Renal & Urology News July-August 2017 digital edition

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Abiraterone Plus ADT Ups Survival First-line use for hormone-sensitive high-risk prostate cancer could be a new standard of care SUPERIOR OUTCOMES AT 3 YEARS In the STAMPEDE trial, upfront use of abiraterone/prednisolone plus ADT versus ADT alone among men with hormone-sensitive locally advanced or metastatic PCa significantly increased the proportion of patients who had failure-free and overall survival and freedom from symptomatic skeletal events at 3 years, as shown here.

100

PERCENTAGE

80

88% 78%

83%

76%

75%

60

45%

40

Abiraterone/ prednisolone plus ADT ADT alone

20 0

No symptomatic skeletal events

Overall survival

Failure-free survival

Source: James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338-351.

RP Survival Benefit Challenged

BY NATASHA PERSAUD MEN WITH LOCALIZED prostate cancer (PCa) treated with radical prostatectomy (RP) survive no longer than those undergoing observation, according to findings from PIVOT (Prostate Cancer Intervention versus Observation Trial).

For the trial, investigators randomly assigned 364 patients to have RP and 367 to undergo observation. During 19.5 years of follow-up, 223 RP patients (61.3%) and 245 observation patients (66.8%) died from any cause; 27 RP patients (7.4%) and 42 observation patients (11.4%) died from PCa. continued on page 7

CVD LINKED TO ANEMIA IN PATIENTS WITH CKD

The risk of coronary heart disease is upped by 41%, study finds.

PAGE 9

BY JODY A. CHARNOW CHICAGO—Adding abiraterone to androgen-deprivation therapy (ADT) as first-line treatment for hormonesensitive locally advanced or metastatic prostate cancer (PCa) improves survival and delays disease progression compared with ADT alone, according to the findings of separate studies presented at the American Society of Clinical Oncology 2017 annual meeting and published in the New England Journal of Medicine (2017;377:338-351; 352-360).

As a result of study findings, researchers say combined therapy with abiraterone and ADT in this population could represent a new standard of care.

In the randomized double-blind phase 3 LATITUDE trial, which

Hypogonadism Ups ED Risk In Testicular CA

BY JODY A. CHARNOW Two new studies suggest that hypogonadism in testicular cancer survivors (TCS) is associated with a number of chronic health problems, including erectile dysfunction (ED), dyslipidemia, hypertension, and metabolic syndrome.

At the 2017 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, researchers reported on a study of 491 TCS showing that 38% of them suffered from hypogonadism, defined as a serum testosterone level of 300 ng/dL or less or the use of testosterone replacement therapy. A significantly higher proportion of hypogonadal men than those with normal testosterone levels had ED (20% vs. 12%), hypertension (19% vs.

11%), and dyslipidemia (20% vs. 6%) “Our findings underscore the need for clinicians to assess testicular cancer survivors for physical signs or symptoms of hypogonadism and to measure testosterone levels in those who do,” continued on page 7

included 1199 patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC), investigators led by Karim Fizazi, MD, PhD, head of the Department of Cancer Medicine at Gustave Roussy, University Paris-Sud in Villejuif, France, found patients who received abiraterone and prednisone in addition to ADT had a 38% decreased risk of death and 53% decreased risk of radiographic progression compared with those who received placebo and ADT. The median length of radiographic progression-free survival was 33.0 months in the abiraterone arm compared with 14.8 months among the placebo recipients, the researchers reported. continued on page 7

IN THIS ISSUE 9

Study finds minimal risk of PCa in men who have a vasectomy

10

Bladder CA patient death risk is linked to smoking intensity

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Prostatic urethral lift benefits are durable out to 5 years

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Mortality risk is greater when MIBC recurrence is symptomatic

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Negative confirmatory PCa biopsies may be a good sign

24

Greater use of RP for high-risk localized PCa reported

25

ED may predict development of Parkinson’s disease

Intensive BP lowering may benefit patients with CKD. PAGE 18

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Evidence Supports Gabapentin for Uremic Pruritus GABAPENTIN is the only treatment for uremic pruritus in patients with advanced chronic kidney disease (CKD) with strong supportive evidence of effectiveness, according to a systematic review. Evidence for other treatments “is weak and limited by small studies with a high risk of bias,”

a team led by Claudio Rigatto, MD, MSc, of the University of Manitoba in Winnepeg, Canada, reported online ahead of print in the American Journal of Kidney Diseases.

Dr. Rigatto and his colleagues reviewed 44 randomized controlled trials involving patients with advanced

CKD (stage 3 or higher) or receiving any form of dialysis. The trials examined 39 different uremic pruritus treatments, including gabapentin, pregabailin, mast cell stabilizers, phototherapy, hemodialysis modifications, and other systemic and topical therapies. “The main finding of our

comprehensive systematic review of treatments for uremic pruritus is that with the exception of the evidence for gabapentin, there remains considerable uncertainty about effective treatments for this important and burdensome symptom in patients with kidney failure,” the researchers wrote. n

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Renal & Urology News 5

Elderly CKD Patient Nephrology Referrals Questioned REFERRALS TO nephrologists may not be warranted for many elderly patients with chronic kidney disease (CKD), who may be managed safely in the primary care setting, British researchers concluded based on a study of CKD patients aged 80 years and older.

