Renal and Urology News - April 2015 Issue

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High Fluid Intake Lowers Stone Risk Meta-analysis finds a reduction in the likelihood of incident and recurrent kidney stones BENEFITS OF HIGH FLUID INTAKE CONFIRMED A meta-analysis showed that high-fluid intake decreased the risks of incident and recurrent kidney stones. The decrease in risks varied according to whether the studies in the meta-analysis were randomized controlled trials or observational studies.

80

80%

70 60 50

60%

Randomized controlled trials Observational studies

60% 51%

40 30 20 10 0

Incident stones

Recurrent stones

Source: Data presented at the National Kidney Foundation’s 2015 Spring Clinical Meetings in Dallas. Poster 147.

BY JODY A. CHARNOW DALLAS—Data from separate studies presented at the National Kidney Foundation’s 2015 Spring Clinical Meetings may help improve clinicians’ ability to manage kidney stones.

In a meta-analysis, researchers found that high fluid intake is effective and appears to be safe for the prevention of incident and recurrent kidney stones.

The other study, in which investigators analyzed 24-hour urine specimens from non-Hispanic whites, demonstrated that age and sex influence the excretion of key urinary factors related to kidney stone risk.

Both studies were led by John C. Lieske, MD, of Mayo Clinic in Rochester, Minn.

The presenting authors, also of Mayo,

CKD, Pregnancy Problems Linked Interarm BP

BY NATASHA PERSAUD “The findings indicate that any kidDifferences WOMEN WITH chronic kidney ney disease—even the least severe, disease (CKD), even stage 1, have such as a kidney scar from a previAffect CV Risk increased risks of adverse pregnancy ous episode of kidney infection, with outcomes, according to a new Italian study. The findings might lead to improved prenatal counseling and monitoring practices of women with CKD during pregnancy.

normal kidney function—has to be regarded as relevant in pregnancy, and all patients should undergo a particularly careful follow-up,” lead researcher continued on page 9

STATIN MEDICATIONS AND GENITOURINARY CANCERS

Mounting evidence suggests a possible role as adjunctive therapy.

PAGE 13

BY JODY A. CHARNOW INCREASED INTERARM systolic blood pressure difference independently predicts cardiovascular (CV) events in patients with chronic kidney disease (CKD), according to a new study.

Borja Quiroga, MD, and colleagues at Hospital General Universitario Gregorio Marañón, in Madrid, Spain, prospectively studied 652 CKD patients with a mean age of 67 years. The study population had a mean follow-up period of 19 months. Of these patients, 136 (20.8%) had diabetes mellitus, 213 (32.6%) had a history of cardiovascular disease, and 327 (50.1%) had dyslipidemia. The interarm systolic blood pressure difference (IASBPD) was 10 mm Hg or greater in 184 patients (28.1%). The investigators noted that previous research found a correlation between an IASBPD of 10 mm Hg or greater and CV risk factors in the general population and in patients with specific conditions such as vascular disease and diabetes mellitus.

were Wisit Cheungpasitporn, MD, and Majuran Perinpam, BSc, respectively.

The meta-analysis included 9 studies: 2 randomized controlled trials (RCTs) with 269 patients and 7 observational studies with 273,685 patients.

High fluid intake—defined as intake sufficient to achieve a minimal urine volume of 2.0–2.5 L/day—was significantly associated with a 60% decreased risk of incident kidney stones in RCTs and a 51% decreased risk in observational studies. In addition, high fluid intake was significantly associated with a 60% decreased risk of recurrent stones in RCTs and an 80% decreased risk in observational studies. continued on page 9

IN THIS ISSUE 5

Vitamin D deficiency is associated with post-transplant UTI

6

Obese women are more likely to develop renal cell carcinoma

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Cancer risk is elevated in hemodialysis patients

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Statins may protect patients from contrast-induced nephropathy

15

Stroke risk increases as glomerular filtration rate declines

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Unhealthy eating habits raise CKD risk in the urban poor

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Hurricane Sandy adversely affected dialysis patients

The lack of adherence to a DASH-style diet found to raise CKD risk among the urban poor PAGE 15

continued on page 9

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ED Drug Use May Worsen RP Results Phosphodiesterase type 5 inhibitor use found to increase risk of biochemical recurrence ORAL ERECTILE DYSFUNCTION DRUGS AND PSA RELAPSE

A study showed that patients who used phosphodiesterase type 5 inhibitors after radical prostatectomy for prostate cancer had a higher risk of biochemical recurrence (BCR). The 5-year BCR-free survival rates for the overall cohort and a subset of propensity score matched patients are shown here.

PDE5 Non-PDE5

84.7% 89.2% Overall cohort

84.6% 89.1% Propensity score matched patients

Source: Michl U et al. Use of phosphodiesterase type 5 inhibitors may adversely impact biochemical recurrence after radical prostatectomy. J Urol. 2015;193:479-483.

BCG Plus Sunitinib Promising

BY JODY A. CHARNOW ORLANDO, Fla.—Intravesical bacillus Calmette-Guérin (BCG) followed by sunitinib shows promise as a treatment for high-risk nonmuscle-invasive bladder cancer (NMIBC), according to the findings of a phase 2 trial.

Alexander M. Helfand, BA, principal investigator Alon Weizer, MD, MS, and

colleagues at the University of Michigan in Ann Arbor presented results from 36 evaluable patients with a median age of 65.9 years who received the combined treatment for high-grade clinical NMIBC without lymph node involvement or distant metastases. The patients received BCG induction followed 2 weeks later continued on page 9

STATIN MEDICATIONS AND GENITOURINARY CANCERS

Mounting evidence suggests a possible role as adjunctive therapy.

PAGE 13

BY JODY A. CHARNOW USE OF ORAL erectile dysfunction drugs after radical prostatectomy (RP) for prostate cancer is widespread, but it may increase the risk of biochemical recurrence, according to a new study.

The study included 4,752 consecutive patients with localized PCa treated with bilateral nerve-sparing RP, of whom 1,110 (23.4%) received selective phosphodiesterase type 5 (PDE5) inhibitors after RP and 3,642 (76.6%) did not. PDE5 inhibitors included sildenafil, vardenafil, and tadalafil. The study population had a median follow-up of 60.3 months.

Overall, the 5-year biochemical recurrence (BCR)-free survival estimates were statistically significantly lower in the patients who used PDE5 inhibi-

Delayed RP Following AS Appears Safe

BY NATASHA PERSAUD ORLANDO, Fla.—Delaying radical prostatectomy after a period of active surveillance (AS) did not appear to lead to worse prostate cancer (PCa) pathology in a prospective AS cohort, researchers reported at the 2015 Genitourinary Cancers Symposium.

“A period of initial surveillance appears to be safe, even for men who later experience Gleason score upgrading,” said first author Christopher J. Welty, MD, MS, of the University of California, San Francisco.

Dr. Welty and his colleagues identified 678 men who met strict AS criteria and then underwent radical prostatectomy (RP) from 1997 to 2013. Criteria for AS included Gleason score 3+3 or below, PSA level 10 ng/mL or below, clinical stage 2 or below, a third or fewer biopsy cores positive, and no more than 50% cancer involvement in any single core. Surveillance consisted of quarterly PSA testing, re-imaging

tors compared with non-users (84.7% vs. 89.2%), Uwe Michl, MD, of the Martini-Clinic Prostate Cancer Center in Hamburg, Germany, and colleagues reported in The Journal of Urology (2015;193;479-483). In multivariate analysis, use of PDE5 inhibitors was independently associated with a 38% increased risk of biochemical recurrence. Dr. Michl’s team propensity score matched 1,102 PDE5 inhibitor users to 1,102 non-users and found that 5-year BCR-free survival rates remained significantly lower in men who used the medications (84.6% vs. 89.1%).

The researchers defined BCR as a PSA of 0.2 ng/mL or greater and increasing after RP. continued on page 9

IN THIS ISSUE 5

Low-grade prostate tumors rarely metastasize

5

Metformin may decrease prostate cancer recurrence risk

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High BMI may be good for some metastatic RCC patients

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Radiation plus ADT beneficial in node-positive prostate cancer

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Time to prostate cancer metastasis affects death risk

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Feature: Statins may hold promise as adjunctive cancer therapy

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Pelvic plexis block may offer better pain control during biopsy

The lack of adherence to a DASH-style diet found to raise CKD risk among the urban poor PAGE 15

continued on page 9

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FROM THE EDITOR EDITORIAL ADVISORY BOARD Medical Director, Urology

Medical Director, Nephrology

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

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

Nephrologists

Urologists

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

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

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

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

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center, Memphis Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc.

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

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

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

Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center, Detroit Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J.

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

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

Renal & Urology News Staff

Editor Jody A. Charnow

Web editor

Natasha Persaud

Production editor Kim Daigneau

Group art director, Haymarket Medical Jennifer Dvoretz

Production manager Krassi Varbanov

Production director Kathleen Millea Grinder

Circulation manager Paul Silver National accounts manager William Canning

Publisher Dominic Barone

Editorial director

Jeff Forster

Senior VP, medical journals & digital products

Jim Burke, RPh

Senior VP, clinical communications group

John Pal

CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 14, Number 3. Published monthly, except for the combined January/February, June/July and November/ December issues, 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. 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 © 2015.

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What Ever Happened to AIDS?

R

ecently, researchers reported on a national study comparing outcomes among the entire U.S. cohort of HIV-infected kidney transplant recipients with appropriately matched HIV-negative controls. The study, published online in the Journal of the American Society of Nephrology, found that HIVinfected patients who were not coinfected with hepatitis C virus had 5- and 10-year graft and patient survival rates similar to those of HIV-negative recipients. The researchers noted that chronic diseases such as end-stage renal disease (ESRD) have now surpassed opportunistic infections as the leading cause of death among HIV-infected patients. The study got me thinking about the evolution of HIV disease in the United States and how AIDS has slipped from public view compared with, say, 2 decades ago.

The Centers for Disease Control and Prevention (CDC) estimates that more than 1.2 million people aged 13 years and older in the United States are living with HIV infection, and the number is increasing. In 2013, an estimated 47,352 people were diagnosed with HIV infection and an estimated 26,688 were diagnosed with AIDS in the United States. HIV/AIDS remains a serious epidemic, yet it gets relatively little coverage in the mainstream media these days, unlike in the past, when AIDS reports appeared almost daily, and, not uncommonly, on newspaper front pages.

One reason, I suspect, is that the advent of highly active antiretroviral therapy (HAART) in the mid-1990s transformed AIDS from a fatal to a chronic illness, at least in the United States. The incidence of opportunistic infections and virus-related malignancies—the main causes of death among AIDS patients—plummeted. In 1995, around the time of HAART’s debut, 50,876 deaths were reported among adults or adolescents diagnosed with AIDS (although these deaths may or may not be related to AIDS), according to the CDC. In 2013, the figure was 13,712.

