this claim.”

The finding of improved early cancer control with RARP comes amid

PSA continued from page 1

gen-deprivation therapy (ADT). All patients had experienced biochemical recurrence of PCa following radical prostatectomy.

Bone scan positivity was observed in 24 hormone-naïve patients (6%) and 65 ADT-treated patients (30%). In both groups, higher PSA levels, greater PSA velocity, and shorter PSA doubling time (PSADT) were associated with a higher probability of bone scan positivity, Dr. Moreira’s team reported in

Donor biopsy continued from page 1

in glomerulosclerosis explained by biopsies being from the same kidney.

The team also found that the percentages of glomerulosclerosis overlapped substantially among the discarded kidneys, the contralateral controls, and the randomly matched controls, at 17.1%, 9%, and 5%, respectively.

Glomerulosclerosis of more than 20% was the only biopsy result that independently correlated with discard, suggesting that this biopsy finding was the only one used in acceptance decisions.

One-year graft survival was 79.5% in contralateral controls and 90.7% in randomly matched controls, compared

RUN0414_Cover_URO.indd 7

mounting evidence that robotic prostate surgery is associated with better perioperative outcomes, such as less blood loss, shorter hospital stays, and fewer anastomotic strictures. “The key question is whether the higher costs of robotic surgery justify these incremental benefits in outcomes,” Dr. Hu said.

In a separate paper published recently online ahead of print in European Urology, Mehrdad Alemozaffar, MD, of Keck Medical Center at the University of Southern California in Los Angeles, and colleagues reported that, compared with men who underwent retropubic radical prostatectomy (RRP), those who underwent robot-assisted laparoscopic radical prostatectomy (RALP) experienced significantly less blood loss (207 vs. 852.3 mL), were significantly less likely to receive a blood transfusion (4.3% vs. 30.3%), and had significantly shorter hospital stays (1.8 vs. 2.9 days).

The study included 903 PCa patients identified among participants in the Health Professionals Follow-up Study (HPFS), a prospective study that enrolled 51,529 U.S. male health pro-

fessionals in 1986. The 903 patients included 282 who underwent RALP and 621 who underwent RRP. The median follow-up time was 2.4 years for the RALP group and 6.8 years for the RRP group.

Among patients with low-risk and intermediate-risk disease, those who underwent RALP were significantly less likely than RRP patients to have a lymph node dissection (35.3% vs.

Renal & Urology News 7

77.1% and 64.8% vs. 94.8%, respectively). The study demonstrated no significant between-group differences in 3- and 5-year recurrence-free survival (RFS) rates. Among men with at least 3 years of follow-up (493 in the RRP group and 99 in the RALP group), the 3-year RFS rates were 89.9% and 88.9% in the RRP and RALP groups,

respectively. Among men with 5 or more years of follow-up (393 in the RRP group and 25 in the RALP group), the 5-year RFS rates were 84.7% and 88%, respectively.

The two groups also had similar proportions of patients with PSMs and extracapsular extension and similar rates of various health-related quality of life outcomes, such as urinary incontinence, urinary obstruction, and sexual and bowel problems, according to the investigators.

“The strength of our populationbased study is that all states within the United States were represented, allowing for a diverse cohort of patients treated by surgeons with varying experience and techniques,” the authors wrote.

The researchers cautioned, however, that their study needs to be interpreted with regard to its limitations.

For example, the study was observational and limited to health professionals, who may have different access and knowledge regarding healthcare options and providers, thereby influencing RRP and RALP. n

Prostate Cancer and Prostatic Diseases (2014;17:91-96).

With recent advances in chemoand immunotherapies for metastatic PCa, early detection of metastasis has become increasingly important, the authors noted. “However, it is not clear when and how patients should be screened for metastasis,” they wrote.

“Bone scans are routinely used to detect metastasis in patients with prostate cancer; however, a significant number of these scans are negative.”

The investigators noted that their findings suggest that more aggressive

and/or advanced disease are associated with a higher risk of a positive bone scan. “Furthermore, they suggest that the factors associated with aggressive and advanced disease such as high PSA levels and short PSADT may be used to stratify patients based on risk of a positive bone scan.”

The researchers created a table combining PSA levels and PSADT to predict the risk of a positive bone scan. For example, among hormonenaïve patients, a PSADT of 9 months or more and a PSA level of 20 ng/mL or higher have a 3% risk of a positive

bone scan. By comparison, patients with a PSADT of 3.0-8.9 months and less than 3 months in addition to a PSA level of 20 ng/mL or higher have a 24% and 44% risk of a positive bone scan, respectively.

Among ADT-treated patients, those with a PSADT of 9 months or more and a PSA level of 20 ng/mL or higher have a 39% risk of a positive bone scan.

For those with a PSADT of 3.0-8.9 months and less than 3 months, as well as a PSA level of 20 ng/mL or higher, have a 57% and 67% increased risk respectively. n

with 91.6% among all deceased-donor transplants in the SRTR,” the researchers reported online ahead of print in the Clinical Journal of the American Society of Nephrology (CJASN).

“If the discarded kidneys had been transplanted with the same graft survival as the transplanted kidneys from the opposite side, many patients may have benefited,” Dr. Kasiske pointed out in an accompanying statement from the American Society of Nephrology (ASN). “All together, these results question whether routine procurement biopsies result in discarding kidneys that could be acceptable for many of the patients who die waiting for a kidney transplant.”

In the other study, which also was

reported online ahead of print in CJASN, Chirag R. Parikh, MD, PhD, of Yale University in New Haven, Conn., and associates evaluated relationships between deceased-donor biopsy reports of acute tubular necrosis (ATN) and delayed graft function (DGF) in a multicenter study.

Among 651 kidneys from 369 donors and four organ-procurement organizations that had been biopsied and then transplanted between March 2010 and April 2012, ATN was reported in 110 (17%). A total of 262 recipients (40%) experienced DGF, and 38 (6%) experienced graft failure.

DGF occurred in nearly half (45%) of the kidneys with reported ATN, compared with 39% of the kidneys

without ATN. No significant difference existed in graft failure for kidneys with reported ATN and without ATN (8% vs. 5%).

Other than finding a modest association between DGF and kidneys donated after cardiac death, the study revealed no significant associations overall between pre-implant biopsyreported ATN and the outcomes of DGF or graft failure.

“Biopsies are listed as the primary reasons for discarding deceased-donor kidneys; however, as currently related to reported acute kidney injury, [procurement biopsies] provide little utility for determining the overall risk of delayed organ function or even premature organ failure,” Dr. Parikh said. n

RARP reduced the likelihood of additional cancer treatment.

3/25/14 10:33 AM

8 Renal & Urology News

APRIL 2014 www.renalandurologynews.com

News in Brief

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

Short Takes PCNL May Raise Risk of Diabetes Mellitus

researchers reported in Blood Purification (2014;37:106-112).

In a study of 248 chronic HD

Percutaneous nephrolithotomy (PCNL) may be associated with an

patients, Japanese investigators found

increased risk of diabetes mellitus.

that patients in the highest tertile of

A team led by Herng-Ching Lin,

erythropoietin resistance index (ERI)

PhD, of Taipei Medical University in

had a fourfold increased risk of all-

Taiwan, studied 3,344 patients with

cause mortality compared with those

nephrolithiasis and compared the

in the lowest tertile.

304 patients who underwent PCNL 5-year follow-up, the PCNL group had

Statin Treatment May Improve ED

a nearly 2-fold increased risk of being

Statins may help improve erectile dys-

diagnosed with diabetes mellitus

function (ED), especially in men who

compared with the non-PCNL group

do not respond to phosphodiesterase

after adjusting for confounders, the

type 5 inhibitors (PDE5i), according

researchers reported online in the

to a recent meta-analysis published

International Journal of Urology.

online ahead of print in the Asian Jour-

with the 3,040 did not. During a

In addition, PCNL was associated

nal of Andrology. The meta-analysis,

with a 79% and 71% increased risk

which focused on five randomized,

of a diabetes mellitus diagnosis com-

placebo-controlled trials looking at

pared with extracorporeal shockwave

statins as a treatment for ED, showed

lithotripsy and endoscopic interven-

that statin treatment was associated

tion, respectively.

with a significant 3.27 point improvement in International Index of Erectile

ESA Resistance Found To Increase Mortality

Function (IIEF) scores in addition to an overall improvement in lipid profiles.

The researchers pointed out, how-

Greater resistance to erythropoiesisstimulating agents (ESA) is associated

ever, that some research suggests

with an increased risk of death among

that statins may decrease testoster-

patients on chronic hemodialysis (HD),

one levels. n

Doling Out Free Drug Samples In a recent online poll, Renal & Urology News asked urologists and nephrologists, “Do you ever reserve free drug samples for uninsured or low income patients?” Here are the results based on 118 responses.

Yes: 72.8%

No: 11.8%

I do not get free samples: 15.2%

0

RUN0414_NewsinBrief.indd 8

10

20

30

40

50

60

70

80

Contrast-Induced AKI Ups Risk of Poor Outcomes C

ontrast-induced acute kidney injury (AKI) after primary percutaneous coronary intervention (PCI) is associated with poor short- and long-term outcomes, according to study findings published online ahead of print in the European Heart Journal.

The study, by Amar Narula, MD, of New York University Langone Medical Center, and colleagues, included 2,968 patients who underwent PCI. AKI developed in 479 (16.1%). Compared with patients who did not experience AKI, those who did had significantly higher rates of net adverse clinical events (NACE), a combination of major bleeding or a composite of major adverse cardiac events (MACE), which included death, reinfarction, target vessel revascularization for ischemia, or stroke) at 30 days (22.0% vs. 9.3%) and 3 years (40.3% vs. 24.6%).

Additionally, AKI sufferers had higher mortality rates at 30 days and 3 years (8.0% vs. 0.9% and 16.2% vs. 4.5%, respectively). On multivariate analysis, AKI was associated with a 53% increased risk of NACE, a 56% increased risk of MACE, and an 80% increased risk of death at 3 years.

