Renal & Urology News - July/August 20119 Issue

J U L Y /A U G U S T 2 0 1 9

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VOLUME 18, ISSUE NUMBER 4

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Newer PCa Drugs Up Survival in mCSPC Investigators reported promising findings from phase 3 trials of apalutamide and enzalutamide NOVEL ANTI-ANDROGENS PROLONG LIFE IN mCSPC In separate phase 3 trials, men who received apalutamide (TITAN) and enzalutamide (ENZAMET) for metastatic castrationsensitive prostate cancer had significantly prolonged survival compared with men who received only standard treatment.

Apalutamide Enzalutamide Standard treatment

2-year survival

82.4%

73.5%

3-year survival

80%

72%

Sources: Davis ID et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019; published online ahead of print June 2.

Chi KN, et al. Apalutamide for metastatic, castration-sensitive prostate cancer.

N Engl J Med. 2019; published online ahead of print May 31.

TITAN

ENZAMET

Fatal PCa Tied to Visceral Fat

BY JODY A. CHARNOW GREATER VISCERAL AND thigh subcutaneous fat are associated with higher risks of advanced and fatal pros­ tate cancer (PCa), according to a new prospective study.

In addition, visceral fat is associated with a higher risk of these outcomes among men with a lower body mass index (BMI). Investigators found no association between any adiposity mea­ sure and total or high­grade PCa. A team led by Barbra A. Dickerman, PhD, of the Harvard T.H. Chan School of Public Health in Boston, said that to their knowledge, their study is the first prospective investigation of directly measured fat distribution and the risk of advanced PCa. Dr Dickerman and

her colleagues studied 1832 Icelandic men in the Age, Gene/Environment Susceptibility­Reykjavik Study. All men underwent baseline computed tomography imaging of fat deposition, bioelectric impedance analysis, and measurement of BMI and waist circum­ ference. Through linkage with nation­ wide cancer registries, the investigators identified 172, 43, 41, and 31 new cases of total, high­grade, advanced, and fatal PCa, respectively, during follow­ up. The median follow­up time was 10.1 years until PCa diagnosis and 10.4 years until PCa death.

Among all men, each 1 standard devia­ tion (SD) increase in visceral fat (85.7 cm2) and thigh subcutaneous fat (39.2 cm2) continued on page 7

BY JODY A. CHARNOW APALUTAMIDE OR enzalutamide added to standard treatment improves survival of patients with metastatic castration­sensitive prostate cancer (mCSPC), according to study find­ ings presented at the 2019 American Society of Clinical Oncology annual meeting in Chicago.

The findings are from the phase 3 TITAN trial, which compared apalu­ tamide plus androgen deprivation ther­ apy (ADT) with ADT alone, and the phase 3 ENZAMET trial, which com­ pared enzalutamide plus standard of care (ADT with or without docetaxel) with standard of care alone. The findings from both trials were published in the New England Journal of Medicine (NEJM).

Statin Users Have Better RC Outcomes INVESTIGATORS WHO studied patients who underwent radical cys­ tectomy (RC) for bladder cancer found that statin use was associated with improved overall and disease­ specific survival compared with non­ use, according to a presentation at the Canadian Urological Association’s 74th Annual Meeting in Quebec City.

The study, led by Armen G. Aprikian, MD, of McGill University Health Centre in Montreal, included 3087 patients with bladder cancer who underwent RC in Quebec from 2000 to 2014 and collected data from 2 years prior to RC to September 2016 or death.

Of these patients, 1448 (46.9%) used statins. The median overall survival (OS) and disease­specific survival was 4.5 years and 10.7 years, respectively, for statin users and 2.5 years and 4.6 years for non­users.

Compared with non­users, statin users had significant 17% and 19% decreased risks of all­cause and disease­specific continued on page 7

In the TITAN trial, men who received apalutamide plus ADT experienced a significant 52% decreased risk of death or radiographic progression compared with those who received placebo plus ADT, Kim N. Chi, MD, of BC Cancer and Vancouver Prostate Centre in Vancouver, British Columbia, and col­ leagues reported. The apalutamide­ treated patients also had a significant 33% decreased risk of death. Median radiographic progression­free survival (rPFS) was 22.1 months in the placebo arm and not reached in the apalu­ tamide group. Median overall survival was not reached in either study arm.

In addition, apalutamide recipients had a significant 61% decreased risk continued on page 7

IN THIS ISSUE 2

Targeted prostate biopsy alone found suboptimal

4

Low albumin prior to ESRD ups post-dialysis mortality

10

Nocturia etiology in men does not differ by race

11

Study finds overuse of PICCs in patients with CKD

12

Neoadjuvant combo reduces high-risk PCa tumor volume

16

Intermediate-risk PCa active surveillance on the rise

17

Q&A: David F. Jarrard, MD, discusses CRPC drug therapy

Electronic algorithms are no substitute for individualized patient counseling.

PAGE 19

2 Renal & Urology News

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Study: Targeted PCa Biopsy Alone Suboptimal IN MEN undergoing a first prostate biopsy, the optimal method for detect­ ing clinically significant cancer (grade group 2 or higher) is the combina­ tion of systematic biopsy and targeted biopsy of lesions visible on magnetic resonance imaging (MRI), according to investigators.

Leonard S. Marks, MD, of the Uni­ versity of California, Los Angeles, and colleagues designed the PAIREDCAP (Prospective Assessment of Image Registration for Diagnosis of Prostate Cancer) trial to answer outstanding questions about the use of MRI-guided prostate biopsy. A total of 300 biopsy-

naïve men (aged 45 to 80) with an el­ evated PSA level (less than 25 ng/mL) or an abnormal digital rectal exami­ nation had multiparametric MRI. Of these, 248 (mean age 65.5 years; 79.4% white) displayed suspicious lesions on MRI (i.e., a PI-RADS version 2 score of 3 or higher) and underwent 12-core

t­ ransrectal ultrasound-guided system­ atic biopsy, followed by cognitive tar­ geted biopsy (3 cores), and softwareassisted fusion targeted biopsy (3 cores) at the same sitting. During cognitive biopsy, a radiologist viewing the MRI directed the clinician to aim at regions of interest. In software fusion biopsy,

www.renalandurologynews.com JULY/AUGUST 2019

the MRI and ultrasound fusion device (Artemis) produced a 3D model of the prostate that included suspicious ­lesions to enable targeting. The remaining 52 men (mean age 63.6 years; 75% white) with no visible lesions on MRI (i.e., a PI-RADS version 2 score of less than 3) underwent systematic biopsy alone.

Overall, 70.2% of significant cancers were detected by combining ­systematic

and targeted biopsy, according to results published online in JAMA Surgery. Cognitive targeted biopsy alone d ­ etected 46.8%, systematic sampling alone, 60.1%, and either cognitive or software ­fusion biopsy, 62.1%.

The distribution of Gleason scores appeared similar among biopsy methods.

As PI-RADS version 2 score or PSA density increased, so did the chances of significant cancer.

According to the investigators, 11.5% to 33.3% of clinically significant c­ ancers would have been missed by using only a single biopsy method. In the subset of 52 men who underwent systematic biopsy alone, for example, 15% had clinically significant cancer missed by MRI. “Our research suggests that the different biopsy methods identify different tumors,” Dr Marks stated in a university news release. “To maximize our ability to

Renal & Urology News 3

identify prostate cancer, we need to take advantage of all the information we can.

Our cancer detection rate, while using different methods in tandem, surpasses that from using either method alone. In this case, one plus one equals three.”

When the MRI is negative for lesions, men at risk of prostate cancer (due to elevated PSA, a prostate nodule, or family history) should still receive systematic biopsy, he noted. ■

4 Renal & Urology News

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Pre-ESRD Low Albumin Ups Post-Dialysis Mortality PATIENTS WITH late-stage chronic kidney disease (CKD) who have low serum albumin levels prior to developing end-stage renal disease (ESRD) have an increased risk of death within 1 year after transitioning to dialysis, data show.

Compared with patients with serum albumin levels of 4.0 g/dL or higher

(reference) prior to dialysis, those with the lowest levels (below 2.8 g/dL) had a statistically significant 2-fold increased risk of death from any cause in 1 year after initiating dialysis, in a fully adjusted model, Elani Streja, MD, PhD, of the University of California Irvine, and colleagues reported in the Journal

of Renal Nutrition. They also had a statistically significant 2.1- and 2.6fold higher risk of cardiovascular- and infection-related mortality, respectively.

Patients who experienced declining serum albumin levels in the pre-ESRD period also had worse 1-year mortality following transition to dialysis. Each

0.5 g/dL decline per year was associated with a statistically significant 55% increased risk of death in a fully adjusted model. Furthermore, serum albumin levels below 2.8 g/dL were associated with a 50% increased risk of hospitalization within 1 year of transitioning to dialysis.

The findings are from a retrospective cohort study that included 29,124 US veterans with advanced CKD transitioning to ESRD. The cohort had a mean age of 67 years. They evaluated the association of pre-ESRD (91 days before transition) serum albumin with 1-year post-ESRD all-cause and cardiovascularand infection-related mortality. During the first year after transition to dialysis, 6236 patients died, for a crude mortality rate of 25.6 deaths per 100 person-years, 468 patients received kidney transplants, and 2027 were lost to follow-up.

Low serum albumin levels also raised the risk of hospitalization after dialysis initiation.