The increased life expectancy of HIV-infected patients and the continued growth of the HIV-infected population have implications for nephrologists and urologists, who may now see more and more of these patients presenting with the same renal and other urinary tract problems seen in the general non-HIV-infected population.

Nephrologists will likely be managing more HIV-infected dialysis and transplant patients, given that chronic kidney disease is a common complication of HIV disease.

Although the care of HIV-infected patients may present concerns and challenges, such as the potential danger of HIV transmission, it should give clinicians some satisfaction to know they are tending to the needs of individuals who, prior to HAART, might not have lived long enough to require their professional services.

Jody A. Charnow Editor

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Contents

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Nephrology 5

ONLINE

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this month at renalandurologynews.com 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 March winner: Edward Schervish, MD

Vitamin D Deficiency Ups Post-Transplant UTI Risk A study of patients undergoing renal transplantation found that vitamin D deficiency was independently associated with an 81% increased risk of urinary tract infection.

Cancer Risk Higher in Dialysis Patients Hemodialysis patients have a cancer incidence 40% higher than expected in the general U.S. population, data show.

CKD Linked to Poor Dietary Habits Non-adherence to a DASH-style diet increased the risk of chronic kidney disease among urban poverty-stricken individuals.

16

Hurricane Sandy Adversely Affected ESRD Patients They experienced higher rates of emergency department visits and hospitalization as well as a slightly higher 30-day mortality rate, researchers reported.

Urology Videos

Some of our recent postings include:

• 4Kscore Finds High-Grade Prostate Cancer

Study: Low-Grade Prostate Tumors Rarely Metastasize Prostate cancer patients with a tumor grade of Gleason 6 or less at the time of radical prostatectomy rarely progress to metastatic disease or die from their cancer.

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Radiation + ADT Beneficial in Node-Positive PCa Men receiving the combination treatment had a 50% decreased risk of 5-year overall mortality compared with the men receiving ADT alone.

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Time to PCa Metastasis Affects Overall Survival In a study of treatment-naïve patients, the median time to death was shortest in men with metastatic disease at diagnosis.

• Kidney Cancer: Evolving Role of Genomic Testing • Benefits of Nocturnal Dialysis • New Findings Could Bypass Transplantation Waitlist

News Coverage

Visit our website for daily updates.

13

Genitourinary Cancers and the Promise of Statins Recent studies add to evidence showing that statins may improve outcomes in patients with prostate and kidney cancer.

Our findings support the feasibility of using early

dialysis as a potential standard of care and protective measure when a hurricane or other ‘notice event’ is anticipated to interrupt dialysis treatment.

See our story on page 16

TOC_004_Neph_RUN0415.indd 4

N U M B E R

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American Transplant Congress Philadelphia May 2– 6 American Urological Association 110th Annual Meeting New Orleans May 15 –19 American Society of Hypertension Annual Scientific Meeting New York May 16 –19 European Renal Association – European Dialysis and Transplant Association 52nd Congress London May 28–31 American Society of Clinical Oncology Annual Meeting Chicago May 29–June 2 Canadian Urological Association Annual Meeting Ottawa June 27–30 International Continence Society Montreal October 6–9

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• Overweight and Metastatic RCC Outcomes

I S S U E

CALENDAR

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Clinical Quiz

1 4 ,

Kidney Week San Diego November 3–8

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Departments 3

From the Editor What ever happened to AIDS?

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News in Brief Low-grade prostate cancer rarely metastasizes

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Practice Management More female physicians are going into nephrology and urology

3/24/15 3:31 PM

4 Renal & Urology News

APRIL 2015

www.renalandurologynews.com

Contents

A P R I L

2 0 1 5

■

VO L U M E

Urology 5

ONLINE

this month at renalandurologynews.com 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 March winner: Edward Schervish, MD

Videos

Some of our recent postings include:

7

9

13

• 4Kscore Finds High-Grade Prostate Cancer

• Benefits of Nocturnal Dialysis

Visit our website for daily updates.

Radiation + ADT Beneficial in Node-Positive PCa Men receiving the combination treatment had a 50% decreased risk of 5-year overall mortality compared with the men receiving ADT alone.

Time to PCa Metastasis Affects Overall Survival In a study of treatment-naïve patients, the median time to death was shortest in men with metastatic disease at diagnosis.

Genitourinary Cancers and the Promise of Statins Recent studies add to evidence showing that statins may improve outcomes in patients with prostate and kidney cancer.

9

Cancer Risk Higher in Dialysis Patients Hemodialysis patients have a cancer incidence 40% higher than expected in the general U.S. population, data show.

15

CKD Linked to Poor Dietary Habits Non-adherence to a DASH-style diet increased the risk of chronic kidney disease among urban poverty-stricken individuals.

16

Hurricane Sandy Adversely Affected ESRD Patients They experienced higher rates of emergency department visits and hospitalization as well as a slightly higher 30-day mortality rate, researchers reported.

Our findings support the feasibility of using early

dialysis as a potential standard of care and protective measure when a hurricane or other ‘notice event’ is anticipated to interrupt dialysis treatment.

See our story on page 16

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N U M B E R

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American Transplant Congress Philadelphia May 2– 6 American Urological Association 110th Annual Meeting New Orleans May 15 –19 American Society of Hypertension Annual Scientific Meeting New York May 16 –19 European Renal Association – European Dialysis and Transplant Association 52nd Congress London May 28–31 American Society of Clinical Oncology Annual Meeting Chicago May 29–June 2 Canadian Urological Association Annual Meeting Ottawa June 27–30 International Continence Society Montreal October 6–9

Vitamin D Deficiency Ups Post-Transplant UTI Risk A study of patients undergoing renal transplantation found that vitamin D deficiency was independently associated with an 81% increased risk of urinary tract infection.

• New Findings Could Bypass Transplantation Waitlist

News Coverage

Study: Low-Grade Prostate Tumors Rarely Metastasize Prostate cancer patients with a tumor grade of Gleason 6 or less at the time of radical prostatectomy rarely progress to metastatic disease or die from their cancer.

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• Kidney Cancer: Evolving Role of Genomic Testing

I S S U E

CALENDAR

Nephrology

• Overweight and Metastatic RCC Outcomes

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Kidney Week San Diego November 3–8

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Departments 3

From the Editor What ever happened to AIDS?

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News in Brief Low-grade prostate cancer rarely metastasizes

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Practice Management More female physicians are going into nephrology and urology

3/24/15 3:32 PM

www.renalandurologynews.com

APRIL 2015

Renal & Urology News 5

News in Brief

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

Short Takes Vitamin D Deficiency Ups Post-Transplant UTI Risk

International Urology and Nephrology.

Vitamin D deficiency is an independent

Bakan, MD, of Goztepe Training and

risk factor for urinary tract infections

Research Hospital, Istanbul Medeniyet

(UTIs) after renal transplantation, a

University in Istanbul, Turkey, and

recent study found.

colleagues, baseline serum uric acid

In a study of 93 IgAN patients by Ali

Young Eun Kwon, MD, of Yonsei Uni-

levels significantly predicted the change

versity College of Medicine in Seoul,

in estimated glomerular filtration rate

Korea, and colleagues measured

(eGFR) after adjusting for various poten-

25-hydrovitamin D3 levels (25(OH)

tial confounders, including age, gender,

D3) in 410 patients 2 weeks prior to

blood pressure, baseline albumin con-

undergoing renal transplantation. Of

centrations and use of ACE inhibitors

the 410 patients, 171 (41.7%) were

and angiotensin receptor blockers.

vitamin D deficient (25(OH)D3 level low-up of 7.3 years, the UTI incidence

FDA Approves First Device to Treat DRA

was significantly higher in the vitamin

The FDA has approved the first device

D deficient than non-deficient patients

to treat dialysis-related amyloidosis

(30.4% vs. 16.7%), the investigators

(DRA), a rare but chronic condi-

reported in Medicine (2015;94:e594).

tion that occurs most often among

Vitamin D deficiency was independent-

patients aged 60 years or older who

ly associated with a significant 81%

have been on dialysis for more than 5

increased risk of UTI.

years. The newly approved device, the

below 10 ng/mL). During a median fol-

Lixelle Beta 2-microglobulin Apheresis

Uric Acid Predicts eGFR Decline in IgAN Patients

Column, removes beta 2-microglobulin

Baseline serum uric acid levels are

beads. It is used in conjunction with

directly proportional to the rate of

hemodialysis. When the Lixelle Column

decline in renal function in patients

is used, the blood passes through the

with IgA nephropathy (IgAN), research-

Lixelle Column before it enters the

ers reported online ahead of print in

dialysis filter.

from the blood using porous cellulose

Using Statins to Prevent CIN In a recent online poll, Renal & Urology News asked its nephrologist and urologist readers, “Are statins a valid approach for preventing contrastinduced nephropathy?”* Here are the results based on 127 responses:

Yes: 35%

No: 24%

Do not know: 40%

0

10

20

30

40

*See feature article about statins on pages 13–14 of this issue.

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Study: Low-Grade Prostate Tumors Rarely Metastasize P

rostate cancer (PCa) patients with a tumor grade of Gleason 6 or less at the time of radical prostatectomy (RP) rare progress to metastatic disease or die from their cancer, according to a new study published online ahead of print in BJU International.

Charlotte F. Kweldam, MD, of Erasmus Medical Center in Rotterdam, The Netherlands, and colleagues studied 1,101 consecutive patients who underwent RP from 1985 and 2013. Of these, 449 (41%) had a Gleason score of 6 or less, 436 (40%) had a Gleason score of 3 + 4, 99 (9%) had a Gleason score of 4 + 3, and 117 (11%) had a Gleason score of 8–10 at surgery.

The median follow-up after surgery was 100 months, during which 197 patients (18%) died, 42 (2.8%) from PCa-related causes. No PCa-related deaths occurred among patients with Gleason 6 or less. Distant metastases occurred in 56 men (5.1%), none of whom had a Gleason score of 6 or less, the researchers reported.

Iron-Based Phosphate Binders, Sevelamer Similarly Effective I

ron-based phosphate binders are as effective as sevelamer for treating hyperphosphatemia and may be useful in managing anemia in dialysis patients, according to a recently published systemic review and meta-analysis.

A team led by Rong Wang, MD, of Shandong Provincial Hospital in Shandong, China, analyzed 8 randomized controlled trials of iron-based phosphate binders with a total of 2,018 dialysis patients. The binders were superior to placebo in decreasing serum phosphorus levels (mean decrease of 2.43 vs. 1.68 mg/dL), the investigators reported in Renal Failure (2015;37:7-15). Iron-based binders and sevelamer decreased serum phosphorus to a similar extent.

Compared with placebo, iron-based binders were associated with significantly higher serum iron and serum transferrin saturation and significantly lower serum total iron binding capacity.

The researchers concluded that “iron-based phosphate binders may represent a new treatment option for dialysis patients.”