AVF Placement Less Likely in Metropolitan Areas R

ates of arteriovenous fistula (AVF) placement in patients approaching hemodialysis in the United States are significantly lower in metropolitan than micropolitan areas, researchers reported online ahead of print in Hemodialysis International.

A micropolitan area, which is a federal designation created in 2003, is defined as an urban area based around an urban cluster with a population of 10,000 to 49,999.

In an analysis of data in the U.S. Renal Data System database (2005-2008) linked to Medicare claims (2003-2008), Alexander S. Goldfarb-Rumyantzev, MD, of Beth Israel Deaconess Medical Center in Boston, and colleagues found that AVF placement rates in metropolitan, micropolitan, and rural areas were 18.5%, 22.4%, and 21.6%, respectively. Patients in metropolitan areas had a significant 20% decreased likelihood of AVF placement compared with those in micropolitan.

The study found no significant difference in AVF placement rates between metropolitan and rural areas.

Study: Overactive Bladder is a Nocturia Risk Factor O

veractive bladder (OAB) is associated with an increased likelihood of nocturia in patients with type 2 diabetes, researchers reported online ahead of print in International Urology and Nephrology.

Min-Shen Chung, MD, of Chang Gung University College of Medicine in Kaohsiung, Taiwan, and colleagues studied 1,301 type 2 diabetics, of whom 59.6% had nocturia (2 or more voids per night) and 25.3% had severe nocturia (3 or more voids per night). OAB was associated with a significant 2.2 times increased risk of nocturia after adjusting for age and diabetes duration. Severe nocturia increased the risk of death nearly twofold independent of age and diabetes duration. n

3/24/14 10:24 AM

www.renalandurologynews.com APRIL 2014

Renal & Urology News 9

Adverse Safety Events Common in CKD Impaired renal function, altered drug clearance, and comorbid conditions are contributing factors

BY DELICIA HONEN YARD ADVERSE safety events in patients with chronic kidney disease (CKD) are common and varied, with frequent association between disparate events, researchers found.

Jeffrey C. Fink, MD, of the University of Maryland Medical System in Baltimore, and colleagues noted in a paper published online ahead of print in the Journal of the American Society of Nephrology that CKD patients are at high risk for adverse safety events because of their impaired renal function, altered drug clearance, comorbid conditions, and frequent hospitalizations.

Dr. Fink’s team looked at the frequency of adverse safety events among non-dialysis CKD patients by examining participants in the Safe Kidney Care cohort study. The analysis revealed that 185 of 267 participants (69.3%) experienced at least one adverse safety event in the class I category (patient-reported

Post-Tx Hip Fracture Rate Declining HIP fractures remain an important complication following kidney transplantation, but the incidence of these fractures has decreased substantially since 1997, according to a new study.

The study, led by Wolfgang C. Winkelmayer, MD, ScD, Associate Professor of Medicine and Director of Clinical Research in the Division of Nephrology at Stanford University of School of Medicine in Palo Alto, Calif., included 69,740 patients who under kidney transplantation from 1997 to 2010. Results showed patients who received a transplant in 2010 had a 44% decreased risk of hip fracture compared with those who received a transplant in 1997, after adjusting for case mix and demographic, dialysis, comorbid, and most transplant-related factors, researchers reported online ahead of print in the American Journal of Transplantation. The risk reduction was 32% after additional adjustment for baseline immunosuppression.

Of the 69,740 patients, 597 experi-

RUN0414_CKDCare.indd 9

adverse safety incidents) or the class II category (hazardous clinical disturbances detected at study evaluations that have the potential for correction with treatment or with medical modification). More than one third (102 participants, or 38.2%) had more than one event, and 48 (18%) suffered at least

Frequent events included high venous hemoglobin and hyperkalemia. one event from each class.

Self-reported hypoglycemia was the most common class I event recorded, with a higher adjusted rate conditional on use of diabetes medication within the last 30 days. The second most common class I event was falling or severe dizziness. Only patients with diabetes

enced a hip fracture during 155,341 person-years of follow-up, which translated into an incidence rate of 3.8 per 1,000 person-years. The 30-day mortality rate was 2.2 deaths per 100 hip fractures.

Dr. Winkelmayer’s group noted that bone loss and fractures are well-known complications of solid organ transplantation, and cited research demonstrating that bone of about 3.9% in the femoral neck has been shown to occur as early as three months post-transplant.

The researchers suggested some possible explanations for the decline in hip fracture risk, including changes in immunosuppressive regimens during the era studied. The attenuation of hip fracture risk after adjusting for baseline immunosuppression suggests that changes in immunosuppressive therapy may be partly responsible for the risk reduction, they stated.

“Tacrolimus largely replaced cyclosporine by the early 2000s and some data suggest that, relative to cyclosporine, tacrolimus may preserve bone mineral density.” In addition, corticosteroids are a well-established risk factor for post-transplant fractures, “and the adoption of steroid-sparing and steroid-minimizing regimens could have contributed to the diminished adjusted risk.” n

reported hypoglycemia. The 42 patients with diabetes who reported falling or severe dizziness were also likely to experience hypoglycemia. Among the 87 patients with diabetes who reported at least one episode of hypoglycemia, 33% also reported falling or severe dizziness.

The most common class II event was high venous hemoglobin, with a value of 13.5 g/dL serving as a safety threshold, according to investigators.

However, no participant had this event when conditional on use of an erythropoiesis-stimulating agent.

The next most common class II event was hyperkalemia (serum potassium greater than 5.5 mEq/L), which became the most common class II event when conditional on the use of a renin-angiotensin-aldosterone system blocker, a potassium-sparing diuretic, a nonsteroidal anti-inflammatory drug, or any other agent that could lead to hyperkalemia.

“The occurrence of these events ranged from sporadic to common but was frequent when considered in aggregate; this demonstrates the susceptibility of the CKD population to complications of medical care,” Dr. Fink and his colleagues wrote. “The causal relationship between treatment, or medications, and the class I and II events as we define them is difficult to confirm, but by focusing our analysis on events that occur conditional on medications that could account for such events, we offer a potential causal link between treatment and adverse safety event with the risk for harmful consequences.”

Participants suffering no adverse safety event were more likely to be older, male, African American, and free of diabetes, with a higher glomerular filtration rate, and were less likely to have had cancer or cardiovascular disease. Those with no events also took fewer medications than those with events. n

Use Transperineal Prostate Biopsy More, Researchers Say MEN who need a prostate biopsy

biopsy typically has been reserved for

should be offered the transperineal (TP)

patients undergoing repeat biopsy,

approach as a possible alternative

either as part of active surveillance for

to transrectal ultrasonography (TRUS)-

low-risk prostate cancer or for a rising

guided biopsy because the former is

PSA level despite a negative TRUS

associated with a much lower risk of

biopsy. The TP approach has some

sepsis, researchers concluded.

drawbacks that have prevented more

Jeremy P. Grummet, MBBS, MS,

widespread use, they pointed out. It usu-

Adjunct Senior Lecturer, Department of

ally requires a general anesthetic, takes

Surgery, Monash University, Melbourne,

longer to perform, and typically involves

and colleagues analyzed the outcomes

taking more cores. The investigators

of 245 TP biopsies and found a zero

concluded that “in today’s environment

rate of hospital re-admission for sepsis,

of rising rates of TRUS-biopsy sepsis

according to an online report in BJU

and antibiotic resistance, we think that

International. In a review of the medical

the risk-benefit ratio has now shifted

literature, Dr. Grummet’s group found

sufficiently to warrant offering TP

that the rate of sepsis after TRUS biopsy

biopsy as an option to all men in whom

appears to be rising, with increasing

a prostate biopsy is indicated.”

rates of multidrug-resistant bacteria

A shift to using TP biopsy is likely

found in rectal flora. The rate of sepsis

to have a significant impact on health

found in published series of TP biopsy

resources, but the savings from its lack

approached zero, they noted. In a total

of infective complications must also be

of 6,609 patients, only five (0.076%)

considered,” they wrote. n

were re-admitted to a hospital for sepsis.

[Editor’s note: An Expert Q&A interview

The investigators explained that TP

with Dr. Grummet is on page 17]

3/25/14 10:02 AM

10 Renal & Urology News

APRIL 2014 www.renalandurologynews.com

PCa Linked to Metabolic Syndrome Study reveals 54% greater risk when the syndrome is present METABOLIC syndrome (MetS) is independently associated with an increased likelihood of a prostate cancer (PCa) diagnosis, but any individual component of the syndrome is not, a new study suggests.

Bimal Bhindi, MD, of the University of Toronto, and colleagues studied 2,235 men without a prior PCa diagnosis undergoing prostate biopsy. Of these, 494 (22.1%) had MetS, which was defined as the presence of any three of the following components: obesity, hypertension, impaired fasting glucose or diabetes, low highdensity lipoprotein-cholesterol, and hypertriglyceridemia.

Having three or more components of MetS versus no component was associated with a 54% increased odds of a PCa diagnosis, a 56% increased odds of clinically significant PCa, and a 56% increased odds of intermediate- or high-grade PCa, Dr. Bhindi’s group reported online ahead of print in European Urology.

In analyses stratified by obesity, the association between MetS and a PCa diagnosis was slightly stronger among obese versus non-obese subjects. After adjusting for obesity, the risk associated with MetS was not attenuated, “sug-

gesting that obesity is not driving this association.”

“Our findings suggest that men with MetS may require a lower threshold for performing biopsy,” the authors concluded. “MetS may be worth considering for potential inclusion in PCa risk calculators in future studies.”

Prostate cancer was not associated with any individual syndrome component.

Individuals with and without MetS had a mean age of 64.9 and 63.6 years, respectively. The study population was 73.2% white, 6.3% black, 8.8% East Asian, and 11.7% mixed ethnicity/ other.

In a recent paper published in BJU International (2013;111:1031-1036), Juan Morote, MD, of Vall d’Hebron Hospital and Research Institute, and his co-investigators reported on a study demonstrating that MetS is associated with an increased risk of more aggressive PCa. The study included 2,408 men who underwent prostatic biopsies.