“In our study, the elderly patients kept under regular surveillance in the nephrology clinic tended to have more advanced renal impairment and were likely to have rapid decline in kidney function,” Mark McClure, MBBS, and colleagues at Dorset County Hospital NHS Foundation Trust in Dorset, UK,

wrote in an article published online ahead of print in the Clinical Kidney Journal. “This suggests that nephrologists were able to correctly identify the patients whom they predicted may require specialist renal input in terms of managing complications of CKD and provision of renal replacement therapy.”

In a retrospective study, Dr. McClure’s team analyzed data from 124 patients aged 80 years or older (mean 84.4 years) referred to the nephrology outpatient clinic at their hospital. Of these, 115 had CKD stage 4 and 9 had CKD stage 5. Of the 124 patients, 66 were kept under regular follow-up in the clinic and 58 were discharged back to primary care. Patients kept under follow-up tended to have a lower median estimated glomerular filtration rate (eGFR) at referral than those discharged back to primary care (22 vs. 26 mL/min/1.73 m 2) and a significantly more rapid decline in mean eGFR over the following 7 years (1.58 vs. 0.357 mL/min/1.73 m2), according to the investigators.

Most elderly patients with CKD may be managed safely in the primary care setting.

In addition, significantly more patients in the follow-up group were started on erythropoietin (12 vs. 3) and significantly more patients initiated dialysis (5 vs. 0). In the follow-up group, 55 (83%) died, with a median time to death of 2.66 years. In the primary care group, 45 patients (78%) died, with a median time to death of 3.57 years, the investigators reported.

The researchers said it is important to recognize that most elderly patients with CKD ultimately will not require or desire renal replacement therapy and may be managed safely in the primary care setting.

“With increasing pressure on newpatient clinic slots, referral of a select group in which a specific intervention is being considered may be more appropriate,” Dr. McClure and his colleagues wrote. “Nephrologists also need to play their role to reduce the workload and should be encouraged to discharge such patients back to primary care after initial review in the clinic.”

Dr. McClure’s group noted that awareness and detection of CKD in the United Kingdom has increased markedly over the past decade. Nationwide, they related, there has been a sustained increase in patients referred to nephrology clinics. “The increased referrals have led to an older patient cohort, for whom specialty nephrology input is of questionable clinical benefit.” n

Cosmos Communications

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FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

New AUA Guidelines Promise Better Care

T

he recently released American Urological Association guidelines for the management of renal mass1 es brought together a multidisciplinary team of experts to perform a rigorous evidence-based systematic review utilizing research from the Agency for Healthcare Research and Quality (AHRQ). Significant changes in the new guidelines include perspectives on the role of renal mass biopsy, a more defined role for thermal ablation, and increased use of active surveillance in elderly or infirmed patients with small renal masses. Notably, the new guidelines call for increased attention to perioperative renal function and more clear guidance on the use of partial versus radical nephrectomy.

Functional recovery after renal cancer surgery is considered a major issue for cancer survivorship. The guidelines include more comprehensive recommendations about assigning chronic kidney disease (CKD) stage, checking for perioperative proteinuria with routine urinalysis, and counseling regarding functional outcomes related to the different treatment strategies. Pathologic evaluation of non-tumorous adjacent renal parenchyma is emphasized (statement #23), as are defined recommendations for referral for nephrology consultation (statement # 8).

To avoid CKD, the guidelines now provide detailed review of the risk/ benefit profile comparing partial to radical nephrectomy. The guidelines recommend considering radical nephrectomy for localized tumors under the following conditions (guideline statement #19): when increased oncologic potential is suggested by tumor size, biopsy (if performed), and/or imaging characteristics. In this setting, radical nephrectomy is generally preferred if all the following criteria are met: 1) high tumor complexity and partial nephrectomy would be challenging even in experienced hands; 2) no preexisting CKD/proteinuria; and 3) normal contralateral kidney and new post-op baseline glomerular filtration rate greater than 45 mL/min/1.73 m2.

Beyond this, most cT1a/b and T2 tumors can be considered for partial nephrectomy. Radical nephrectomy may be required based on surgical discretion in patients who do not meet these criteria and in whom partial nephrectomy may not be possible or advisable even in experienced hands.

Despite efforts to increase awareness of the potential benefits of nephronsparing approaches, partial nephrectomy remains underused. A main goal of the guidelines is to refocus the physician and care team on the evaluation and implications of CKD, on the renal functional tradeoffs of surgery, and on the need to increase nephrology involvement in the care of these patients.

As such, the guidelines should provide practicing urologists a valuable resource in the evaluation and management of this patient population.

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 1. www.auanet.org/guidelines/renal-mass-and-localized-renal-cancer-new-(2017).

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 John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology 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 Web editor Production editor Group art director, Haymarket Medical Production manager Production director Circulation manager National accounts manager Group Publisher Editorial director

Jody A. Charnow Natasha Persaud Kim Daigneau Jennifer Dvoretz Brian Wask Kathleen Millea Grinder Paul Silver William Canning Chad Holloway Kathleen Walsh Tulley

General manager, medical communications

Jim Burke, RPh

CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 16, Number 4. Published bimonthly 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 © 2017.

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Abiraterone plus ADT continued from page 1

The independent data and safety monitoring committee overseeing the study unanimously recommended that the trial be unblinded and patients in the placebo arm be allowed to receive abiraterone.

The treatment arms had similar numbers of patients who experienced serious adverse events, but the abiraterone arm had higher rates of grade 3 hypertension and hypokalemia, the investigators reported.

New standard of care “Given these findings, I believe that the addition of abiraterone to androgen

RP survival benefit continued from page 1

The between-group d ­ ifferences were not statistically significant, the researchers reported in the New England Journal of Medicine (2017; 377:132-142).

