Renal & Urology News - Nov/Dec 2016 Issue

NOV EMBER /DECEMBER 2016

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VOLUME 15, IS SUE NUMBER 9

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www.renalandurologynews.com

Drug Sequences for mCRPC Probed Regimens that include cabazitaxel may offer an edge in terms of cumulative overall survival, data suggest ORDER OF mCRPC MEDICATIONS COMPARED A new study comparing 3 different sequences of docetaxel, cabazitaxel, and either enzalutamide or abiraterone found no significant difference in overall survival among patients with metastatic castration-resistant prostate cancer. The median survival associated with each of the sequences, in months, is shown here.

DOC

CAB

ART

37.3

DOC

ART

CAB

36.0

ART

DOC

CAB

30.1

DOC=docetaxel ART=androgentargeted receptor agent therapy (either enzalutamide or abiraterone) CAB=cabazitaxel

Source: Angelergues A, et al. Efficacy of cabazitaxel, abiraterone, enzalutamide and docetaxel sequence in men with metastatic castration-resistant prostate cancer (mCRPC) in real life practice: The multinational, retrospective, observational CAT study. Poster 744P Ann Oncol 2016;27 (Suppl 6): vi254.

BY JODY A. CHARNOW NEW STUDIES presented at the 2016 congress of the European Society for Medical Oncology in Copenhagen may provide insight into the sequential use of new agents for treating metastatic castration-resistant prostate cancer (mCRPC).

Based on a study of 344 mCRPC patients treated with at least 2 new agents (abiraterone, enzalutamide, or cabazitaxel) after experiencing disease progression on docetaxel, investigators in Italy led by Orazo Caffo, MD, of Santa Chiara Hospital in Trento, reported that using cabazitaxel in a sequence of new agents may offer an advantage in terms of cumulative overall survival.

The median overall survival was 11.9 months for patients treated first with a

New PCa Screening Plan Proposed Hyponatremia INVESTIGATORS have proposed a “In our algorithm, we recommend Raises Kidney new approach to prostate cancer (PCa) that a biopsy should not be performed screening in which a PSA level of 1.5 unless the risk of an aggressive tumor Stone Risk ng/mL or higher should prompt pri- is significant, and following a thorough mary care physicians to consider referring patients to a urologist for further evaluation. Men who have a PSA level below 1.5 ng/mL would have a routine follow-up PSA test in 5 years.

discussion of benefits and risks with the patient,” the investigators, led by E. David Crawford, MD, of the University of Colorado, Denver, wrote in Urology continued on page 22

VITAMIN C FOR ANEMIA IN DIALYSIS PATIENTS

New study findings may point the way to optimal dosing.

PAGE 21

BY JODY A. CHARNOW CHICAGO—Hyponatremia, osteoporosis, and proton pump inhibitor (PPI) use emerged as risk factors for kidney stones in separate studies presented at the American Society of Nephrology’s 2016 Kidney Week meeting.

The hyponatremia finding is based on a case-control study led by Naoto Tominaga, MD, PhD, of the Division of Endocrinology and Metabolism at Georgetown University Medical Center in Washington, D.C. Using the electronic health records of 3.2 million unique patients in the MedStar Health system, Dr. Tominaga’s team identified 21,232 patients with kidney stones (cases) and a like number of controls (no kidney stones) matched by age, sex, and race.

The mean follow-up was 1345 days. The risk of kidney stones was higher for all hyponatremia categories. Kidney stone patients had 10% increased odds of prior hyponatremia as well as a 1.4 times, 2.3 times, and 5.2 times increased odds of

new androgen-receptor targeted agent therapy (ART)—either abiraterone or enzalutamide—and then with cabazitaxel and 13.4 months for those treated initially with cabazitaxel and then by either abiraterone or enzalutamide.

Patients who received abiraterone first followed by enzalutamide, or the reverse sequence, had a median overall survival of 8.3 months, a significantly lower survival compared with the cabazitaxelcontaining sequences.

Of the 344 patients 86% had bone metastases, 55% had nodal involvement, and 16% had visceral metastases.

The researchers reported that 190 patients received abiraterone as second-line therapy and 105 received the continued on page 22

IN THIS ISSUE 4

ALP declines predict better radium-223 outcomes

9

Prostate cancer incidence lower in HIV-infected men

9

Hypogonadism increases the risk of prostate cancer progression

13

Study links renal stone formation to higher testosterone levels

24

Nivolumab shows efficacy for metastatic urothelial cancer

26

Racial disparity in prostate cancer treatment characterized

28

Alpha blockers increase the odds of ureteric stone clearance

Results of the first long-term U.S. study of urea for SIADH reported PAGE 17

continued on page 22

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ALP Decline with Radium-223 Is a Positive Sign DECLINES IN alkaline phosphatase (ALP) may predict better outcomes in patients receiving treatment with radium-223 for metastatic castrationresistant prostate cancer (mCRPC), according to study findings presented at the European Society for Medical Oncology 2016 congress in Copenhagen.

Xtandi_004-5_RUN1216.indd 4

As part of a prospective single-arm phase 3b study, investigators led by Daniel Heinrich, MD, of Akershus University Hospital in Lorenskog, Norway, studied 696 mCRPC patients who received at least 1 radium-223 cycle in an international early access program. At week 12, 398 patients

(57%) had a confirmed decline in ALP from baseline and 298 (43%) did not.

Compared with the group that did not have an ALP decline, the group that did had a significant 70% decreased risk of death and a 53% decreased risk of first symptomatic skeletal event, Dr Heinrich and his colleagues reported.

More patients with a confirmed ALP decline received 5–6 radium-223 injections than those with no ALP decline (94% vs 33%).

The investigators noted that identifying a reliable marker of efficacy for radium-223 would help in the clinical management of mCRPC patients. n

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Renal & Urology News 5

Intensive HD Effective for Hyperphosphatemia INTENSIVE HEMODIALYSIS (HD), particularly nocturnal HD, reduces serum phosphorus levels and decreases the need for phosphate binders, investigators concluded in a new review.

“Hyperphosphatemia is a ubiquitous complication of end-stage renal disease,” Michael Copland, MD, of

the University of British Columbia in Vancouver, and colleagues concluded in the American Journal of Kidney Diseases (2016;68:S51-S58). “Upon detailed examination of dietary phosphorus intake and dialytic clearance, much of the need for phosphate binders can be attributed to the cumulative

number of hours of treatment with conventional HD. Intensive HD is an efficacious intervention for hyperphosphatemia and can lower or eliminate the need for phosphate binders.”

Dr. Copland’s group noted that short daily and nocturnal schedules in the Frequent Hemodialysis Network (FHN)

trial reduced serum phosphorus levels by 0.6 and 1.6 mg/dL, respectively, relative to 3 sessions per week. In the daily arm of the FHN trial, intensive HD significantly lowered estimated phosphate binder dose per day; in the nocturnal arm, intensive HD led to binder discontinuation in 75% of patients.

In addition, Dr. Copland’s group cited a single-center prospective cohort study by Juan Carlos Ayus, MD, and colleagues published in Kidney International (2007;71:336-342) showing that mean cumulative phosphorus clearance was 2452 mg/week with short daily HD (6 sessions per week each lasting 3 hours) compared with only 1572 mg/week with conventional HD (3 sessions per week each lasting 4 hours). Mean serum phosphorus levels with short daily HD fell from 6.26 mg/dL at baseline to 4.58 and 4.20 mg/dL after 6 and 12 months of follow-up, respectively. In the conventional HD arm, mean serum phosphorus levels remained near 5 mg/dL during follow-up. n

FDA Adds Testosterone Warnings THE FDA announced that it has approved class-wide labeling changes for all prescription testosterone products.

The agency added a new warning and updated the “Abuse and Dependence” section of product labels to include new safety data from the published literature and case reports regarding risks associated with abuse and dependence of testosterone and other anabolic androgenic steroids (AAS).

“Abuse of testosterone, usually at doses higher than those typically prescribed and usually in conjunction with other AAS, is associated with serious safety risks affecting the heart, brain, liver, mental health, and endocrine system,” the FDA said in a news release. “Reported serious adverse outcomes include heart attack, heart failure, stroke, depression, hostility, aggression, liver toxicity, and male infertility.” n

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Contents

NOVEMBER/DECEMBER 2016 ■ VOLUME 15, ISSUE NUMBER 9

Urology 9

ONLINE

16

this month at renalandurologynews.com 26

Clinical Quiz Take our latest quiz at renalandurologynews.com/ ClinicalQuiz

28

Answer correctly and you will be entered to win a $50 American Express gift card.

Congratulations to our recent winners: October: Richard Glassock, MD November: Efrain Flores, MD

Cabozantinib Superior for Untreated Advanced RCC Progression-free survival is longer with cabozantinib than sunitinib as first-line therapy for previously untreated patients with intermediateor poor-risk advanced RCC. Racial Gap Found in PCa Treatment Black and Hispanic prostate cancer patients were less likely to undergo radical prostatectomy, radiotherapy, or cryotherapy than their white counterparts.

Alpha Blockers Help Clear Large Ureteric Stones Passage of large stones is 49% more likely in patients who receive medical expulsive therapy with alpha blockers, according to a recent systematic review and meta-analysis.

17

Urea May Offer Cheaper SIADH Option The first long-term results of a U.S. study of urea as a treatment for the syndrome of inappropriate antidiuretic hormone secretion suggest it is safe and effective.

18

High Uric Acid in ICU Patients Raises AKI Risk Each 1 mg/dL increment in uric acid at admission to an intensive care unit is associated with 29% increased odds of incident acute kidney injury, study finds.

21

Optimal Vitamin C Dose for Anemia In Hemodialysis Patients Unclear Pending future studies, the latest findings suggest that HD patients should not take more than 120 mg per day.