The researchers observed no significant difference in the detection rate of PCa overall between men with MetS and those without it (34.5% and 36.4%, respectively). They did find, however, that patients with MetS had a significantly higher rate of high-grade PCa (Gleason score 8-10) than those without MetS (35.9% vs. 23.9%). Multivariate analyses confirmed that MetS was not associated with the risk of PCa, but was associated with a significant 75% increased risk of high-grade tumors.

In a separate study of 11,541 men with coronary heart disease, Yaacov Richard Lawrence, MD, of Sheba Medical Center in Tel HaShomer, Israel, and colleagues, found no significant association between MetS and PCa. The cohort included 6,119 (53%) patients with neither diabetes nor MetS; 3,376 (29%) with MetS but not diabetes; 560 (5%) with diabetes but not MetS; and 1,486 (13%) with both MetS and diabetes. During a median follow-up of 12.7 years, 459 new PCa cases were recorded, the researchers reported in Prostate Cancer and Prostatic Diseases (2013;16:181-186). After adjusting for age, the investigators found that diabetic patients had a significant 46% lower risk of PCa than non-diabetics. n

IV to Oral Vitamin D Switch Beneficial SWITCHING from intravenous (IV) to oral activated vitamin D may offer similar control of secondary hyperparathyroidism in patients on chronic hemodialysis (HD) with lower doses of the drug, according to a new Canadian study.

The study, led by Michel Vallée, MD, of Hôpital MaisonneuveRosemont in Montreal, included 88 chronic HD patients receiving IV alfacalcidol three times a week.

Investigators switched the patients to the same dose of alfacalcidol given orally three times a week during HD sessions. The mean alfacalcidol dose administered was 2.1 ug three times a week. After three months, serum parathyroid hormone (PTH) levels decreased significantly from 80 to 59 pmol/L and total serum calcium levels increased significantly from 2.34 to 2.40 mmol/L, the researchers reported in BMC Nephrology (2014;15:27). In addition, the alfacalcidol dosage was significantly

More Intensive Radiotherapy May Be Better HIGHER doses of radiotherapy control localized prostate cancer (PCa) more effectively than lower doses 10 years after treatment and reduce the need for follow-up androgen-deprivation therapy, according to a phase 3 trial.

The open-label, randomized controlled trial involved 422 men who had been assigned to escalated-dose conformal radiotherapy and 421 men who had been assigned to control-dose conformal radiotherapy for the treatment of histologically confirmed localized PCa with PSA levels below 50 ng/ mL. The men in the escalated-dose group received 74 Gy in 37 fractions, whereas the control group members received 64 Gy in 32 fractions—the standard dose at the time the study was designed.

The men joined the study between January 1998 and December 2001. The previously reported 5-year outcomes pointed to the benefits of the dose-

RUN0414_PCa_MetS.indd 10

escalation radiotherapy regimen. Now, these results have been shown to be maintained over a median follow-up of 10 years.

As of August 2011, 118 patients in each group had died. Only 91 of these 236 deaths were due to prostate cancer.

Overall survival at 10 years was 71% in each group, but more men in the control group (221, or 57%) than in the escalated-dose group (170, or 43%) experienced biochemical progression or progressive disease. At the 10-year mark, biochemical progression-free survival was 55% in the escalated-dose group versus 43% in the control group.

The improvement in biochemical control of the cancer did not translate into an improvement in metastasesfree survival, PCa-specific survival, or overall survival. At a median follow-up of 10 years, however, escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy

(ADT) demonstrated an advantage in biochemical progression-free survival, concluded David P. Dearnaley, MD, a uro-oncology professor at The Institute of Cancer Research, London, United Kingdom, and fellow investigators in The Lancet Oncology.

Having recorded a significant delay in the reported time to initiation of longterm salvage ADT in the escalated-dose group, Dr. Dearnaley’s group noted that this advantage must be balanced against the known small increase in bowel side effects from the five extra treatments required by the escalateddose treatment plan. Although men receiving the higher-dose radiotherapy were more likely than controls to experience treatment adverse effects (AEs), few men had severe AEs. Because the men in the higher-dose group were less likely to require follow-up hormone therapy, they were more likely to avoid the side effects from that treatment. n

decreased during the study period, with a mean reduction of 0.44 μg per dose. Oral administration of the medication was associated with an annual cost reduction of $197,678 in Canadian dollars ($178,305 U.S.) and annual nursing time reduction of 25 days.

“To our knowledge, this is the first study to show such findings,” the researchers noted.

They concluded that their findings suggest that intermittent oral administration of alfacalcidol is even more effective than an equivalent IV dosage with respect to suppressing PTH. “For maintaining serum PTH levels within target limits or for compliance purposes, intermittent oral administration of alfacalcidol in an HD unit is a much more costeffective strategy [than IV administration],” the authors wrote. n

3/24/14 10:24 AM

www.renalandurologynews.com APRIL 2014

Renal & Urology News 11

Sildenafil Improves Post-PCa Therapy Erections SILDENAFIL citrate taken daily during and after radiotherapy for localized prostate cancer (PCa) may improve post-treatment erectile function compared with placebo, a study found.

The study, led by Michael J. Zelefsky, MD, of Memorial Sloan-Kettering Cancer in New York, is the first randomized, prospective, controlled trial to demonstrate that a phosphodiesterase type 5 inhibitor is useful as a rehabilitation strategy in patients undergoing radiotherapy for PCa, according to a report published online ahead of print in The Journal of Urology.

Dr. Zelefsky’s team randomized 279 PCa radiotherapy patients to receive either sildenafil citrate 50 mg or pla-

cebo daily. The drug or placebo was initiated three days prior to radiotherapy and continued daily for six months.

At 12 months, erectile function scores, as measured using the International Index of Erectile Function, were significantly better for the sildenafil citrate group than for placebo recipients,

with 73% of the medication recipients reporting mild or no erectile dysfunction (ED) compared with 50% of placebo recipients.

At 24 months, erectile function scores were no longer significantly better in the sildenafil citrate arm, but 81.6% of sildenafil citrate recipients

had functional erections (with or without ED medications) compared with 56.0% of placebo recipients, a significant difference between the groups.

The sildenafil citrate group had higher sexual desire scores despite completing drug therapy 18 months prior, according to the investigators. n

Drug Speeds GI Recovery Post-RC ALVIMOPAN speeds gastrointestinal (GI) recovery and shortens hospital length of stay after radical cystectomy (RC), according to a recent report.

In a multicenter, randomized, placebo-controlled trial, the mean time to GI recovery was 5.5 days among the 143 alvimopan-treated subjects compared with 6.8 days for

patient: MARK SMITH PSA 6.2 Gleason Score 6 Oncotype DX GPS

8

CAN MARK CONFIDENTLY CHOOSE

ACTIVE SURVEILLANCE ?

the 137 placebo recipients, researchers reported online ahead of print in European Urology. The mean hospital length of stay was 7.4 days in the alvimopan group versus 10.1 days in the placebo arm. The alvimopan group also experienced fewer postoperative ileus-related episodes (8.4% vs.

29.1%). All of these differences between the groups were statistically significantly.

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“Adding alvimopan to a standardized care pathway provides further meaningful improvements in early in-hospital postoperative outcomes for patients undergoing RC,” the investigators, led by Cheryl T. Lee,

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MD, of the University of Michigan in Ann Arbor, concluded. “As such, alvimopan use represents an impor-

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tant advancement in surgical quality of care with the potential to reduce health care costs.” n

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12 Renal & Urology News

■ NKF 2014, Las Vegas

APRIL 2014 www.renalandurologynews.com

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

Controversies in Blood Pressure Management in Hemodialysis

BY TARA I. CHANG, MD, MS

Editor’s note: The author will discuss this topic during a presentation at the National Kidney Foundation’s 2014 Spring Clinical Meetings, which will be held April 22-26 at the MGM Grand in Las Vegas

HYPERTENSION is a major modifiable risk factor for myocardial infarction, stroke, heart failure, and other cardiovascular diseases. A majority of patients on hemodialysis (HD) have hypertension, and cardiovascular disease is the leading cause of death in these patients.1 However, there are many controversies regarding blood pressure (BP) management in HD. First, although accurate BP measurements are the cornerstone of hypertension management, the best method of measuring BP in HD patients remains uncertain.

Clinicians generally use in-center BP measurements taken pre- and post-dialysis to guide treatment decisions, yet studies have shown that these measurements correlate poorly with interdialytic ambulatory BP monitoring (considered to be the gold standard of BP measurement).2-4 Because incorporating ambulatory BP monitoring into routine clinical practice is impractical, some studies have examined standardized in-center BP measurements or home-based BP measurements. They found that these methods better predict left ventricular hypertrophy and cardiovascular and allcause mortality.5-7 However, persuading busy dialysis units to use standardized BP measurements or over-burdened patients to measure blood pressure at home may prove challenging.

Optimal BP targets Optimal BP targets in HD patients are another controversial issue. While patients with preserved kidney function have a direct linear association between BP and adverse cardiovascular outcomes,8 in patients on HD, lower BP

RUN0414_NKF.Controversies.indd 12

is associated with higher risks of death or cardiovascular events, and higher BP has shown weak or even no association with adverse outcomes. For example, in a study of 69,590 North American HD patients, pre-dialysis systolic BP less than 120 mm Hg was associated with a 5.5-fold higher risk of death at one year, whereas patients with pre-dialysis systolic BP greater than 200 mm Hg had only a 1.5-fold higher risk compared with the reference group (systolic BP 160-180 mm Hg)9. Similar findings have been shown in patients on hemodialysis from around the world.10 The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines recommend targeting a pre-dialysis BP of less than 140/90 mm Hg and postdialysis blood pressure below 130/80 mm Hg, but acknowledge that the evidence to support these guidelines is weak.11 A 2009 expert committee convened by the NKF’s Kidney Disease: Improving Global Outcomes (KDIGO) program reviewed the evidence and concluded that, aside from aggressively treating BP over 200 mm Hg, no specific recommendations on BP targets could be made.12 Moreover, there is potential harm associated with trying to achieve lower BP in HD patients. An audit of dialysis units in the U.K. showed that intradialytic hypotension was more common in units that had more patients achieving post-dialysis BP targets.13 Intradialytic hypotension is associated with myocardial stunning,14 vascular access thrombosis,15 and death.16-18 The Blood Pressure in Dialysis Patients (BID) trial, a pilot study that will randomize patients on HD to low (110140 mm Hg) or standard (155-165 mm Hg) systolic BP targets, is currently underway (NCT01421771). If this trial is expanded into a full-scale randomized clinical trial, the results will help to clarify optimal BP targets in HD patients.