“To the best of our knowledge, this is the first study examining the association of serum albumin concentrations and its change in advanced CKD patients with early outcomes after transitioning to ESRD,” the authors wrote.

Study strengths include the large sample size and capture of comprehensive data on comorbidity status in the pre-ESRD period, the authors noted. In addition, the investigators were able to calculate serum albumin changes prior to dialysis initiation because they had repeated serum albumin measurements available. Dr Streja’s team also pointed out study limitations. The study included patients using the Veterans Affairs health system and its laboratory services in the year prior to starting dialysis. Consequently, study findings may not be generalizable to other populations. Furthermore, their study might be susceptible to survivor bias because they were only able to look at patients who survived the late-stage CKD to post-ESRD transition period. “Because of the design of our cohort, we were unable to examine CKD patients who died before transitioning to ESRD, which may limit generalizability,” they wrote. “Thus, our study cohort may consist of a ‘relatively healthy’ subset of late CKD patients.” ■

Contents

www.renalandurologynews.com

JULY/AUGUST 2019

J U LY / A U G U S T 2 0 1 9

■

Urology 2

ONLINE

this month at renalandurologynews.com

10

12

Clinical Quiz Test your knowledge by taking our latest quiz at renalandurologynews.com/ run-quiz

17

HIPAA Compliance Read timely articles on various issues related to keeping protected health information secure.

Drug Information Search a comprehensive drug database for prescribing and other information on more than 4000 drugs.

Neoadjuvant Combo Reduces PCa Tumor Volume In a phase 2 trial, abiraterone plus prednisone and leuprolide was superior to leuprolide alone in shrinking tumors prior to radical prostatectomy in patients with high-risk prostate cancer.

Pharmacotherapy for CRPC: An Update In a Q&A, David F. Jarrard, MD, Professor of Urologic Surgery at the University of Wisconsin in Madison, discusses important issues in the management of castrationresistant prostate cancer.

4

Pre-ESRD Low Albumin Ups Post-Dialysis Mortality Serum albumin levels below 2.8 g/dL before dialysis predicts an increased risk of death within 1 year after initiating dialysis.

11

Sodium Bicarbonate Benefits CKD Patients With Metabolic Acidosis Compared with standard care, treatment with sodium bicarbonate decreased the risk of kidney disease progression and death.

14

Donor Gender Does Not Affect KT Patient Survival The sex of kidney donors and recipients does not influence patient or graft survival, data suggest.

News Coverage Visit our website for daily reports on the latest developments in clinical research.

RCC Ablation Technique Influences Survival Time Cryoablation is associated with longer overall survival than heat-based thermal ablation for cT1a renal cell carcinoma, a study found.

VOLUME 18, ISSUE NUMBER 4

CALENDAR 2019 International Continence Society Annual Meeting Gothenburg, Sweden September 3–6 American Society of Nephrology Kidney Week 2019 Washington, DC November 5–10 Society of Urologic Oncology 20th Annual Meeting Washington, DC December 4–6 2020 Annual Dialysis Conference Kansas City, MO February 8–11 Genitourinary Cancers Symposium San Francisco, CA February 14–16 European Association of Urology Annual Congress 2020 Amsterdam, The Netherlands March 20–24 National Kidney Foundation 2020 Spring Clinical Meetings New Orleans March 25–29

Nephrology

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

Study: Targeted PCa Biopsy Alone Suboptimal Detection of clinically significant tumors may be improved by combining systematic biopsy and targeted biopsy of suspicious lesions on MRI.

Renal & Urology News 5

15

Kidney Disease Care for Type 2 Diabetics: Dawn of a New Era? Phase 3 trials show that SGLT2 inhibitors and GLP-1 receptor agonists can slow progression of diabetic nephropathy.

We are confident that in the near future we will

be able to propose curative strategies for high-risk localized prostate cancer in a similar fashion as is standard of care in breast cancer.

See our story on page 12

20

Departments 6

From the Medical Director RCC and advanced CKD pose a transplant dilemma

10

News in Brief CKD anemia risk decreases with increasing altitude

19

Ethical Issues in Medicine Predictive analytics versus individualized patient care

20

Practice Management Timely responses to PHI breaches imperative

6 Renal & Urology News

JULY/ AUGUST 2019 www.renalandurologynews.com

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

RCC in Advanced CKD: A Transplant Dilemma

N

on-dialysis patients with advanced CKD diagnosed with renal malignancies grapple with the dual threat of renal failure and cancer progression. When choosing between functional or oncologic risks, many patients will ask about renal transplantation. Discussions of this option are complicated by statistical realities: According to UNOS, of nearly 1 million solid organ transplants performed over the last 30 years, less than 12% occurred in patients older than 65. In 2018, approximately 25,000 of 130,000 potential kidney recipients were older than 65. Of these, only 18% received a transplant, with a median wait greater than 5 years.1 Unfortunately, overall survival rates in renal transplantation are lowest when ESRD is attributable to cancer.

These data suggest that in the RCC demographic, few patients are transplanted, wait times are long, and outcomes appear worse. In a small series from Mayo Clinic, only 15% of patients rendered surgically anephric for sporadic RCC underwent subsequent transplantation (median of 22 months). All transplant recipients were less than 70 years old, had cT1a tumors, and underwent a pre-nephrectomy transplant evaluation.2 Such issues raise the question of how to manage active renal masses in non-dialysis patients with CKD stage 3b or worse when oncologic treatment poses a real risk to initiating renal replacement therapy (RRT) and a less than 1 in 5 chance of a subsequent transplant. Data support strong consideration for oncologic risk stratification using renal mass biopsy and an initial period of active surveillance (AS) for most localized RCCs in patients at high perioperative risks for RRT. These include a growing awareness of lead/length time biases, our burgeoning understanding of RCC biology, and the development of effective systemic therapies for advanced disease.

Judicious AS for patients with localized RCC with significant ­co-morbidities, including advanced CKD, is part of most major guidelines. A growing literature regarding the safety of delayed management, comparative risks, survival estimates, and triggers for intervention are available.3 Ultimately, the outcome is an amalgam of biology, case selection, clinical experience, and patient preference, but a great pause should occur before rendering a patient in need of RRT from a localized renal mass. Comparing the Kaplan-Meier estimates for localized renal cancer under AS with those of patients on RRT, ask this question: Which survival curve would you rather be on?

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

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 UC 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 Chief Executive Officer Inova Health System Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology CCLCM (ret.)

Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California Irvine James M. McKiernan, MD John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology Columbia University College of Physicians and Surgeons, New York City Kenneth Pace, MD, MSc, FRCSC Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center, Memphis Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc. Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center Detroit Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J.

Renal & Urology News Staff Editor

Jody A. Charnow

Web editor

Natasha Persaud

Production editor Group art director, Haymarket Medical

Jennifer Dvoretz

Senior production manager

Krassi Varbanov

Director of production Director of audience insights National accounts manager Associate director, editorial services

Louise Morrin Boyle Paul Silver William Canning Lauren Burke

Vice president, content, medical communications Kathleen Walsh Tulley General manager, medical communications President, medical communications CEO, Haymarket Media Inc.

1. https://unos.org/data/transplant-trends/ 2. Boswell TC, Sharma V, Westerman ME, et al. Frequency and predictors of renal transplantation among patients rendered surgically anephric for sporadic renal cancer. Urology. 2019;126:134-139.

3. McIntosh AG, Ristau BT, Ruth K, et al. Active surveillance for localized renal masses: Tumor growth, delayed intervention rates, and >5-yr clinical outcomes. Eur Urol. 2018;74:157-164.

Kim Daigneau

Jim Burke, RPh Michael Graziani Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 18, Number 4. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018.

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 © 2019.

www.renalandurologynews.com JULY/AUGUST 2019

Graft failure and anemia continued from page 1

45 mL/min/1.73 m2), the rates were 19.9% vs 2.1%, respectively.

The investigators observed no significant differences in dose of methylprednisolone or mycophenolate mofetil or in tacrolimus trough level by patients’ anemia status. Anemic recipients were more likely to receive erythropoiesis stimulating agents (ESA) and reninangiotensin system blockers.

“Our findings implied that we should take into account not only Hb levels but also allograft function while determining the treatment strategy for PTA,” Dr Kakuta and the team concluded in a poster presentation.

“It is my personal opinion that there should be a PTA management algorithm to correct anemia and vigilance for chronic rejection surveillance to avoid early graft loss,” said Edgardo Laurel, MD, a transplant nephrologist at Banner–University Medicine Transplant Institute in Phoenix, Arizona, who was not involved with the study.

Clinicians should treat PTA with ESAs and intravenous iron, especially if patients’ eGFR is below 60 mL/ min/1.73 m2 and iron indices are low, Dr Laurel said. Clinicians should avoid excessive dosing with ESAs and be careful not to raise Hb levels above 12 g/dL, he said.

The new study is not the first to asso­ revious ciate PTA with graft loss. A p

K+ binder benefits continued from page 1

Dialysis and Transplant Association Congress in Budapest, Hungary, and in the Journal of the American Society of Nephrology.

In addition, half as many SZC patients required rescue therapy to reduce their serum potassium (2.1% vs 5.1%).

Binder can normalize intradialytic serum levels of potassium, researchers reported.