What you need to know about putting patient information on the cloud.

Job Board

News Coverage Visit our website for daily updates as well as on-site coverage of major medical meetings.

PCa Incidence Lower in HIV-Infected Men The incidence of prostate cancer is 30% lower among men with HIV compared with men in the general population.

Nephrology

HIPAA

Be sure to check our latest listings for professional openings across the United States.

CALENDAR

29

Smoking Predicts Worse Outcomes in CKD Patients Current smokers have a 48% higher risk of allcause mortality and 37% higher risk of cancer compared with those who have never smoked.

It remains possible that high serum potassium

values simply are a marker for severe, life-threatening illnesses, such as sepsis, acute myocardial infarction, and trauma.

See our story on page 21

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Genitourinary Cancers Symposium Orlando, FL February 16–18 Annual Dialysis Conference Long Beach, CA March 11–14 National Kidney Foundation 2017 Spring Clinical Meetings Orlando, FL April 18–22 American Transplant Congress Chicago April 29–May 3 American Urological Association Annual Meeting Boston May 12–16 American Society of Clinical Oncology Annual Meeting Chicago June 2–6 European Renal Association-European Dialysis and Transplant Association 54th Congress Madrid June 3–6 Canadian Urological Association Annual Meeting Toronto June 24–27

30

Departments 8

From the Medical Director RCC Adjuvant Therapy: Calculating Value

13

News in Brief Kidney stones may be linked to elevated testosterone

30

Practice Management How to respond to patients’ negative online reviews

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8 Renal & Urology News

NOVEMBER/DECEMBER 2016 www.renalandurologynews.com

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

RCC Adjuvant Therapy: Calculating Value

E

ffective adjuvant therapy for solid tumors is the holy grail of surgery.

Adjuvant systemic therapies have remained elusive in urologic tumors, with none currently approved. Dozens of adjuvant renal cell carcinoma (RCC) clinical trials have been reported evaluating radiation, first-generation immunotherapies, and monoclonals alone or in combination. None have been clinically successful. Intense efforts have been undertaken to study targeted therapies in high risk, non-metastatic RCC after surgical resection. Two such trials recently reported include ECOG’s ASSURE (Adjuvant Sorafenib and Sunitinib for Unfavorable Renal Carcinoma) trial and Pfizer’s STRAC (Sunitinib Trial in Adjuvant Renal Cancer). ASSURE randomized 1943 patients (647 to sunitinib, 649 to sorafenib, 647 to placebo), while STRAC randomized 615 patients (306 to sunitinib, 309 to placebo). ASSURE reported no difference in disease-free survival (DFS) or overall survival (OS),1 whereas STRAC reported improved DFS among centrally reviewed cases (HR=0.76) but no difference in OS.2 The difference in reported outcomes has sparked considerable discussion. Given conflicting results, how do we decide if we should recommend adjuvant therapy for high-risk fully resected RCC? First, we need to define a framework of what constitutes healthcare “value” in oncology. The Institute of Medicine has identified 6 elements of value in cancer care: safety, effectiveness, efficiency, patient-centeredness, timeliness, and equity. Of these, the American Society of Clinical Oncology selected only 3 for its value framework; effectiveness, toxicity, and efficiency (cost).3 A thoughtful tool with which to assess these tradeoffs is the drug abacus (www.drugabacus. org), an online calculator allowing users to assign “value” in various domains such as incremental survival benefit and trade it off versus efficacy, novelty of mechanism, toxicity, cost of development, burden of disease, and other factors. It then compares your “value price” to the manufacturer’s price.

When high-level trials fail to produce a consistent and reproducible result, healthcare teams must contextualize the possible survival benefits in view of their risks and costs. Physicians and provider organizations must define and improve value because ultimately value is determined by how medicine is practiced.3 Adjuvant treatments for RCC are no exception.

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

1. Haas NB, Manola J, Uzzo RG, et al Lancet. 2016;387:2008-2016.

2. Ravaud A, Motzer RJ, Pandha HS, et al N Engl J Med. 2016; published online ahead of print Oct 9.

3. Young RC. N Engl J Med. 2015;373:2593-2595.

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Medical Director, Urology

Medical Director, Nephrology

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

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

Urologists

Nephrologists

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

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

R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto

David S. Goldfarb, MD Professor, Department of Medicine Clinical Chief New York University Langone Medical Center Chief of Nephrology, NY Harbor VA Medical Center

Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD, FACS President, Cleveland Clinic Regional Hospitals & Family Health Centers Professor & Horvitz/Miller Distinguished Chair in Urological Oncology 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

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

Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J.

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 Production director Circulation manager National accounts manager Group Publisher Editorial director

Krassi Varbanov Kathleen Millea Grinder Paul Silver William Canning Chad Holloway Kathleen Walsh Tulley

Senior VP, medical journals & digital products

Jim Burke, RPh

CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 15, Number 9. Published monthly, except for the combined January/February, June/July and November/ December issues, by Haymarket Media, Inc., 275 7th Avenue, 10th 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 © 2016.

12/6/16 4:03 PM

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NOVEMBER/DECEMBER 2016

Renal & Urology News 9

PCa Incidence Lower in HIV-Infected Men HIV-INFECTED MEN on antiretroviral therapy have a lower incidence of prostate cancer compared with those in the general population, new study findings suggest.

The study also found that the incidence of other common non-AIDSdefining cancers—colorectal and lung

cancer—is lower among HIV-infected men and women.

Using the LifeLink Health Plan Claims Database, Jeannette Y. Lee, MD, of the University of Arkansas for Medical Sciences in Little Rock, and colleagues analyzed data from 63,221 commercially insured individuals aged 18

years and older with at least 1 claim with a diagnostic code for HIV and at least 1 filled prescription for an antiretroviral medication. The investigators estimated the number of expected cancer cases in the general population for each genderbased age group using incidence rates from the Surveillance, Epidemiology

and End Results program. The incidence of PCa was 30% lower among HIV-infected men compared with men in the general population, Dr Lee’s group reported in the Journal of Cancer Epidemiology (2016;2138259).

The finding of a lower PCa incidence in HIV-infected men confirms previous reports. Although it was suggested that the decreased incidence may be associated with lower use of PSA testing, Dr Lee and her colleagues noted that a study comparing men with and without HIV infection in California found no difference with regard to PSA screening.

For the overall study cohort, the incidence of colorectal cancer and lung cancer was 31% and 30% lower compared with the general population. HIVinfected individuals had 46-fold higher incidence of Kaposi sarcoma, 30.5-fold higher incidence of anal cancer, 9.8fold higher incidence of Hodgkin lymphoma, and 4.2-fold higher incidence of non-Hodgkin lymphoma. ■

Hypogonadism Linked to PCa Progression HYPOGONADISM in prostate cancer (PCa) patients eligible for active surveillance (AS) is associated with an elevated risk of disease progression, according to an online report in Oncotarget.

In a study of 338 PCa patients who met AS criteria but opted to undergo radical prostatectomy, Matteo Ferro, MD, of the European Institute of Oncology in Milan, Italy, and colleagues found that hypogonadism (defined as a serum testosterone level below 300 ng/dL) was associated with a significant 11.6-, 3.6-, 10-, and 2.2-fold increased odds of upstaging, upgrading, unfavorable disease, and positive surgical margins, respectively, compared with men who had testosterone levels of 300 ng/dL or higher.

In addition, each 10 ng/dL increment in testosterone was associated with a significant 8%, 3%, 7% decrease in the odds of upstaging, upgrading, and unfavorable disease, respectively, the investigators reported. ■

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Renal & Urology News 13

News in Brief

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

Short Takes Chronic Periodontitis Increases ED Risk

decreased odds of prostate cancer in

Chronic periodontitis is associated with

of bladder cancer in female patients,

a significantly increased risk of erectile

the investigators reported in the Journal

dysfunction (ED), according to the find-

of Hypertension (2017;35:170-177).

ings of a recent systematic review and

Use of ACE inhibitors and angiotensin-

meta-analysis published in the Interna-

receptor blockers was not associated

tional Journal of Impotence Research.

with a lower risk.

male patients and 19% decreased odds

In an analysis of data from 4 casestudy involving 213,006 participants,

Removal of Patiromer’s Boxed Warning Approved

a team led by Zhigang Zhao, MD,

The FDA has approved removal of a

of Guangzhou Medical University in

boxed warning from the patiromer

Guangzhou, China, found that chronic

(Veltassa) drug label related to the

periodontitis was associated with a

timing of drug administration.

control studies and 1 cross-sectional

nearly 2.3-fold increased odds of ED,

The boxed warning stated that the drug, which is indicated for the

Urinary Cancer Risk Lower in Spironolactone Users

treatment of hyperkalemia, should be

Spironolactone use by hypertensive

other oral medications. The updated

patients is associated with a lower

label will now recommend patients

risk of some urinary cancers, accord-

take patiromer at least 3 hours before

ing to a new study.

or after other oral medications. De-

Ya-Wen Chuang, MD, of the ­Taichung

taken at least 6 hours before or after

tails of this information will appear in

Veterans General Hospital in Taichung,

the dosage and administration section

Taiwan, and collaborators analyzed

(Section 2) of the drug interactions

data from 32,167 hypertensive patients

section (Section 7) of the label. Data

with urinary cancers enrolled in Taiwan’s

from the patiromer drug-drug interac-

National Health Insurance Research Da-

tion program has been added to the

tabase. In adjusted analyses, spirono-

Clinical Pharmacology section of the

lactone use was associated with 12%

label (Section 12).