“This study confirms that aggressive treatment usually is not necessary,” coauthor Gerald L. Andriole, MD, director of Washington University’s Division of Urologic Surgery, said in a news release issued by the university. “We hope the findings will steer doctors away from recommending surgery or radiation to their patients with nonaggressive early-stage prostate cancer and patients away from thinking it’s necessary.”

“Our results demonstrate that for the majority of men with localized prostate cancer, selecting observation for their treatment choice can help them live a similar length of life, avoid death from

Hypogonadism, ED risk

continued from page 1

lead investigator Mohammad Issam Abu Zaid, MBBS, Assistant Professor of Medicine at Indiana University School of Medicine in Indianapolis, said in an ASCO press release.

The patients, who had a median age of 38 years at evaluation, were participants in the Platinum Study, which aims to follow the lifelong health of men who received cisplatin chemotherapy for testicular cancer. Although it has been known that hypogonadism occurs in a significant proportion of TCS, this study is among the first to examine its relationship with longterm health complications in North American patients, according to the press release.

Renal & Urology News 7

deprivation therapy can be considered as a new standard of care for men with high-risk de novo metastatic prostate cancer,” Dr. Fizazi told meeting attendees.

The study included 597 and 602 men randomly assigned to received abiraterone/prednisone or placebo, respectively, in addition to ADT. During a median follow-up time of 30.4 months, 406 deaths and 593 radiographic progression events occurred, the researchers reported.

The men in the study received their diagnosis of mHNPC 3 months or less before randomization. To be included in the trial, they needed to have least 2 of 3 risk factors: a Gleason score of 8 or higher, 3 or more bone metastases, or 3 or more visceral metastases.

STAMPEDE trial The other study, the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trial, compared abiraterone/prednisolone plus ADT and ADT alone in men with hormone-sensitive locally advanced or metastatic PCa. The trial, led by Nicholas D. James, PhD, of the University of Birmingham in the UK, included 1917 patients randomly assigned to receive ADT alone (957 patients) or the combination therapy (960 patients). During a median follow-up of 40 months, 184 men in the combination arm and 262 in the ADTalone arm died.

The 3-year failure-free survival rates were 75% in the combination arm com-

pared with 45% in the ADT alone arm, the researchers reported. The 3-year overall survival rates were 83% and 76%, respectively, and the 3-year rates of freedom from symptomatic skeletal events were 88% and 78%, respectively.

Compared with the ADT alone arm, the combination group had a 71% decreased risk of treatment failure (defined as radiologic, clinical, or PSA progression or death from PCa), 54% reduction in the risk of symptomatic skeletal events, and a 37% decreased risk of death.

“So our opinion is that abiraterone acetate and prednisolone should be part of the standard of care for men starting longterm androgen deprivation,” Dr. James told colleagues during an ASCO meeting presentation. n

prostate cancer and prevent harms from surgical treatment,” lead investigator Timothy J. Wilt, MD, MPH, of the Minneapolis Veterans Affairs Health Care System, said in the same release. “Physicians can use information from our study to confidently

“It would be a disservice to dismiss surgery as a viable option for patients with intermediate-risk prostate cancer,” Dr. Andriole said. “For these patients, and for some men with high-risk prostate cancer, surgery is often beneficial, as are other treatments such as radiation.”

PIVOT also showed that adverse events requiring treatment, such as urinary incontinence and erectile dysfunction, were significantly more common with surgery than observation (17.3% vs.

4.4% and 14.6% vs. 5.4%, respectively) through 10 years.

Treatment for disease progression was far less common after RP than observation (33.5% vs. 59.7%), but most progression in this cohort involved asymptomatic disease, local progression, or biochemical recurrence.

The researchers noted that observation, PSA monitoring, and biopsy-based active surveillance are underused. They

suggested raising the PSA and biopsy thresholds for intervention.

The current findings generally confirm and extend the PIVOT results at 10 years of follow up. During the original trial, conducted during the early era of PSA testing 1994 to 2002, 731 men (mean age, 67; median PSA, 7.8 ng/mL) with nonmetastatic, node-negative stage 1 to 2 PCa of any grade were randomly assigned to RP or observation (i.e., palliative therapy or chemotherapy for symptomatic or metastatic progression). The results were published in the New England Journal of Medicine (2012;367:203-213).

The researchers said their findings also generally agree with results from the SPCG-4 (Scandinavian Prostate Cancer Group Study Number 4) trial, which was conducted before the PSA testing era, and ProtecT (Prostate Testing for Cancer and Treatment), which was conducted in the later era of PSA testing. n

and ­insulin. The researchers defined hypogonadism as a total testosterone level less than 288 ng/dL and/or an LH level above 10 IU/L, or ongoing androgen replacement therapy.

TCS with normal testosterone levels in adjusted analyses, the investigators reported in Andrology (2017; published online ahead of print).

The investigators defined MetS according to criteria established by the 2005 National Cholesterol Education Program Adult Treatment Panel III. Patients had to meet 3 of the following criteria for a MetS diagnosis: systolic blood pressure (BP) 130 mm or higher and/or diastolic BP 85 mm Hg or higher; fasting glucose 100 mg/dL or higher; high-density lipoprotein level below 40 mg/dL; and waist circumference 102 cm or higher.

Results also showed that the TCS group had significantly higher mean HbA1c levels (5.4% vs. 5.3%) and waist measurements (95.7 vs. 91 cm) than controls. n

Aggressive treatment is not necessary for most cases of localized PCa, researchers say. r­ecommend observation as the preferred treatment option for men with early prostate cancer.”