Antihypertensive drug use Despite the controversies regarding BP measurement and optimal BP targets for HD patients, the use of antihypertensive medications in these patients

does seem to confer benefits. A metaanalysis of eight randomized clinical trials in 1,679 patients on dialysis (including some patients on peritoneal dialysis) demonstrated that active antihypertensive treatment significantly reduced the risk of cardiovascular events, all-cause mortality, and cardiovascular mortality by 29%, 20%, and 29%, respectively, compared with controls.19 The eight trials included in the meta-analysis used a variety of antihypertensive medication classes, including beta-blockers, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers, but none was compared head-to-head.

Thus, recommendations regarding the preferential use of specific drug classes remain largely based on extrapolation from non-dialysis populations (e.g., beta-blockers following a myocardial infarction). Of note, in the recent Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) study,20 HD patients with left ventricular hypertrophy and hypertension randomized to an atenololbased regimen had lower rates of heart failure and other cardiovascular events compared with patients receiving a lisinopril-based regimen. However, this was a relatively small study (200 patients) with predominately AfricanAmerican patients (86%).

In summary, there are a number of controversies regarding BP management in HD patients, including the optimal method of measurement, appropriate and safe BP targets, and whether certain classes of antihypertensive medications are preferred over others. Despite these ongoing uncertainties, controlling BP to a level of less than 140/90 mm Hg pre-dialysis using a combination of pharmacologic and non-pharmacologic therapies (e.g., maximizing ultrafiltration, reducing sodium exposure in the diet and dialysate, and extending the duration and frequency of HD), without precipitating intradialytic hypotension, is a reasonable goal. Future studies that will put these controversies to rest are clearly needed. n For more information about the NKF 2014 Spring Clinical Meetings, visit

www.nkfclinicalmeetings.org Tara Chang, MD, MS, is an instructor in medicine (nephrology) at the Stanford University School of Medicine in Palo Alto, Calif.

REFERENCES 1. U.S. Renal Data System, USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and EndStage Renal Disease in the United States, National Institutes of Health, Editor 2013: Bethesda, MD. 2. Agarwal R, Lewis RR. Prediction of hypertension in chronic hemodialysis patients. Kidney Int 2001;60:1982-1989.

3. Agarwal R, Peixoto AJ, Santos SF, Zoccali C. Preand postdialysis blood pressures are imprecise estimates of interdialytic ambulatory blood pressure.

Clin J Am Soc Nephrol 2006;1:389-398.

4. Fagugli RM, Ricciardi D, Rossi D, et al. Blood pressure assessment in haemodialysis patients: comparison between pre-dialysis blood pressure and ambulatory blood pressure measurement. Nephrology 2009;14::283-290.

5. Agarwal R, Brim NJ, Mahenthiran J, et al. Out-ofhemodialysis-unit blood pressure is a superior determinant of left ventricular hypertrophy. Hypertension 2006;47:62-68.

6. Khangura J, Culleton BF, Manns BJ, et al. Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis. BMC Nephrol 2010;11:13.

7. Agarwal R. Blood pressure and mortality among hemodialysis patients. Hypertension 2010;55:762768.

8. Lewington S, Clarke R, Qizilbash N, et al. Agespecific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903-1913.

9. Li Z, Lacson E Jr, Lowrie EG, et al. The epidemiology of systolic blood pressure and death risk in hemodialysis patients. Am J Kidney Dis 2006;48:606-615.

10. Robinson BM, Tong L, Zhang J, et al. Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2012;82::570-580.

11. National Kidney Foundation. Clinical practice guidelines and clinical practice recommendations 2006 Update. Am J Kidney Dis 2006;48:S1-S322 (suppl 1).

12. Levin NW, Kotanko P, Eckardt KU, et al. Blood pressure in chronic kidney disease stage 5D-report from a Kidney Diseaes: Improving Global Outcomes controversies conference. Kidney Int 2009;77:273-284.

13. Davenport A, Cox C, Thuraisingham R. Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension. Kidney Int 2008;73:759-764.

14. Burton JO, Jefferies HJ, Selby NM, McIntyre CW. Hemodialysis-induced cardiac injury: determinants and associated outcomes. Clin J Am Soc Nephrol 2009;4:914-920.

15. Chang TI, Paik J, Greene T, et al. Intradialytic hypotension and vascular access thrombosis. J Am Soc Nephrol 2011l;22:1526-1533.

16. Shoji T, Tsubakihara Y, Fujii M, Imai E. Hemodialysisassociated hypotension as an independent risk factor for two-year mortalty in hemodialysis patients.

Kidney Int 2004;66:1212-1220.

17. Tislér A, Akócsi K, Borbás B, et al. The effect of frequent or occasional dialysis-associated hypotension on survival of patients on maintenance haemodialysis. Nephrol. Dial. Transplant 2003;18:2601-2605.

18. Tislér A, Akócsi K, Hárshegyi I, et al. Comparison of dialysis and clinical characteristics of patients with frequent and occasional hemodialysis-associated hypotension. Kidney Blood Press Res 2002;25:97-102.

19. Heerspink HJ, Ninomiya T, Zoungas S, et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systemic review and meta-analysis of randomised controlled trials. Lancet 2009;373:1009-1015.

20. Agarwal R, Sinha AD, Pappas MK, et al. Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial. Nephrol Dial Transplant 2014 (Epub ahead of print).

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Renal & Urology News 13

n FEATURE

Omega-3s and PCa: What to Advise Patients A major study suggests that high blood levels of omega-3 fatty acids increase prostate cancer risk, but some researchers are not convinced BY DELICIA HONEN YARD

O

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fried fish—as well as fish oil supplement intake show a decreased risk of PCa. “People who have a lifelong high intake of fish have some of the lowest rates of prostate cancer or prostate cancer mortality, such as Eskimo men and Japanese men,” he said.

3s beat 6s

© THINKSTOCK

n July 10, 2013, Theodore M. Brasky, PhD, of the Ohio State University Comprehensive Cancer Center in Columbus, and colleagues published a study in the Journal of the National Cancer Institute (2013;105:11321141) that they said confirms previous reports of increased prostate cancer (PCa) risk among men with high blood levels of long-chain omega-3 polyunsaturated fatty acids. Two months later, a team led by James J. DiNicolantonio, PharmD, of the Mid America Heart Institute at Saint Luke’s Hospital in Kansas City, Mo., and Wegmans Pharmacy in Ithaca, N.Y., presented its own take on those results, noting in Missouri Medicine (2013;110:292-295) that “the Brasky paper only demonstrates an association between plasma phospholipid omega-3s and subsequent prostate cancer risk; it cannot prove that omega-3 fatty acids (and particularly fish oil) cause prostate cancer.”

Dr. DiNicolantonio and his coauthors, including two cardiovascular physicians, further contended that a more thorough review of the pertinent literature suggests that increased omega-3 fatty acid consumption does not increase PCa risk, and notably decreases PCa mortality, while “most certainly” reducing risk for sudden death and cardiovascular events “I think that when you actually read the Brasky paper, one would not be concerned with fish oil supplements increasing the risk of prostate cancer, but the press releases that came after-

Mackerel (above) are among the fish rich in omega-3 fatty acids.

wards confused clinicians and the public alike, causing a lot of panic,” Dr. DiNicolantonio told Renal & Urology News. “Also, it is highly likely that a lot of people stopped their fish oil supplements based on inappropriate conclusions drawn from this study, and it would be a shame for patients on fish oil supplements to lose the cardiovascular protection that has been shown for decades with these supplements.”

Dr. DiNicolantonio pointed out that Dr. Brasky and his co-authors analyzed data from a single blood measurement of omega-3 status, and that one omega3 blood draw—particularly one that does not measure omega-3 levels in red blood cells, which is a more accurate

reflection of chronic omega-3 intake— cannot implicate fish oil supplements as causing PCa. “Patients should not stop their fish oil supplements based on the Brasky paper,” Dr. DiNicolantonio said.

The National Institute of Health’s (NIH’s) MedlinePlus service names mackerel, tuna, salmon, sturgeon, mullet, bluefish, anchovy, sardines, herring, trout, and menhaden as the fish especially rich in omega-3 fatty acids.

When asked what misconception about the relationship between omega-3 fats and PCa he would most like to clear up, Dr. DiNicolantonio noted that a plethora of prior studies looking at fish intake—particularly fatty fish and non-

Dr. DiNicolantonio and associates have submitted for publication a paper in which they show that maintaining a low ratio of omega-6 fatty acids (found in corn, safflower, sunflower, and soybean oils, as well as in nuts and seeds) to omega-3 fatty acids is probably one of the best measures for reducing carcinoma, particularly carcinoma promoted by COX-2 activity, such as PCa. Physicians who want to help men prevent the development of PCa should urge these patients to eat less of the leaner fish, such as tilapia, which has higher omega-6 content and lower omega-3 content, and to eat more fatty fish such as salmon, he advised. The fish should be baked, not fried.

“Fish from the ocean will have the desired higher omega-3 content and lower omega-6 content than will farmraised fish, because fish get their high levels of omega-3 from eating oceanic algae,” Dr. DiNicolantonio explained.