HD Outcomes in the Elderly A recent study of 2507 hemodialysis patients found that those aged 75 years and older had a higher 2-year mortality rate than those younger than 75 years, but a similar 2-year hospitalization rate. n ≥ 75 years 35 30

n < 75 years 35

34.7%

30

25

25

20

20

15

15.8%

10 5 0

34.0%

33.3%

15 10 5

2-year mortality rate

0

2-year hospitalization rate

Source: Seckinger J et al. Morbidity, mortality and quality of life in the ageing haemodialysis population: results from the ELDERLY study.

Clin Kidney J 2016; published online ahead of print.

NewsInBrief_RUN1216.indd 13

Higher Testosterone Levels May Hike Renal Stone Risk E

levated levels of serum testosterone may promote formation of renal stones, researchers in India reported in the International Journal of Applied & Basic Medical Research (2016;6:241-244).

Kapil Gupta, PhD, and colleagues at the Adesh Institute of Medical Sciences and Research in Punjab, India, conducted a case-control study that included 108 men: 78 diagnosed with urolithiasis (cases) and 30 age-matched healthy controls. Mean levels of total serum testosterone and serum dihydrotestosterone were significantly higher in cases (5.52 ng/dL and 419 pg/mL, respectively) compared with controls (4.36 ng/dL and 300.1 pg/mL, respectively). Cases and controls were similar with respect to mean levels of free testosterone and serum estradiol levels as well as mean age and body mass index.

Report: Older Age Should Not Preclude Partial Nephrectomy P

artial nephrectomy (PN) and radical nephrectomy (RN) are associated with similar survival outcomes among elderly patients, a new study suggests.

The study, by researchers at the Johns Hopkins School of Medicine in Baltimore led by Mark W. Ball, MD, included 787 patients aged 65 years and older with solitary cT2-T2 renal masses. Of these, 437 (55.5%) underwent PN and 350 (44.5%) underwent RN. The median follow-up was 36 months. In unadjusted analyses, PN was associated with better cancer-specific survival (CSS) than RN at 5 years (100% vs. 87.5%) and 10 years (100% vs. 80.2%), the researchers reported in Urology (2016; published online ahead of print). PN also was associated with better overall survival (OS) at 5 years (80.2% vs. 65.4%) and 10 years (60.6% vs. 35.1%). In multivariate analysis, PN and RN patients had similar CSS and OS. Perioperative outcomes and complication rates were similar between the treatment groups.

The authors concluded that “age alone should not be a contraindication to nephron-sparing surgery.”

SHPT Surgical Procedures Found Equally Effective T

otal parathyroidectomy alone (TPTX) or with autotransplantation (TPTX+AT) is safe and equally effective for the surgical management of otherwise uncontrollable secondary hyperparathyroidism (SHPT), according to a study published in Annals of Surgery (2016;264:745-753).

In a randomized, controlled pilot study, Katja Schlosser, MD, of Agaplesion Evangelisches Krankenhaus Mittelhessen in Giessen, Germany, and colleagues compared TPTX and TPTX+AT in 100 patients on long-term dialysis and otherwise uncontrollable SHPT. The main outcome was rate of recurrent disease within a 3-year follow-up period after surgery. Of the 100 patients, 52 underwent TPTX and 48 TPTX+AT. Persistent SHPT developed in 1 TPTX patient and 2 TPTX+AT patients. None of the TPTX patients and 4 of the TPTX+AT patients experienced recurrent SHPT. PTH increased in the TPTX+AT group and was significantly higher at the end of follow-up compared with the TPTX group (98.2 vs 31.7 pg/mL).

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Cabozantinib Superior for Untreated Advanced RCC

BY JODY A. CHARNOW CABOZANTINIB IS SUPERIOR to sunitinib as first-line treatment of previously untreated patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), investigators reported at the European Society for Medical Oncology 2016 congress in Copenhagen.

In the randomized phase 2 CABOSUN study comparing the drugs, a team led

by Toni K. Choueiri, MD, Director of the Lank Center or Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, found that the median progression-free survival (PFS)—the study’s primary endpoint—

was significantly longer in cabozantinib than sunitinib recipients (8.2 vs.

5.6 months), corresponding to a 46% improvement in PFS favoring cabozantinib. In addition, cabozantinib treatment was associated with a clinically meaningful and statistically significant 31% decrease in the rate of disease pro-

gression or death, Dr. Choueiri and his colleagues reported.

The objective response rate also was significantly greater in the cabozantinib than sunitinib group (46% vs 18%), the investigators reported.

After a median follow up of 22.8 months, the median overall survival was 30.3 months for cabozantinib compared with 21.8 months for sunitinib.

The study, which was sponsored by the National Cancer Institute in Bethesda, Maryland, included 157 patients, of whom 80.9% had intermediate-risk and 19.1% had poor-risk disease as defined by criteria established by the International Metastatic Renal Cell Carcinoma Database Consortium. The median follow-up was 20.8 months.

In addition, 36.3% of patients had bone metastases, 46% had ECOG Performance Status (PS) 0, 41% had ECOG PS 1, and 13% had ECOG PS 2.

Investigators randomly assigned patients 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off).

Progression-free survival is longer with cabozantinib than sunitinib.

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“The results … support the potential of cabozantinib to become a new therapeutic option for previously untreated patients following their diagnosis with advanced kidney cancer,” Dr Choueiri, chair of the CABOSUN study, said in a press release. “Not only has cabozantinib surpassed sunitinib, the current standard of care, in progression-free survival and objective response rate, cabozantinib’s effects on progressionfree survival were also consistently favorable across patient stratification subgroups including IMDC intermediate versus poor-risk groups and presence or absence of bone metastases.”

The FDA approved cabozantinib on April 25 for the treatment of advanced RCC in patients previously treated with anti-angiogenic medications. In an interview with Renal & Urology News, Dr. Choueiri said the findings from the phase 2 study might be sufficient to win an indication for front-line use.

“This is up to the regulatory authorities to decide, but I think we have a strong signal here that this drug is superior,” Dr. Choureiri said. n

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www.renalandurologynews.com

■ ASN 2016, Chicago

NOVEMBER/DECEMBER 2016

Renal & Urology News 17

American Society of Nephrology’s Kidney Week 2016, Chicago

Urea May Offer Cheaper SIADH Option Researchers present results from the first long-term study of Urea USP in the United States Urea Raises Sodium Levels In a small study, patients with the syndrome of inappropriate antidiuretic hormone secretion experienced increased serum sodium levels while on urea therapy. Shown here are the mean levels (in mEq/L) at baseline after 1 week and 6 months of treatment.

150

BY JODY A. CHARNOW THE FIRST LONG-TERM results of a U.S. study of urea as a treatment for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) suggest it is safe and effective and could be an inexpensive alternative to other medications.

Urea may provide another option for patients who are intolerant of demeclocycline (a mainstay of SIADH therapy in the United States) or who cannot afford this drug or tolvaptan, according to investigators led by Gregory Braden, MD, of the University of Massachusetts Medical School-Baystate Medical Center in Springfield.

For more than 35 years, urea has been used for the long-term treatment of

A Clue to BP Dips During Patiromer Use DECREASED SODIUM absorption may explain blood pressure (BP) reductions observed with patiromer treatment for hyperkalemia in patients with low aldosterone levels and low plasma renin activity (PRA), investigators reported.

BP reductions in patients who do not have low aldosterone levels and low PRA may be due to aldosterone reduction and/ or decreased sodium absorption, according to a research team led by Matthew R. Weir, MD, of the University of Maryland School of Medicine in Baltimore.

Patiromer is a novel potassium-binding polymer approved for treating hyperkalemia. It binds potassium in the gastrointestinal tract using calcium rather than sodium ions as the counter-exchange ion to bind potassium. During the 12-week phase 3 OPAL-HK trial, which enrolled 243 patients with chronic kidney disease and hyperkalemia (serum potassium level 5.1 mEq/L or higher), patiromer

KW_SIADH_Urea_RUN1216.indd 17

120

126

132

136

Baseline

1 week

6 months

90 60 30 0

Source: Braden G et al. Urea for SIADH: The first U.S. long-term results. Presented in poster format at Kidney Week 2016 in Chicago, Nov. 15-20. Poster 499.

SIADH in Europe, where it is the treatment of choice for the syndrome, Dr. Braden said.

Urea USP is made by Merck in Germany and is available in the United States from MEDISCA, a Canadian compounding company, through the wholesale distributor Cardinal Health,

decreased serum aldosterone concordantly with serum potassium and was associated with decreases in BP, the researchers noted. It is unclear whether BP reductions were due to decreased aldosterone alone, or if reduced sodium absorption with patiromer also contributed to the observed BP effect, they added. To find out, Dr Weir and his collaborators performed a post hoc analysis of the initial treatment phase of OPAL-HK, examining the effect of patiromer on BP in patients with low serum aldosterone and low PRA at baseline.

The 24 patients who had low aldosterone and low PRA at baseline experienced a significantly greater decline in systolic and diastolic BP (−7.8 and −7.6 mm Hg, respectively) than the 219 patients who did not (−5.5 and −3.5, respectively), Dr. Weir’s group reported.

At baseline, the low aldosterone/ low PRA group had a mean systolic BP of approximately 145 mm Hg and the group without low aldosterone/low PRA had a mean systolic BP of about 140 mm Hg. At week 4, the low aldosterone/low PRA group had a mean systolic BP of about 138 mm Hg and the group without low aldosterone/low PRA had mean systolic BP of about 136 mm Hg. ■

Dr. Braden noted. In a 6-month trial, he and his colleagues examined the effects of Urea USP in 6 SIADH patients, all of whom had hypouricemia (uric acid levels below 4 mg/dL). The patients took Urea USP—which was mixed in fruit syrup or juice—at a dose of 10–15 grams orally twice daily. For the first

week, patients were instructed to limit oral fluid intake to 1000 mL daily.