“By demonstrating preliminary efficacy and safety for sodium zirconium cyclosilicate, the trial opens a new avenue for controlling hyperkalemia in patients on hemodialysis,” Dr Fishbane told Renal & Urology News. “In subsequent studies, it will be interesting to learn whether SZC treatment permits

study of 1139 kidney transplant recipients, which was published in BMC Nephrology (2019;20:51), found that any PTA was associated with a significant 3-fold and 1.8-fold increased risk of death-censored graft failure 180 to 1251 days post-transplant (early period) and 1252 days post-transplant and beyond (late period), respectively. Severe PTA (Hb level below 11 g/dL) was associated with significant 7.6- and 2.6-fold increased risks, respectively, in the early and late periods.

Inadequate Hemodialysis Prior To Transplant Ups DGF Risk KIDNEY TRANSPLANT recipients with

Receiving inadequate pre-transplant

inadequate hemodialysis (HD) before

KT/V was significantly associated with

transplantation have increased risks for

longer hospitalization.

delayed graft function (DGF) and longer

“Strategies aimed to improve dialysis

hospitalization, Aparna Padiyar, MD, of

compliance could potentially reduce

University Hospitals Cleveland Medical

risk of DGF and shorten hospitaliza-

Center, and colleagues reported at the

tion,” Dr Padiyar’s team stated.

2019 American Transplant Congress

Graft failure risk increased 1.8-fold with each 1 g/dL decrease in Hb

Renal & Urology News 7

in Boston.

In their single-center retrospective

Commenting on the new study, Edgardo Laurel, MD, a transplant nephrologist at Banner–University

analysis of 101 consecutive kidney

Medicine Transplant Institute in Phoenix,

transplant recipients, 37 (36.6%) missed

Arizona, noted that the association of

1 or more HD in the month before trans-

missed HD sessions with worse out-

plantation (average 0.79; maximum 7).

comes is well known. “It is not surprising

Missing dialysis was significantly asso­

that kidney transplant recipients who

Dr Laurel cited a study published in Transplantation Proceedings (2015; 47:1178-1181) showing that PTA contributes to cardiovascular morbidity by deteriorating left ventricular function and increasing carotid-femoral pulse wave velocity, and this contributes to worse graft function. In another study of kidney transplant recipients published in Transplantation Proceedings (2016;48:878-883), investigators demonstrated that PTA was associated with an increased risk of a 50% or greater increase in serum creatinine level, a return to chronic dialysis, or subsequent kidney transplantation. ■

ciated with the need for urgent dialysis

have missed HD or inadequate dialysis

prior to transplantation, most often

prior to transplantation are at increased

for hyperkalemia, even though pre-

risk of increased length of stay during

transplant serum potassium levels did

their transplant hospitalizations, most

not differ markedly for this group.

likely due to uremia and fluid overload,”

the relaxation of dietary potassium restrictions or an increase in dialysate potassium concentration.”

Overall, SZC was well tolerated.

Serious adverse events occurred in 7% and 8% of patients in the SZC and placebo groups, respectively. Two people in the SZC group had angina pectoris that was considered unrelated to treatment. The most common complaint was gastrointestinal disorders.

Interdialytic weight gain was comparable between groups, indicating no excess risk of fluid retention with SZC. DIALIZE is the first randomized, placebo-controlled trial to evaluate a potassium binder in HD patients. “The results indicate that sodium zirconium cyclosilicate is an option for the management of hyperkalemia in this setting,” Dr Fishbane and colleagues stated.

The study was relatively short, so longer studies evaluating clinical end points such as hospitalization and cardiovascular events are still needed.

This study was funded by AstraZeneca, the makers of SZC (Lokelma). ■

KT vitamin D guidelines

The proportion of patients who expe-

Dr Laurel told Renal & Urology News.

rienced DGF was significantly higher

He noted that missed HD prior to trans-

among patients who missed 1 or more

plantation cannot explain the increased

HD sessions than those who did not

risk for DGF, but superimposing fluid

(86.4% vs 18.6%).

overload or uremia could be a factor.

Use of renin-angiotensin-system

Dr Laurel said he advocates trans-

blockade before transplant correlated

plant program monitoring and enforce-

with both missed dialysis and DGF, the

ment of dialysis adherence among

investigators reported.

potential transplant recipients. ■

continued from page 1

every 2 weeks for 2 months, then monthly for 22 months. In the study, a low dose corresponded to a minimum recommended intake of 400 IU per day.

At 24 months, vitamin D levels were significantly higher in the high-dose (43.1 vs 25.1 ng/mL at study inclusion) than in the low-dose group (25.1 vs 20.2 ng/ mL at study inclusion). The incidence of fractures was significantly lower in the high-dose than low-dose group (1% vs 4%). The investigators observed no differences between the groups in the risks of diabetes, major cardiac events, new cancers, or death. High-dose cholecalciferol was well tolerated, with no increased risks of vascular calcification, hypercalcemia, or hyperphosphatemia.

“Our study shows that currently recommended doses of vitamin D are not sufficient to protect patients from the risk of fracture after kidney transplantation,” Dr Courbebaisse said in the press release. “This challenges advice in the

current international KDIGO guidelines, which recommend using low doses of cholecalciferol similar to those recommended for the general population.”

Commenting on the study, ERAEDTA President Carmine Zoccali, MD, of CNR-IFC, Ospedali Riuniti, Reggio Calabria, Italy, said: “The VITALE trial is important because it

Recommended doses of vitamin D may be too low for fracture prevention. shows that high-dose vitamin D is an effective way of lowering the rate of fractures after kidney transplantation, with a very low risk of any side effects.

More broadly, we see yet again that other benefits for vitamin D seen in observational studies are not reflected when supplementation is tested in randomized controlled trials.” ■

www.renalandurologynews.com JULY/AUGUST 2019

Newer PCa drugs continued from page 1

of initiating cytotoxic chemotherapy, according to investigators.

Based on study findings, the trial’s independent monitoring committee recommended unblinding to allow patients in the placebo group to cross over to the apalutamide arm.

In the TITAN (Targeted Investiga­ tional Treatment Analysis of Novel Anti-androgen) trial, Dr Chi and col­ leagues randomly assigned 525 patients to receive apalutamide 240 mg per day plus ADT and 527 to receive placebo plus ADT. Patients had a median age of 68 years. Of the entire study popula­ tion, 16.4% had undergone prostatec­ tomy or received radiotherapy, 10.7% had received prior docetaxel therapy, and 62.7% had high-volume disease.

At the first interim analysis, with a median 22.7 months of follow-up, the proportion of men with rPFS at 24 months was 68.2% in the apalutamide arm and 47.5% among placebo recipi­ ents. At 24 months, the overall sur­ vival rate was significantly higher in

Visceral fat and fatal PCa continued from page 1

was associated with a 31% and 37% higher risk of advanced and fatal PCa, respectively, Dr Dickerman’s team reported in Cancer.

The associations between visceral fat and aggressive and fatal PCa were stronger among men with a BMI less than 27 kg/m2 and were statistically sig­ nificant only among these men. In this group, each 1-SD increase in visceral fat was associated with a 2-fold higher risk of advanced and fatal PCa in a fully adjusted model.

In addition, Dr Dickerman and her collaborators found that each 5 kg/m2 increase in BMI was associated with 52% and 56% greater risks of

Better RC outcomes continued from page 1

mortality, respectively, in multivariable analysis.

The investigators also analyzed out­ comes of 2215 patients (71.8%) who had more than 1 year of follow-up after RC. Of these, 1082 (48.8%) used statins. These patients had a signifi­ cant 19% decreased risk of both allcause and disease-specific mortality, compared with non-users, in adjusted analyses. Dr Aprikian and colleagues

the apalutamide than placebo group: 82.4% vs 73.5%.

The rates of grade 3 or 4 adverse events were similar in the apalutamide and placebo groups: 42% and 41%, respectively. The rates of study discon­ tinuation due to AEs were 8% and 5%, respectively.

Based on the TITAN findings, Janssen Pharmaceutical Companies, which developed apalutamide (Erleada), submitted a supplemental New Drug Application to the FDA seeking approval of apalutamide for the treatment of men with mCSPC. Apalutamide already is approved the treatment of nonmetastatic castrationresistant prostate cancer.

In the ENZAMET trial, enzalu­ tamide plus standard care with tra­ ditional nonsteroidal anti-androgens (NSAA), namely flutamide, bicalu­ tamide, or nilutamide, with or without docetaxel was associated with a sig­ nificant 33% decreased risk of death compared with standard care alone, Christopher J. Sweeney, MBBS, of the Dana-Farber Cancer Institute in Boston, and colleagues reported. The

advanced and fatal PCa, respectively.

Obese men (BMI 30 kg/m2 or higher) had 2.5- and 2.6-fold higher risks of advanced and fatal disease, respectively.

Each 1-SD (10.3 cm) increase in waist

Obese men vs those with a healthy BMI had a 2.6-fold higher risk of fatal PCa. circumference was associated with ­ 40% and 45% higher risks of advanced and fatal PCa, respectively.

“The identification of the adiposity phenotypes at highest risk of clinically relevant prostate cancer may help to

found no significant difference in over­ all or disease-specific survival between patients who started statins after RC and those who already used statins before RC. Previous studies looking for associa­ tions between statin use and bladder cancer have yielded mixed findings.

A study of 574 patients who under­ went transurethral bladder resection for nonmuscle-invasive bladder can­ cer found that statin use was indepen­ dently associated with nearly 2-fold increased odds of cancer recurrence

3-year overall survival (OS) rate was 80% in the enzalutamide group com­ pared with 72% in the group receiv­ ing standard care only. In addition, at 3 years, 64% of the enzalutamide arm remained on study treatment compared with 36% of patients receiving standard of care alone.