Achieving a favorable ratio of omega6 fats to omega-3 fats is also being studied by William J. Aronson, MD, chief of urologic oncology at the West Los Angeles Veterans Affairs Medical Center and a clinical professor of urol-

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14 Renal & Urology News

APRIL 2014 www.renalandurologynews.com

What the Experts Say William J. Aronson, MD, University of California Los Angeles “At this point I’m advising a heart-healthy diet and weight loss if needed, because cardiovascular disease is still the number 1 cause of death in prostate cancer patients. I don’t even mention fish oil.”

James J. DiNicolantonio, PharmD, Mid America Heart Institute at Saint Luke’s Hospital, Kansas City, Mo “Patients should not stop their fish oil supplements based on the Brasky paper.”

ogy at University of California Los Angeles. Yet Dr. Aronson’s work is focused not on preventing PCa but on delaying its progression.

He and his colleagues recently demonstrated that men with PCa who ate a low-fat diet and took fish oil supplements for four to six weeks prior to radical prostatectomy later had lower levels of pro-inflammatory substances in their blood and a lower Cell Cycle Progression score in their prostate tissue (as compared with a control Western diet group), suggestive of potential beneficial effects of the low-fat diet plus fish oil capsules, according to a report in Cancer Prevention Research (2014;7:97-104).

“The subtlety between preventing prostate cancer development and prostate cancer progression is that as men get older, most of them probably have small foci of these slower-growing prostate cancers, and no one ever finds them clinically,” Dr. Aronson pointed out. “So if you’re preventing something, how are you doing it? Is the action on the cells that might become cancer, or are you having the action on the foci of cells in there that are cancer and just preventing them from becoming clinical cancer?”

Dr. Aronson acknowledged that the answer to this complex question remains unknown. “Our next trial, which is launching in April, will randomize men with prostate cancer who have elected active surveillance to either a control group or a group that gets fish oil capsules combined with a low-fat diet.”

According to Dr. Aronson, the typical ratio of omega-6 fats to omega-3 fats in the American diet is approximately 15

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Eric A. Klein, MD, Glickman Urological and Kidney Institute, Cleveland Clinic “My message to patients is not that omega-3s aren’t important for health—they are. But most patients get an adequate amount of omega-3 in their diet, and taking extra is not helpful, and could be harmful.”

to 1. The typical ratio in the Asian diet is 4 to 1, and PCa is less prevalent among men living in Asia. “In our recently reported clinical trial, we manipulated the diet and fish oil capsules so the omega-6-to-omega-3 ratio was 2 to 1,” Dr. Aronson recounted. “So it was a favorable ratio, and we saw potentially favorable effects on the cancer.”

For now, Dr. Aronson does not counsel his PCa patients to consume fish oil. “At this point I’m advising a heart-healthy diet and weight loss if needed, because cardiovascular disease is still the number 1 cause of death in prostate cancer patients. I don’t even mention fish oil.

But if the patient brings it up, I simply say, ‘We’re really interested in that, and we’re doing more research in that important area. But I don’t recommend it.’”

Supplements not the answer Although Dr. Aronson’s research interventions include fish oil supplements, he makes a point of not relying solely on these products to strike the preferred balance between omega-6 and omega-3 fats. “Many people have the strategy of, ‘Let’s just give a pill,’ because that’s what everybody wants—they want to eat a lousy diet and do whatever they want and then just take a pill [to make up for nutritional deficits].

Eric A. Klein, MD, could not agree more. “You can protect your health by eating a balanced diet without overeating calories and exercising every day.

Taking a supplement to make up for deficiencies in one of the behaviors that can actually help you doesn’t work.”

Dr. Klein, who is the chairman of

Stephen J. Freedland, MD, Duke University School of Medicine, Durham, N.C. “At this point, if you’re taking omega-3s, I wouldn’t necessarily stop it, but I certainly wouldn’t recommend you go out and start taking them to slow prostate tumor growth.”

the Glickman Urological and Kidney Institute at the Cleveland Clinic in Cleveland, was a co-investigator along with Dr. Brasky as well as the national medical study coordinator for the National Cancer Institute’s Selenium and Vitamin E Cancer Prevention Trial (SELECT), on which the findings by Dr. Brasky’s team were based.

“There’s actually a pretty easy overview here,” Dr. Klein said. “The article [by Dr. Brasky and colleagues] fits with almost all the nutritional supplement literature that has looked at the effect of taking extra doses of vitamins or nutrients or other supplements and so forth. It showed pretty clearly across the board that if you’re deficient in those, the extra doses will help prevent diseases caused by those deficiencies. If you are replete in those substances—so, if you’re serum levels of omega 3 or vitamin E or selenium or whatever else are normal—taking extra is not going to help you. And in a subset of patients, taking extra is harmful. That’s what the main findings in Fish Rich in Omega-3 Fatty Acids Mackerel Tuna Salmon Sturgeon Mullet Bluefish Anchovy Sardines Herring Trout Source: National Institutes of Health

SELECT showed—higher incidence in prostate cancer in men who took highdose vitamin E—and that’s what this study shows, too: that higher plasma levels of omega-3s are bad for you.”

Taking too much can harm People need to realize that seemingly harmless, innocuous substances we consume in moderate amounts through our diets can be harmful when taken in excess, Dr. Klein said. “My message to patients is not that omega-3s aren’t important for health—they are. But most patients get an adequate amount of omega-3 in their diet, and taking extra is not helpful, and could be harmful. That’s my mantra for all nutritional supplements that have looked at prostate cancer and most other cancers as well.

That’s the way I look at it because that’s the recurring theme in all these studies.”

The most biologically available form of nutrients is in dietary consumption, and because these nutrients act not in isolation but in concert with many other molecules in the diet, Dr. Klein advocates dietary intake over supplement use. He illustrated the point with this example: “Some older studies suggest that eating pizza prevents prostate cancer, so research was done to look at whether one of the main ingredients in tomato sauce, lycopene, prevents prostate cancer. Well, it doesn’t when you just take it in isolation.

“Taking an isolated substance doesn’t deliver what one of my colleagues has called ‘the whole biological action package.’ Eating certain foods is certainly healthy, but picking out one particular component of that food and believing that that’s in and of itself the healthiest part of that food may not be correct.”

The bottom line, Dr. Klein said, is that everybody needs omega-3s to live normally, “but we don’t need extra omega-3. That doesn’t help unless you’re deficient.”

In Dr. Klein’s view, more research on the topic is not needed. “I think there are plenty of studies out there showing that nutritional supplements don’t prevent cancer or other major causes of morbidity in humans,” he noted.

Another prostate cancer specialist, however, is not ready to give up on the groundwork Dr. Klein has helped to lay. “It would be great if we could do a SELECT-type trial—a 30,000-person randomized trial to look at whether omega-3s could prevent prostate cancer, or maybe look at men who have prostate cancer to see if we can prevent progression,” said Stephen continued on page 16

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Omega-3 fatty acids continued from page 14

J. Freedland, MD, associate professor of both surgery and pathology at Duke University School of Medicine in Durham, N.C. He concedes, however, “I just don’t see the interest from the NIH at this point to fund that type of study.”

Dr. Freedland’s own research has shown that tumors in mice grew more slowly when the mice were given a diet heavy in fish oil rather than in saturated fats, corn oil, or even olive oil, which is generally considered to be a “healthy” oil. He can understand how these observations can take on a life of their own.

“There’s a fair amount of epidemiological literature linking fish intake with lower prostate cancer risk and lower risk

of progression,” Dr. Freedland said.

“People have often said, ‘Well, if fish is good, it must be the fish oil, and omega3s are good for you, and therefore we’ll jump on the omega-3 bandwagon.’ So, traditionally, the thought has been that omega-3s are good for you. Obviously, the new data that is kind of causing us to rethink it is that [Brasky] paper that says maybe they’re not so good.”

Dr. Freedland would like to get to the bottom of the issue, though. “If you take a supplement of omega-3—keep eating what you’re eating, and take a few pills—is that going to make a difference?

The answer is, we don’t know,” he said.

“It could be harmful, it could be helpful.

But it’s a question that I’m asked pretty much every day at the clinic. So I think it is very clinically relevant.”

He tells his male patients that there

certainly are data showing that eating fish is healthy and that the more omega3s animals eat, the slower their tumors grow. But he also informs these men that a recent study suggests that high blood levels of omega-3s are harmful.

Dr. Freedland ultimately shares the following advice with his patients: “At this point, if you’re taking omega-3s, I wouldn’t necessarily stop it, but I certainly wouldn’t recommend you go out and start taking them to slow prostate tumor growth.”

He added: “People are always going to clamor for taking a pill, and what I really try to get them focused on is viewing the big picture, viewing their entire lifestyle and trying to make more broad changes to how they eat and how they exercise.”

How can clinicians keep a clear head

Renal & Urology News 16

and sort through the onslaught of information regarding omega-3 intake and similar findings? “I think the challenge is, with exception of these big 20,000-person, 30,000-person, even 2,000-person trials, none of these answers are definitive,” Dr. Freedland said. “When a good, well-done study is published in a big journal and is picked up by the media, all of a sudden people start to think that’s the answer.”

He pointed out, however, that there is no easy answer when it comes to these types of studies. “At the end of the day, it’s clear we’re missing pieces, or have pieces that don’t fit together, but you still have to treat patients and make recommendations. So I think a healthy degree of skepticism and moderation are probably in general good skills for readers of the literature to have.” n

Computed Tomography May Prostate Cancer Death More Be Avoidable for Small Stones Likely with Watchful Waiting BEDSIDE ultrasound (US) may help emergency department physicians decide which patients with renal colic require treatment, according to study findings published in the Western Journal of Emergency of Medicine (2014;15:96-100).

The retrospective single-institution study, led by Jeff Riddell, MD, of the University of California San FranciscoFresno, included 125 patients with computed tomography (CT)-proven renal calculi and documented bedside US results. The overall sensitivity of US for detecting hydronephrosis was 78.4%.

The overall sensitivity of a positive US finding of either hydronephrosis or visualized stones was 82%. The sensitivity of bedside US for detecting hydronephrosis was significantly higher among patients with stones 6 mm or larger in diameter than among those who had smaller stones (90% vs. 75%).