Prior to urea treatment, patients had a mean serum sodium level of 126 mEq/L. This rose to 132 mEq/L after 1 week of treatment and 136 mEq/L after 6 months of therapy, Dr. Braden’s group reported. The mean plasma osmolality increased from 266 mOsm/ kg H 2O at baseline to 287 mOsm/kg H 2O after 6 months. Mean serum uric acid levels increased from 2.7 mg/ dL before urea therapy to 3.8 mg/dL after 1 week of urea therapy (normalized) and 4.7 mg/dL after 6 months.

Additionally, the fractional excretion of uric acid was elevated at the time of SIADH diagnosis and decreased to normal after 1 week of therapy and remained normal (less than 12%) during the 6 months of treatment.

Urea is a little distasteful, but not terribly so, and patients can drink whatever they want, Dr. Braden said. “It’s a real quality of life issue,” he said. ■

Microalbuminuria On the Rise In the Healthy Obese Population MICROALBUMINURIA has been increas-

Examination Survey (NHANES), Dr.

ing in prevalence since 2001 among

Harhay, of Drexel University College

obese but otherwise healthy individuals

of Medicine in Philadelphia, and col-

in the United States, new findings show.

leagues identified 3180 obese adults

Risk factors for albuminuria in these indi-

(body mass index [BMI] 30 kg/m2 or

viduals may be distinct from traditional

higher) who had no evidence of other

risk factors, researchers concluded.

commonly assessed albuminuria risk

“Physicians who find their obese

factors, such as diabetes, hyperten-

patients to be generally healthy may

sion, or reduced kidney function. The

not consider screening for albumin-

prevalence of microalbuminuria (spot

uria, although obesity itself is a risk

urine albumin/creatinine above 30 but

factor for albuminuria and kidney

less than 300 mg/g) in the healthy

disease,” lead investigator Meera

obese individuals, who accounted for

N. Harhay, MD, told Renal & Urology

24% of all obese NHANES participants,

News. “Physicians may [want to] con-

increased significantly from 3.2% in

sider screening obese and morbidly

2001–2002 to 8.1% in 2013–2014, Dr.

obese adults for albuminuria regard-

Harhay and her colleagues reported.

less of the absence of other co-exist-

Among morbidly obese individuals

ing medical conditions like diabetes or

(BMI 40 kg/m2 or higher) in the healthy

hypertension.”

cohort, the prevalence of microalbu-

Using 2001 to 2014 data from the National Health and Nutrition

minuria rose from 3.4% in 2001–2002 to 13.5% in 2013–2014. ■

© SHUTTERSTOCK / MENZL GUENTER

The articles on this page and pages 18–21 report on study findings presented at the American Society of Nephrology’s 2016 Kidney Week meeting in Chicago, November 15–20.

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American Society of Nephrology’s Kidney Week 2016, Chicago

High Uric Acid in ICU Patients Increases AKI Risk HIGH PLASMA uric acid levels in critically ill patients independently predict an increased risk of incident acute kidney injury, according to new study findings.

In a prospective study of 115 patients admitted to intensive care units, investigators at Brigham and Women’s Hospital in Boston led by Anand Srivastava, MD, MPH, found that the 29 patients who experienced AKI had significantly higher mean plasma uric acid levels than the 86 patients who did not (5.5 vs. 4.2 mg/dL). On multivariable analysis, each 1 mg/dL increment in uric acid at ICU admission was associated with 29% increased odds of incident AKI, after adjusting for age, sex, baseline estimated glomerular filtration rate (eGFR), and APACHE II score.

“Uric acid may lead to kidney injury via endothelial dysfunction, vasoconstriction, oxidative stress, and intra-tubular obstruction,” Dr. Srivastava explained in an interview with Renal & Urology News. “Upon entry to the intensive care unit, higher uric acid levels are associ-

ated with an increased risk of acute kidney injury in critically ill patients. A randomized-placebo controlled trial of pharmacologic uric acid lowering should be considered to reduce the risk of acute

kidney injury in critically ill patients.”

The investigators defined incident AKI using KDIGO (Kidney Disease: Improving Global Outcomes) criteria.

The patients with and without AKI

did not differ significantly with respect to racial and gender composition, age, and APACHE II score, but the AKI group had significantly lower mean eGFR (76.2 vs 92.4 mL/min/1.73 m2). n

B:14.5” T:14” S:13.5”

F p

A A

C

Omega-3s May Offer Obesity Paradox Clue

•

•

•

OMEGA-3 FATTY ACIDS may explain the obesity paradox observed in patients with advanced chronic kidney disease (CKD), researchers reported.

In a prospective cohort study of 155 hemodialysis (HD) patients, Ana

R 1 N [ 2 K (

Rita Martins, MD, of DaVita Óbidos, Portugal, and colleagues found that higher body mass index (BMI) was associated with significantly higher incorporation of eicosapentaenoic

a a t e

(EPA) and docosahexaenoic (DHA) omega-3 fatty acids into red blood cell (RBC) membranes, and higher

P n

EPA-DHA incorporation into RBC membranes was associated with a

A w c G c

significantly lower number of cardiovascular events.

Dr. Martins’ team concluded that there appears to be a consistent association between obesity and higher omega-3 incorporation into RBC membranes. n

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Early RRT for AKI May Cut Risk of Dialysis Dependence B:14.5” T:14” S:13.5”

EARLY INITIATION of renal replacement therapy (RRT) for acute kidney injury (AKI) in critically ill patients may decrease dependence on long-term dialysis, investigators reported.

A systematic review and meta-analysis of 9 randomized controlled trials that included a total of 1599 critically ill patients showed that early RRT was associated with a significant 45%

decreased risk of becoming dialysis dependent compared with late RRT, Rhea Bhargava, MD, of the University of Missouri-Kansas City School of Medicine, and colleagues concluded.

Patients who had early RRT had a shorter stay in the intensive care unit (by a mean of 1.41 days) and shorter hospital length of stay (by a mean of 5.1 days) versus patients who had late RRT. n

B:10.25”

S:9.25”

T:9.75”

al s

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20 Renal & Urology News

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NOVEMBER/DECEMBER 2016 www.renalandurologynews.com

American Society of Nephrology’s Kidney Week 2016, Chicago

ESRD, Death Linked to Abnormal Potassium Levels PATIENTS WITH abnormally low or high serum potassium levels have significantly greater risks of end-stage renal disease (ESRD) and premature death, researchers reported.

For the CKD Prognosis Consortium, Csaba P. Kovesdy MD, chief of nephrology at the Memphis VA Medical Center B:7.25” and The Fred Hatch Professor of T:7” Medicine at the University of Tennessee S:7”

Health Science Center in Memphis, and colleagues examined serum potassium values across 26 diverse, international cohorts: 15 general populations, 9 chronic kidney disease (CKD) popu-

lations, and 2 populations at high cardiovascular risk. Among 1,538,508 participants (average age 52, 42% female, and 14% black), average serum potassium level at baseline was 4.3 mmol/L. Average estimated glomerular filtration rate (eGFR) was 84 mL/min/1.73 m2.

Overall, 14% had albuminuria, and 38% took antihypertensive medications.

Meta-analyses revealed increased risks of all-cause mortality for participants with potassium values below 3.5 or above 5 mmol/L, over an average 7 years of follow up. The lowest risk category was 4 to 4.5 mmol/L, within the center of the normal range.

Compared with a reference value of 4.2 mmol/L, the odds for all-cause mortality were 22% higher at 5.5 mmol/L and 31% higher at 3.2 mmol/L. Similar risks were observed for cardiovascular mortality and ESRD. The investigators adjusted for a range of demographic

Induction of malignant arrhythmias could explain the increased mortality risk.

B:10.25”

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T:10”

and clinical variables, including age, sex, race, diabetes, systolic blood pressure, antihypertensive medications, cardiovascular disease, heart failure, total cholesterol, body-mass index, smoking, eGFR, and albuminuria.

When the researchers tested for interactions between eGFR and potassium, the association of potassium with low eGFR below 30 mL/min/1.73 m2 slightly weakened in the case of ESRD only.

“The association between hypo- and hyperkalemia and mortality could be explained by the induction of malignant arrhythmias and their consequences, such as hypotension, myocardial ischemia, and sudden cardiac death, although the present analyses cannot elucidate the direct causal role of abnormal potassium in the observed outcomes,” Dr. Kovesdy told Renal & Urology News.

The relationship, if any, between abnormal potassium levels and ESRD is less clear. Hypokalemia could lead to tubulointerstitial fibrosis, according to the investigators. Hyperkalemia simply may serve as a marker of more severe CKD or it may indirectly harm kidney function, such as following cardiac events. n

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www.renalandurologynews.com NOVEMBER/DECEMBER 2016

Hyperkalemia May Increase Mortality Risk

BY NATASHA PERSAUD HOSPITALIZED patients whose potassium levels rise above 5.5 mEq/L have an increased risk of early death, new findings suggest.

Using electronic medical records for 17,317 patients (average age 50.2) treated 2014 to 2015 at Hennepin County Medical Center, an academic metropolitan safetynet hospital in Minneapolis, David T. Gilbertson, PhD, co-Director of the Chronic Disease Research Group, part of the Minneapolis Medical Research Foundation in Minneapolis, and colleagues analyzed the distribution of serum potassium values and the risk of in-hospital mortality. Of these patients, 35.6% had diabetes, 27.4% had chronic kidney disease (CKD), and 18.6% had congestive heart failure, conditions that have been linked with greater risks of hyperkalemia.

The investigators found the lowest risks of early death among individuals with serum potassium levels between 3.5 and 5.0 mEq/L. The death rate

Renal & Urology News 21

Optimal Vitamin C Dose for Anemia In Hemodialysis Patients Unclear Pending future research, patients should avoid taking more than 120 mg per day

BY JODY A. CHARNOW NEW STUDY FINDINGS may help researchers arrive at the optimal dose of vitamin C (ascorbic acid) supplementation for improving anemia in hemodialysis (HD) patients.