Metformin May Cut Prostate Cancer Recurrence Risk M

etformin may decrease the risk of biochemical recurrence (BCR) among men treated for prostate cancer (PCa), according to a recent systematic review and meta-analysis.

Investigators pooled results from 8 retrospective cohort studies and 1 case-control study published before August 2014. The drug was associated with a marginal 18% decreased risk of BCR and an approximately 50% reduction in the BCR risk among men who received external beam radiation therapy (EBRT), the researchers reported online ahead of print in Prostate Cancer and Prostatic Disease. Metformin use was not associated with BCR risk among men who underwent radical prostatectomy.

“A plausible explanation for the beneficial effects of metformin along with EBRT may be the radiation-sensitizing properties of metformin,” the researchers wrote.

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High BMI May Be a Plus for Some RCC Patients ORLANDO, Fla.—Findings from separate studies presented at the 2015 Genitourinary Cancers Symposium may provide insight into the relationship between body mass index (BMI) and renal cell carcinoma (RCC).

In a study led by Laurence Albiges, MD, of Dana-Farber Cancer Institute in Boston, overweight or obesity was associated with better overall and progression-free survival among patients who received targeted therapy for metastatic clear-cell RCC. In a separate study of 2 large prospective cohorts, Kathryn M. Wilson, ScD, a research associate in epidemiology at the Harvard School of Public Health in Boston, and colleagues showed that obesity significantly raised RCC risk among women and significantly increased the risk of fatal RCC among men.

of 117,097 women followed since 1976, and the Health Professionals Follow-up Study, which consisted of 48,268 men followed since 1986.

Women who were obese (BMI 30 kg/m2 or higher) immediately prior to RCC diagnosis had a significant 38% increased risk of RCC compared with

women who had a normal BMI (18.5– 24.9 kg/m2) immediately prior to diagnosis, after adjusting for potential confounders. Their risk of fatal RCC also was elevated, but not significantly. Obese men had a non-significant higher risk of RCC compared with men who had a normal BMI, but they had a significant 2.6 S:7”

times increased risk of fatal RCC. Among women, obesity at baseline was associated with a significant 88% increased risk of RCC and a significant 2-fold increased risk of fatal RCC. Among men, obesity at baseline was not significantly associated with an increased risk of fatal RCC. n

Obesity is linked to a higher risk of fatal RCC in men, data show.

The study by Dr. Albiges’ group included 4,657 patients with metastatic RCC who received targeted therapy in phase 2-3 clinical trials. At initiation of targeted therapy, 1,829 patients (39%) were normal or underweight (body mass index [BMI] less than 25 kg/m2) and 2,828 (61% were overweight or obese (BMI 25 kg/m2 or higher). The high BMI group had a significantly longer median overall survival than the low BMI group (23.4 vs. 14.5 months), a difference that translated into a 17% decreased risk of death in the high BMI group in adjusted analyses. In addition, the high BMI group had a significant 18% decreased risk of progression. When stratified by histologic subtype, the favorable outcome associated with high BMI was observed only in patients with clear-cell RCC, Dr. Albiges’ team reported.

“In an external cohort, we validate BMI as an independent prognostic factor for improved survival in mRCC,” the authors concluded.

Given that the survival benefit was observed only in patients with clearcell RCC, they hypothesized that lipid metabolism may be modulated by fatladen tumor cells.

The study by Dr. Wilson and colleagues included participants in the Nurses’ Health Study, which consisted

RCC-Auryxia_006-7_RUN0415.indd 6

INDICATION AURYXIA is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis.

IMPORTANT SAFETY INFORMATION Contraindication: AURYXIA is contraindicated in patients with iron overload syndromes.

Iron Overload: Iron absorption from AURYXIA may lead to excessive elevations in iron stores. Assess iron parameters, serum ferritin and TSAT, prior to and while on AURYXIA. Patients receiving IV iron may require a reduction in dose or discontinuation of IV iron therapy.

Overdose: AURYXIA contains iron. Iron absorption from AURYXIA may lead to excessive elevations in iron stores, especially when concomitant IV iron is used.

Accidental Overdose of Iron: Accidental overdose of iron containing products is a leading cause of fatal poisoning in children under 6 years of age. Keep this product out of the reach of children.

Patients with Gastrointestinal Bleeding or Inflammation: Safety has not been established.

Pregnancy Category B and Nursing Mothers: Overdosing of iron in pregnant women may carry

3/24/15 3:25 PM

B:15.5” T:15.5”

www.renalandurologynews.com APRIL 2015

Renal & Urology News 7

Radiation + ADT Beneficial in Node-Positive PCa B:15.5” T:15.5”

ORLANDO, Fla.—Radiation treatment (RT) added to androgen-deprivation therapy (ADT) is associated with a significant survival benefit in patients with clinically node-positive prostate cancer (PCa), according to study findings presented at the 2015 Genitourinary Cancers Symposium.

The study, led by Jason A. Efstathiou, MD, DPhil, of the Department of Radiation Oncology, Massachusetts General Hospital in Boston, included 3,540 men diagnosed with primary clinically node-positive PCa without distant metastases from 2004–2011.

Of these, 32.2% S:7” received ADT alone

and 51.4% received RT plus ADT. The remaining patients received RT alone or neither ADT nor RT. After propensity score matching to adjust for possible selection biases, 318 patients remained in each group. Men receiving RT plus ADT had a significant 50% decreased risk of 5-year over-

all mortality compared with the men receiving ADT alone, the investigators reported.

“These findings, if appropriately validated, suggest that re-evaluation of current practice guidelines may be warranted,” the authors concluded in a poster presentation. n

For the control of serum phosphorus levels in patients with chronic kidney disease on dialysis

AURYXIA™ (ferric citrate) IS THE FIRST AND ONLY ABSORBABLE-IRON–BASED PHOSPHATE BINDER CLINICALLY PROVEN TO MANAGE HYPERPHOSPHATEMIA1-6

• Proven control of serum phosphorus within KDOQI guidelines (4.88 mg/dL at Week 56)7,8 • Demonstrated safety and tolerability profile over 52 weeks B:10.25”

S:10”

T:10.25”

• Each AURYXIA tablet contains 210 mg ferric iron, equivalent to 1 g ferric citrate

References: 1. Fosrenol [package insert]. Wayne, PA: Shire US, Inc.; 2014. 2. Phoslyra [package insert]. Waltham, MA: Fresenius Medical Care North America; 2011. 3. PhosLo Gelcaps [package insert]. Waltham, MA: Fresenius Medical Care North America; 2012. 4. Renagel [package insert]. Cambridge, MA: Genzyme Corporation; 2014. 5. Renvela [package insert]. Cambridge, MA: Genzyme Corporation; 2014. 6. Velphoro [package insert].

Waltham, MA: Fresenius Medical Care North America; 2014. 7. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 Suppl 3):S1-S201. 8. Data on File 1, Keryx Biopharmaceuticals, Inc.

n

a risk for spontaneous abortion, gestational diabetes, and fetal malformation. Rat studies have shown the transfer of iron into milk. There is possible infant exposure when AURYXIA is taken by a nursing woman.

e atal his

Pediatric: The safety and efficacy of AURYXIA have not been established in pediatric patients.

Adverse Events: The most common adverse events with AURYXIA were diarrhea (21%), nausea (11%), constipation (8%), vomiting (7%), and cough (6%).

Gastrointestinal adverse reactions were the most common reason for discontinuing AURYXIA (14%).

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Drug Interactions: Doxycycline should be taken at least 1 hour before AURYXIA. Consider separation of the timing of the administration of AURYXIA with drugs where a reduction in their bioavailability would have a clinically significant effect on safety or efficacy.

Please see Brief Summary on following page.

You may report side effects to Keryx at 1-844-44KERYX (844-445-3799).

©2015 Keryx Biopharmaceuticals, Inc. 01/15 PP-AUR-US-0075

3/24/15 3:25 PM

8 Renal & Urology News

APRIL 2015 www.renalandurologynews.com

Time to PCa Metastasis Affects Overall Survival ORLANDO, Fla.—The time to prostate cancer (PCa) metastasis in treatment-naïve patients and after patients have started androgen-deprivation therapy is associated with overall survival (OS), according to the findings of separate studies presented at the 2015 Genitourinary Cancers Symposium.

In a study of 92 PCa patients with metastatic disease, Shusuke Akamatsu, MD, PhD, of the Vancouver Prostate Centre and Department of Urologic Sciences at the University of British Columbia in Vancouver, and colleagues found that patients who have metastatic PCa at the time of their diagnoT:7”

sis have significantly shorter OS than PCa patients who develop metastases while their tumors are sensitive to castration or after they become castration resistant.

Of the 92 patients, 35 had metastases at diagnosis (de novo-M), 26 developed metastases while the cancer was still

BRIEF SUMMARY AURYXIA™ (ferric citrate) tablets contain 210 mg of ferric iron equivalent to 1 g ferric citrate for oral use.

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

CONTRAINDICATIONS AURYXIA is contraindicated in patients with iron overload syndromes (eg, hemochromatosis).

WARNINGS AND PRECAUTIONS Iron Overload: Iron absorption from AURYXIA may lead to excessive elevations in iron stores. Increases in serum ferritin and transferrin saturation (TSAT) levels were observed in clinical trials. In a 56-week safety and efficacy trial in which concomitant use of AURYXIA and IV iron was permitted, 55 (19%) patients treated with AURYXIA had a ferritin level >1500 ng/mL as compared with 13 (9%) patients treated with active control.

Assess iron parameters (eg, serum ferritin and TSAT) prior to initiating AURYXIA and monitor iron parameters while on therapy. Patients receiving IV iron may require a reduction in dose or discontinuation of IV iron therapy.

Accidental Overdose of Iron: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6 years of age.

Keep this product out of the reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

Patients with Gastrointestinal Bleeding or Inflammation: Patients with inflammatory bowel disease or active, symptomatic gastrointestinal bleeding were excluded from clinical trials. Safety has not been established in these populations.

ADVERSE REACTIONS Adverse reactions to a drug are most readily ascertained by comparison with placebo, but there is little placebo-controlled experience with AURYXIA, so this section describes adverse events with AURYXIA, some of which may be disease-related, rather than treatment-related. A total of 289 patients were treated with AURYXIA and 149 patients were treated with active control (sevelamer carbonate and/or calcium acetate) during the 52-week, randomized, open-label, active control phase of a trial in patients on dialysis.

A total of 322 patients were treated with AURYXIA for up to 28 days in three short-term trials. Across these trials, 557 unique patients were treated with AURYXIA; dosage regimens in these trials ranged from 210 mg to 2,520 mg of ferric iron per day, equivalent to 1 to 12 tablets of AURYXIA. In these trials, adverse events reported for AURYXIA were similar to those reported for the active control group. Adverse events reported in more than 5% of patients treated with AURYXIA in these trials included diarrhea (21%), nausea (11%), constipation (8%), vomiting (7%), and cough (6%).