Renal & Urology News 7

“Physicians and patients with prostate cancer now have a new treatment option with enzalutamide, and this is especially relevant for men who cannot tolerate chemotherapy and have a lower burden of disease seen on scans,” Dr Sweeney said in an ASCO press release.

The decreased risk of death asso­ ciated with enzalutamide treatment was more pronounced in men with low-volume disease and in those with­ out planned docetaxel treatment,

i­ nvestigators reported. Among patients with low-volume disease, the enzalu­ tamide group had a significant 52% decreased risk of death compared with patients taking other NSAAs, with 3-year OS rates of 90% vs 82%. Among patients with high-volume disease, the enzalutamide group also had a signifi­ cant 26% decreased risk of death, with 3-year OS rates of 71% vs 63%.

In the patients with no planned early docetaxel therapy, enzalutamidetreated men had a significant 49% decreased risk of death compared with those taking another NSAA, with 3-year OS rates of 83% vs 70%. Among those with planned early docetaxel therapy, the enzalutamide recipients had a non-significant 9% decreased risk of death, with 3-year OS rates of 73% vs 74%.

“Our current data support the claim that early enzalutamide prolongs sur­ vival within 3 years in the entire trial population but provide limited support that it prolongs overall survival within 3 years in patients who received early docetaxel treatment,” the investigators wrote in the NEJM paper. ■

elucidate the mechanisms linking obe­ sity with aggressive disease and target intervention strategies,” the investiga­ tors concluded.

Dr Dickerman’s team noted that the prospective design of their study “minimizes the likelihood of reverse causation, whereby the disease or its treatment influences fat distribution.

Furthermore, the use of gold-standard measures of fat distribution enabled us to examine the obesity–prostate cancer link with higher resolution than studies of BMI and waist circumference.”

In an accompanying editorial, Celina H. Shirazipour, PhD, and Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, com­ mented that the new findings, in addi­ tion to existing evidence related to

obesity and PCa, “highlight the need to examine lifestyle interventions that target fat loss in promoting optimal prostate cancer outcomes.”

Based on the new findings and the existing body of knowledge on diet and exercise, “new opportunities arise for knowledge development and practice for researchers and clinicians.”

Investigators might benefit from includ­ ing measures that assess visceral fat as outcomes in interventions, and clinicians would benefit from collecting knowl­ edge of fat location in addition to total weight, Drs Shirazipour and Freedland wrote. “This information, alongside exist­ ing outcome measures such as inflamma­ tory markers, may be beneficial in indi­ cating whether prostate cancer risks are being targeted during treatment.” ■

The survival benefit of enzalutamide was greater in men with low-volume disease.

Cancer-specific and overall survival were greater in statin users than in non-users. compared with non-use, investigators reported in BMC Cancer (2015:15:120).

In an earlier study published in BMC Cancer (2011;11:409), investigators who compared 88,125 cases (patients with primary cancers) and 362,254 matched

controls from 574 general practices in the United Kingdom found that statin use for more than 4 years was associ­ ated with significant 29% increased odds of bladder cancer compared with non-use. Researchers who studied 1502 patients treated with RC and pelvic lymphadenectomy without neoadjuvant therapy found that statin use had no significant effect on disease recurrence and cancer-specific survival on multi­ variable analysis, according to findings published in The Journal of Urology (2013;190:487-492). ■

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News in Brief

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

Short Takes AKI Tied to Proton Pump Inhibitor Use in CKD

colleagues studied 6258 patients

Proton pump inhibitor (PPI) use by

cryoablation and 2322 treated with

patients with chronic kidney disease

heat-based thermal ablation. After

(CKD) is associated with increased

propensity score matching, the

risks for acute kidney injury (AKI) and

cryoablation group had significantly

death, investigators reported at the

longer median overall survival than the

56th European Renal Association-Euro-

patients treated with heat-based ther-

pean Dialysis and Transplant Associa-

mal ablation (11.3 vs 10.4 years), the

tion Congress in Budapest, Hungary.

researchers reported in the Journal of

In a prospective cohort study that

Vascular and Interventional Radiology.

with cT1a RCC: 3936 treated with

included 3023 patients with CKD PPIs had significant 54% and 35%

Potential Therapy for Lupus Nephritis Shows Promise

increased risks for AKI and death,

Obinutuzumab added to standard of

respectively, compared with non-users

care medications showed enhanced

of PPIs, in adjusted analyses, accord-

efficacy compared with placebo as

ing to Sophie Liabeuf, MD, of Jules

a treatment for proliferative lupus

Verne University of Picardie, Amiens,

nephritis in adults in the phase 2

France, and colleagues.

NOBILITY trial.

stages 3 to 5, patients who used

The trial compared obinutuzumab

RCC Ablation Technique Influences Survival Time

and placebo in combination with

Patients with cT1a renal cell carcinoma

mycophenolic acid and corticoste-

(RCC) have better overall survival if

roids. A significantly larger proportion

they receive treatment with cryoabla-

of the obinutuzumab vs placebo arm

tion instead of heat-based thermal

achieved a complete renal response

ablation, a study found.

at 1 year, the study’s primary end

either mycophenolate mofetil or

point, according to a press release

Jing Wu, MD, of Second Xiangya Hospital, Central South ­University,

from Genentech, which is developing

Changsha, Hunan, China, and

the drug.

Anemia More Likely as CKD Advances Higher chronic kidney disease stages are associated with increasing risks of anemia, according to a new study. Shown below are the proportions of patients in CKD stages 3-5 who developed anemia within 5 years.

100

90.6%

98.8%

80.8%

80 62.3% 60 40 20 0

3a

3b

CKD Stage

4

5

Source: Vestergaard SV, Heide-Jørgensen U, Van Haalen H, et al. Incidence of anemia in patients with chronic kidney disease—A population-based cohort study. Presented at the 56th European Renal Association-European Dialysis and Transplant Association congress in Budapest, Hungary, June 13 to 16. Abstract FP398.

Kidney Transplant Patient Survival Is Improving L

ong-term survival of kidney transplant recipients and their grafts has been steadily improving, according to data presented at the 2019 American Transplant Congress in Boston.

Based on data from 385,687 recipients in the United Network for Organ Sharing (UNOS) who survived for the first year following transplantation, investigators found that kidney transplant recipients experienced significantly decreased risks of mortality and graft loss from 1991 to 2017.

Bhamidipati Murthy, MBBS, MD, and colleagues from Baylor College of Medicine in Houston classified patients according to 5-year periods during which they received their transplants: 1991-1995 (reference), 1996-2000, 2001-2005, 20062010, and 2011-2017. Compared with the reference period, those receiving their kidneys in 1996-2000, 2001-2005, 2006-2010, and 2011-2017 experienced a significant 13%, 13%, 15%, and 16% decreased risk of death, respectively, and 8%, 10%, 12%, and 16%, decreased risk of graft loss, respectively.

Nocturia Etiology in Men Does Not Differ By Race N

octuria in white and black male patients does not differ in etiology, a team from SUNY Downstate College of Medicine in Brooklyn, New York, reported in the Canadian Journal of Urology.

Matthew R. Epstein, MD, and colleagues analyzed 24-hour frequency volume charts completed by men aged 18 years or older seeking treatment for lower urinary tract symptoms at a Veterans Affairs urology clinic from 2008 to 2016. They classified patients as having nocturia owing to small bladder capacity (SBC), nocturnal polyuria (NP), mixed nocturia (SBC plus NP), or “other” (neither SBC nor NP). Among the white and black patients, 24% and 26%, respectively, had NP, 27% and 30% had SBC, and 30% and 28% had mixed nocturia. Overall, the investigators found no significant difference in the distribution of underlying nocturia etiology by race.

“Accordingly, race should not play a role in the evaluation of patients seeking treatment for nocturia,” they concluded.

Anemia Risk in CKD Patients Is Lower at Higher Altitudes A

nemia is less likely to develop in patients with chronic kidney disease (CKD) who live at higher altitudes, according to a report in the American Journal of Kidney Diseases.

Yue-Harn Ng, MD, of the University of New Mexico in Albuquerque, and collaborators analyzed data from the initial screening visits of 120,429 participants in the Kidney Early Evaluation Program (KEEP). Although participants lived in places as high as 2809 meters, 95% lived at elevations of 1360 meters or less, according to the investigators. After adjusting for sex, age, race, ethnicity, and other potential confounders, each 1-km increment in elevation was associated with significant 33% decreased odds of anemia, Dr Ng’s team reported. They found no interaction between estimated glomerular filtration rate and elevation with anemia.

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Sodium Bicarbonate Benefits CKD Patients With Metabolic Acidosis Treatment shown to decrease the risk of kidney disease progression and death

Renal & Urology News 11

PICC Overuse in Hospitals Documented ALTHOUGH GUIDELINES such as Choosing Wisely recommend

SODIUM BICARBONATE treatment of metabolic acidosis in patients with chronic kidney disease (CKD) improves renal outcomes and survival, researchers reported at the 56th European Renal Association-European Dialysis and Transplant Association Congress in Budapest, Hungary.

In a prospective open-label study, patients with CKD and metabolic acidosis who took sodium bicarbonate (SB) tablets had a lower risk of a doubling of serum creatinine (the study’s primary end point), initiation of renal replacement therapy (RRT), and death than those who received standard care (SC).