The current findings suggest that HD patients should not take more than 120 mg per day, according to William D. Sirover, MD, of Cooper Medical School of Rowan University in Camden, New Jersey, who represented the research group that originally consisted of himself and Garry Handelman, PhD, of the University of Massachusetts in Lowell.

“The problem is that vitamin C gets metabolized to oxalate and escalating dosages of vitamin C could increase plasma oxalate levels. If plasma oxalate levels surpass 30 µM, that could be a concern for oxalate precipitating in tissues and causing pathologic effects,” Dr. Sirover said. “Available literature indicates that achieving a plasma vitamin C level of 70–100 µM may be the most effective and safe range for reducing erythropoiesis-stimulating agent (ESA) dose, as plasma vitamin C levels in this range are not associated with plasma oxalate levels exceeding 30 µM.”

William D. Sirover, MD

At this time, the clinical issue is to identify an ascorbic acid dose that maintains plasma vitamin C levels of 70–100 µM, without plasma oxalate surpassing 30 µM. In a study of 197 HD patients, Dr Sirover and colleagues examined the safety and efficacy of escalating doses of ascorbic acid supplementation: 50–75, 100–120, and 150 mg or more per day.

These doses resulted in mean pre-HD plasma levels of 38.9, 48.9, and 258.1 µM, respectively. The corresponding

pre-HD plasma oxalate levels were 17.3, 22.5, and 40.5 µM, respectively.

“Plasma oxalate levels were above 30 µM in patients who took 150 mg or more of ascorbic acid per day, so our data tell us that ascorbic acid supplementation to this degree may be too much for patients,” Dr. Sirover said.

Based on their findings, the team concluded that, for now, HD patients should avoid an ascorbic acid dose exceeding 120 mg per day.

In addition, “our present understanding is that moderate ascorbic acid supplementation, which we defined as up to 120 mg per day, is not associated with concerning increases in plasma oxalate,” Dr. Sirover told Renal & Urology News. However, in the study, patients who received moderate ascorbic acid supplementation had plasma ascorbic acid levels lower than 70 µM, which may be insufficient for lowering ESA resistance.

“An important clinical objective is to find out what dose of ascorbic acid will achieve a plasma vitamin C level of 70 to 100 µM without surpassing concerning levels of plasma oxalate,” Dr. Sirover said. n

rose to above 80% for those with potassium values 7 mEq/L and greater. Potassium values above 6.0 mEq/L were associated with 43.5 times greater odds of mortality compared with values below 5.0 mEq/L. Hypokalemic patients with potassium values below 3 mEq/L had a 12.3% increased death rate.

“It is unclear how much of the observed mortality is directly attributable to hyperkalemia—or hypokalemia—and potentially preventable.

It remains possible that high serum potassium values simply are a marker for severe, life-threatening illnesses, such as sepsis, acute myocardial infarction, and trauma,” Dr. Gilbertson told Renal & Urology News. “More intense efforts targeted to prevent severe hyperkalemia in patients with diabetes, CKD, and heart failure may be warranted.” n

KW_VitC_RUN1216.indd 21

Vitamin D Effects on Mineral Biomarkers Probed CALCITRIOL and paricalcitol increase fibroblast growth factor 23 and sclerostin levels and decrease certain bone turnover markers while achieving sustained suppression of parathyroid hormone levels in patients with chronic kidney disease and secondary hyperparathyroidism, according to a new study.

The findings are from a post-hoc analysis of the PACE (Paricalcitol versus Calcitriol for Efficacy and Safety) study, an open-label phase 4 trial, which randomized 110 patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) to receive the drugs.

Investigators performed primary analyses on 107 of them. The PACE study demonstrated that both vitamin D receptor agonists (VDRAs) had minimal effects on calcium and phosphorus. A team led by Stuart M. Sprague, DO, of North Shore

University Health System—University of Chicago, conducted the post-hoc analysis because few studies have examined the effect of VDRAs on other mineral biomarkers in CKD patients.

Dr. Sprague and his colleagues identified 76 of the 107 patients who had serum available for analysis at baseline and week 24. The calcitriol and paricalcitol groups each had 38 patients.

By week 24, both drugs had significantly decreased iPTH levels as well as the bone turnover markers bone-specific alkaline phosphatase (BSAP) and tartrate resistant acid phosphatase 5b (TRAP) and significantly increased levels of fibroblast growth factor 23 (FGF 23), and sclerostin, with no significant difference between treatment groups. Paricalcitol, but not calcitriol, significantly increased 1,25 dihydroxyvitamin D levels.

In the calcitriol and paricalcitol groups, mean FGF-23 levels (in RU/mL) rose from 298 and 227 at baseline, respectively, to 482 and 418 at 24 weeks; mean sclerostin levels (in pmol/L) rose from 617 and 666 at baseline to 705 and 818 at 24 weeks. Mean BSAP levels (in µg/L) dipped from 14.1 and 13.2 to 10.4 and 10.2; mean TRAP levels in U/L) dropped from 4.49 and 3.21 to 3.42 and 2.48.

“Based upon the PACE trial, most patients with CKD have comparable PTH reduction with similar changes in calcium and phosphorus,” Dr. Sprague told Renal & Urology News. “Both VDRAs comparably increase FGF23 and sclerostin. Further studies are required to determine whether increases in FGF 23 may have systemic detrimental effects and increases in sclerostin may contribute to low bone turnover.” n

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mCRPC drug sequence continued from page 1

drug as third-line therapy; 41 patients received enzalutamide as first-line therapy and 96 received it as thirdline therapy; and 113 patients received cabazitaxel as first-line therapy and 143 received it as third-line therapy.

The findings confirm that the activity of the new agents decreases when used as third-line therapy compared with second-line therapy, Dr. Caffo and colleagues concluded.

First-line docetaxel beneficial In a separate multinational retrospective study of 560 mCRPC patients, Antoine Angelergues, MD, of European Georges Pompidou Hospital in Paris, and colleagues found no significant difference in overall survival among 3 treatment sequences: docetaxel followed by cabazitaxel and then ART (group 1, 129 patients); docetaxel followed

by ART and then cabazitaxel (group 2, 390 patients); and ART followed by docetaxel and then cabazitaxel (group 3, 41 patients). The median survival times for patients in these groups were 37.3, 36.0, and 30.1 months, ­respectively. In

Hyponatremia continued from page 1

chronic, recent, and chronic and recent hyponatremia, respectively, compared with controls.

A link between hyponatremia and kidney stone risk is plausible, Dr. Tominaga said, noting that studies have shown that hyponatremia is associated with an increased risk for osteoporosis, and the latter is associated with kidney stone development.

“Low sodium concentrations appear to lead to mobilization of calcium from bone, which could increase urine calcium excretion. These studies suggest that mechanism should be sought and

PCa screening plan continued from page 1

(2016;96:116-120). “These discussions should emphasize that the purpose of screening is the early identification of potentially lethal disease, and that in most cases low-risk tumors, if identified, do not require immediate treatment.”

Under their proposed new approach, primary care physicians (PCPs) would refer to urologists those patients who have a PSA level of 1.5 ng/mL or higher or abnormal digital rectal examination

Cvr_jumps_vUro_RUN1216.indd 22

therapy. The treatment selection in the future should—and will—be guided by genomic markers, not simply clinical factors or generic 1-size-fits-all sequences of treatments,” he said.

Neal D. Shore, MD, National Urology Research Director for 21st Century Oncology in Myrtle Beach, South Carolina, said the new studies continue to address the ongoing challenges that clinicians face when deciding on patient-physician shared decision

­making with the goal of optimizing both patient outcomes and tolerability.

“The combined data from the authors represent multiple institutional experiences with varying sequential lines of CRPC therapies,” observed Dr. Shore, who has been involved extensively in clinical trials of medications for treating prostate cancer and was among the first investigators to study the use of radium-223 in combination with abiraterone acetate for advanced PCa. “The analyses are both retrospective and with modest patient populations per treatment arms, and thus [one] may question the authors’ conclusions, albeit their data are worthy of review whereby it may confirm or possibly challenge some clinicians’ practical experiences to date,” Dr. Shore said.

“Ongoing concerns regarding CRPC paradigms for optimizing patient lines of therapy will need to address immunotherapy, targeted alpha therapy, novel oral hormonal therapy, and taxane based therapy. The issues of sequence and/or combination strategies, health-related quality of life, as well as accessibility and affordability of these therapies will require ongoing review and evaluation.” n

Medical Center, who was not involved in the new study but has conducted extensive research into the metabolic mechanisms of kidney stone disease.

In a separate study of 96,092 participants in the Nurses’ Health Study II (3402 with osteoporosis and 57,338 without), Megan Prochaska, MD, a fellow at Brigham and Women’s Hospital in Boston, and colleagues found that osteoporosis was associated with a significant 39% higher risk of kidney stones compared with individuals who did not have low bone density in multivariate analysis.

Osteoporosis also was associated with higher 24-hour urinary calcium excretion.

“The association of lower bone mineral density with kidney stones is quite consistent, and even convincing in both human and animal data,” Dr. Goldfarb commented. “It’s possible that increased bone turnover is responsible for stones,

but it’s also possible that abnormal tubular calcium absorption is responsible for the bone disease.”

Lastly, Pietro Manuel Ferraro, MD, PhD, of the Catholic University of the Sacred Heart in Rome, Italy, and colleagues found that PPI use was associated with a significant 12% higher risk of incident kidney stones after adjusting for multiple variables. Use of histamine receptor-2 blockers was associated with a significant 13% increased risk.