Lower all-cause mortality was found for men with intermediate-risk PCa treated with RP (59.7% vs. 74.2%), but not for those with low- or high-risk disease.

Commenting on the study, Timothy D. Gilligan, MD, MSc, of Cleveland Clinic, observed: “We can now cure 19 out of 20 cases of testicular cancer, but a significant number of testicular cancer survivors have low testosterone, and that can affect other aspects of their health. Based on this study and others, clinicians should ask testis cancer survivors whether they have symptoms of low testosterone and should watch for signs of associated health problems.”

In the other study, a team led by Aleksander Giwercman, MD, of Lund University, Malmö, Sweden, studied 92 TCS (mean age 31 years at diagnosis) with a mean 9.2 years of follow-up and 92 age-matched controls. The researchers analyzed blood samples for lipids, total testosterone, luteinizing hormone (LH), glucose,

Metabolic syndrome was more common among hypogonadal than eugonadal TCS. Metabolic syndrome (MetS) was present in 15.2% of the TCS group—36% among those with hypogonadism— and 9.8% of controls. Hypogonadal TCS had 4.4 times higher odds of MetS compared with controls and 15 times higher odds of MetS compared with

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Contents

J U LY / A U G U S T 2 0 1 7 ■ V O L U M E 1 6 , I S S U E N U M B E R 4

Urology 12

ONLINE

16

this month at renalandurologynews.com 24

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

25

HIPAA Compliance The latest column discusses ways to train staff members so they have a firm grasp of regulations.

Drug Information

9

14

Job Board

18

News Coverage Visit our website for daily reports on the latest medical developments.

Focal Therapy for Prostate Cancer: An Update In this Ask the Experts feature, 3 surgeons give their perspective on the challenges and potential benefits of high-intensity focused ultrasound, cryotherapy, and other modalities.

RP for High-Risk PCa Rises Sharply The proportion of men with high-risk localized prostate cancer undergoing radical prostatectomy increased from 26% to 42% from 2004 to 2013.

ED May Predict Parkinson’s Disease A study of men in Taiwan found that erectile dysfunction is associated with a 52% higher risk of Parkinson’s disease in adjusted analyses.

International Continence Society Annual Meeting Florence, Italy September 12–15 American Society for Radiation Oncology Annual Meeting San Diego September 24–27 American Society of Nephrology Kidney Week 2017 New Orleans October 31–November 5 Genitourinary Cancers Symposium San Francisco February 8–10, 2018

26

Nephrology

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

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

Symptomatic MIBC Recurrence Worse Symptom-detected recurrence after radical cystectomy is associated with a higher death risk than surveillance-detected recurrence.

CALENDAR

22

Anemia Ups CVD Rates in NDD-CKD Patients In a study, the risks of coronary artery disease and peripheral artery disease were 41% and 80% higher, respectively, among anemic versus non-anemic patients.

Optimal Iron Status in HD Reported Serum ferritin levels below 90 ng/mL and TSAT of 20% or higher achieved the best hemoglobin results, according to researchers in Japan.

Intensive BP Lowering Benefits CKD Patients Patients with chronic kidney disease treated to a target systolic blood pressure of less than 120 mm Hg were 28% less likely to die.

Study Supports Sevelamer Use Hemodialysis patients who switch from a calcium-based phosphate binder to sevelamer may experience a survival benefit.

Departments 6

From the Medical Director New AUA guidelines for managing renal masses promise better care.

10

News in Brief Radiation therapy may prolong abiraterone treatment

26

Practice Management Advice for negotiating better contracts with insurers

CORRECTION

Men with Gleason 3 + 4 = 7 prostate cancer otherwise

eligible for curative intervention should be fully informed as to the avoidable risk associated with use of active surveillance.

See our story on page 9

An article on page 11 in the May/ June 2017 issue (Cholesterol Linked to High-Grade PCa) incorrectly stated that each 1 mg/dL increase in total cholesterol was associated with 23% greater odds of high-grade PCa. The correct unit of cholesterol is 10 mg/dL.

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Active Surveillance May Be Wrong Strategy for Intermediate-Risk PCa New study finds no favorable subset of patients likely to benefit

BY NATASHA PERSAUD ACTIVE SURVEILLANCE may not be an appropriate strategy for patients with intermediate-risk prostate cancer (PCa), according to researchers.

In a retrospective cohort study of men who underwent radical prostatectomy (RP), the rate of adverse findings was 24.7% among patients with low-volume intermediate-risk (LVIR)

Rate of adverse pathologic findings is higher versus low-risk patients. disease compared with 5.8% and 4.7% for those with low-risk (LR) and verylow-risk (VLR) disease, respectively, Hiten D. Patel, MD, MPH, and colleagues at Johns Hopkins University School of Medicine in Baltimore reported in JAMA Oncology. Men with LVIR had a 4.5-fold greater risk of adverse pathologic findings compared with men who had LR disease

and ­5.1-fold greater risk compared with those who had VLR disease.

The study included 1264 men with clinically localized VLR, 4849 with LR cancer, and 608 with LVIR as defined

by National Comprehensive Cancer Center (NCCN) criteria: Gleason pattern 3 + 4, T2a–b, 1–2 positive cores, and PSA below 20 ng/mL. Of the 150 LVIR patients with adverse pathologic findings at RP, 141 (94%) were upgraded to at least Gleason 4 + 3 PCa or grade group (GG) 3. Just a few had the other prespecified features: seminal vesicle invasion or positive lymph nodes. Age, race, family history of PCa, and cancer volume did not appear to play a role in outcomes.