During the 52-week active control period, 60 patients (21%) on AURYXIA discontinued study drug because of an adverse event, as compared to 21 patients (14%) in the active control arm. Patients who were previously intolerant to any of the active control treatments (calcium acetate and sevelamer carbonate) were not eligible to enroll in the study. Gastrointestinal adverse events were the most common reason for discontinuing AURYXIA (14%).

AURYXIA is associated with discolored feces (dark stools) related to the iron content, but this staining is not clinically relevant and does not affect laboratory tests for occult bleeding, which detect heme rather than non-heme iron in the stool.

USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. It is not known whether AURYXIA can cause fetal harm when administered to a pregnant woman. Animal reproduction studies have not been conducted.

The effect of AURYXIA on the absorption of vitamins and other nutrients has not been studied in pregnant women. Requirements for vitamins and other nutrients are increased in pregnancy. An overdose of iron in pregnant women may carry a risk for spontaneous abortion, gestational diabetes, and fetal malformation.

Labor and Delivery: The effects of AURYXIA on labor and delivery are unknown.

Nursing Mothers: Data from rat studies have shown the transfer of iron into milk by divalent metal transporter-1 (DMT-1) and ferroportin-1 (FPN-1).

Hence, there is a possibility of infant exposure when AURYXIA is administered to a nursing woman.

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

Geriatric Use: Clinical studies of AURYXIA included 106 subjects aged 65 years and older (33 subjects aged 75 years and older). Overall, the clinical study experience has not identified any obvious differences in responses between the elderly and younger patients in the tolerability or efficacy of AURYXIA. OVERDOSAGE No data are available regarding overdose of AURYXIA in patients. In patients with chronic kidney disease on dialysis, the maximum dose studied was 2,520 mg ferric iron (12 tablets of AURYXIA) per day. Iron absorption from AURYXIA may lead to excessive elevations in iron stores, especially when concomitant IV iron is used.

In clinical trials, one case of elevated iron in the liver as confirmed by biopsy was reported in a patient administered IV iron and AURYXIA. PATIENT COUNSELING INFORMATION Dosing Recommendations: Inform patients to take AURYXIA as directed with meals and adhere to their prescribed diets. Instruct patients on concomitant medications that should be dosed apart from AURYXIA. Adverse Reactions: Advise patients that AURYXIA may cause discolored (dark) stools, but this staining of the stool is considered normal with oral medications containing iron.

AURYXIA may cause diarrhea, nausea, constipation, and vomiting. Advise patients to report severe or persistent gastrointestinal symptoms to their physician.

Keryx Biopharmaceuticals, Inc. ©2015 Keryx Biopharmaceuticals, Inc. Printed in USA

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Median time to death was shortest in men with metastatic disease at diagnosis.

(ADT) in 415 PCa patients who experienced biochemical recurrence after primary local therapy but had non-metastatic disease. The median follow-up was 6.4 years.

Patients who had metastases identified 1, 2, and 3 years after the start of ADT had a significant 7.6 times, 5.7 times, and 5.8 times greater risk of death, respectively, than patients who did not have metastases at those time points.

The study also showed that the time to metastasis from identification of castration-resistant disease is significantly associated with OS. Patients who had metastases identified 1, 2, and 3 years after ADT initiation had a significant 4.4, 4.6, and 5.2 times greater risk of death, respectively, than patients who did not have metastases identified at those time points, according to the investigators.

Of the 415 patients in the study, 217 (52%) underwent radical prostatectomy with or without radiation therapy and 198 (48% underwent radiation therapy alone as their primary treatment. n

T:10”

DRUG INTERACTIONS Doxycycline is an oral drug that has to be taken at least 1 hour before AURYXIA. Oral drugs that can be administered concomitantly with AURYXIA are: amlodipine, aspirin, atorvastatin, calcitriol, clopidogrel, digoxin, doxercalciferol, enalapril, fluvastatin, levofloxacin, metoprolol, pravastatin, propranolol, sitagliptin, and warfarin. There are no empirical data on avoiding drug interactions between AURYXIA and most concomitant oral drugs.

For oral medications where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, consider separation of the timing of the administration of the two drugs. The duration of separation depends upon the absorption characteristics of the medication concomitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate release or an extended release product. Consider monitoring clinical responses or blood levels of concomitant medications that have a narrow therapeutic range.

castration-sensitive (CSPC-M), and 31 developed metastases after their cancer became castration-resistant (CRPC-M).

The median time to death from diagnosis was 12.3, 15.8, and 3.7 years in the CSPC-M, CRPC-M, and de novo-M groups, respectively. The median time to death from metastasis was 5, 2.6, and 3.7 years, respectively, and the median time to death from CRPC was 2.7, 3, and 0.9 years, respectively.

The median time to metastasis in the CSPC-M and CRPC-M groups was 4.4 and 11.4 years, respectively.

“Regardless of the timing of metastasis,” Dr. Akamatsu and colleagues concluded, “survival of more than 10 years after initial diagnosis is possible in cases that did not have metastasis at initial presentation.”

In the other study, Loana Valenca, MD, of the Dana-Farber Cancer Institute, Harvard Medical School, Boston, and colleagues explored the association between time to PCa metastasis and overall survival after the start of androgen-deprivation therapy

3/24/15 3:26 PM

www.renalandurologynews.com APRIL 2015

Cancer Risk Higher in HD Patients PATIENTS WITH end-stage renal disease (ESRD) receiving hemodialysis (HD) are at elevated risk of cancer, according to a new study.

Anne M. Butler, PhD, and colleagues from the University of North Carolina at Chapel Hill calculated cancer incidence rates for almost a half million adults in Medicare’s ESRD program who received dialysis therapy between 1996 and 2009.

According to results published online ahead of print in the American Journal of Kidney Diseases, the investigators observed a constant rate of cancers in patients, from 3,923 to 3,860 cases per 100,000 persons per year. Over 13 years, the rate of kidney cancer rose, while the rates of other cancers, such as colon and lung, declined.

Fluid intake, stone link continued from page 1

In 2014, the American College of Physicians (ACP) released a new guideline for preventing recurrent kidney stones in adults. For patients who have had 1 or more prior kidney stone episodes, the guideline recommends increased fluid intake spread throughout the day to achieve a urine volume of at least 2 L/day.

Kidney stone specialist David S. Goldfarb, MD, clinical chief of nephrology at New York University Langone Medical Center in New York, pointed out the ACP’s guidelines suggest that evidence for the efficacy of increasing fluid intake is weak and leave an impression that increasing fluid intake is not an important prescription for patients with kidney stones. “We know that it is an extremely important prescription, not just because it’s efficacious, but because it’s inexpensive and because it’s safe,” Dr. Goldfarb said.

Randomized controlled trials have already provided convincing evidence

Renal & Urology News 9

of the safety and efficacy of increasing fluid intake, he said. Adding in what is understood about urine chemistry, “we know that increasing fluid intake leads to a reduction in supersaturation.”

The notion that more studies are needed to confirm that increasing fluid intake can prevent kidney stones is incorrect, said Dr. Goldfarb, who is president of the ROCK [Research on Calculus Kinetics] Society and director of kidney stone prevention and treatment programs at New York Harbor VA Healthcare System. The new study provides “additional confirmatory evidence” of the safety and efficacy of high fluid intake for preventing kidney stones, he told Renal & Urology News.

Dr. Goldfarb’s usual fluid prescription for kidney stone prevention is 96 ounces per day, assuming the weather is not very hot and the patient is not exercising too much or experiencing increased bowel losses of water.

He typically instructs patients to think of 96 ounces in terms of 8 × 12 (8 12-ounce or 12 8-ounce portions).

“You need a way to visualize this. “It’s

not enough to say to people, ‘drink a lot,’ you have to say what a lot means.”

The other study by Dr. Lieske and colleagues included 416 female and 293 male subjects (mean age 64.6 and 66.5 years, respectively). Results showed that urinary calcium declined with age, and levels were higher in males than females. An increase in serum creatinine caused urine calcium to decrease.

Urinary oxalate excretion was greater in males despite no difference in oxalate intake, “suggesting sex differences in metabolism or other food intake,” Dr. Lieske and his collaborators wrote in a poster presentation. Urinary uric acid excretion correlated positively with body mass index and estimated glomerular filtration rate (as calculated using cystatin C). Cystatin C correlations with uric acid may relate to hyperuricemia and inflammation, according to the researchers.

“Age and sex influence the excretion of key urinary factors related to kidney stone risk and should be taken into account when evaluating kidney stone parameters,” the authors concluded. n

IASBPD should be considered at high risk of CV events, and probably intensive control and early treatment could improve their prognosis.”

The researchers explained that in most instances, a difference in BP between arms is due to subclinical atherosclerosis, but other possible causes include coarctation of the aorta, aortic aneurism, connective tissue disorders, vasculitis, and thoracic compression.

For the study, the investigators defined CV events as myocardial infarction, congestive heart failure and/or a left ventricular ejection fraction of less than 45%, ischemic or hemorrhagic cerebrovascular accident, peripheral vascular

disease, and other ischemic conditions.

Dr. Quiroga and colleagues acknowledged 3 study limitations. First, they used simultaneous BP measurements, whereas other researchers assessed IASBPD using sequential measurements. “However, in our opinion, simultaneous measurement better reflects real blood pressure and enables comparison between arms,” Dr. Quiroga’s group said, noting that they used the same device to avoid bias. Second, the data are from a single center, so the findings should be confirmed in community-based studies including CKD patients. Lastly, the study population had a high prevalence of CV comorbidities. n

assessed pregnancy outcomes prospectively for periods between 2000 and 2013.

The risk of adverse pregnancy outcomes increased with CKD stage, according to results published online ahead of print in the Journal of the American Society of Nephrology. The combined risk of pre-term delivery, need for care in the neonatal intensive care unit, and small infant size for gestational age was 34% for women with stage 1 CKD compared with 90% for women with stages 4 to 5. Similarly, the risk of severe cases of the above was 21% in stage 1 patients compared with 80% in patients with stages 4 to 5.

Classic risk factors could not fully explain the excess risks associated with

CKD. Women with stage 1 CKD who gave birth prematurely were 3.1 to 3.7 times more likely to have hypertension, proteinuria, or systemic disease (such as diabetic nephropathy or lupus).

However, women with stage 1 CKD without these extra conditions still had almost twice the risk of adverse pregnancy-related outcomes.

“By definition, patients with stage 1 CKD have normal kidney function; therefore, the significant differences compared with the low-risk control population demonstrate that kidney function impairment is not the only element to be taken into consideration for risk assessment in CKD pregnancy,” the researchers stated. n

In the HD population, the 5-year cumulative cancer incidence was 9.5%. The incidence of any cancer was 1.4 times higher than the background cancer incidence in the general U.S. population in 2000. The risk for kidney cancer and bladder cancer was 4 times and 1.6 times higher, respectively.