The study included 187,330 participants in the Health Professionals Follow-up Study and the Nurses’ Health Study I and II. A total of 3245 incident symptomatic stone events occurred during a cumulative follow-up of 1,903,725 person-years. n

(DRE) results. Urologists then would explore possible causes for elevated PSA or abnormal DRE results, including PCa, benign prostatic hyperplasia, and prostatitis. For patients suspected of having PCa, urologists would consider ordering genomic tests such as the Prostate Health Index, 4Kscore, or SelectMDx assays.

Patients deemed to be at high risk for aggressive cancer would be considered for transrectal ultrasound-guided prostate biopsy. Patients at low risk for aggressive cancer would be referred to their PCPs for repeat PSA testing in 1 year.

This algorithm is similar to that used for an elevated blood sugar, where an abnormal result triggers another test, such as an A1C hemoglobin test, the investigators stated.

PCPs, who order approximately 90% of PSA screening tests, are confused about the messages they receive regarding PSA, Dr. Crawford’s group stated. “We believe that a simple message using a PSA cutoff of 1.5 ng/ mL is reflective of what PCPs often experience with conditions such as mild hypertension and prediabetes,”

they wrote. “In this paper, we have presented an alternative approach in which screening is performed for men with at least a 10-year life expectancy.”

Previous research has shown that men with a PSA level of 1.5 ng/mL or higher at a younger age are at increased risk for the development of any PCa and significant PCa later in life. The investigators also reported data from BioReference Laboratories, Inc., showing that approximately 30% of men aged 45 to 70 years have a PSA level of 1.5 ng/mL or above. n

addition, findings suggest that docetaxel given in the first-line setting appears to be associated with longer radiologic and/or clinical progression-free survival, and ART does not appear to influence the activity of cabazitaxel, according to the investigators.

The median duration of follow-up for groups 1, 2, and 3 was 33.7, 31.1, and 23.7 months, respectively.

“The question of sequencing therapies in mCRPC is an important one.

Unfortunately, it will not likely be answered in prospective clinical trials,” said Benjamin Maughan, MD, PharmD, clinical instructor, genitourinary oncology, Huntsman Cancer Institute, University of Utah in Salt Lake City.

“This makes the institutional, retrospective results very important.”

The trend emerging from various research groups seems to indicate that there is no specific sequence that is ideal for the broad group of mCRPC patients, according to Dr. Maughan. “The studies clearly and consistently document that each therapy is less efficacious when used later in therapy as opposed to earlier in therapy,” he told Renal & Urology News.

“Also, these studies highlight the value of personalized or precision medicine.”

studied,” said kidney stone specialist David S. Goldfarb, MD, professor of medicine at New York University’s Langone Medical Center and chief of nephrology at New York Harbor VA

Osteoporosis, proton pump inhibitor use also identified as stone risk factors.

In large, unselected groups of patients such as those in these 2 studies, 1 sequence is not superior to another, Dr. Maughan said.

A role for genomic markers “However, we know from prospective studies that certain predictive markers, such as AR-V7 status, HS3DB status, etc., are important in ­choosing

The activity of the new agents decreases when used later in the course of therapy.

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Drug Shows Efficacy for Metastatic Urothelial Cancer NIVOLUMAB shows encouraging efficacy and acceptable safety in patients with previously treated metastatic urothelial cancer, researchers reported at the European Society for Medical Oncology 2016 congress in Copenhagen.

Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer

Center in New York, and colleagues studied 78 patients with metastatic urothelial cancer who received nivolumab 3 mg/kg IV every 2 weeks until progression or discontinuation. The patients were unselected by PD-L1 expression status. Of these, 52 received 2 or more previous therapies. At a mini-

mum follow-up of 9 months, 23.1% of patients were on monotherapy and 23.1% switched to combination therapy. Treatment discontinuation was mainly due to disease progression.

With regard to overall efficacy, the objective response rate (ORR) was 24.4%, median progression-free sur-

vival (PFS) was 2.8 months, and median overall survival was 9.7 months, according to the investigators. The median time to response was 1.5 months.

The ORR was 26.2% among patients who had PD-L1 expression of less than 1% and 24% among those with PD-L1 expression of 1% or greater, the researchers reported. Median PFS was 5.5 months and 2.8 months, respectively. Grade 3 or 4 treatmentrelated adverse events occurred in 21.8% of patients. n Statement of Ownership, Management and Circulation 1. Publication Title: Renal & Urology News 2.

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Nephrology Fellowship Entrants Down Researchers document an 8% dip in 2015-2016 compared with the previous academic year FEWER PHYSICIANS entered adult nephrology fellowship training in the United States in the 2015–2016 academic year compared with 2013–2014, according to a new report.

As measured by first-year fellows in adult nephrology training programs accredited by the Accreditation Council for Graduate Medical Education, 434 physicians entered these programs in 2015–2016, a decline of 8% from the 473 physicians who entered the programs in the previous academic year, according to a report prepared for the American Society of Nephrology by the George Washington University Health Workforce Institute (GWU-HWI).

Preliminary numbers indicate a slight subsequent increase in 2016–2017, the report noted. “Despite the uncertainty around the number of future trainees, the overall balance between new entrants and retirements means that the basic trend in total supply is one of continued growth for the foreseeable

Job Prospects Improve A recent survey revealed that a smaller proportion of physicians who had searched for a job after completing an adult nephrology fellowship in 2016 reported difficulty in finding a satisfactory position compared with 2014 and 2015.

70 60 50 40

60.3%

52.3%

30 20 10 0

2016

2015

Source: George Washington University Health Workforce Institute. The US Adult Nephrology Workforce 2016 Developments and Trends. Prepared for the American Society of Nephrology.

future,” the report stated. “This reflects the fact that the number in training in recent years is well above the numbers 20 and 30 years ago.”

As of January 2016, 10,100 patient care physicians listed nephrology as their first or second specialty, according

BY NATASHA PERSAUD

Overweight patients (BMI 25–29.9 kg/

OBESE MEN are at higher risk of dying

m2) had a 1.9 times increased risk, but

from prostate cancer (PCa) than normal

this was not statistically significant.

Neither weight category was associ-

treatment with radical prostatectomy

ated with biochemical recurrence or

(RP), a new study finds.

castration-resistant PCa, as they were in

The findings do not imply obesity causes more aggressive PCa, Adriana

the team’s past studies.

For the study, Dr. Vidal and colleagues

Vidal, MD, of Cedars Sinai Medical

retrospectively analyzed data from 4268

Center in Los Angeles, and colleagues

veterans who underwent RP within the

wrote in an online report in Prostate

Shared Equal Access Regional Cancer

Cancer and Prostatic Diseases. “Rather,

Hospital (SEARCH) database. Over 6.8

obesity may be associated with other

years, 1384 men had biochemical recur-

factors such as poor diet or lack of

rence, castration-resistant PCa devel-

exercise, which we could not adjust for,

oped in 117 patients, and 84 died from

which may explain this association,”

their cancer. The investigators accounted

they wrote. Obesity might represent a

for competing causes of death.

modifiable risk factor for the disease.

Compared with normal-weight patients

Future studies with larger populations are warranted to confirm the findings

(BMI less than 25 kg/m2), obese

and rule out other possible causes of

patients (BMI 30 kg/m and above)

increased PCa mortality, according

had a statistically significant 2-fold

to the researchers. For example, it is

increased risk of PCa-specific mortality

possible that obese men treated with

in a fully adjusted model accounting for

androgen deprivation have low testos-

pathologic and clinical characteristics.

terone suppression. n

2

Nephrology_workforce_RUN1216.indd 25

2014

Year of fellowship completion

Obesity Increases Prostate Cancer Death Risk After RP weight individuals following primary

56.3%

to the American Medical Association Masterfile of all physicians in the United States. In 2014, 8000 nephrologists filed Medicare claims.

The GWU-HWI researchers found that the proportion of female adult nephrologists is growing slowly.

Kidney Donors May Face Risk of Bone Loss

BY NATASHA PERSAUD KIDNEY DONORS with mild reductions in renal function display abnormal levels of bone biomarkers for 3 years after donation, according to a new study.

For the ALTOLD (Assessing Long Term Outcomes in Living Kidney Donors) study, a team led by Bertram L. Kasiske, MD, of Hennepin County Medical Center in Minneapolis, and Rajiv Kumar, MD, of Mayo Clinic in Rochester, Minnesota, prospectively compared markers of mineral and bone metabolism in 182 kidney donors (unilateral nephrectomy) and 173 healthy controls suitable for donation matched by age and gender.

At 6 and 36 months after donation, donors had significantly higher serum levels of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor 23 (9.5% and 8.4%) compared with controls, the investigators reported in Kidney International (2016;90:734-736).

Donors also had increased phosphate excretion reflected by reduced tubular

Currently, only 25% of active nephrologists are female, but 36% of nephrology fellows—the future workforce—is female, according to the report.

The GWU-HWI researchers found “a noticeable improvement” in adult nephrology fellows’ experience in the job market compared with 2015 and 2014. In 2016, 52.3% of fellows completing an adult nephrology fellowship who had searched for a job indicated it was difficult to find a satisfactory position compared with 60.3% and 56.3% in 2015 and 2014, respectively. The expected annual incomes by practice location were $200,500 in a small city, $199,500 in a suburban area, $183,000 in the inner city, and $187,000 in another area within a major city.

In a survey of nephrologists aged 55 years and older, researchers found that 67.3% and 69% them indicated they were very satisfied with medicine as a career and with nephrology as a specialty, respectively. n

phosphate reabsorption (–7.0% and –5.0%) and serum phosphate concentrations (–6.4% and –2.3%).