Among 508 men with LVIR men (83.6%) who met all LR criteria other than biopsy grade, 108 (21.3%) were found to harbor adverse pathologic findings. Of the 271 men with LVIR (44.6%) who met all VLR criteria beside biopsy grade, 50 (18.5%) demonstrated adverse surgical pathologic findings, the researchers reported.

According to current NCCN guidelines, some LVIR patients may consider AS, but the practice is controversial.

“Our observations suggest use of AS may place similar men with Gleason 3 + 4 = 7 (GG2) cancer at risk of adverse outcomes that could have potentially been avoided with immediate intervention,” Dr. Patel and colleagues wrote. “This study could have important implications for men with LVIR prostate cancer electing AS, and further study is clearly needed.”

The researchers attempted additional risk stratification of the LVIR group using preoperative clinical and pathologic criteria, but none defined a favorable subgroup with rates of adverse pathologic findings as low as those of VLR and LR patients. On multivariate analysis, PSA density predicted adverse pathologic findings, but Gleason score had the greatest impact.

“Men with Gleason 3 + 4 = 7 prostate cancer otherwise eligible for curative intervention should be fully informed as to the avoidable risk associated with use of active surveillance,” they wrote.

Study limitations included lack of magnetic resonance imaging and molecular and/or genetic test results, which prevented additional risk stratification. ■

Anemia Ups CVD Rates in NDD-CKD Patients

Renal & Urology News 9

Vasectomy Poses Minimal Risk of PCa

BY NATASHA PERSAUD VASECTOMIES are associated with minimal risk of prostate cancer, according to a new systematic review and meta-analysis.

“We have demonstrated that any risk, if present, is sufficiently small that it is unlikely to be of clinical importance,” a team led by R. Jeffrey Barnes, MD, of Mayo Clinic in Rochester, Minnesota, reported online in JAMA Internal Medicine. “We believe that this meta-analysis, drawing on 3 decades of epidemiologic literature, provides sufficiently robust data to inform clinical care and supports the current guidelines of the American Urological Association.”

The review and meta-analysis included 53 studies (16 cohort study involving 2,563,519 men, 33 casecontrol studies involving 44,536 men, and 4 cross-sectional studies involving 12,098,221 men). The researchers found no significant association between vascectomy and high-grade (Gleason score 8 or higher), advanced (typically T3–4, positive nodes, or metastasis), or fatal PCa. When the researchers analyzed data from 7 cohort studies and

In a study, 61.4% of patients with stage 3 to 4 chronic kidney disease had anemia.

Results published in Advances in Therapy showed that anemic patients had a significantly higher mean number of cardiovascular comorbidities than those without anemia (1.27 vs 0.95).

Anemic patients were 41% and 80% more likely than patients without anemia to have coronary heart disease and peripheral arterial disease, respectively, the researchers reported.

Patients were classified as anemic if they had a physician-­confirmed diagnosis of anemia, were prescribed treatment for anemia, or had a hemoglobin level less than 12 or 13 g/dL (in women and men, respectively), according to the 2012 Kidney Disease: Improving Global Outcomes clinical practice guideline for the evaluation and management of CKD. Hypertension was the underlying cause of CKD in 56.3% of the total population, and it was an underlying cause of CKD in a significantly greater proportion of anemic patients compared with non-anemic patients (59.4% vs. 51.4%).

Compared with non-anemic patients, the anemia group was significantly older (mean 66.5 vs. 62.5 years).

Based on questionnaire responses from 867 patients, the study found that cardiovascular conditions were significantly associated with activity impairment, lower QoL, and worse effects of kidney disease in anemic patients, but not in non-anemic patients. ■

6 case-control studies that were deemed to have a low risk of bias based on the Newcastle-Ottawa Scale, they found a weak but significant 5% increased risk of PCa in the cohort studies and a similar but a nonsignificant 6% greater odds of PCa in the 6 case-control studies.

The investigators calculated that the absolute increase in lifetime risk of PCa associated with vasectomy was just 0.6% and that vasectomy would be responsible for only 0.5% of PCa cases in the population.

“At most, there is a trivial association between vasectomy and prostate cancer that is unlikely to be causal; therefore, concerns about prostate cancer should not preclude the use of vasectomy as an option for long-term contraception,” Dr. Barnes and colleagues concluded. ■

© KATERYNA KON/SCIENCE PHOTO LIBRARY / GETTY IMAGES

BY NATASHA PERSAUD ANEMIA IN patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) is associated with cardiovascular disease (CVD) and diminished quality of life, according to a new study of real-world practice in Europe.

Adrian Covic, MD, PhD, of Grigore T. Popa University of Medicine and Pharmacy in Romania, and colleagues reviewed data from 1993 patients with stage 3–4 CKD treated by 216 nephrologists and 26 endocrinologists from the Adelphi CKD Disease-Specific Programme in France, Germany, Italy, Spain, and the United Kingdom. Of these, 1223 (61.4%) had anemia, and 698 (35%) were prescribed treatment for anemia. Anemia prevalence increased with CKD stage, Dr. Covic’s group reported.

The investigators evaluated quality of life (QoL) using the EuroQol EQ-5D-3L, Kidney Disease Quality of Life, and Work Productivity and Activity Impairment questionnaires.