Abnormal US findings or the presence of hematuria enabled identification of all patients with stones 6 mm or larger in diameter who would benefit from medical expulsive therapy.

The study also showed that US sensitivity increased along with stone number.

The sensitivity was 75% for patients with a single stone, 94% for patients with 2 stones, and 100% for those with 3 stones.

The authors noted that microscopic hematuria was absence in 23% of cases, including 4 patients with stones larger than 10 mm in diameter.

Dr. Riddell and his colleagues stated that in their study, patients without evidence of stones on emergency

RUN0413_Omega3.indd 16

department bedside US and without hematuria could be safely assumed to have stones less than 6 mm if detected on CT. “Given that these smaller stones typically do not require surgical intervention and do not appear to benefit from medical expulsive therapy, we hypothesize that clinical assessment followed by urinalysis and bedside US could obviate the need for CT in this subset of patients,” they noted.

Dr. Riddell’s group noted that noncontrast CT is widely considered the gold standard for diagnosing urinary stones in emergency department patients, but it is costly and time-consuming and it exposes patients to significant doses of ionizing radiation.

The researchers acknowledged a number of study limitations, including incomplete documentation, missing charts, and variance in the quality of information recorded. Additionally, their cohort only included patients with a final diagnosis of renal colic and not all patients presenting to the emergency department with flank pain, they pointed out. “Inclusion of patients with CT-proven stones only may have introduced bias,” they observed.

More than half of the patients diagnosed with colic in the emergency department did not receive CT imaging, the researchers noted. Those who had CT scans may have had more severe symptoms and subsequently a higher grade of obstruction, possibly leading to an overestimation of the frequency of hydronephrosis. n

PATIENTS with early prostate cancer

In addition, results showed that the

(PCa) are substantially less likely die

RP group overall had a significant 43%

from the disease if they undergo radical

decreased risk of distant metastases,

prostatectomy (RP) instead of watchful

but the decreased risk was greater

waiting, especially if they are younger

among men younger than 65 (51% vs.

than 65 years, a study found.

32%). The decreased risk associated

The finding emerged from the

with RP varied by tumor risk. Compared

Scandinavian Prostate Cancer Group

with the watchful-waiting group, RP

Study Number 4, in which investigators

patients with low- and intermediate-risk

randomly assigned 695 men with early

tumors had a significant 60% and 51%

PCa to undergo RP or watchful waiting.

decreased risk of distant metastases.

During the study, 200 of 347 men in the

Patients with high-risk tumors had a non-

RP group and 247 of the 348 men in the

significant 19% decreased risk.

watchful-waiting group died.

At 18 years of follow-up, RP was asso-

The RP group had a significant overall 51% decreased risk of receiving

ciated with an overall significant 44%

androgen-deprivation therapy (ADT),

decreased risk of death from PCa com-

with a large reduction observed in men

pared with watchful waiting, Anna Bill-

younger than 65 compared with older

Axelson, MD, PhD, of Uppsala University

men (61% vs. 40%). The risk reduction

Hospital in Uppsala, Sweden, and

did not differ by tumor risk.

colleagues reported in The New England

“The hypothesis-generating subgroup

Journal of Medicine (2014;370:932-

analyses and the large proportion of

942). Men younger than 65 years had

long-term survivors in the watchful-wait-

a significant 55% risk reduction, where

ing group who never required palliative

older men had a non-significant 25%

treatment provide support for active sur-

decreased risk.

veillance as an alternative in adequately

Overall, at 18 years of follow-up men

selected groups,” the investigators

in the RP group had a significant 29%

concluded. “However, the overall long-

decreased risk of death from any cause,

term disease burden is also a reminder

but the decrease was significant only in

that factors other than survival should

men younger than 65 years (who had

be considered when counseling men

a 50% decreased relative risk). Older

with localized prostate cancer; the risk

men had a non-significant 8% decreased

of metastases and ensuring palliative

relative risk.

treatments also affect quality of life.” n

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Renal & Urology News 17

Sidestepping Sepsis via Transperineal Prostate Biopsy Although transrectal ultrasonography (TRUS)-guided biopsy is the most commonly used technique for making the histologic diagnosis of prostate cancer, rising rates of readmission rates for subsequent sepsis have given urologic surgeon Jeremy P. Grummet, MBBS, MS, FRACS, pause. Chair of the Genito-Urinary Cancer Multidisciplinary Team at Alfred Health in Melbourne, Victoria, Australia, Dr. Grummet performs almost ­exclusively transperineal prostate biopsies, with a postprocedural sepsis readmission rate of zero to date, as he and his colleagues have reported in BJU International.

Dr. Grummet discussed his change in practice with Renal & Urology News.

BY DELICIA HONEN YARD What inspired you to examine the issue of sepsis rates following transrectal vs transperineal (TP) prostate biopsy?

Dr. Grummet: Like other urologists, I was trained in doing TRUS biopsies. It was, and still is, considered the norm, and the risk of sepsis was accepted as part of it, so we always gave prophylactic antibiotics for it.

I continued doing TRUS biopsies in my own practice, but despite the usual prophylactic quinolones, I was seeing too many men in my own and my colleagues’ practices coming back to the hospital septic. And these guys were sick. They felt awful, and sometimes needed intensive care support—all this just because of a minor diagnostic procedure.

But we had started to do TP biopsies as a confirmatory biopsy for active-surveillance patients, so we gained some experience with this approach as well.

As TP biopsy avoids breach of the rectal wall altogether, it seemed logical

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on the other hand, requires booking your patient onto an operating list, having more sophisticated equipment, and giving a general anesthetic, and it takes considerably longer to do (although once you’ve got the process streamlined, it’s less than 20 minutes).

So not only do you need additional resources, if you’re a busy practicing urologist it’s hard to make the mental shift to offering TP biopsy. But it’s a procedure that’s easy enough to learn, so the learning curve shouldn’t be a barrier.

In your 2014 BJU International study (“Sepsis and ‘superbugs’: should we favour the transperineal over the transrectal approach for prostate biopsy?”), you state that there has been a noticeable rise in the rate of TRUS-biopsy sepsis with the increasing prevalence of multi-resistant organisms. How can wider use of TP biopsy help to combat this?

that it would carry a much lower risk of sepsis, so we checked the literature as well as our own experience.

Is TP prostate biopsy considered controversial?

Dr. Grummet: I don’t think TP biopsy is controversial in terms of cancer detection. There’s no reason why it should be inferior to TRUS biopsy in this regard, and the evidence to date supports that.

Rather, the controversy is based on whether we as urologists have access to the necessary equipment and to the operating-room time needed to perform TP biopsy, as it typically requires a general anesthetic.

What would stop physicians from adopting TP prostate biopsy?

Dr. Grummet: A TRUS biopsy under local anesthetic can be performed in the urologist’s office in under 10 minutes. So it’s quick, easy, relatively cheap, and very convenient. You can even do it between consultations. TP biopsy,

It’s very rare for a patient to have a contraindication to TP biopsy. ­—Jeremy P. Grummet, MBBS, MS, FRACS

Dr. Grummet: TP biopsy essentially renders multiresistant organisms irrelevant. These bacteria are becoming more and more common in rectal flora.

But as long as they stay in the rectum, they don’t cause an issue, as is the case with TP biopsy. TRUS biopsy, on the other hand, allows entry of these multiresistant rectal bacteria via the biopsy gun directly into the vascular prostate, and thereon into the bloodstream.

In your study, none (zero) of 245 patients who underwent TP prostate biopsy had to be readmitted to the hospital for sepsis infection, whereas the rate of sepsis after TRUS biopsy is as high as 5%. Why is it so important to reduce the rate of post-biopsy sepsis even further, to the point of changing the gold standard of prostate biopsy (TRUS)?

Dr. Grummet: First of all, I think it’s important to remember that TRUS biopsy sepsis rates are usually lower than 5%, although that rate has certainly been reported. Our own region’s sepsis rate is more in the order of 1%–2%. But I would argue that even that’s too high given the morbidity that sepsis causes, especially when we have an alternative available where sepsis is exceedingly rare.

Many practicing colleagues would seem to agree that current rates of sepsis are a real concern as evidenced by the increasing use of carbapenems such as meropenem as prophylaxis for TRUS biopsy. Whilst this is a well-meaning attempt to minimize TRUS biopsy sepsis in individual patients, it is surely a step backwards in preventing further development of multiresistant bacteria, such as CRE [carbapenem-resistant enterococci], which the CDC has labeled an urgent threat to public health. Carbapenems are almost never required in TP biopsy for treatment as sepsis rarely occurs, and are certainly not needed for prophlyaxis.

So TP biopsy can reduce the continued on page 18

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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Grummet continued from page 17

morbidity of sepsis in individual patients as well as potentially help reduce the public health risk of antibiotic resistance. In doing so, TP biopsy could also reduce the enormous financial costs of these problems. These offsets must also be borne in mind when we consider the cost of the procedure of TP biopsy itself, and our group is researching this at the moment.

Why didn’t you do a direct comparison between patients undergoing TP prostate biopsy and patients undergoing TRUS biopsy?

Dr. Grummet: That was beyond the scope of our resources at the time, and our research group [the Victorian Transperineal Biopsy Collaboration, or VTBC] hadn’t been keeping a prospective database of TRUS biopsies. But we currently have a full-time researcher looking at this now.

In your report you state that TP biopsy should be offered to all men in need of prostate biopsy, but is there a subset of patients who are particularly unfit for this approach?

Dr. Grummet: It’s very rare for a patient to have a contraindication to TP biopsy.

I have only turned down one so far.

The only contraindications that come to mind are if the patient cannot fully flex his hips, as TP biopsy requires the

patient to lie in the extended lithotomy position, or if the patient has a prosthesis such as an inflatable penile prosthesis or an artificial urinary sphincter, as the tubing of these devices may be at risk of puncture. However, if such prostheses are in place, it’s usually because of treatment for prostate cancer, not during the diagnostic process, so this would be very rare.