“These results suggest that patients with ESRD are uniquely at risk for developing cancer while receiving hemodialysis treatment,” the researchers stated.

Cancer incidence was higher for certain patients, including seniors, men, non-Caucasian and non-

Interarm BP and CV risk continued from page 1

Cardiovascular events occurred in 58 patients (8.5%). An IASBPD of 10 mm Hg or greater was associated with a significant 80% increased risk of CV events after adjusting for classical risk factors such as a history of CV disease, Dr. Quiroga’s group reported online ahead of print in Nephrology Dialysis Transplantation.

“Our findings led us to hypothesize that patients with CKD can stratify their CV risk with regular monitoring of blood pressure,” the authors wrote.

“In addition, patients with increased

Hispanic ethnicities, people without diabetes, new dialysis patients, and transplant candidates.

The investigators suggest several possible explanations for the higher cancer rates among dialysis patients, including ESRD-associated immunodeficiency and nutritional abnormalities. In addition, uremic and dialysis-induced immune dysfunction may interact with cancer risk factors such as tobacco.

“Our findings of differential cancer incidence among certain subgroups highlight the need to potentially reevaluate target cancer screening practices,” the researchers wrote. n

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CKD and pregnancy

continued from page 1

Giorgina Barbara Piccoli, MD, of the University of Torino in Italy, said in a news release. “Conversely, we also found that a good outcome was possible in patients with advanced CKD, who are often discouraged to pursue pregnancy.”

For the study, the investigators compared pregnancy outcomes in 504 women with CKD and 836 women without CKD, hypertension, diabetes, obesity, cardiovascular disease, or any other severe disease that might affect pregnancy. The women were participants in 2 separate cohorts from the Torino-Cagliari Observational Study (TOCOS), which

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www.renalandurologynews.com APRIL 2015

Delayed RP continued from page 1

with transrectal ultrasound (TRUS), and serial prostate biopsy (median 2).

Men who had immediate surgery after their PCa diagnosis were 66% less likely to have unfavorable pathology than those who delayed RP for at least 6 months (median 19 months).

This finding is not surprising because surgery was only recommended to men who had signs of occult, higher-risk disease on follow-up; very few elected surgery for other reasons, according to the researchers.

To clarify whether the timing of RP played a role in PCa pathology, the researchers conducted a separate analysis of 54 men managed on AS who initially met AS criteria, then upgraded to Gleason 3+4 disease during surveillance and underwent surgery. These patients were matched to 162 men who underwent immediate RP on the basis of clinical stage, PSA, and Gleason grade

ED drug use after RP continued from page 1

The investigators said they believe that, to their knowledge, the study is the first to identify an adverse effect of selective PDE5 inhibitors on biochemical outcome following RP. They noted that the finding was unexpected given the previously reported antineoplastic effects of PDE5 blockade in different animal models. In addition, they pointed out that their data contrast with study findings reported

by Anthony H. Chavez, MD, of Scott & White Healthcare in Temple, Tex., and colleagues in the Asian Journal of Andrology (2013;15:246-248), which showed that the use of PDE5 inhibitors in ED patients without a history of PCa was associated with a decreased PCa incidence rate.

Dr. Michl and colleagues, who noted that PDE5 inhibitors are widely used to treat ED following RP, stated that they can only speculate about possible causes of an adverse effect of selective PDE5 inhibitors on biochemical outcomes. Conceivable causes include the effects of the drugs on the immune system, autonomic nerve development, and angiogenesis. Although their findings are based on a large number of patients, the researchers acknowledged that the study had limitations. These include the retrospective design and the use of data from patients at a single center. In addition, the investigators pointed out that they lacked information on the type of

Cover-jump_Uro_RUN0415.indd 9

immediately prior to treatment. The investigators found the timing of RP was not associated with adverse pathology.

“Men who may have had more significant prostate cancer than was appreciated detected on their initial biopsy do not appear to have worse pathologic outcomes as a result of waiting to be treated,” Dr. Welty explained. “In fact, they may gain some benefit by delaying treatment-related morbidity.”

In a separate study presented at the symposium, researchers reported that the percentage of positive cores in PCa patients eligible for AS predicts pathologic upstaging and upgrading at RP. The finding is based on a study of 405 RP patients fulfilling the Memorial Sloan-Kettering Cancer Center criteria for AS (PSA level 10 ng/mL or less, clinical stage 2a or less, Gleason score 6 or less, 2 or fewer positive cores, and less than 50% cancer in any 1 core).

The researchers observed upstaging in 195 patients (48%) and upgrading in 55 (13%). Patients who were upstaged and

PDE5 inhibitor and its dose and exact duration and frequency of use.

The absence of such specific medication use data from the analysis is a serious flaw of the new study, said John P. Mulhall, MD, of Memorial SloanKettering Cancer Center in New York, where he is the Director of Sexual & Reproductive Medicine, which provides care for men who have suffered sexual difficulties resulting from cancer or cancer treatment. “This is an analysis that is entirely predicated upon defining exposure without their

The study is limited by a lack of specific information about PDE5 inhibitor use. being adequate or detailed exposure information present within the paper,” said Dr. Mulhall, who noted that the database used in the study was never constructed to look at this problem.

“You need to know what that exposure is to define whether it’s linked or not [to biochemical recurrence].”

Dr. Mulhall pointed out that PDE5 inhibitors have been available commercially for nearly 17 years without any indication that they might be associated with an elevated risk of biochemical recurrence. “If there truly was a 38% increased risk [of biochemical recurrence], it is inconceivable that we

Renal & Urology News 9

BCG plus sunitinib continued from page 1

Christopher J. Welty, MD, MS

upgraded at RP had a mean of 18.2% and 16% positive cores, respectively, whereas those who were not upstaged and upgraded had a mean of 15.5% and 11.1% positive cores, respectively.

The investigators defined upstaging as the presence of pT3 or greater disease and upgrading as a Gleason score greater than 6 in the final RP specimen. n

would not, by now, have seen a signal of this effect.”

The researchers asked patients if they used PDE5 inhibitors regularly or did not use the drugs, but did not define regular or non-use, Dr. Mulhall observed.

“It is very likely that the patients in the non-use group have used Viagra,” he said. Additionally, using the drugs regularly “could mean anything from 1 time a week to daily.” Failure of the authors to define what they meant by “use” is a major limitation of the analysis, he said.

Dr. Mulhall pointed out that the study population consisted of men with localized PCa. In these patients, biochemical recurrence, if it occurs, typically does so within 36 months of RP. Additionally, PDE5 inhibitors usually would be used for penile rehabilitation in the first 6 to 24 months after surgery. “The fact that we don’t see a signal of this in the Kaplan-Meier data (no significant difference between the groups at 36 months) at that time makes me think that there’s something else going on with these patients, and it’s got nothing to do with the medication,” Dr. Mulhall said.

He called the new paper “dangerous” as it sends an alarming message to patients and physicians without the data being truly definitive.” He concluded that “from a scientific standpoint, where any new data may radically change a treatment protocol because of treatment toxicity, the data upon which such a change in treatment is based should be robust, definitive, and corroborated, which these data are not at this time.” n

by 28 days of treatment with 50 mg sunitinib. The primary outcome was complete response based on biopsy and cytology at 3 months. If 25 or more of the patients achieved a 3-month complete response, then the treatment would be considered for further study, according to the investigators.

The initial cancer stage was T1 in 19 patients, Ta in 9, and carcinoma in situ in 8. Thirteen patients had a treatment delay for a median of 12 days and a dose reduction to 37.5 mg. Of the 36 patients, 26 (72%) had a complete response at 3 months. One patient completed a second cycle of BCG plus sunitinib for incomplete response and had a complete response at 6 months.

BCG maintenance therapy was administered to 21 patients. The study population had a 77% rate of 2-year recurrence-free survival.

A total of 133 adverse events (AE) occurred in 34 patients, including 6 AEs in 5 patients that were grade 3 or higher: thrombocytopenia, diarrhea, shingles, extremity rash/pain and hand-foot syndrome.

“There may be a role for complementary therapies alongside BCG in order to improve complete response, which has been shown to predict future recurrence and progression of disease,” said Helfand, who is a fourthyear medical student.

The researchers concluded that BCG plus sunitinib may produce outcomes superior to BCG alone.

“BCG induction and maintenance therapy have been the mainstay of treating high-risk nonmuscle-invasive bladder cancer for 30 years,” Helfand said. “But in essence we haven’t been able to improve on rates of complete response with BCG after induction.

We were seeking a way to try to find a compound that would work as a complementary therapy to BCG. What we decided to do was to use sunitinib, which would complement the anti-angiogenic effects of BCG on urothelial tumor cells. Using a VEGF inhibitor like sunitinib would perhaps enable complete response over that of BCG alone.”

“The promising results of this trial provide data that anti-angiogenic agents may be useful tools for lessening the burden of non-muscle invasive bladder cancer recurrence and intervention,” said Dr. Weizer, associate professor of urology and medical director of the University of Michigan Comprehensive Cancer Center. n

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Renal & Urology News 13

n FEATURE

Genitourinary Cancers and the Promise of Statins Data suggest the cholesterol-lowering drugs may be useful as adjunctive treatment

BY JODY A. CHARNOW

Prostate cancer Dr. Hamilton’s team looked at statin use and survival outcomes among 1,364 men placed on ADT because of rising PSA levels after primary or salvage radiother-

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Statins may slow the growth of a prostate tumor (above) by impeding production of testosterone from cholesterol.

apy. Statin users had a significant 36% decreased risk of overall and cancer-specific mortality compared with non-users.

“This study adds to the growing body of evidence that statin medications may inhibit prostate cancer growth,” Dr. Hamilton said. He added, however, there is not enough evidence to support starting patients on statin therapy to improve PCa outcomes.

The study by Dr. Harshman and colleagues built on preclinical findings out of the laboratory of Philip W. Kantoff, MD, at Dana-Farber showing that statins likely compete with the androgen DHEAS for uptake by the transporter SLCO2B1, which may result in decreased androgen stores for the tumor cell.

Using their institutional clinical database, Dr. Harshman’s team identified 926 men with hormone-sensitive PCa who were treated with ADT; about a third

were taking a statin at the time of ADT initiation. Statin users had a significantly longer mean time to disease progression than non-users (27.5 vs. 17.4 months).

“While this work needs to be validated prospectively, it suggests that statins may impact prostate cancer by decreasing the tumor’s available androgen pool, and could be a valuable adjunct to our current therapies for prostate cancer,” Dr. Harshman said.

In addition, a recently published crosssectional study of 323,426 men aged 65 years or older found that statin use was associated with a lower likelihood of having an abnormal screening PSA. For example, after adjusting for age, 6.2% of men taking a daily simvastatin dose higher than 40 mg had a PSA level above 4 ng/mL versus 8.2% of non-statin users, according to a report in Urology (2014;84:1058-1065).