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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 RT May Prolong Abiraterone Treatment in mCRPC Patients

Taiwan, analyzed serum levels of

Radiation therapy (RT) may prolong

with various stages of chronic kidney

abiraterone treatment among men

disease. A tryptophan level below

with metastatic castration-resistant

44.20 µM was the strongest predictor

prostate cancer (mCRPC) who

of a rapid decline in estimated glo-

experience disease progression while

merular filtration rate (sustained ­annual

on the drug, according to findings

decrease of 5% or more), with a 55.6%

published in Anticancer Research

sensitivity and 87% specificity.

175 metabolites in 52 diabetic patients

2017;37:3717-3722).

Florence, Italy, and colleagues studied

FDA Approves Betrixaban For VTE Prophylaxis

32 mCRPC patients who had received

The FDA has approved betrixaban

RT after abiraterone initiation. The

(Bevyxxa, Portola) for venous throm-

median duration of abiraterone treat-

boembolism (VTE) prophylaxis in adult

ment was 5.9 months prior to RT and

patients hospitalized for an acute

7.2 months after RT, the researchers

medical illness who are at risk for

reported. The median progression-

thromboembolic complications due to

free survival was 12.6 months from

moderate or severe restricted mobility

the start of abiraterone treatment and

and other VTE risk factors.

Beatrice Detti, MD, of AOU Careggi,

9.6 months from RT administration.

In a randomized, double-blind trial comparing extended-duration

Tryptophan Is Prognostic In Diabetic Nephropathy

­betrixaban (35 to 42 days) to a short

Lower tryptophan levels may have

in acutely medically ill hospitalized

potential as a prognostic marker for

patients with VTE risk factors, fewer

diabetic nephropathy, researchers

VTE events were observed in the

in reported online in the Journal of

betrixaban than enoxaparin arm (4.4%

­Diabetes Investigation.

vs. 6%). Betrixaban recipients had a

duration of enoxaparin (6 to 14 days)

Chien-An Chou, MD, and colleagues

25% relative risk reduction compared with the enoxaparin arm.

at Chang Gung University in Taoyuan,

HD Patient Readmission Rates Hemodialysis patients readmitted to a hospital within 30 days of discharge have a 2-fold higher risk of death in the following year versus those with no readmissions, according to a study.

Readmission rates vary depending on the number of days since hospital discharge, as shown here.

0–7 days: 35.9% 8–14 days: 23.9% 15–30 days: 40.2% 0

10

20

30

40

Source: Plantinga LC, et al. Early hospital readmission among hemodialysis patients in the United States is associated with subsequent mortality. Kidney Int. 2017; published online ahead of print.

Smoking Intensity Predicts Bladder CA Patient Death G

reater smoking intensity is associated with an increased risk of death among patients with bladder cancer, according to study findings presented at the American Urological Association 2017 annual meeting in Boston.

In a study of 14,077 adult bladder cancer patients who smoked, a team led by Mark L. Gonzalgo, MD, of the University of Miami Miller School of Medicine, found that, for the entire cohort, the median overall survival (OS) time was 4 years and the 5-year OS rate was 43.7%.

The median overall survival time for patients smoking less than 1, 1–2, and more than 2 packs of cigarettes per day (PPD) was 4.2 years, 3.9 years, and 4.1 years, respectively. The 5-year survival rates among patients smoking less than 1, 1–2, and more than 2 PPD were 45.1%, 43.1%, and 43.6%, respectively. On multivariate analysis, patients smoking 1–2 PPD and more than 2 PPD had a significantly higher risk of death compared with those smoking less than 1 PPD.

Most HD Patient Bloodstream Infections Due to Catheters M

ost bloodstream infections (BSIs) in hemodialysis (HD) are attributable to catheter use, according to a new study finding published online ahead of print in the Clinical Journal of the American Society of Nephrology (CJASN).

Duc Bui Nguyen, MD, of the Centers for Disease Control and Prevention in Atlanta, and colleagues analyzed data from 160,971 dialysis events reported by 6005 U.S. outpatient HD facilities. These included 29,516 BSIs, 149,722 intravenous antimicrobial starts, and 38,310 episodes of pus, redness, or increased swelling at the HD access site. The investigators found that 77% of BSIs were related to catheter access. Sixty-three percent of BSIs and 70% of access-related BSIs occurred in patients with central venous catheters.

“Our findings emphasize the need for hemodialysis facilities to improve infection prevention and vascular access care practices,” Dr. Nguyen said in a news release from the American Society of Nephrology, which publishes CJASN.

Positive LN Prostate Cancer Care Patterns Characterized M

ost prostate cancer patients found to have lymph node (LN) metastases at the time of radical prostatectomy (RP) are initially managed with observation, researchers reported online ahead of print in the Journal of Urology.

Using the National Cancer Data Base, Piotr Zareba, MD, MPH, and colleagues at Memorial Sloan Kettering Cancer Center in New York identified 7791 men who had LN metastases at the time of RP. Of these, 63% were managed initially with observation, 20% with androgen-deprivation therapy (ADT) alone, 5% with radiotherapy (RT) alone, and 13% with ADT and RT. Younger age, lower comorbidity burden, and adverse pathologic features were associated with an increased likelihood of receiving combination treatment with ADT and RT. The combination treatment was associated with a significant 31% lower risk of death compared with observation.

www.renalandurologynews.com

JULY/AUGUST 2017

Renal & Urology News 11

CKD Linked to Red, Processed Meat Substituting nuts, legumes, or low-fat dairy foods would reduce the risk, according to a study Benefits of Food Substitution According to a study, replacing 1 serving of red and processed meat with 1 serving of another food source of dietary protein would reduce the risk of chronic kidney disease as follows: 40

PERCENTAGE

HIGHER LEVELS of red and processed meat intake are associated with an elevated risk of chronic kidney disease (CKD), whereas higher levels of intake of low-fat dairy products, nuts, and legumes are associated with a lower risk, according to a new study.