For the study, Antonio Bellasi, MD, PhD, of ASST Papa Giovanni XXIII in Bergamo, Italy, and colleagues randomly assigned 740 patients with CKD and metabolic acidosis to receive SB (376 patients) or standard care (SC, 364 patients). The study population had a mean age of 67.8 years, mean creatinine clearance of 30 mL/min, and mean serum bicarbonate level of

21.5 mmol/L. The mean follow-up periods in the SB and SC groups were 30.3 and 29.6 months, respectively.

The average dose of sodium bicarbonate was about 6-7 g/day. Overall, 87 patients reached the primary end point: 25 (6.6%) in the SB group and 62 (17%) in the SC group, the investigators reported. The SB group had

Patients experienced a 50% decreased risk of initiating renal replacement therapy. a significant 64% lower risk of a doubling of serum creatinine compared with the SC group, Dr Bellasi’s team reported.

At the end of the study, 26 patients (6.9%) in the SB group and 71 (19.5%) in the SC group had initiated RRT. The SB group had a significant 50%

decreased risk of RRT initiation compared with the SC group.

Lastly, 12 patients (3.1%) in the SB group and 25 (6.8%) in the SC group died. Compared with the SC group, the SB group had a 57% decreased risk of death, according to the investigators.

SB had no significant effect on hospitalizations, blood pressure, or total body weight.

Separately, a systematic review and meta-analysis of the effect of treatment of metabolic acidosis in CKD published online June 13 in the Clinical Journal of the American Society of Nephrology concluded that “current clinical trial evidence suggests that oral alkali supplementation or a reduction of dietary acid load improved serum bicarbonate levels and may slow the progression of kidney disease, on the basis of very-low- to ­moderate-certainty clinical evidence.”

The review, by Sankar D. Navaneethan, MD, of the Baylor College of Medicine in Houston, included 14 clinical trials that included a total of 1394 participants. ■

against using peripherally inserted central catheters (PICCs) in patients with moderate to advanced chronic kidney disease (CKD), many CKD patients are still receiving PICCs while in the hospital, according to a new study.

Of 20,545 patients who had PICCs placed within the Michigan Hospital Medicine Safety Consortium, 4743 (23.1%) had an estimated glomerular filtration rate (eGFR) of less than 45 mL/min/1.73 m2 and 699 (3.4%) were receiving hemodialysis (HD), David Paje, MD, MPH, of the University of Michigan in Ann Arbor, and colleagues reported in the Annals of Internal Medicine. In the intensive care unit (ICU), 30.9% of patients with PICCs had an eGFR less than 45 mL/min/1.73 m2. In general medicine units, that proportion was 19.3%.

“In conclusion, despite guidelines that recommend against the use of

Study: SPS Associated With Serious GI Events OUTPATIENT USE OF sodium polystyrene sulfonate (SPS), a cationexchange resin, is associated with serious adverse gastrointestinal (GI) events, corroborating previous case reports of intestinal injury, investigators reported in JAMA Internal Medicine.

Of 1,853,866 adults older than 66 years in Ontario, Canada, 27,704 received SPS during the period 2003 to 2015, Manish M. Sood, MD, of The Ottawa Hospital, and colleagues reported. The investigators matched SPS users (median age 78 years) to non-users using high-dimensional propensity scores, accounting for age, sex, diabetes, congestive heart failure, acute kidney injury, chronic dialysis, and hyperkalemia history.

Higher hospitalization risk Compared with non-use, SPS use was associated with a 1.9-fold higher risk of hospitalization or emergency department visits within 30 days of initial prescription. The composite GI end point encompassed intestinal ischemia

or thrombosis, GI ulceration or perforation, or resection or ostomy. There were 37 events (0.2%) among SPS users and 18 events (0.1%) among nonusers at an incidence rate of 23 vs 11.0 per 1000 person-years, respectively. SPS recipients had a 4.5-, 1.8-, and 1.3-fold higher risk of intestinal ischemia or thrombosis, GI ulceration or perforation, or resection or ostomy, respectively.

Subset analysis In a subset of patients matched by estimated glomerular filtration rate and serum potassium, SPS users still had a 2.9-fold higher risk for the composite end point, according to the investigators.

The study found no significant difference in adverse GI events by comorbidities, reduced kidney function, history of hyperkalemia, or use of renin-angiotensin-aldosterone system blockade.

In 2009, the FDA warned of the risk of intestinal necrosis with administration of sorbitol along with SPS and recommended avoiding this combination.

But study analyses showed adverse GI

effects occurred with SPS even after the 2009 warning.

“These findings require confirmation and suggest that clinicians should exercise caution in prescribing sodium polystyrene sulfonate,” Dr Sood and his colleagues wrote.

Monica Parks, MD, and Deborah Grady, MD, MPH, of the University of California, San Francisco, agreed with the caution in an accompanying editorial: “Given the evidence, sodium polystyrene sulfonate should not be used to reduce serum potassium levels. There are a number of other approaches to treating elevated serum potassium levels, including dietary restriction of potassium, potassium-wasting diuretics, and lower doses or discontinuation of medications that increase serum potassium.”

The editorialists hesitated to recommend new hyperkalemia drugs. “Newer cation-exchange agents are entering clinical use,” they noted, “but data describing their success in reducing hyperkalemia are limited, and there is very little data regarding long-term safety.” ■

PICCs in patients with CKD, we found that such practice is common in the hospital setting,” the authors wrote.

“Now more than ever, interventions that operationalize and implement guideline recommendations and offer alternative strategies for venous access in patients who need vein preservation for hemodialysis are necessary.”

The creation of an arteriovenous fistula is the preferred choice for HD and more likely to succeed when the native venous segment in CKD patients has not been injured by an indwelling vascular catheter, such as a PICC, the investigators explained.

Advanced CKD patients with PICC placement in the ICU vs medical wards were more likely to experience major complications such as venous thromboembolism (5.6% vs. 3.5%).

Overall complication rates were comparable, however.

For 25.8% of CKD patients, PICC dwell time was less than 5 days, a duration favoring alternative venous access devices. ■

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Neoadjuvant Combo Reduces PCa Tumor Volume

BY JOHN SCHIESZER NEOADJUVANT therapy that combines abiraterone acetate plus prednisone (AAP) and leuprolide prior to radical prostatectomy significantly reduces tumor size in men with highrisk localized prostate cancer (PCa) and may decrease the risk of biochemical recurrence compared with leuprolide alone, according to a new study.

The study is the first to compare AAP plus leuprolide and leuprolide alone in this setting, according to a research team led by Eleni Efstathiou, MD, PhD, Associate Professor, Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center in Houston.

In a phase 2 open-label trial, Dr Efstathiou and colleagues randomly assigned 65 patients (median age 61 years) 2:1 to AAP plus leuprolide vs leuprolide alone for 3 months followed by radical prostatectomy. Even though they found no statistically significant differences in organ-confined disease, tumor volume measures were significantly lower in the combination therapy arm,

remain disease free after median followup of 7 years. For prostate cancer, that would be the equivalent of a cure.”

The investigators also sought to identify potential biomarkers for AAP benefit or treatment resistance. They found that glucocorticoid receptor (GR) overexpression correlated with persistent

tumors in the AAP plus leuprolide group. The presence of nuclear androgen receptor splice variant (ARv7) correlated with persistent tumors in both treatment arms. “We looked very closely for markers that could be associated with improved outcomes or resistance to treatment,” Dr Efstathiou told Renal

Abiraterone added to prednisone and leuprolide superior to leuprolide alone. and lower tumor epithelium volume correlated with significantly improved biochemical recurrence-free survival (RFS) after 4 or more years of follow-up. The 3-year RFS rate was 89% among men with a tumor epithelial volume of 0.3 cc or less compared with 61% for those with a volume greater than 0.3 cc, the investigators reported in European Urology.

Tumors pretreated with AAP plus leuprolide vs leuprolide alone had less proliferation and less androgen signaling expression compared with leuprolide alone.

‘Equivalent of a cure’ Optimal therapy for high-risk localized prostate cancer remains an unmet need, Dr Efstathiou said. “The chance of its relapsing after localized definitive treatment are about 70%,” she said. “We observed that about 60% of men on the combined treatment arm had disease that was confined to the prostate,” she said.

“We now have long-term follow-up and can verify that the men who achieved limited tumor volume following ­treatment

FS:7.125”

& Urology News. “This ­information has been instrumental for subsequent studies. We are currently actively looking at identifying such predictors of outcome in the original biopsies of these men with high-risk disease so that we can guide their treatment. We are confident that in the near future we will be

B:16.75” T:16.25” S:15.25”

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B:16.75” T:16.25” S:15.25”

able to propose curative strategies for high-risk localized prostate cancer in a similar fashion as is standard of care in breast cancer. It is a unique opportunity to change the course of the disease and the lives of our patients with high-risk localized disease.”

Longer follow-up needed “This is a significant hypothesis generating paper identifying potential bio-

markers such as Arv7 and GR activation in this high-risk patient population,” commented Leonard G. Gomella, MD, Prostate Cancer Chairman at the Sidney Kimmel Cancer Center and the Clinical Director of the Jefferson Sidney Kimmel Cancer Network, Philadelphia. “Much longer follow-up and larger numbers of patients will be needed before this can be adopted as a standard of care,” Dr Gomella said.

Robert Dreicer, MD, Associate Direc­ tor for Clinical Research and the Deputy Director of the University of Virginia Cancer Center, Charlottesville, said much more follow-up is warranted and studies will need to have end points that include metastasis-free survival and OS. “The findings were modest, and this is clearly not yet ready for introduction into clinical practice. It remains an investigational construct.”