I should also point out that you can even do a TP biopsy on patients without a rectum (e.g., post-abdominoperineal resection) and we have done a couple of these. It’s by no means as accurate, as you have to use a transabdominal ultrasound probe, which is not related to the template grid, but it’s feasible.

Is TP biopsy now your main recommendation for men undergoing biopsy?

Dr. Grummet: About a year ago, I asked myself the question: “If I had to have a prostate biopsy myself, what would I choose?” And the answer was a resounding “TP biopsy.” I think this question is always a pretty telling one in terms of what we should be offering our patients.

So, yes, my prostate biopsy practice is almost entirely TP for both first and repeat biopsies. But I have the luxury of access to the right equipment and to operating-room time for TP biopsy, and these are the main constraints preventing many other urologists from doing the same.

I tell patients who need a biopsy that there are two main ways of doing it, and I explain the pros and cons of each. The question then usually comes back to me, “So why would anyone choose a TRUS biopsy?”

But for urologists who have limited access to TP biopsy, I would recommend that they at least consider TP biopsy for any repeat biopsy, whatever the indication for that may be, and also for any patient with risk factors for TRUS biopsy sepsis, such as prior quinolone use or recent overseas travel—particularly to Asian countries where multiresistant bacteria are endemic.

In your own practice, how does TP prostate biopsy compare with TRUS biopsy in terms of sepsis occurrence?

Dr. Grummet: As mentioned above, our local region’s rate of TRUS biopsy sepsis is less than 2%, but so far there continue to be zero cases of sepsis in our research group’s experience of TP biopsy and we have now done over 400 (unpublished).

What is your next step in evaluating or promoting the increased use of TP prostate biopsy over TRUS-guided prostate biopsy?

Dr. Grummet: I’m very lucky to have been able to gather together a powerhouse of Australian clinical urology researchers in Declan Murphy, Mark Frydenberg, Nathan Lawrentschuk,

and Daniel Moon to form the VTBC, so we have a few irons in the fire at present!

We have aligned our database with the Ginsburg Study Group’s minimal dataset for TP biopsy with a view to international collaboration.

We are currently evaluating the human and financial costs of TRUS biopsy and its rate of sepsis versus TP biopsy and its near-zero rate. This is obviously a major factor in whether a change of practice is feasible on a larger scale. We are also assessing possible risk factors for TRUS biopsy sepsis, so that patients might be better selected for one technique or another while a transition is made towards TP biopsy more generally.

Last year I ran a workshop in Melbourne for urologists and urology trainees wanting to take up TP biopsy.

This drew great interest, so I’m planning another one this year.

Also along with colleagues from all around Australia and New Zealand, I have lobbied our region’s urological society (USANZ) for action in further evaluation and promotion of TP biopsy. USANZ has a proud tradition of proactively working to improve the care of urology patients, as evidenced by their promotion of active surveillance for low-risk prostate cancer via the PRIAS study (www.prias-project. org), and has agreed to our requests regarding TP biopsy, so I’m very excited about that. n

Blood Transfusions Up RCC Patient Mortality PERIOPERATIVE blood transfusion (PBT) is associated with an increased risk of death among patients who undergo surgery for non-metastatic renal cell carcinoma (RCC), according to a new study.

A team at Mayo Clinic in Rochester, Minn., led by Stephen A. Boorjian, MD, studied 2,318 patients who underwent partial or radical nephrectomy for non-metastatic RCC. They defined PBT as a transfusion of allogenic red blood cells during surgery or post-operative hospitalization. Of the 2,318 patients, 498 (21%) received a PBT. The median number of units transfused was 3. The median followup was 9.1 years.

Five-year cancer-specific and overall survival rates were significantly lower for patients who received a PBT (68% vs. 92% and 56% vs. 82%, respectively), Dr. Boorjian’s group reported online ahead of print in BJU

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International. On multivariate analysis, receipt of PBT was associated with a significant 23% increased risk of death, but the association between receipt of PBT and death from RCC and tumor recurrence did not reach statistical significance, according to the investigators.

The study found that the risk of allcause mortality increased along with the number of units transfused. Each unit transfused was associated with an 8% increased risk of death, the researchers reported.

“While these results represent outcomes from a single tertiary care centre, and external validation is needed, continued efforts to limit the use of blood products in these patients are needed,” the authors concluded.

In addition, the researchers found that patients who received a PBT were significantly older at the time of surgery and significantly more likely to

be female. Study results also showed that they were more likely to have symptomatic presentation and adverse pathologic features.

The authors cited previous studies showing that nephrectomy is associated with a PBT rate ranging from 2.5%-18.1%.

Dr. Boorjian and his colleagues noted that the retrospective, non-randomized study design were limitations of their investigation. Patients who did and did not receive a PBT had significant clinicopathologic differences, they pointed out. Even with adjusted analyses, “these discrepancies may not have been entirely accounted for, and may therefore have impacted our reported findings.”

In addition, they noted, “the decision for PBT was based on the discretion of the treating physicians, without adherence to specific criteria thresholds for transfusion.”

Previous studies have demonstrated an increased risk of cancer recurrence in patients receiving a PBT after surgery for colon, hepatic, and esophageal cancers, the researchers noted. Studies have produced conflicting results with respect to genitourinary malignancies. For example, a retrospective study published in the American Journal of Surgery (1988;156:374-380) found that among patients who underwent surgery for prostate cancer (PCa), those who received a PBT had a higher frequency of recurrence and cancerrelated death compared with patients who did not receive a PBT. A study published more recently in Urologic Oncology (2008;26:364-367), however, found that PBT in men undergoing radical retropubic prostatectomy for clinically localized PCa did not appear to influence the risk of biochemical failure. n

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Practice Management Cutting down on no-shows requires understanding who is not keeping appointments and why BY TAMMY WORTH

The culprits The first thing an office needs to know to reduce the number of no-shows is to understand who is not keeping appointments and why. Hertz said offices can expect to have, on average, a 5%-6% no-show rate and not have a big problem. Anything much higher needs to be analyzed.

It’s the job of the practice administrators, not the doctors, to figure out what’s going on. He said they need to look at the patients and find out if there are common threads.

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“You have to identify what is causing it, what groups they are, if there are key themes that link them together,” Hertz said. “Maybe many have a doctor who constantly runs three hours late and the patients give up.” It also could be that the doctor tells patients they are okay and that they should come back in a month, and the patients just don’t return.

Hertz said it’s worth making a phone call to the patients to ask why they didn’t show up. And any no-show should receive a call to reschedule.

Avoiding a loss One of the main strategies a lot of physicians use to reduce no-shows is charging patients a fee for a missed appointment. Although this can work in some cases, Elizabeth Woodcock, of Woodcock & Associates in Atlanta, said charging needs to be combined with prevention.

“You need to make sure you’re doing a good job internally before starting to charge,” she said. “We want to see patients … the intention isn’t to charge, but to make sure they show up.”

One of the main things physicians can do is have a phone reminder system. Woodcock said it’s a good idea to call people at least two days before the visit. This might also be combined with a text reminder three to four hours prior to the appointment.

An option to use with this kind of system is creating a response so patients can push a certain number if they are going to miss the appointment. This can be a good way to catch people who might not call into the office. Office staff should be cautious of telling patients to be prepared to pay their co-pay during the message.

It may keep people who are having

© THINKSTOCK

K

en Hertz is a consultant for the Medical Group Management Association and teaches physicians how to reduce the number of patients who don’t show up for appointments—patients like himself.

Hertz has a family history of cardiovascular disease, is a noncompliant diabetic, and typically only exercises on the day or two before his physicals.

Two years ago, he missed his annual stress test because he was travelling for work. He has never gone back in for the testing.

Hertz is the typical patient who misses an appointment and falls off of the cliff. This is especially problematic because he is a friend of the physician and knows most of the people in the practice. No one ever called to followup and he never thinks to make the call.

When doctors think of no-show patients, they often understand that it is like having an empty seat on a plane: You still incur overhead costs for the flight, but have lost the chance for potential revenue. Many times, however, these patients don’t return for the visit, checkup or tests needed and it can have a dramatic affect on the quality of their care.

On average, medical offices can expect to have a 5%-6% no-show rate, a consultant said.

financial difficulty from making their appointments.

Another way to reduce no-shows is by paying special attention to new referrals. If patients have never been to the practice before, make sure they know how to get there and why they were referred. Hertz said it is common to have a primary care provider call an office, say they need an appointment for a patient, and the patient doesn’t know the doctor actually scheduled an appointment. Woodcock said it is always wise to call new patients, particularly if there was a long wait time, because they might have gone somewhere else.

Calling well in advance when there is a long time between appointments is good practice even for established patients. If a patient is going to be seen once every few months, twice a year or annually, it is a good idea to make sure you sent them ample reminders.

“If a patient has prostate cancer and is seen by the urologist once a year, you can’t schedule a year in advance and give them a small card and call the night before,” Woodcock said.

She recommends creating a list by month. If a patient needs to be seen in February of next year, for instance, indicate on the calendar to call in January to set up an appointment. Hertz recommends creating a tickler file that triggers office staff to send out reminder cards a month in advance of appointments that are set a long way out. The cards can ask patients to call to confirm or reschedule prior to the appointment.

“This way, you are actively managing care, and not just with appointments a year out,” Woodcock said. “Patients are really asking for it, and we have not as an industry done it.” n Tammy Worth is a freelance medical journalist based out of Blue Springs, MO.

Want to improve your practice? Look for our tips on how to handle equipment issues, adjust to EHRs, ­comply with HIPAA, and more at www.renalandurologynews.com/practice.

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■ Special to Renal & Urology News

CROWNWeb Data Management: Supporting Infection Control and Hospitalization Rate Reduction An overview of how data from the Centers for Medicare & Medicaid Services’ CROWNWeb system could provide additional support to infection control and hospitalization rate-reduction efforts.