The finding is from a study of 11,952 adults who participated in the Atherosclerosis Risk in Communities study. Individuals were aged 44–66 years at their baseline examination in 1987– 1989. They had filled out a 66-item food frequency questionnaire (FFQ). The primary outcome was development of CKD stage 3, defined as a decrease in estimated glomerular filtration rate (eGFR) of 25% or greater from baseline, resulting in an eGFR of less than 60 mL/min/1.73 m2.

During a median follow-up of 23 years, CKD stage 3 developed in 2632 individuals. Those in the highest quintiles of red meat and processed meat consumption had a significant 23% higher risk of CKD than those in the lowest quintile in adjusted analyses, Bernhard Haring, MD, MPH, of the University of Würzburg in Würzburg, Germany, and colleagues reported online ahead of print in the Journal of Renal Nutrition (2017;27:233-242). Individuals in the highest quintiles of intake of nuts, legumes, and low-fat dairy products had

31%

30 20

18%

20%

10 0

Nuts

Legumes

Low-fat dairy foods

Source: Haring B, Selvin E, Liang M, et al. Dietary protein sources and risk for incident chronic kidney disease: Results from the Atherosclerosis Risk in Communities (ARIC) study. J Ren Nutr. (2017;27:233-242).

a significant 19%, 17%, and 25% lower risk of CKD, respectively, compared with those in the lowest quintiles.

In addition, the researchers reported that replacing 1 serving of red and processed meat with 1 serving of nuts, legumes, or low-fat dairy foods, would reduce the risk of CKD by a significant 18%, 20%, and 31%, respectively.

Substituting fish and seafood for red and processed meat did not significantly reduce CKD risk.

“These results emphasize the potential role of dietary protein sources rather than total protein intake for developing kidney disease,” Dr. Haring and his colleagues concluded.

Study strengths include the use a large

diverse, community-based prospective cohort with long follow-up and structured assessment of dietary intake and covariates, researchers noted. The study had limitations, however. For example, intake of any particular food “occurs within a complex pattern of food consumption and lifestyle. Therefore, residual and unmeasured confounding may explain part of the results, although our analyses adjusted for many potentially confounding factors.” In addition, changing dietary habits and food supply over time may not have been captured adequately by the researchers’ FFQs. In an editorial accompanying the new report, Jaimon T. Kelly, RD, of Bond University in Bond, Australia, and Juan

Jesus Carrero, PhD, of the Karolinska Institutet in Stockholm, Sweden, commented that “the exciting article” by Dr. Haring and colleagues “suggests that we should consider the differences between protein sources in retarding CKD progression. Because plant protein is not consumed in isolation, the way of implementing these observations into clinical practice is by targeting changes in the overall pattern of eating.”

The new findings complement a study published recently in the Journal of the American Society of Nephrology (2017;28:304-312) showing that red meat intake may increase the risk of end-stage renal disease (ESRD) in the general population. Researchers analyzed data from the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese adults in Singapore.

A total of 951 ESRD cases developed during a mean follow-up of 15.5 years.

Individuals in the highest quartile of red meat intake (median 48.8 g/day) had a significant 40% increased risk of ESRD compared with those in the lowest quartile (median 12.5 g/day). The investigators reported that replacing 1 serving of red meat with 1 serving of poultry, fish, eggs, or soy and legumes would result in a 62.4%, 48.6%, 44.9%, and 50.4% reduction in the relative risk of ESRD, respectively. ■

PROSTATE CANCER (PCa) patients on active surveillance (AS) who have no cancer found on a confirmatory biopsy may be considered a less rigorous AS regimen, according to investigators.

In a study of 224 PCa patients managed with AS, investigators at Cleveland Clinic led by Ryan Berglund, MD, found that absence of cancer on a confirmatory biopsy is associated with a significant 49% decreased odds of grade reclassification and 68% decreased odds of volume reclassification compared with those who had a positive confirmatory biopsy.

“Overall, our findings suggest that very low volume disease, reflected by a negative confirmatory biopsy, may be a strong prognostic indicator for slower grade and volume reclassification, independent of age, PSA density, and stage,” Dr. Berglund’s group wrote in a paper published online ahead of print

in Urology. “It is possible that very low volume of disease may exhibit a more indolent natural history.”

The investigators concluded that a less intense surveillance regimen may be considered for men with a negative confirmatory biopsy.

Of the 224 patients, 111 (49.6%) had a negative confirmatory biopsy and 113 had a positive biopsy. Both groups had a median age of 65 years and similar racial composition. The median followup was 55.8 months.

The typical AS regimen at Cleveland Clinic consists of clinic visits every 6–12 months with PSA measurements and digital rectal examinations, a confirmatory biopsy within 12 months of the initial diagnostic biopsy, and routine surveillance biopsies, the researchers stated.

Dr. Berglund and his colleagues said their results are comparable to those of

previous studies. For example, a singleinstitution retrospective study of 286 AS patients by Lih-Ming Wong, MD, and colleagues showed that men with no cancer found on a second biopsy had a 53% reduction in overall risk of reclassification, according to a report in European Urology (2014;66:406-413).

Study reveals a reduced likelihood of grade and volume reclassification.

A subset analysis revealed a 64% decreased risk of volume-related reclassification, but, contrary to the findings of the new study, no significant association with risk of grade reclassification.