The effect was more pronounced with

higher statin dose, longer statin duration, and higher statin potency.

In an interview with Renal & Urology News, Stephen J. Freedland, MD, an investigator involved in that study, explained that anti-neoplastic effects of statins are biologically plausible.

Cholesterol makes up almost onethird of cell membranes, he said, and cancer cells, because they divide prolifically, require more cholesterol. “If you deprive the body of cholesterol, you deprive the tumor of cholesterol,” said Dr. Freedland, professor of surgery (urology) at Cedars Sinai Medical Center in Los Angeles, where he is director of the Center for Integrated Research on Cancer and Lifestyle. “That alone could cause the tumor to grow slower.”

Dr. Freedland pointed out that prostate tumors make their own testosterone from cholesterol. “If there’s less cholesterol, the tumor has a harder time making testosterone.” Animal studies suggest that reductions in cholesterol levels are associated with a decrease in androgen levels in the tumor, he said.

Kidney cancer The study by Dr. McKay’s team was a pooled analysis of 4,736 patients who participated in phase 2 and 3 clinical trials of targeted therapy. The study population included 1,059 patients treated with sunitinib, 772 with sorafenib, 896 with axitinib, 457 with temsirolimus, 208 with temsirolinum plus interferon-alpha, 393 with bevacizumab plus temsirolimus, 391 with bevacizumab plus interferon-alpha, and 560 with interferon-alpha. Of the 4,738 patients, 511 used statins. Statin use was associated with a significant improvement in overall survival compared with non-use

© VOISIN / PHANIE / SCIENCE SOURCE

R

ecent studies have added to mounting evidence that statins have beneficial health effects apart from their approved indication for lowering cholesterol, including anti-cancer properties and protection against contrast-induced nephropathy.

At the 2015 Genitourinary Cancers Symposium in February, for example: • Robert J. Hamilton, MD, MPH, of the University of Toronto, and colleagues presented findings linking statin use with improved survival among prostate cancer (PCa) patients placed on androgen-deprivation therapy (ADT) for post-radiotherapy biochemical failure.

• Lauren C. Harshman, MD, of DanaFarber Cancer Institute, Harvard Medical School, Boston, and colleagues reported that among PCa patients receiving ADT, statin use at the time of ADT initiation was associated with delayed disease progression.

• Researchers led by Rana R. McKay, MD, also of Dana-Farber, reported that statin use was associated with improved survival among patients with metastatic renal cell carcinoma (RCC) treated with targeted therapy.

Studies to date provide intriguing evidence that statins could have a role as adjunctive treatment for urinary and other cancers, researchers say, and they make a strong case for conducting the prospective, randomized, intervention trials required to prove that statins cause the observed beneficial effects.

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(25.6 vs. 18.9 months), a difference that translated into a nearly 22% decreased risk of death in adjusted analyses. Statin use was not associated with a significant improvement in progression-free survival.

The researchers also examined statin use versus non-use by therapy type. In adjusted analyses, statin use was associated with a significantly decreased risk of death among patients treated with therapies targeting vascular endothelial growth factor or mammalian target of rapamycin (risk reductions of about 25% and 34%, respectively). Statin use did not affect survival in patients treated with interferon-alpha. Statin users and non-users had similar adverse event rates.

Statins could represent a potential adjunct therapeutic option for patients with metastatic RCC, the authors concluded.

A recently published study in Urologic Oncology (2015;33:e11-17) shows that statins also may benefit patients undergoing surgery for RCC. Samuel D. Kaffenberger, MD, a urologic oncology fellow at Memorial Sloan-Kettering Cancer Center in New York, and colleagues analyzed data from 916 RCC patients who underwent radical or partial nephrectomy at Vanderbilt University in Nashville, Tenn., from 2000 to 2010. The median follow-up was 42.5 months. The 3-year overall and disease-specific survival rates were 83% and 91%, respectively, for statin users versus 77% and 84% for non-users.

Other cancers Investigators also have observed the putative anti-cancer effects of statins in non-urinary malignancies. In a study of 128,675 post-menopausal women in the Women’s Health Initiative—of whom 10,474 used statins at baseline—statin use was associated with a significant 20% decreased likelihood of a diagnosis of latestage breast cancer, according to a report published online ahead of print in Cancer Causes and Control. A meta-analysis of 6 case-control studies that included a total of 5,993 cases of gastric cancer and 54,800 matched controls concluded that statin use is associated with a 44% decreased risk of gastric cancer, researchers reported in the Journal of Cancer Research and Therapeutics (2014;10:859-865).

Conflicting studies Not all studies have demonstrated that statins have anti-cancer effects. For example, a population-based cohort study published online ahead of print in the European Journal of Cancer found that men using any statins had a 25% increased risk of high-grade PCa and

Statins-Feature_013-4_RUN0415.indd 14

Stephen J. Freedland, MD

Samuel D. Kaffenberger, MD

a 16% increased risk of any PCa compared with men not on any medication.

The study, by Tobias Nordström, MD, of Karolinska Institutet in Stockholm, Sweden, and colleagues included 185,667 men having a first recorded PSA test and 18,574 men having a first prostate biopsy in Sweden. In another study, Japanese researchers using the FDA’s Adverse Event Reporting System database and a large claims database found an association between statin use and an increased risk of colorectal and pancreatic cancer, according to a report in the International Journal of Medical Science (2015;12:223-233).

reduction in the incidence of a number of cancer types, including RCC and prostate and colorectal cancer, he pointed out. Mechanistically, statins have been shown to exhibit anti-neoplastic activity at physiologic concentrations by a number of potential mechanisms, but whether these data translate into a survival benefit remains unknown, he said.

Large-scale retrospective clinical studies have exhibited mixed results in terms of effects on survival in many cancers, including RCC. Specifically, some large clinical series of patients undergoing radical or partial nephrectomy for RCC have shown a survival advantage for patients on statins, whereas others have not.

“Given the demonstrated safety profile and numerous proven health benefits of statins, along with encouraging preclinical data, clinical trials are certainly warranted in renal cell carcinoma and other cancer types,” Dr. Kaffenberger said. “Unfortunately, since there is little financial incentive for pharmaceutical companies to invest in clinical trials for drugs which are off-patent, funding for these trials will be difficult to obtain.”

Too early for cancer therapy Despite multiple studies suggesting that statins have anti-cancer effects, it remains unproved whether the medications are directly responsible for the benefits observed in those studies, Dr. Freedland said. Other factors, and not statin use per se, may account for the apparent protective effects observed in the studies conducted so far, he said. One factor may be fundamental differences between statin users and non-users. Data show, for example, that statin users are more health conscious. “They’re the ones who went to the doctor to get screened for cholesterol,” Dr. Freedland said.

Memorial Sloan-Kettering’s Dr. Kaffenberger agreed that it is too early to start prescribing statins as part of cancer treatment. “It would be premature to recommend adjunctive statin therapy for the purpose of improving survival in patients with cancer at this time,” Dr. Kaffenberger said. “While there is promising epidemiologic and mechanistic evidence for an antineoplastic effect of statins in a number of different cancer types, including renal cell carcinoma and prostate cancer, the clinical evidence for use of statins as adjunctive anticancer agents is conflicted.”

Large, population-based epidemiologic studies have commonly shown a

Contrast-induced nephropathy In addition to their possible anti-cancer effects, statins might prove useful as prophylaxis against contrast-induced nephropathy (CIN), as demonstrated in 2 randomized, controlled trials published in the Journal of the American College of Cardiology (2014;63:62-70; 71-79). In a study of 504 patients with acute coronary syndrome (ACS) scheduled for invasive cardiac procedures, Mario Leoncini, MD, of Prato Hospital in Prato, Italy, and colleagues assigned 252 patients to receive rosuvastatin (40 mg on admission, followed by 20 mg/day) and 252 to receive no statin (controls). The incidence of CIN was significantly lower in the statin than nostatin group (6.7% vs. 15.1%), which

in adjusted analyses represented a 62% decreased odds of CIN. The other study, by Yaling Han, MD, PhD, of Shenyang Northern Hospital in Shenyang, China, and colleagues, included 2,998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD). These patients were undergoing coronary or peripheral arterial angiography with or without percutaneous intervention. The investigators assigned 1,498 patients to receive rosuvastatin 10 mg/day for 5 days and 1,500 patients to receive standard care (controls). The statin group had a significantly lower incidence of CIN than controls (2.3% vs. 3.9%).

For both studies, investigators defined CIN as an increase in serum creatinine level of 0.5 mg/dL or greater or 25% or more above baseline within 72 hours after exposure to contrast medium.

Recent meta-analyses also support the use of statin treatment to lower CIN risk.

A meta-analysis of 13 prospective randomized controlled trials totaling 5,803 patients with contrast exposure found that patients who received periprocedural statin treatment to prevent CIN had a lower overall incidence of CIN compared with controls (3.6% vs.

6.9%), Wisit Cheungpasitporn, MD, of Mayo Clinic in Rochester, Minn., and colleagues reported online ahead of print in Renal Failure. Statin use was associated with a significant 51% decreased risk of CIN. All patients received intravenous fluid hydration for CIN prevention. In a meta-analysis of 9 prospective randomized studies of high-dose statin treatment compared with placebo for CIN prevention showed that statin treatment was associated with a significant 55% decrease odds of CIN, according to an online report in the American Journal of Therapeutics. The studies included in the meta-analysis, which was conducted

by Alexandros Briasoulis, MD, PhD, of Wayne State University/Detroit Medical Center, and colleagues, had a total of 2,480 statin recipients and 2,504 controls.

An Iranian study, however, did not find a beneficial effect of a statin in preventing CIN. The study, which was published in ARYA Atherosclerosis (2014;10:252258), included 236 patients referred for elective computed tomography angiography. Investigators randomly assigned 115 patients to receive atorvastatin (80 mg/day) and 121 to receive placebo from 24 hours before to 48 hours after contrast administration. The atorvastatin and placebo groups did not differ significantly in the incidence of CIN (4.3% vs. 5.0%), although the atorvastatin group experienced significantly less of an increase in serum creatinine after contrast administration. n

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Renal & Urology News 15

CKD Linked to Poor Dietary Habits Researchers assessed the effects of non-adherence to a DASH-style diet among urban poor POOR DIETARY HABITS are associated with an increased risk of chronic kidney disease (CKD) among povertystricken urban residents, according to a new study.

Based on the finding, researchers concluded that dietary habits “may represent a target for interventions aimed at reducing disparities in CKD.” The study included 2,058 community-dwelling adults aged 30–64 years (mean 48 years) living in Baltimore classified into poverty and nonpoverty groups. Researchers led by Deidre C. Crews, MD, ScM, of Johns Hopkins University School of Medicine in Baltimore, evaluated subjects’ adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, which is high in fruits and vegetables, moderate in low-fat dairy products, and low in animal protein, but with substantial amounts of plant protein from legumes and nuts.