Renal & Urology News 13

Emmanuel S. Antonarakis, MD, Associate Professor of Oncology at Johns Hopkins Sidney Kimmel Comprehensive Center in Baltimore, said the new findings are intriguing and support the view that more complete androgen suppression may lead to greater tumor regression, but more questions about neoadjuvant treatment with androgen deprivation plus abiraterone will need to be answered. n

B:11.25”

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Donor Gender Does Not Affect KT Patient Survival KIDNEY DONOR GENDER has no significant impact on long-term recipient and graft survival, new study findings suggest.

A team led by Adnan Sharif, MBChB, MD, a transplant nephrologist at University Hospitals Birmingham in the United Kingdom, analyzed data

available for 25,140 kidney transplants.

Of these, 13,414 kidneys (53.4%) were from male donors and 15,690 (62.4%) of recipients were male. After up to 10 years of follow-up, the sexes of the donors and recipients made no sigT:7.5" nificant difference in patient or graft survival. Male and female recipients of S:7"

female kidneys, however, had significant 11% and 19% decreased risks of delayed graft function or primary nonfunction, Dr Sharif’s team reported in a poster presentation at the 56th European Renal Association-European Dialysis and Transplant Association Congress in Budapest, Hungary.

Results showed that recipients of female donor kidneys had significantly higher creatinine levels at 1 year posttransplant, regardless of recipient gender. Male recipients of female donor kidneys had 1-year creatinine levels that were, on average, 6.3% higher than those of male recipients of male donor kidneys. Similarly, female recipients of female donor kidneys had 1-year creatinine levels that were, on average, 4.1% higher than the levels among female recipients of male donor kidneys, Dr Sharif and colleagues reported.

The investigators concluded that “this study is reassuring for patients and professionals alike with regards to equivalent patient and graft survival for kidney transplant recipients, regardless of donor sex.” ■

Gout Is More Severe in KT Recipients GOUT IS MORE severe and difficult to treat in patients with a history of kidney transplantation (KT) than in those without a KT history, new data suggest.

T:10.25" S:9.75"

The study included 312 patients

with gout. Of these, 25 (8%) had a KT history and 287 did not. Compared with the no-KT group, the KT group had a significantly higher prevalence of severe uncontrolled gout (27% vs 8%) and tophi (36% vs 17%) and higher rates of allopurinol discontinuation or physician perceived contraindication to allopurinol (44% vs 23%), Mark D. Brigham, of Trinity Partners in Waltham, Massachusetts, and colleagues reported in Transplantation Proceedings. The most common reason for allopurinol discontinuation was lack of efficacy (patients inadequately controlled) in both cohorts, followed by hepatic impairment in the KT group and renal impairment in the no-KT group.

“The high prevalence of gout among patients with KT and increased health risks associated with severe gout compound the potential importance of these findings and underscores the need for further investigations in this area,” the authors noted. ■

11110434_2019_HP_Brief_Summary_M4.indd 1

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Renal & Urology News 15

n FEATURE

Kidney Disease Care for Type 2 Diabetics: Dawn of a New Era? Studies document renal benefits of canagliflozin, dapagliflozin, empagliflozin, and dulaglutide

BY JODY A. CHARNOW

K

or death from renal or cardiovascular (CV) causes compared with placebo among patients with type 2 diabetes and kidney disease. Investigators presented the findings at the 2019 World Congress of Nephrology in Melbourne, Australia, on April 15.

The presentation coincided with online publication of the findings in The New England Journal of Medicine.

• DECLARE (Dapagliflozin Effects on Cardiovascular Events)-TIMI 58, which demonstrated that patients with type 2 diabetes treated with dapagliflozin experienced a significant 24% decreased risk of the study’s primary composite renal ­outcome of a sustained 40% decline in estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) to below 60, ESRD, or death from renal or CV causes compared with placebo recipients. Investigators reported the findings at the American Diabetes Association’s 79th Scientific Sessions in San Francisco in June.

• EMPA-REG OUTCOME (Empag­ liflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), which in a post-hoc analysis demonstrated that empagliflozin improves kidney outcomes compared with placebo in patients with type 2 diabetes regardless of whether or not they have heart failure (HF), according to findings published in June in Circulation: Heart Failure. A previous post-hoc analysis showed that the drug significantly decreased the risk of renal function decline in the overall study population.

• REWIND (Researching Cardio­vas­ cular Events with a Weekly Incretin in Diabetes), which showed that treating type 2 diabetes in patients at least 50 years old with dulaglutide was associated with a significant 15% decreased risk of a composite outcome of new macroalbuminuria, a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. A separate a­ nalysis showed

that dulaglutide treatment was associated with a significant 12% decreased risk of the study’s primary CV outcome of the first occurrence of the composite end point of non-fatal myocardial infarction, non-fatal stroke, or death from CV causes. Results of both analyses were published online ahead of print on June 7 in The Lancet.

• AWARD-7, which showed that the GLP-1 receptor agonist dulaglutide significantly slowed eGFR decline compared with insulin glargine therapy in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD). The investigators published their findings last year in The Lancet Diabetes & Endocrinology.

“This is an exciting time for patients with, or at risk for, chronic kidney disease in diabetes. SGLT2 inhibitors and GLP-1 receptor agonists will be drugs of choice for glycemic control and organ protection—kidney and heart—in patients with or at risk of continued on page 16

© THEVISUALMD / SCIENCE SOURCE

idney disease management in patients with type 2 diabetes may be entering a new era, according to researchers.

Recently reported findings from phase 3 randomized clinical trials provide strong evidence of the renal benefits of medications belonging to 2 classes of diabetes drugs: sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists.

The medications include the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin and the GLP-1 receptor agonist dulaglutide.

Key trials setting the stage for this possible evolution in care include: • CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation), which showed that treatment with canagliflozin was associated with a significant 30% decreased risk of the trial’s primary composite outcome of end-stage renal disease (ESRD), a doubling of serum creatinine level,

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists slow progression of chronic kidney disease in patients with type 2 diabetes.

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AS for Intermediate-Risk PCa Increasing Uptake was greater for favorable vs unfavorable intermediate-risk prostate cancer, data show USE OF ACTIVE surveillance (AS) for intermediate-risk prostate cancer (PCa) nearly doubled from 2010 to 2015 in the United States, according to new national data. AS adoption increased the most among older men and those with favorable intermediate-risk disease.

Vinayak Muralidhar, MD, of DanaFarber Cancer Institute, Brigham and Women’s Hospital, Boston, and his colleagues used the Surveillance, Epidemiology, and End Results Active Surveillance/Watchful Waiting database to identify 52,940 men with intermediate-risk PCa (cT2b-c, Gleason score 7, or PSA 10-20 ng/mL). Of these, 22,224 (42.0%) were initially managed with radiation therapy (RT), 27,493 (51.9%) with radical prostatectomy (RP), and 3223 (6.1%) with AS. Use of AS increased from 3.7% in 2010 to 7.3% in 2015, the team reported in Cancer. AS uptake significantly increased from 7.2% to 14.9% among

CKD care in diabetics continued from page 15

CKD,” said Katherine R. Tuttle, MD, Professor of Medicine at the University of Washington in Seattle and principal investigator on the AWARD-7 trial.

Breakthrough drugs “Overall, I’m genuinely excited about these drug classes. I think they represent a breakthrough for people living with type 2 diabetes,” said Joseph Vassalotti, MD, Chief Medical Officer for the New York-based National Kidney Foundation. “After the seminal ACE inhibitor and angiotensin receptor blocker studies, an avalanche of negative diabetic kidney disease randomized trials intervened. These new therapies should re-invigorate nephrologists and inspire careers in kidney disease care and investigation.”

“These agents should be used early in the armamentarium of diabetes management for sure, and perhaps prediabetes,” said CREDENCE investigator George L. Bakris, MD, Professor of Medicine and Director of the Comprehensive Hypertension Center at University of Chicago Medicine.

Dr Bakris said he predicts that SGLT2 inhibitors in particular, because they reduce oxidative stress and ­inflammation,

men with favorable intermediaterisk disease and increased to a lesser extent among men with unfavorable intermediate-risk disease: 2.2% to 3.8%. The likelihood of AS was 4-fold higher for favorable than unfavorable ­intermediate-risk patients.

AS was used in 7.3% of cases in 2015, up from 3.7% in 2010, according to a study.

The mean age of men adopting AS significantly decreased from 69.9 to 67.9 years, suggesting increasing physician comfort with the approach. The likelihood of AS was 1.5- and 3-fold higher among men aged 70 years and older than those aged 60 to 69 years and younger than 60 years, respectively.

would have renal and CV benefits in patients without diabetes, although the effects would not be as robust as in patients with diabetes.

“SGTL2 inhibitors should not be thought of as diabetes drugs only, but rather cardiorenal risk reducing drugs that have glucose lowering as a side effect,” Dr Bakris said.

“Based on the CREDENCE results, we now have a single therapy—canagliflozin—that improves the metabolic profile, reduces renal failure, and improves cardiovascular outcomes in patients with type 2 diabetes and albuminuric chronic kidney disease,” said CREDENCE investigator Kenneth W. Mahaffey, MD, Professor of Medicine at Stanford University School of Medicine in Stanford, California, where he is Vice Chair of Clinical Research in the Department of Medicine.