Serum calcitriol (1,25-dihydroxyvitamin D3) concentrations were significantly lower in donors (–17.1% and –12.6%) at the same time points, whereas 25-hydroxyvitamin D concentrations were significantly higher (21.4% and 19.4%). The investigators observed no alterations in calcium. Together, the findings suggest reduced glomerular filtration rate and calcitriol synthesis, resulting in secondary hyperparathyroidism.

At 6 and 36 months, the researchers observed significantly higher concentrations of the bone resorption markers carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%).

They also found increases in the bone formation markers osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%). The findings possibly indicate impaired bone metabolism in kidney donors.

“Elevated PTH concentrations occurring as a result of reduced 1,25(OH)2D3 synthesis and attendant negative calcium balance could serve as the driver of altered bone metabolism and osteocyte activity following kidney donation,” the researchers wrote. n

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Racial Gap Found in PCa Treatment Black and Hispanic men are less likely to have radical surgery, radiotherapy, or cryotherapy than white men

BY NATASHA PERSAUD BLACK MEN with clinically localized prostate cancer (PCa) continue to receive definitive treatment less often than white and Asian men, a new study finds. Undertreatment of Hispanic patients is another worrisome trend.

Persistent disparities in treatment for black men and emerging disparities in Hispanic men, regardless of stage at presentation, “likely represent a significant predictor of higher mortality in underserved populations,” Kelvin A. Moses, MD, PhD, of Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, and colleagues concluded in Urology.

Their analysis of 327,636 patients diagnosed with localized PCa 2004 to 2011 from the SEER-17 (Surveillance, Epidemiology and End Results) database revealed that black and Hispanic patients were 27% and 5% less likely, respectively, to receive any treatment (radical prostatectomy, external beam radiation therapy, brachytherapy, or cryotherapy) than white patients.

Disparities similarly emerged when investigators examined patients by D’Amico risk classification (with and without questionable PSA values): black patients had a significant 19%, 26%, and 38% lower odds of receiving definitive treatment than similar white

Blacks Less Likely Than Whites to Be Treated The odds of receiving definitive prostate cancer treatment are lower in blacks than whites, regardless of D’Amico risk category, a study found. Shown here are the percentages by which the odds of definitive treatment are lower, according to risk category.

!

!

!

LOW RISK

MEDIUM RISK

HIGH RISK

19% Lower Odds

26% Lower Odds

38% Lower Odds

Source: Moses KA, et al. Racial/ethnic disparity in treatment of prostate cancer: Does cancer severity matter. Urology. 2016; published online ahead of print.

patients in the low, medium, and highrisk categories, respectively. By Gleason score alone, black men with Gleason 7 or 8–10 cancer were undertreated compared with white men who had even lower risk disease (Gleason 6 or below).

Disparities appeared in other ways.

Younger men typically receive PCa treatment in greater numbers than older men, yet black patients, who were diagnosed at earlier ages, were still less likely to receive treatment.

The researchers also investigated whether geographic location played a role. A racial disparity existed in U.S.

regions with a population greater than 12,000. Dr. Moses and colleagues said they believe socioeconomics only partly explain the lack of access to specialty care. Neither PCa overtreatment in whites nor a higher comorbidity in blacks seemed likely.

Hispanic men with intermediate- or high-risk disease were 11% and 21% less likely, respectively, to be treated than white men with similar risks. Asian patients were as likely as white patients to be treated for their cancers, although they were diagnosed at older ages and presented with more advanced disease.

Dr. Moses and colleagues suggested policy changes, patient education, and workforce diversification to address the disparities. On a clinical front, “the plethora of data showing that AA [AfricanAmerican] men experience improved outcomes with surgery is clearly not being imparted to patients, implicating a potential lack of physician communication with patients regarding shared decision-making and discussion of benefits/ risks of various treatment modalities.”

In accompanying editorial, Christopher P. Filson, MD, MS, of Emory University in Atlanta, remarked that the current study did not consider differences in insurance coverage and access to care.

Noting that Dr. Moses’ team calls for an action plan “to eradicate the seemingly obstinate inequalities related to prostate cancer care based on patient race,” Dr. Filson pointed out that this already was set in motion with the passage in 2012 of the Affordable Care Act (ACA).

“It remains to be seen how racial disparities related to prostate cancer care will change in the post-ACA environment over the long-term,” Dr. Filson wrote. “Nonetheless, I remain optimistic that the ACA will have made a significant dent in these tenacious discrepancies in the access to—and quality of—prostate cancer care among persons of color.” ■

Benefits of Uric Acid-Lowering Drug Confirmed COMBINATION THERAPY with lesinurad and allopurinol increases the percentage of gout patients who achieve target serum uric acid levels, a benefit that persists for least 2 years, according to the findings of an extension study presented at the annual meeting of the American College of Rheumatology in Washington, D.C. The 12-month extension study, led

by Kenneth G. Saag, MD, MSc, of the University of Alabama at Birmingham, enrolled 716 gout patients who participated in the 12-month phase 3 core studies (CLEAR 1 and CLEAR 2). Patients in the lesinurad 200 mg plus allopurinol arm or lesinurad 400 mg plus allopurinol arm of the core studies and were enrolled in the extension trial continued on their therapies. Patients who received allopurinol alone in the core studies were randomized to receive

RacialDisparities_RUN1216.indd 26

either lesinurad 200 mg or 400 mg in addition to allopurinol.

In the core studies, about 65% of patients in the lesinurad 200 mg group and about 80% in the lesinurad 400 mg group had a serum uric acid level below

Lesinurad enables more gout patients to reach target serum uric acid levels.

6 mg/dL — the efficacy endpoint — at the end of the studies. These proportions remained constant over the 12 months of the extension study.

In the core studies, about 30% of patients who received allopurinol alone had a serum uric acid level below 6 mg/dL

at the end of these studies. The proportion increased to about 70% after 1 month of receiving lesinurad 200 or 400 mg in addition to their allopurinol treatment, and remained relatively constant for the duration of the extension study.

The extension study revealed no new safety concerns.

Lesinurad was approved by the FDA on December 22, 2015 for use in patients fail to achieve target serum uric acid levels while on xanthine oxidase inhibitors alone. Xanthine oxidase inhibitors decrease uric acid production. Lesinurad inhibits uric acid reabsorption by the kidneys, thereby increasing renal excretion of uric acid.

“Gout is predominately a disease of under excretion of serum urate, and most of our focus has been on xanthine oxidase inhibition, which targets an important pathway but not the primary

pathway for most individuals,” Dr. Saag told Renal & Urology News. He called the availability of a new uricosuric agent an important advance in the treatment of gout.

“About half the people who take the standard dose of allopurinol, 300 mg per day, don’t achieve the serum urate target of 6 [mg/dL] or below,” Dr. Saag said. “It really emphasizes the importance of having new therapies for managing gout.”

Whenever possible, he said, clinicians should make an effort to dose escalate xanthine oxidase inhibitors, either allopurinol or febuxostat, “since we know that these drugs at higher doses, in people who can tolerate them, are efficacious.” For patients who cannot tolerate higher doses or whose uric acid levels remain high despite dose escalation, “this is where the addition of a uricosuric drug like lesinurad would fit in.” ■

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Alpha Blockers Help Clear Large Ureteric Stones

BY NATASHA PERSAUD MEDICAL EXPULSIVE therapy with alpha blockers can promote clearance of ureteric stones 5 mm and larger, a new systematic review and meta-analysis confirms.

“These results support current guideline recommendations advocating a role

for alpha blockers in patients with ureteric stones,” John M. Hollingsworth, MD, MS, of the University of Michigan in Ann Arbor, and colleagues stated in the British Medical Journal.

The investigators reported a 49% greater likelihood of ureteric stone passage with an off-label alpha blocker

compared with no treatment or placebo. Treated patients with stones 5 mm or larger had a 57% greater likelihood of stone clearance. The study revealed no treatment benefit for patients with smaller ureteric stones.

Given that ureteric stones smaller than 5 mm pass easily without treatment,

this finding was unsurprising, according to the investigators.

For their updated meta-analysis, the team pooled data from 55 randomized controlled trials of moderate quality involving 5990 patients published up to July 2016. Although tamsulosin was most commonly studied medication, they observed no significant differences with other alpha blocker medications, such as alfuzosin, doxazosin, naftopidil, silodosin, or terazosin.

Stone location—either lower, middle, or upper ureter—had no bearing on results. Alpha adrenergic receptors are concentrated in the lower ureter but they exist along the entire ureter, the investigators highlighted.

Likelihood of stone passage increased by 49% in patients who received the drugs.

The mean time to stone passage was a significant 3.79 days sooner in patients who received alpha blockers compared with controls. Few serious adverse events were reported, and these were similar between treated and control patients.

The researchers cited a study published in Lancet (2015:25;386:341-349) in which Robert Pickard, MD, of Newcastle University in Newcastle upon Tyne, UK, and colleagues concluded that medical expulsive therapy (tamsulosin and nifedipine) did not differ from placebo in its effect on ureteric stone clearance. A high rate of spontaneous stone passage among controls, however, might explain the results, according to Dr. Hollingsworth and colleagues. In addition, they noted that Dr. Pickard’s group defined stone passage as the absence of the need for additional intervention for stone clearance within 4 weeks after randomization, although imaging evidence has been the standard approach to assessing stone clearance.

“Given the low risk profile of these drugs and their wide therapeutic window, our findings suggest that clinicians who manage patients with ureteric colic should consider prescribing a course of an alpha blocker, unless it is medically contraindicated,” Dr. Hollingsworth and colleagues concluded. The investigators estimated that 4 patients would need to be treated for 1 patient to see a benefit. n

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Study: AKI Common in Pediatric ICUs Higher risk of death and need for renal-replacement therapy observed in severe cases ACUTE KIDNEY injury (AKI) among critically ill children and young adults is common and is associated with higher mortality risk and other poor outcomes, according to researchers.