The researchers calculated a DASH diet adherence score for each participant

Stroke Risk Increases as GFR Declines STROKE RISK increases linearly with decreasing glomerular filtration rate (GFR) and increasing albuminuria, according to a systematic review and meta-analysis published online ahead of print in Nephrology Dialysis Transplantation.

Stroke risk increased by 7% with each 10 mL/min/1.73 m2 decrease in GFR and by 10% with each 25 mg/ mmol increase in albumin-creatinine

based on 9 nutrient targets: protein, total fat, saturated fat, cholesterol, fiber, magnesium, calcium, potassium, and sodium.

Subjects who met the DASH target for a nutrient received a score of 1, and participants who achieved an intermediate target for a nutrient received a score of 0.5.

The highest achievable total score was 9.

Compared with the highest DASH score tertile (2.5–8), the lowest tertile (0–1) was associated with 3-fold greater adjusted odds of CKD in the poverty group, but was not associated with CKD in the nonpoverty group, Dr. Crews’ team reported in the Journal of Renal Nutrition (2015;25:103-110).

“To our knowledge, this is the first report comparing dietary patterns in the context of socioeconomic disparities in CKD,” Dr. Crews and her colleagues wrote. “In our study, participants living in poverty consumed diets lower in several potentially renal-protective nutrients than consumed by the nonpoverty participants, including potassium.”

Unhealthy eating put urban poverty-stricken individuals at higher CKD risk.

Of the 2,058 participants, 42% fell into the poverty group, which included individuals whose self-reported household income was less than 125% of the 2004 Department of Health and Human Services poverty guideline (family of 4

earning less than $23,562 annually). The non-poverty group included individuals with higher self-reported household income. The investigators defined CKD as an estimated glomerular filtration rate below 60 mL/min/1.73 m2.

The median DASH score for the study population was 1.5. Only 4.5% of the poverty group and 6.1% of the nonpoverty group had dietary patterns consistent with the DASH diet, according to the investigators. The poverty group had significantly higher cholesterol and lower fiber, magnesium, calcium, and potassium intake than the nonpoverty group, but the 2 groups had similar intake of saturated fat and sodium.

In a discussion of study limitations, the authors noted that, because of the study’s cross-sectional design, a direct causal relationship between DASH diet adherence and CKD cannot be inferred and reverse causality (for example, a CKD diagnosis affecting adherence to a DASH-style diet) is possible. n

Abiraterone’s Survival Edge Confirmed ABIRATERONE ACETATE treatment prolonged survival by a median of 4.4 months among chemotherapy-naïve patients with metastatic castrationresistant prostate cancer, according to a new study.

The study results, published online in The Lancet Oncology, “strengthens the rationale for use of abiraterone acetate early” in the course of the disease, wrote lead researcher Charles J. Ryan, MD, associate professor of medicine and urology at the University of California San Francisco, and colleagues.

For the study, researchers randomly assigned 1,088 asymptomatic or mildly

symptomatic chemotherapy-naïve patients to receive oral abiraterone acetate (1,000 mg daily) with prednisone (5 mg twice daily) or placebo with the same dose of prednisone. After a median follow-up of 49.2 months, 65% of patients in the abiraterone group and 71% in the placebo group died.

The median survival time was 34.7 months in the abiraterone arm compared with 30.3 months in the placebo group, a survival difference that was “both clinically and statistically significant,” according to the investigators.

The survival benefit was accompanied by a delay in the onset of symp-

toms and need to use opiates for PCarelated pain, the researchers reported.

The median time to opiate use in the abiraterone and placebo groups was 33.4 and 23.4 months, respectively.

Adverse events of special interest that were more common in the abiraterone group included cardiac disorders, increased alanine aminotransferase, and hypertension. Some of these effects may have been related to mineralocorticoid excess.

The findings, which are from the final analysis of the phase 3 COU-AA-302 trial, confirmed interim results favoring abiraterone. n

ratio, researchers led by Philip Sydney in Australia, reported. Results did not differ by stroke subtype, sex, and varying prevalence of cardiovascular risk factors.

The systemic review and meta-analysis included 63 cohort studies with a total of 2,085,225 participants) and 20 randomized clinical trials with a total of 168,516 participants). n

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Survival Similar with Renal Cryo Techniques LAPAROSCOPIC and percutaneous cryoablation for small renal masses are associated with similar overall and recurrence-free 5-year survival, researchers reported online ahead of print in Urology.

A team led by Jihad H. Kaouk, MD, of the Center for Laparoscopic and Robotic Surgery, Glickman Urologic and Kidney Institute, Cleveland

Clinic, and colleagues analyzed data from 412 patients who underwent cryoablation for small renal masses from 1997 to 2012. Of these, 275 underwent laparoscopic cryoablation (LCA) and 137 underwent percutaneous cryoablation (PCA). The LCA group had a significantly longer median follow-up time than the PCA

group (4.41 vs. 3.15 years), according to the investigators.

The estimated probability of 5-year overall and recurrence-free survival was 89% and 79%, respectively, for the LCA group and 82% and 80%, respectively, for the PCA group, the investigators reported. The differences between groups were not statistically significant. n

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Masson, MD, of the University of

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Hurricane Sandy Adversely Affected ESRD Patients Emergency department visit and hospitalization rates increased in wake of storm dialysis there than those in comparison groups 1 and 2 (23% vs. 9.3% and 6.3%, respectively).

The 30-day mortality rate for the study group was significantly higher than that of comparison group 1 (1.47%) and slightly but not significantly higher than that of comparison group 2 (1.6%).

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PATIENTS WITH end-stage renal disease (ESRD) in the regions affected

by Hurricane Sandy in October 2012 experienced higher rates of emergency department (ED) visits and hospitalization as well as a slightly higher 30-day mortality rate, according to a new study.

Using claims data from the Centers for Medicare & Medicaid Services,

Death rates increased slightly among dialysis patients hard hit by Hurricane Sandy.

researchers compared a study group of ESRD patients in the areas most affected by the hurricane (New Jersey and New York City) with 2 comparison groups: (1) ESRD patients living in states unaffected by Sandy during the same period; and (2) ESRD patients living in the Sandy-affected region a year prior to Sandy (October 1, 2011 through October 30, 2011).

Of 13,264 study group patients, 59% received early dialysis in 70% of the New York City and New Jersey dialysis facilities. The ED visit rate was 4.1% for the study group compared with 2.6% and 1.7% of comparison groups 1 and 2, respectively, the researchers reported in the American Journal of Kidney Diseases (2015;65:109–115). The hospitalization rate for the study group was 4.5%, which was significantly higher than the 3.2% and 3.8% rates for comparison groups 1 and 2, respectively.

In addition, among patients who visited the ED, those in the study group were significantly more likely to receive

News-HurricaneS_RUN0315.indd 16

Early dialysis important “Our findings support the feasibility of using early dialysis as a potential standard of care and protective measure when a hurricane or other ‘notice event’ is anticipated to interrupt dialysis treatment,” the authors wrote. “Emergency preparedness and response depend on good planning and strong day-to-day systems. Many dialysis providers routinely organize early dialysis for patients in advance of major holidays, suggesting that systems are in place to provide such care in advance of a major storm.”

The investigators stated that, from a preparedness perspective, “dialysis facilities should consider having plans in place to provide early dialysis to patients in advance of predictable disasters such as hurricane and to ensure their ability to function in a disaster.”

In a statement prepared by the National Kidney Foundation (NKF), which publishes the American Journal of Kidney Diseases, corresponding author Nicole Lurie, MD, Department of Health and

Human Services Assistant Secretary for Preparedness and Response, stated that the research clearly showed that delaying dialysis can have devastating health effects for patients with ESRD. “The good news is that we saw a lot of patients receiving dialysis before the storm hit. That type of advance planning by patients and their facilities should become routine nationwide,” she said.

“Everyone involved should know what to do when their facilities might close— patients should know where to go, and facilities should be able to provide a surge in early dialysis care so treatment is not delayed. At the end of the day, that helps people and their communities be more resilient.”

Room for improvement Dr. Lurie pointed out that 40% of patients did not receive early dialysis, meaning “there is still plenty of room for dialysis patient and facility improvement. I hope these findings serve as a rallying cry not just for the dialysis community, but for all for people with any type of chronic health condition and their care providers to plan for emergencies.”

“This is an important analysis of the impact of Hurricane Sandy in October 2012 on individuals treated with incenter hemodialysis that ultimately helps the dialysis community better anticipate what might go wrong, improve emergency plans for disaster scenarios, and more rapidly respond to protect the health of our patients during emergencies,” said Joseph Vassalotti, MD, NKF’s Chief Medical Officer. “The study reflects another step forward to improve the education and training of patients and dialysis clinic staff, following the widely recognized poor response to Hurricane Katrina in August 2005.”

Although the new study had a number of strengths—such as the use of Medicare data, which cover nearly all of the nation’s ESRD patients—it also had some limitations, including lack of access to sufficiently granular data on sustained power outages and facility damage, “which may have enabled us to better understand the utilization pattern seen.” n

Pelvic Plexus Block Better For Bx Pain PELVIC PLEXUS BLOCK is more effective than conventional periprostatic block for controlling pain during transrectal ultrasound (TRUS)-guided prostate biopsy, according to a new study.

In a prospective, double-blind study, Tarun Jindal, MD, of Apollo Gleneagles Hospital in West Bengal, India, and collaborators randomly assigned 139 men undergoing TRUS-guided biopsy into 1 of 3 groups. One group included 47 patients who received intrarectal local anesthesia (IRLA) with 10 mL 2% lidocaine jelly along with pelvic plexus block (PPB) with 2.5 mL 2% lidocaine injection. In PPB, lidocaine is injected bilaterally directly into the pelvic plexus, thereby blocking all nerve fibers and thus having a theoretical advantage over periprostatic nerve block (PNB).

PNB is considered the gold standard for lessening pain from biopsy needle insertion, but it has not been found to be completely satisfactory. In PNB, lidocaine is instilled bilaterally at the junction between the bladder, prostate, and seminal vesicle with the aim of blocking the posterolateral neurovascular bundle carrying the main nerve supply to the prostate.

Patients reported less pain with PPB than periprostatic nerve block.

A second group consisted of 46 patients who received IRLA with PNB. The third group included 46 patients who received only IRLA without any type of nerve block. Patients rated their level of pain from 0 to 10 (worst pain) on a visual analogue scale (VAS) during the biopsy procedure and 30 minutes after the procedure.

The mean pain score during biopsy was significantly lower in the PPB group compared with the PNB group (2.91 vs.

4.0), the investigators reported online ahead of print in BJU International.

Both the PPB and PNB groups reported significantly lower pain scores than the group with no nerve block, which reported a mean score of 5.4. The researchers found no significant difference in mean pain scores among the 3 groups 30 minutes after the procedure. n

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Renal & Urology News 17

Delaying RP Safe with Low-Risk PCa Putting off surgery for up to 12 months does not raise odds of adverse pathologic outcomes sured the effect of delayed RP on pathologic upgrading, upstaging, nodal metastases, and positive surgical margins.