“Canagliflozin is the first drug in 18 years to show a benefit on renal and CV outcomes in this patient population,” Dr Mahaffey said.

As a result of the CREDENCE findings, the American Diabetes Association, in an update to its 2019 Standards of Care, said clinicians should consider use of a SGLT2 inhibitor in type 2 diabetes patients with diabetic nephropathy who have an eGFR of 30 mL/min/1.73 m2 or higher and have albuminuria exceeding 300 mg/g to

Men residing in the West, Northwest, or Midwest were nearly twice as likely to select AS compared with men living in the Northeast and South. Black race and higher socioeconomic status, but not insurance status, also were associated with higher AS uptake.

Importantly, the investigators examined early survival outcomes by comparing the cohort with intermediate-risk disease to a cohort of 45,915 patients with low-risk disease. Cancer-specific mortality at 5 years was no worse among men with low-risk disease opting for AS rather than definitive treatment.

Significantly worse cancer-specific survival was observed for men with unfavorable intermediate-risk PCa who underwent AS compared with those who received RT or RP: 1.3% vs 0.5%.

Among men with unfavorable intermediate-risk PCa, AS was associated with a significant 2.5-fold increased risk of dying from their cancer than men

who received RT or RP, in adjusted analyses. A nonsignificant difference was observed for men with favorable risk disease who selected AS instead of treatment: 1.0% vs 0.2%.

“Therefore, the current study data affirm NCCN [National Comprehensive Cancer Network] guidelines indicating that caution should be applied when considering AS for men with favorable intermediate-risk disease as we await longer follow-up data regarding population-wide outcomes with AS,” Dr Muralidhar and the team stated.

They also acknowledged an increase in AS among patients with unfavorable intermediate-risk disease, which is outside of NCCN standard of care: “This may represent ‘indication creep’ from trends in patients with lower risk disease, or provider unawareness of risk features defining favorable versus unfavorable intermediate-risk disease,” they suggested. ■

decrease the risk of kidney disease progression and CV events.

Javed Butler, MD, MPH, a cardiovascular researcher who led the EMPA-REG OUTCOME post hoc analysis comparing renal outcomes associated with empagliflozin use by HF status in diabetics, said it is “quite likely” SGLT2 inhibitors and GLP-1 receptor agonists will lead to a major shift in diabetic kidney disease management. In terms of the drugs’ CV benefits, “we might use these agents in

metabolism, adiposity, and other physiologic processes, he noted. “This raises the possibility that the benefit may extend to non-diabetic patients as well,” he said.

With these agents, a patient’s doctors will need to communicate clearly with each other. high-risk patients irrespective of any other consideration,” said Dr Butler, the Patrick Lehan Chair of Cardiovascular Research at the University of Mississippi Medical Center in Jackson. “They may become first-line therapies, but we have to wait and see.” Importantly, he said, these are not competitive, but complementary, and the CV benefit may necessitate use of both SGLT2 inhibitors and GLP-1 receptor agonists, regardless of glycemic control.

SGLT2 inhibitors have a wide range of pharmacodynamic effects on the kidney, heart, and vasculature, as well as on

Coordination of care needed Although SGLT2 inhibitors and GLP-1 receptor agonists may represent a significant advance in the treatment of type 2 diabetes and its complications, maximally tolerated doses of ACE inhibitors and angiotensin receptor blockers remain an important component of type 2 diabetes management, Dr Vassalotti pointed out. In addition, assimilation of SGLT2 inhibitors and GLP-1 receptor agonists into the management of type 2 diabetes will make coordination of care imperative among various subspecialists (such as nephrologists, endocrinologists, and cardiologists) and primary care physicians, he said. “Clear communication among caregivers is necessary to avoid situations such as one clinician placing a patient on an SGLT2 inhibitor and another doctor taking the patient off the drug because of lack of familiarity with the drug class,” he said.

Dr Mahaffey also acknowledged the importance of inter-specialist communication. “We need to consolidate our care pathways for these patients by coordinating treatment plans across clinicians who care for these patients,” he said. ■

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Renal & Urology News 17

Pharmacotherapy for CRPC: An Update At the 2019 annual meeting of the American Urological Association (AUA), David F. Jarrard, MD, was a member of the instructional faculty in a session titled “AUA Castration Resistant Prostate Cancer (CRPC) Guidelines and Therapeutic Advances in Metastatic Prostate Cancer.” Dr Jarrard is Professor of Urologic Surgery at the University of Wisconsin, where he holds the John P. Livesey Chair in Urologic Oncology. He also is Associate Director for Translational Research at the University of Wisconsin Carbone Cancer Center.

How would you sum up the changes in the management of CRPC that have occurred in recent years?

Dr Jarrard: The field of advanced prostate cancer and CRPC is rapidly evolving, and the 2018 AUA guidelines are undergoing revision. We should have a new set of guidelines available by May 2020. When we think about the management of CRPC, it’s important to differentiate between metastatic symptomatic disease and early non-metastatic, asymptomatic disease. There has been a remarkable change in options for patients with M0 CRPC where previously none existed.

These include enzalutamide and apa­ lu­ tamide, which recently received ap­prov­al in this space. These drugs are now being used earlier in the disease course where previously they were employed in the pre- and post-chemotherapy space only for symptomatic metastatic CRPC. When should the newer oral anti­ androgens be used in asymptomatic nonmetastatic CRPC?

Dr Jarrard: Generally, if an individual has a very slowly rising PSA and is asymptomatic in this space, observation is one option. However, if the PSA doubling time is less than 10 months, it’s reasonable to think about treatment with apalutamide or enzalutamide.

The risks and benefits need to be discussed. This is clearly an area that urologists need to be involved in and need to be familiar with the application and side effects of these agent.

Has the advent of the novel anti­ androgens, and data supporting their use earlier in advanced prostate cancer, changed the role of chemotherapy?

Dr Jarrard: Chemotherapy still has an important role in the management of CRPC. Generally, it’s used in metastatic symptomatic CRPC. Most oncologists would use an oral agent such as apalutamide or enzalutamide before considering chemotherapy, but it remains an option in castrationresistant disease. There are several indications when one might want to consider using it earlier, even before anti-androgens. For example, one might want to use docetaxel as primary therapy for individuals who have very rapidly progressing PSAs and extensive metastases, including large lymph nodes, widespread bony disease, and visceral metastases.

improvement in radiographic progression-free survival in these patients.

What follow-up imaging is warranted in the CRPC setting?

Dr Jarrard: Traditional imaging consists of computed tomography scans of the abdomen and pelvis and bone scans. If the PSA is rising rapidly, imaging should be done more often.

The advent of newer types of imaging has really changed our management of the disease. Fluciclovine F18 PET scans can help identify metastatic disease in patients with rising PSAs after local treatment. We also have a new generation of imaging in terms of PSMA PET imaging that looks to be extremely sensitive in picking up small amounts of disease that are outside of the prostate. This is going to change our approach to a lot of these patients.

M0 CRPC is potentially going to be a shrinking stage in terms of numbers because newer generation imaging modalities will likely find metastatic cancer in many patients who have a rising PSA in this setting.

Which patients with metastatic CRPC would benefit from sipuleucil-T versus antiandrogens?

Dr Jarrard: Sipuleucil-T is indicated for asymptomatic or minimally

What are the patient characteristics that enter into the therapeutic decisionmaking process?

Dr Jarrard: Quality of life is a very important aspect to consider when we think about the management of patients in the M0 CRPC space. Older patients who have other health issues and have poor performance status may opt for continued observation in this setting.

Conversely, someone who has rapidly rising PSA in this ­castration-resistant space may opt for treatment with either apalutamide or enzalutamide.

There are some potential side effects associated with these medicines, but clearly the data demonstrate a marked

symptomatic metastatic CRPC. One may want to consider it before an oral anti-androgen. The data clearly indicate that there’s a role for this drug in the modern treatment of patients.

Often, we consider using this drug before chemotherapy because it allows us to administer this drug in these relatively asymptomatic patients, when they have a good performance status and may derive the most benefit from this drug compared with much later in the disease. Studies that have looked at optimal use of this approach have indicated that below a PSA of 20 ng/mL is often a good marker for considering use of sipuleucil-T. Sipuleucil-T has side effects that are on the more minor side for the majority of patients. These are often considered flu-like and are usually treated with ibuprofen and rest.

What are some important considera­ tions in preserving bone health?

Dr Jarrard: Bone health is a critical aspect of our management of these patients. Often, issues with bone health arise later in the disease.

Fractures related to bone density loss can be lethal in elderly patients with advanced prostate cancer. Current recommendations for bone health would be to consider getting a DEXA scan and generating a FRACS score to help determine bone density prior to being placed on androgen deprivation therapy. Most patients will benefit from being placed on vitamin D and calcium supplements. In patients with CRPC who are undergoing therapy, one can also consider, if patients have an at-risk FRACS score, being placed on an agent that prevents bone loss such as denosumab or zoledronic acid.

In this situation, denosumab has some advantages in that it is subcutaneous and doesn’t require the individual going to an infusion center.

Are there other agents we can consider with unique mechanisms of treatment in CRPC?

Bone health is a critical aspect of managing men with CRPC. ­—David F. Jarrard, MD

Dr Jarrard: Another therapeutic consideration is radium-223, which is indicated for patients with CRPC and symptomatic bone metastases.