BY ONIEL DELVA, BA, AND JAMILA SEATON, MPH Serious infections that require hospitalization are among the major risks of renal replacement therapy. Infections can affect patients in any healthcare setting—e.g., peritonitis in an individual on peritoneal dialysis, septicemia in a hemodialysis patient, or something that is not directly related to the patient’s treatment such as a pulmonary infection or pneumonia. Infections are the second leading cause of death among hemodialysis patients.1 In 2011, the Centers for Disease Control and Prevention (CDC) estimated that about 37,000 bloodstream infections occur each year among kidney dialysis patients with central lines, and of patients who get a bloodstream infection from having a central line, up to one in four die.

Furthermore, since 1993, hospitalization rates among hemodialysis patients have increased an estimated 47% for bloodstream infection and an estimated 87% for vascular access infection.2 The Centers for Medicare & Medicaid Services (CMS) requires that facilities establish and maintain a data-driven Quality Assessment and Performance Improvement (QAPI) Program that focuses on indicators related to improved health outcomes and the prevention and reduction of medical errors.3 This program, which is an element of the Conditions for Coverage for End-Stage Renal Disease Facilities (ESRD CfCs), requires facilities to implement an infection control plan. Furthermore, § 494.80(d) of the ESRD CfCs indicates that facilities must perform monthly assessments of the frequency of patient hospitalizations to help develop patient treatment plan and expectations for care. These data must be continuously monitored and available for review during CMS survey visits. For years, facilities have

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stored patient infection and hospitalization data in their internal computer systems or manually, but facilities now have the ability to utilize CMS’ CROWNWeb data collection system to assist them with their data management efforts, and as a means of reporting this data directly to CMS.

CROWNWeb Overview CROWNWeb is a secure Web-based data collection system that is primarily used by Medicare-certified dialysis facilities to capture and report clinical and administrative ESRD data to CMS in real time. The system retains pertinent information that is reported to CMS in support of the ESRD CfCs, ESRD Network goals, the CMS National Quality Strategy and the Three Aims, Dialysis Facility Compare (DFC), the ESRD Quality Incentive Program (QIP), as well as the United States Department of Health & Human Services’ National Action Plan to Prevent HealthcareAssociated Infections: Roadmap to Elimination. While the data collected in CROWNWeb are used to assist facilities with meeting the requirements of specific CMS initiatives, dialysis treatment providers can take advantage of the system’s ability to capture facility and personnel details, patient treatment summaries, and clinical performance data to support their efforts in using data to monitor facility performance and the quality of clinical care, and to identify opportunities for improvement.

Support for Infection Control and CMS Initiatives According to the ESRD Prospective Payment System, Quality Incentive Program Rule published in the Federal Register, facilities must report infections through the CDC’s National Healthcare Safety Network (NHSN)

Figure 1: Example of CROWNWeb’s Infection Fields.

as part of the ESRD QIP. The NHSN gathers infection data that are used to assist facilities with earning their ESRD QIP points, and to obtain an overview of surveillance efforts. However, the CROWNWeb system, which captures data related to the quality of patient treatment efforts, features a simplified “Infection” section where facilities can submit data if there were any infection-related challenges that impacted a hemodialysis or peritoneal dialysis patient’s treatment during the reporting month. When submitting their clinical performance data, facilities can indicate if a patient has an infection, whether the infection was access-related, and if it required hospitalization (see Figure 1 for an example of the “Infection” fields in CROWNWeb).

Reporting infection and hospitalization data through CROWNWeb provides the ESRD community immediate

access to information that complements CMS standards and programs such as the Fistula First Catheter Last (FF/CL) initiative. Established by CMS in 2003, the Fistula First initiative provides a means to help improve care for people with chronic kidney disease by increasing arteriovenous (AV) fistula placement and use in suitable hemodialysis patients.

It is important that ESRD patients, a population vulnerable to infection, receive dialysis care in a way that reduces the risk of healthcare acquired infections. Thus, it is important that infection rates within facilities be monitored. Using CROWNWeb’s data, facilities are able to determine if patients with a particular access type are contracting infections more than other patients, as well as if these patients are being hospitalized more frequently. In addition, authorized

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ESRD stakeholders could use this data to analyze if patients within particular facilities are being hospitalized more frequently. These factors help serve as indicators of the health of the ESRD population and the quality of services being provided by facilities.

The use of ESRD-specific infection data for the general population is important for surveillance purposes.

However, as a central repository for all ESRD patient data and the ESRD registry, CROWNWeb helps describe the health of the ESRD population.

This data could be analyzed as a tool to measure facility quality improvement efforts as well as CMS initiatives to ensure that infection and hospitalization rates are decreasing with the implementation of CMS standards.

Monitoring Hospitalization Trends Hospitalization rates are an important indicator of patient morbidity and quality of life.4 Dialysis patients are admitted to the hospital approximately twice a year on average, and spend an average of 12 days in the hospital each year.4 Collecting and understanding data on the frequency of hospitalization and the diagnoses associated with potentially preventable hospitalizations assist in efforts to improve patient outcomes, patient satisfaction, and play an important role in providing cost-effective health care.4 Per V520 of the ESRD Program Interpretive Guidance—used by state surveyors to assess ESRD facilities’ compliance with CMS regulatory requirements—facilities must track patient hospitalizations at least monthly to determine the stability of hospitalization rates. This includes tracking extended hospitalizations, which

are defined as hospitalizations longer than 15 days, and frequent hospitalizations—more than three hospitalizations in a month.

In an additional effort to help improve the overall quality of care for ESRD beneficiaries, CMS has implemented a three-part goal (“the Three Aims”) that challenges facilities, healthcare workers, and beneficiaries across the nation to work in collaboration to improve site-specific care by incorporating goals that foster a nation of healthier people, better health care for individuals, and reduced health care cost for all beneficiaries (through better quality care).

Data entry into CROWNWeb helps support these initiatives by displaying ESRD patient care results, and giving facilities a way to monitor trends in indicators such as patient hospitalizations and promote prevention practices.

CROWNWeb enables facilities to capture details regarding the length and frequency of patient hospitalizations by allowing them to enter multiple records per patient per month. The system’s “Hospitalization” section allows facilities to note the hospital admission and discharge dates, as well as information on the type of event that resulted in the hospitalization. (See Figure 2 for an example of the hospitalization fields in CROWNWeb.)

More Information Medicare-certified dialysis facilities utilize CROWNWeb to meet §494.180(h) of the 2008 updated ESRD CfCs, which calls for the electronic submission of administrative and clinical data to CMS. The system collects clinical performance data that are used in CMS’ Quality Measures Project, as well

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Figure 2: Example of CROWNWeb’s H ­ ospitalization Fields.

as gathers data for the agency’s ESRD QIP. CROWNWeb was released nationally on June 14, 2012, and is utilized by more than 5,800 dialysis facilities throughout the United States and U.S. territories.

For more information on the CROWNWeb system and an overview of how the dialysis community is using CROWNWeb to meet CMS data submission requirements, visit the Project CROWNWeb website at www.projectcrownweb.org, or go to www.qualitynet.org and click on the ESRD tab. n The work on which this publication is based was performed under Contract Number HHSM-500-2011-00157G, titled “CROWNWeb Outreach, Communication, and Training,” funded by the Centers for Medicare & Medicaid Services, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department

of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

The authors assume full responsibility for the accuracy and completeness of the ideas presented. They welcomes comments on the ideas presented; please send comments to CRAFT@projectcrownweb.org.

Publication Number: FL-OCT-2013OCTT2-10-1392 REFERENCES: 1. Centers for Disease Control and Prevention. Dialysis Safety. Updated Dec. 7, 2012. Available at http:// www.cdc.gov/dialysis/patient/index.html. Accessed Aug. 9, 2013.

2. Centers for Disease Control and Prevention. National Healthcare Safety Network (NHSN). Updated Jan. 24, 2013. Available at http://www.cdc.gov/nhsn/ psc_da_de.html. Accessed Aug. 9, 2013.

3. Centers for Medicare & Medicaid Services. Measures Assessment Tool. Oct. 3, 2008. Available at http:// www.cms.gov/Medicare/Provider-Enrollment-andCertification/SurveyCertificationGenInfo/downloads/ SCletter09-01.pdf. Accessed Aug. 9, 2013.

4. University of Michigan Kidney Epidemiology and Cost Center. Guide to the 2012 Dialysis Facility Reports: Overview, Methodology, and Interpretation. July 2012. Available at http://www.dialysisreports.org/ Methodology.aspx. Accessed Aug. 9, 2013.

Dancing Exercises Found to Ease Urinary Incontinence A PROGRAM combining pelvic floor muscle exercises with virtual-reality rehabilitation in the form of danc-

strengthen their pelvic floor muscles.

Chantale Dumoulin, PhD, of the School of

of women (91%) said they were very satisfied with treatment.

ing proved to be an efficient and satisfying treatment

Rehabilitation at University of Montreal in Quebec,

As Dr. Dumoulin pointed out in a statement issued

in a small study of older women with mixed urinary

and fellow investigators reported online ahead of

by the University of Montreal, compliance with the pro-

print in Neurourology and Urodynamics that most

gram is a key success factor, as more practice will lead

study participants attended the weekly treatment

to stronger pelvic floor muscles. “Our challenge was to

older (mean age 70.5 years) with at least two weekly

sessions (91%), adhered to home exercise (92%), and

motivate women to show up each week,” Dr. Dumoulin

episodes of mixed urinary incontinence. The partici-

completed the three evaluations (96%). Compliance

said. “We quickly learned that the dance component

pants were evaluated twice before and once after a

was higher among these patients than among women

was the part that the women found most fun and didn’t

12-week training program incorporating pelvic floor

receiving usual care.

want to miss.”

incontinence.

The study focused on 24 women aged 65 years and

muscle exercises and virtual-reality rehabilitation. In

Postintervention, the frequency and quantity of urine

The dance period also served as a way for the women

this initiative, a series of dance exercises were added

leakage decreased to a greater degree than seen in

to exercise pelvic floor muscles that are traditionally

to a physiotherapy program by means of a video-game

the usual-care group, and patient-reported symptoms

static and to learn how to contract those muscles

console. The effort was designed to help the women

and quality of life improved significantly. The majority

­during daily activity to prevent urine leakage. n

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