Dr. Eggener’s group reported that 16,818 patients underwent RP within 6 months or less, whereas 894 had RP at 6–9 months, 169 at 9–12 months, and 62 at more than 12 months from their diagnostic biopsy. Upgrading, upstaging, and nodal metastases were found in 45% of men.

In multivariable analysis, higher PSA level, more than 2 positive biopsy cores, 34% or more positive biopsy cores, time from biopsy more than 12 months, and black race each independently and significantly increased the composite risk of adverse pathology.

Compared with patients who had a PSA level of 0.1–2.4 ng/mL, those with a level of 4.1–9.9 ng/mL had an 87% increased odds of adverse pathology. The presence of 3 or more positive biopsy cores was associated with a sig-

Radical Cystectomy Methods Result in Similar Outcomes PROSTATE capsule-sparing and nerve-

reported in The Journal of Urology

sparing radical cystectomy are associ-

(2015;193:64-70). The researchers

ated with similar functional and oncologic

observed a similar pattern with sexual

outcomes, a new study suggests.

function and found no difference in

The study, led by Alon Z. Weizer,

recurrence-free, metastasis-free, or over-

MD, of the University of Michigan

all survival. The 2 groups also had similar

Comprehensive Cancer Center in

perioperative outcomes and complica-

Ann Arbor, enrolled 40 patients.

tion rates, as well as similar rates of inci-

Investigators randomized 20 patients

dentally detected prostate cancer. The

each to undergo each surgical approach

mean operative time was 395 and 411

and stratified them by Sexual Health

minutes in the prostate-capsule sparing

Inventory for Men score (greater than

and nerve-sparing groups, respectively.

21 vs. 21 or less). A score of 21 of

Dr. Weizer and his colleagues acknowl-

less indicates sexual dysfunction. The

edged, however, that their study was

primary endpoint was 12-month overall

underpowered due to a lack of patient

urinary function as measured by the

accrual. It is unclear whether statistically

Bladder Cancer Index, which consists of

significant differences in urinary and sex-

34 items in a total of 3 primary domains:

ual function between the 2 approaches

urinary, sexual, and bowel. Scores range

may have emerged had they attained

from 0 to 100 points, with higher scores

their target recruitment of 82 patients.

corresponding to better health states.

Urinary function at 12 months

“Nevertheless, our study findings improve our understanding of urinary

decreased by 13 and 28 points in the

and erectile function outcomes after

prostate capsule and nerve sparing

prostate capsule sparing and nerve

groups, respectively, a non-significant

sparing approaches as well as the onco-

difference between groups, the authors

logic implications of the approaches.” n

News-PCaPathology_RUN0315.indd 17

A study of 17,943 patients found that about half of them had adverse pathologic outcomes at radical prostatectomy.

nificant 68% increased odds of adverse pathology compared with fewer than 3 positive cores. Men with at least 34% positive cores had a significant 28% increased odds compared with those who had less than 34% positive cores.

Magnesium May Benefit HD Patients HIGHER MAGNESIUM levels, via their effect on phosphorus levels, may lower all-cause and cardiovascular mortality risk in hemodialysis (HD) patients, according to a new study.

“In accordance with the recent in vitro studies showing the protective role of Mg on phosphate-induced calcifications of [vascular smooth muscle cells], we found that the mortality risk of patients with hyperphosphatemia was significantly attenuated with increasing serum Mg levels,” stated Yoshitaka Isaka, MD, of Osaka University Graduate School of Medicine in Japan and colleagues in PLOS One. “This finding suggests that, in addition to current strategies to reduce phosphate load, increasing Mg levels may also help to attenuate the cardiovascular risk of patients with hyperphosphatemia.”

Conventional therapies, such as dietary restriction and dialysis, have been only moderately effective at controlling phosphate levels, the researchers pointed out.

As high serum magnesium potentially carries risks, such as oversuppression of parathyroid hormone, patient mag-

Compared with patients who underwent RP within 6 months or less from the time of their biopsy, those who underwent RP more than 12 months after biopsy had 70% increased odds.

Patients who underwent RP 6–9 months and 9–12 months after biopsy were not at increased risk of adverse pathology.

Black race was associated with 16% increased odds compared with whites.

Dr. Eggener’s team cautioned that their findings should be interpreted within the context of study limitations. “Our study design creates an inherent selection bias as we only analyzed patients who underwent surgery,” they stated. “This bias should be considered when generalizing our study’s findings to any patient diagnosed with low-risk PCa.” In addition, the researchers pointed out that they were unable to evaluate biochemical recurrence after RP, “a more clinically meaningful end point than pathologic findings.” n

nesium levels would need to be monitored, according to the researchers.

The investigators analyzed data from more than 142,000 HD patients in the Renal Data Registry of the Japanese Society for Dialysis Therapy in 2009.

They categorized patients into 3 groups by serum magnesium levels: the lower group had less than 2.7 mg/dL magnesium; the intermediate group had 2.7 to less than 3.1 mg/dL; and the higher group had 3.1 mg/dL or more.

Within a year, 11,401 patients died, 41.7% from cardiovascular causes.

Among patients in the 4th quartile of serum phosphorus (6 mg/dL or higher), those in the lower- and intermediate-magnesium groups had a significant 52% and 58% increased odds of all-cause mortality, respectively, and 64% and 42% increased odds of cardiovascular mortality, respectively, compared with patients in the 2nd quartile of serum phosphorus (reference, 4.1 to less than 5.1 mg/dL). In contrast, patients in the higher-magnesium group had no significantly increased risk of all-cause or cardiovascular mortality.

The researchers suggest several possible ways to increase magnesium in dialysis patients with hyperphosphatemia, such as increasing the dialysate magnesium level and prescribing magnesium-containing phosphate binders. n

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MEN WITH LOW-RISK prostate cancer (PCa) in the United States can delay undergoing radical prostatectomy (RP) for up to 12 months after their cancer diagnosis without experiencing an increased risk of adverse of pathologic outcomes, according to a new study.

“Men may safely use the time following their initial biopsy to consider management options and obtain a restaging biopsy, if recommended,” researchers concluded in Urologic Oncology (published online ahead of print).

The study also found that approximately half of men with low-risk PCa experience an adverse pathologic outcome at RP. Using the National Cancer Database, a team at the University of Chicago led

by Scott E. Eggener, MD, analyzed data from 17,943 patients with low-risk PCa who underwent RP. They identified patients who delayed RP by more than 6 months after cancer diagnosis and mea-

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Practice Management T

he face of urology and nephrology could change dramatically in the next decade. According to the Association of American Medical Colleges, 26% of practicing nephrologists and 7.2% of urologists were female in 2013. However, women currently account for 39% of nephrology residents and almost 23% of urology residents.

What does this mean for physician practices? Practices should plan ahead to create positive workforce changes accommodating the needs of future physicians.

said Leslie Rickey, MD, Fellowship Director, Female Pelvic Medicine and Reconstructive Surgery, Yale School of Medicine in New Haven, Conn., and president of the Society of Women in Urology.

“It might be time to reconsider the notion that more hours equal greater dedication and a better physician,” Dr. Rickey said. “It doesn’t mean that some degree of ‘scheduled predictability’ that allows doctors to dedicate time to their families or outside activities implies that a physician is any less committed to optimal patient care.”

A broader demographic Just 5 years ago, if a practice came to Dan Jennings of The Medicus Firm looking for a female urologist, he was hard-pressed to find a candidate. Now, about 1 in every 5 or so responses he gets when advertising for urology positions are from women. This is a good thing, he said, particularly in communities with a lot of male physicians and an increasing number of female urology patients.

It’s not a surprise to find that, on average, female physicians tend to work fewer hours than men. Studies have shown that women doctors work approximately 7 or 8 fewer hours a week than their male counterparts.

Making change As more women enter the fields, practices may need to be more flexible.

Martin Osinski, owner of the recruiting firm NephrologyUSA, said it will likely be bigger offices that are able to make changes. In these groups, he has seen part-time schedules, reduced call loads, or hiring solely for dialysis rounding or office visits.

Jennings said women are moving to urology because there tends to be fewer emergency surgeries. For this reason, some groups may allow people to schedule surgeries only 2 to 3 days a week in the mornings.

Dillon said it will likely be groups having a hard time getting candidates

Maternity leave is one of the most important considerations when integrating women into practices. This should be dealt with proactively.

What groups should be aware of, however, is that flexing schedules is not just for female providers.

According to Cejka Search, 22% of male and 44% of female physicians in 2011 worked part-time schedules.

This trend is not likely to change, as the number of dual-career families increase, more women enter the field, older physicians cut back, and more millennials enter the field,

PractMan_RUN0415.indd 18

that will have to be most willing to bend. He has seen small hospitals in rural areas ship evening and weekend surgeries to other places so their physicians don’t have to come in. Some groups might be amenable to splitting schedules and letting 2 women work half time to fill one full time equivalent position.

“If someone wants to take some call but only every other week, offices

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Practices may need to adjust schedules, time off, and compensation as the number of female urologists and nephrologists grows BY TAMMY WORTH

On average, female physicians tend to work fewer hours than their male counterparts.

will have to make an adjustment in compensation somehow,” Dillon said. “They are going to have to be creative.”

Dr. Rickey said that one of the most important aspects of integrating women into the practice is dealing with maternity leave.

“There are still many women who struggle with childbearing and when to do it and how it will look in practice,” she said.

Practices need to deal with it proactively, she said. Time off and effective compensation should be built into a contract so the physician doesn’t have to ask for it when the time comes. One option may be to navigate the issue through the use of short-term disability.

This way, the physician gets compensated and other doctors don’t have to feel like they are paying for their break.

Moving up A physician’s ultimate goal is to become a partner. Unfortunately, this doesn’t exactly jibe with flexible scheduling.

A solution to this is to allow women to remain as employees and avoid call or work fewer hours. Dillon said people often won’t buy in as a partner

if they are only receiving part-time pay. Some practices let women “take a portion of partner.” They can work one-third or one-half of the call other doctors work and only pay in and reap the rewards of an equal amount of partnership.

“Medicine has changed and doctors who are coming up in this day are not going to work like their dad or grandfather did,” Dillon said.

To have women in partnership takes a pathway that is not always available.

Dr. Rickey said she has had a host of “wonderful male mentors” during her career, but contends it will be increasingly important as more women enter the field to have tenured females in these roles.

“If you look around and don’t see people that look like you in those positions, you can’t see yourself there,” she said. “It is harder to relate and see yourself in those roles.”

Of the 126 urology residency programs in the nation, Dr. Rickey said she knows of 3 that have women as department chairs, hardly reflective of the 10% of women practicing in the field. n Tammy Worth is a freelance medical journalist based in Blue Springs, MO.

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