Contraindications to the use of this drug include visceral metastases. It is an option for patients anywhere along the course of the disease. This is an important discussion to have with patients as well as medical oncologists. ■

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Renal & Urology News 19

Ethical Issues in Medicine T

he promise of so-called “big data” for improving the quality, safety, and efficiency of health care is vast. With continual improvements in the capability of electronic medical record (EMR) systems to link to external patient registries and analyze and interpret larger amounts of data, the potential expands for physicians to more accurately diagnose and effectively treat illness.

Big data is typically characterized by its “volume, velocity, and variety,” which translates to large amounts of easily and rapidly accessible, diverse, heterogenous patient data that had not been previously available for analysis.1 Big data can be used for traditional analytic approaches, but it is now being touted for predictive analytics (PA) applications using machine learning and artificial intelligence.

Electronic algorithms of care PA is the use of electronic algorithms for clinical decision support that forecasts future events in real time. Proponents argue that this approach will help clinicians make important clinical decisions in the clinic or at the bedside. For example, it could be used when deciding which patients will benefit most from ICU-level care or which patient will have more post-operative complications. PA used in machine learning

will be on the front lines for ensuring that this emerging technology does not interfere with high-quality, individualized, patient-centered care.

What will physicians need to know about a PA algorithm when using it in the care of their patients? In general, physicians should apply the same critical thinking and analysis to evaluating decision support as they already do for assessing the methodology and applicability of a conventional evidence-based study. First, they should ask themselves how the PA algorithm was developed and validated. Different stakeholders have different values. In developing an algorithm, a hospital may be subtly and differentially concerned about cost, a physician about workflow, and a patient about adverse outcomes or quality of life. The more individuals know about how a model was developed, the more confident they can be that it accounts for these diverse considerations.

Another important point is whether an appropriate sample of patients was included in a model’s development. If a model was designed without sufficient samples of specific populations or if those populations have worse health outcomes due to social factors, the results of the PA algorithm may reinforce existing health disparities and worsen health equity.4

Electronic algorithms that forecast outcomes may adversely affect provision of individualized, patient-centered care. algorithms of image detection for diabetic retinopathy are well validated and have already been demonstrated to be successful.2 With this technology and its wider application, however, there is the potential for misuse, bias, and less equity if it is not used properly. Using large data sets linked to extensive patient registries allows for the possibility of great benefit but also harm.3 Physicians, who have ethical and professional obligations to represent patients’ best interests,

What about conflicts of interest in the development of PA for patient care? It is easy to review conflict of interest disclosures in a peer-reviewed study, but these conflicts may not necessarily be transparent in a PA model. Physicians likely want to know what variables were used in creating the model, or if some stakeholders had a profit incentive that may interfere with objective model development.

Finally, the results of a PA algorithm may compromise physicians when

© TOM WERNER / GETTY IMAGES

Predictive analytics could improve care, but also compromise a physician’s ability to act in a patient’s best interest BY DAVID J. ALFANDRE, MD

Ultimately, physicians are responsible for applying evidence to individual patients.

helping a patient to decide on treatment. If a model recommends against offering a surgical intervention but the model was deliberately designed primarily to improve the overall health of a population or reduce health care costs, then it may be at odds with an individual patient’s needs and preferences and conflict with a physician’s obligation to advocate for the best interests of that patient.

Obligation to the patient remains Some have suggested that PA technology is more hype than substance.5 Although the ability of big data and PA to improve our predictive power will continue to grow, it retains some of the same challenges and limitations of evidence-based medicine. Ultimately, physicians are responsible for applying evidence to individual patients and using it as part of a shared decisionmaking process to identify and advocate for what is best for that patient. PA models will have vastly more data, but they are not yet close to eliminating all uncertainty in clinical care.

All of these considerations raise an important question: Will PA provide additional data for discussion, or will it be used as a definitive clinical answer that is provided to the patient?

Regardless of how this technology will be used in health care, clinicians will always be needed to discuss and apply information to the patient in the room.

This will help ensure patients’ interests continue to be adequately represented. ■ David J. Alfandre MD, MSPH, is a health care ethicist for the National Center for Ethics in Health Care (NCEHC) at the Department of Veterans Affairs (VA) and an Associate Professor in the Department of Medicine and the Department of Population Health at the NYU School of Medicine in New York.

The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the NCEHC or the VA. REFERENCES 1. Price WN 2nd, Cohen IG. Privacy in the age of medical big data. Nat Med. 2019;25:37-43.

2. Gulshan V, Peng L, Coram M, et al. Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. JAMA. 2016;316:2402-2410.

3. Shah ND, Steyerberg EW, Kent DM. Big data and predictive analytics: recalibrating expectations.

JAMA. 2019;320:27-28.

4. Cohen IG, Amarasingham R, Shah A, et al. The legal and ethical concerns that arise from using complex predictive analytics in health care. Health Aff. 2014:33.7:1139-1147.

5. Emanuel EJ, Wachter RM. Artificial intelligence in health care: Will the value match the hype? JAMA. 2019; published online May 20, 2019. doi:10.1001/ jama.2019.4914.

20 Renal & Urology News

JULY/AUGUST 2019 www.renalandurologynews.com

Practice Management I

n May, the Department of Health and Human Service’s Office for Civil Rights (OCR) reached a settlement with Touchstone Medical Imaging, based in Franklin, Tennessee, in a case that highlights the importance of responding promptly and effectively to potential breaches of protected health information (PHI).

Touchstone must pay a $3 million fine and adopt a corrective action plan because, according to OCR, it neglected to do anything after both OCR and the Federal Bureau of Investigation notified them that a breach had occurred.

Touchstone’s servers allowed search engines to expose more than 300,000 patients’ PHI. The organization said no information was breached, but, according to OCR, this was not the case. OCR said it determined Touchstone did not look into the incident until months after the organization was notified of it, nor did it contact patients in a timely manner.

And when investigating, OCR found other issues: Touchstone did not have a thorough risk analysis or business associate agreements in place with vendors.

How an organization reacts to breaches may differ depending on the size of the practice and amount and kind of data compromised. Regardless

response plan is not only part of HIPAA rules, it is an organizational best practice, said Abby Bonjean, an associate at Polsinelli LLP, a law firm that handles HIPAA breach cases.

Practices need to create policies and procedures for dealing with breach responses and identifying people who are part of the response team. The policies should map out steps so members of the team know where they would report an incident and how that information will be passed along to ensure important parties know the details.

“If there is a phishing attack and an employee clicks on a link that gives someone access to the employee’s account, you need to make sure they know who to notify within the organization,” Bonjean said.

Resolving in-house Practices hire Polsinelli to help resolve breaches of all sizes, Bonjean said, but that does not mean providers always need to outsource their response.

“HIPAA is designed to be scalable,” said Kim Stanger, a partner at Holland & Hart LLP. “It was never intended to force people to hire consultants at $20,000 a whack.”

For instance, if PHI is stolen and the information was encrypted according

A quick efficient response to a breach can sometimes mean the difference between OCR pursuing a settlement or closing the case. of the breach’s scope, though, a quick efficient response can sometimes mean the difference between OCR pursuing a settlement or closing the case.

Preparing for a breach Most organizations do not plan for breaches before they occur. It is usually not until after a laptop is stolen or someone clicks on a phishing email that organizations even think about breach response. Developing an incident

to HIPAA security rules, it does not have to be reported, Stanger said.

Bonjean said a practice’s compliance officer can also do an in-house breach risk assessment if the breach was very small and the information was not highly sensitive. If there is a low probability that any information was compromised, it does not have to be reported to OCR, she said.

For instance, if PHI is faxed to the wrong recipients, the compliance

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Timely and appropriate responses to breaches of protected health information may help practices avoid penalties BY TAMMY WORTH

HIPAA rules require health care organizations to develop an incident response plan.

officer can talk with the people who did it to ensure they understand how not to do so again. Then the officer can contact the individual who received the information to make sure he or she is not going to tell anyone. Practices can send letters to recipients who mistakenly receive somebody else’s PHI cautioning about HIPAA penalties associated with releasing PHI, Stanger said.

“It helps document what you’ve done, and you look better with OCR and the individuals who were breached,” Stanger said. “Showing you have taken these appropriate steps will go a long way to mitigating your risk.”

Reporting requirements Current HIPAA rules say breaches of unsecured PHI impacting fewer than 500 patients need to be reported to OCR within 60 days of the end of the calendar year in which it was discovered. If more than 500 patients’ records were breached, OCR must be notified within 60 days of the date of discovery of the breach. HIPAA also requires that providers report a breach of information to the individuals whose records were compromised within 60 days of the time the breach was discovered.

With larger breaches, particularly electronic ones, the stakes and penalties

can increase dramatically and rapidly.

Stanger said groups will likely need to bring in outside consultants. These organizations can do forensic work to track how the breaches started and what information has been released.

Among the most important tasks following a large breach is to correct the situation immediately, Stanger said.

“If you correct it in 30 days and you didn’t act with willful neglect, you can usually [avoid] HIPAA penalties,” he said. “But if you fail to do a required breach report because you don’t want adverse publicity, you are going to be subject to mandatory penalties.”

Stanger said he has always been able to resolve breaches without penalties if the clients have documented corrective action and performed a breach report.

While taking corrective action and containing a breach incident, Bonjean said, it would be wise to secure other areas as well. A breach impacting 500 or more individuals automatically triggers an OCR investigation. When OCR looks into a compliance program, providers frequently get caught without required security measures such as risk analyses or business associate agreements. ■ Tammy Worth is a freelance medical journalist based in Blue Springs, MO.