In a large, prospective, multinational study that included 4683 patients aged 3 months to 25 years (median age 5.5 years) admitted to intensive care units (ICUs), AKI developed in 1261 (26.9%) patients and severe AKI developed in 543 (11.6%). Severe AKI was associated with 77% higher odds of death by day 28 after adjustment for 16 covariates, investigators led by Stuart L. Goldstein, MD, of the Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio, reported online in The New England Journal of Medicine (NEJM).

Sixty (11%) of the 543 patients with severe AKI died compared with 105 (2.5%) of the 4140 patients without severe AKI. In addition, severe AKI was associated with increased use of renalreplacement therapy (RRT) and mechanical ventilation and longer ICU stays.

Independent predictors of death were use of vasoactive support, RRT, and mechanical ventilation, which were associated with 4.7, 3.4, and 3.0 times higher odds of death, respectively, com-

Mortality Risk Factors A large study identified the following independent risk factors for death among critically ill children and young adults with severe acute kidney injury. The number of times by which the presence (versus the absence) of these factors increased the odds of death are shown here.

5 4

4.7× 3.4×

3

3.0×

2 1 0

Vasoactive support

RRT

Mechanical ventilation

Source: Kaddourah A et al. Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med. 2016; published online ahead of print.

pared with the corresponding absence of these interventions.

Assessment of AKI based on plasma creatinine level alone failed to identified AKI in 67.2% of patients with low urine output, and the mortality rate was higher among patients with low urine output than those with normal urine output (7.8% vs 2.9%), the investigators reported.

Dr. Goldstein’s team used the Kidney Disease: Improving Global Outcomes criteria to define AKI. The defined severe AKI as stage 2 or 3 AKI (plasma

creatinine level 2 or more times the baseline level or urine output less than 0.5 mL per kilogram of body weight per hour for at least 12 hours) and was assessed for the first 7 days of intensive care.

Further, the study showed that the daily prevalence of AKI increased progressively from 14.5% to 20.4% over a period of 7 days. Patients with stage 1 AKI on day 1 were significantly more likely to experience progression to stage 2 or 3 by day 7 than patients without AKI on day 1 (14.1% vs 2.9%), Dr. Goldstein and his colleagues reported.

The researchers said their study results provide informative comparisons with those of a recent multicenter study of adults: the Acute Kidney Injury– Epidemiologic Prospective Investigation (AKI-EPI) study. Although the rates of overall and severe AKI (57.3% and 38.9%, respectively) were higher in the adult study than the corresponding rates in the pediatric study, the associations between AKI and mortality and morbidity are similar. “We speculate that the relatively lower rates of acute kidney injury observed in our study represent greater renal reserve in children,” Dr. Goldstein’s team wrote.

Study strengths included a large, multicenter cohort that enabled a robust evaluation of relationships between exposure and outcome, a prespecified protocol, operational definitions, and an analysis plan and enumerated complete standardized diagnostic criteria for AKI, the investigators stated.

They also acknowledged study limitations. The observational study design precluded making statements regarding causal relationships among AKI, exposures, and outcomes observed. In addition, the investigators did not assess for the potential effect of the specific cause of AKI on patient outcomes. n

Smoking Predicts Worse Outcomes in CKD Patients

BY NATASHA PERSAUD PATIENTS WITH CHRONIC kidney disease (CKD) who are current smokers have significantly higher risks of death, cardiovascular disease, and cancer, according to a new analysis of SHARP (Study of Heart and Renal Protection). Researchers did not find faster kidney disease progression.

In the study of 9270 CKD patients, current smokers had a 48% higher risk of all-cause mortality compared with those who had never smoked, Jonathan Emberson, PhD, of the University of Oxford in the United Kingdom, and colleagues reported in the American Journal of Kidney Diseases (2016;68:338340). Death from cancer and respiratory causes more than doubled. Smokers also had a 36% higher rate of vascular events from atherosclerotic and nonatherosclerotic causes.

Cancer risk was 37% higher among current smokers over a median 5 years

AKI_children_RUN1216.indd 29

of follow up. In particular, the risks of lung and upper aerodigestive tract cancers (i.e., malignancy of the lips, mouth, tongue, nose, throat, vocal cords, esophagus, or trachea) increased by 9.31 and 4.87 times, respectively.

Death risk is 48% higher in current smokers vs. those who never smoked.

“These results are important because individuals with CKD are already at substantially increased risk for a wide variety of diseases, including cardiovascular disease, cancer, progression of kidney disease, and death,” Dr. Emberson and colleagues stated. From 10% and 15% of CKD patients currently smoke, according to estimates.

The team separately assessed 6245 patients not receiving dialysis at baseline for kidney disease progression.

ESRD incidence did not differ significantly for current, former, and never smokers, nor did eGFR decline. This finding differs from past studies and may reflect differences in methodology and confounding variables, according to an accompanying editorial by Esteban Cedillo-Couvert, MD, and Ana C. Ricardo, MD, MPH, of the University of Illinois at Chicago. The cause of CKD did not appear to influence results.

Strengths of the SHARP study included its prospective design, large population, and validation of events.

Some details on smoking were lacking, however, including starting age, types of cigarettes used, smoking status during follow-up, and years since quitting.

“For patients with CKD who smoke, the potential benefit from cessation

would be substantial and certainly much larger than any drug treatment that is used for cardiovascular or nephroprotection,” Dr. Emberson and colleagues stated. “These benefits have not been properly appreciated by nephrologists and primary care physicians, and there is a need for smoking cessation programs to be established as pivotal components of the care of patients with CKD.” In their editorial, Drs. CedilloCouvert and Ricardo observed: “Although the study did not show a significant association between smoking and CKD progression, given the overwhelming evidence from this and prior studies regarding the adverse effects of smoking and the costs that it represents to health care systems, public health efforts should continue to focus on prevention of smoking initiation, as well as smoking cessation among current smokers.” n

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Practice Management Responding appropriately to negative online patient reviews can help physicians protect their reputation BY TAMMY WORTH

Pick your battles If you find out a patient has placed a bad review of your office online, you first have to decide if it is in your best interest to acknowledge it. If you have a thick skin and there are just a few,

which you respond is going to be different for every physician.”

You also have to gauge whether reaching out will actually remedy the situation. If talking to a patient may help you improve the care you provide, it may be worth a phone call.

Online monitoring The easiest, and most costly, way to know if people are writing bad reviews is to hire an online monitoring service to track what is being said about your office. These often charge on a monthly basis.

It costs a lot less to have staff do the work. You need to designate a specific person to do this work and have him monitor the net regularly. He should have a list of public review sites to check including Yelp, Healthgrades, and RateMDs (3 of the most commonly viewed).

“It can be the office manager, but it doesn’t have to be,” Fox said. “Some people enjoy, and get, social media and you may want to have them take charge.”

How to react If you are employed by a hospital, responding to negative reviews will be easy. Many big hospitals have monitoring

When responding to an online complaint, do not discuss anything related to a patient’s treatment or describe it in any way. you may want to ignore them, said Rich Sharp, senior vice president of digital at ReviveHealth in Nashville, Tennessee.

“What it really boils down to is, does the crowd say 1 thing — and is it positive — and does that outweigh 1 or 2 bad reviews,” he said. “The point at

On The Web PM_RUN1216.indd 30

systems and online reputation management program.

If you are on your own, the job of responding to negative reviews falls to your office. The person who is monitoring your presence could also be in charge of responses. Fox and Sharp offer these tips for a rapid response:

© THINKSTOCK

A

decade ago, people who wanted to find a new doctor would ask their friends and family for recommendations. Today, people look to online reviews, expanding their reach exponentially. In 2014, Becker’s Healthcare reported that nearly half of people they surveyed would even go out of network for physicians with good reviews.

“It’s another form of ask-your-neighbor,” said Kim Fox, senior vice president at Brentwood, Tennessee-based strategic communication firm, Jarrard Phillips Cate & Hancock, Inc. “They are just able to ask a lot more neighbors than they used to be able to.”

People like to use the internet as a medium for complaints. When people are happy with a service, they may tell 1 person, but irritated or dissatisfied patients want to tell the world, Fox said. How complaints are managed can make or break your patient relationships and online reputation.

Physicians should not feel awkward about asking satisfied patients to review them online.

Templated responses. Fox recommends having 10 to 12 templates ready to use. This allows you to connect with the patient quickly, which is important.

It also provides enough variety that it does not look like you are repeating yourself. She recommends running the responses by an attorney to make sure they are HIPAA compliant.

Mind HIPAA. Do not discuss anything related to a patient’s treatment or describe it in any way. If you cannot tell who the person is by his or her online post, do not give away any identifying information. Give generic responses to any comments a patient makes.

Go offline. If the situation is sensitive or you feel like you may breach HIPAA by responding, Sharp recommends responding strictly through back channels. If you can respond online, Fox said to respond with the template, give them a number at which to reach you, and do not take part in any other public conversation with the patient.

Take the high road. Avoid being combative. Connecting with the patient in a meaningful way can help

you understand why the patient is dissatisfied and potentially improve your practice. In other words, Fox recommends being “positive, polished, and compassionate.”

Finally, a good way to balance out negative reviews is to have more positive ones. You should not feel awkward about asking patients to review you online, Fox said.

“It’s OK to ask happy patients to rate you,” she said. “Just say, ‘We love patients like you and would like more of them.’ Don’t be afraid to do it.”

If you do not personally want to make the request of patients, you can have your office staff or nurse do it. Or you can send a handwritten note to patients asking them to let others know how satisfied they are by writing a review.

Fox also encourages physicians to thank anyone who gives a good review.

“Don’t just respond to trolls,” she said.

“Designate someone to respond to those that give wonderful reviews as well.” ■ Tammy Worth is a freelance medical journalist based in Blue Springs, MO.

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

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