Dr. Berglund’s team also cited a study

by K. Clint Cary, MD, and colleagues, which found that among 242 men with 3 or more biopsies, a negative confirmatory biopsy was associated with 72% lower odds of overall reclassification.

That study, which was published in European Urology (2014;66:337-342), did not differentiate between grade- and volume-related reclassification.

Dr. Berglund and his colleagues acknowledged some limitations of their study. The study was observational and, as such, subject to selection bias “and imbalance in unquantified variables.” In addition, the limited median follow-up time of 55.8 month may not fully capture the natural history of slow-progressing PCa. Third, it remains to be determined how the endpoints of grade and volume reclassification ultimately will reflect overall or cancer-specific survival. ■

IMAGES: © SHUTTERSTOCK

Negative Confirmatory PCa Biopsy is a Good Sign

12 Renal & Urology News

JULY/AUGUST 2017 www.renalandurologynews.com

Symptomatic MIBC Recurrence Worse Risk of death from time of radical cystectomy is 74% higher compared with asymptomatic recurrence

PUL Benefits Durable Out To 5 Years PROSTATIC URETHRAL lift (PUL) in men with bothersome lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia offers rapid improvement in symptoms and other outcomes out to 5 years, data show.

The finding is from a prospective, randomized, blinded trial comparing PUL with a sham control procedure.

PUL involves permanent placement of UroLift implants that hold open the lateral lobes of the prostate to decrease urinary obstruction. The trial included 206 men aged 50 years or older with benign prostatic hyperplasia (BPH) and an International Prostate Symptom Score (IPSS) greater than 12, a peak flow rate (Qmax) of 12 mL/sec or less, and a prostate volume of 30–80 cc.

IPSS improvement following PUL was 88% greater than that of the sham procedure at 3 months. LUTS and quality of life (QOL) were significantly improved by 2 weeks, with return to preoperative physical activity within 8.6 days, Claus G. Roehrborn, MD, of the University

How Post-RC Recurrence Is Detected Predicts Survival After radical cystectomy (RC) for muscle-invasive bladder cancer, median overall survival times, in months, are longer in patients with recurrence detected by routine surveillance rather than symptoms, as shown below.

25

24.8

n Asymptomatic recurrence n Symptomatic recurrence

20

Months

BY NATASHA PERSAUD CHICAGO—Among muscle-invasive bladder cancer (MIBC) patients, those with symptom-detected recurrence after radical cystectomy (RC) have a higher mortality risk than those with surveillance-detected recurrence, according to research presented at the recent American Society of Clinical Oncology 2017 annual meeting.

In a study of 463 RC patients who had recurrent disease—71 detected by routine surveillance and 107 identified by symptoms—Chelsea Osterman, MD, of the University of Pennsylvania in Philadelphia, and colleagues found that the symptomatic recurrence group had a 74% increased risk of death from the time of surgery and nearly 2-fold increased risk of death from the time of recurrence. The investigators adjusted for disease characteristics, including pathologic tumor stage, positive lymph nodes, lymphovascular invasion, positive surgical margins, and cancer recur-

15.6

15

13.7

10

5.2

5 0

After RC

From time of recurrence

Source: Osterman C, Alanzi J, Lewis J, et al. Association between symptomatic versus asymptomatic recurrence and survival in bladder cancer. Data presented at the American Society of Clinical Oncology 2017 annual meeting in Chicago.

J Clin Oncol. 35, 2017 (suppl; abstr e16021).

rence site, as well as age at RC, obesity, and race.

Patients with asymptomatic recurrence detected during routine surveillance experienced better median overall survival (OS) after RC (24.8 vs. 15.6 months) and from time of recurrence (13.7 vs.

of Texas Southwestern Medical Center in Dallas, and colleagues reported in the Canadian Journal of Urology (2017;24:8802-8813). Improvement in IPSS, QOL, Qmax, and BPH Impact Index Qmax sustainable through 5 years, with improvements of 36%, 50%, 44%, and 52%, respectively.

“As it is rare that any prospective study in BPH extends beyond 5 years, we believe this report demonstrates that PUL has reached maturity as a standard of care for BPH,” the investigators stated.

Over the 5 years, 19 (13.6%) of the 140 PUL patients needed surgical retreatment because of failure to cure.

Sexual function was stable over 5 years with no de novo, sustained erectile or ejaculatory dysfunction.

PUL has been demonstrated to be tolerable under local anesthesia in the office setting and to offer rapid recovery and relief typically without the need for postoperative catheters, according to the researchers. The procedure also has been shown to provide improvements in symptoms, urinary flow, and QOL through 5 years and to uniquely preserve both ejaculatory and erectile function, Dr. Roehrborn and colleagues stated. “Because of these characteristics for many men suffering from BPH, PUL may be a preferred treatment choice,” they concluded. n

5.2 months). The 5-year OS rate after RC was 14.1% in the asymptomatic group versus 10.3% in the symptomatic group. The 1-year OS rate from the time of recurrence was 55.7% in the asymptomatic group compared with 29.4% in the symptomatic group.

Previous studies may have overestimated survival due to earlier disease detection. “Symptomatic patients were diagnosed with recurrence a median of 1.7 months prior to asymptomatic patients in the present study, yet their median survival from recurrence was 8.2 months less,” Dr. Osterman told Renal & Urology News.

The median time to recurrence was 9.7 vs 11.5 months for symptomatic and asymptomatic recurrence patients, respectively – a difference of 52 days.

“The earlier time to recurrence of the symptomatic tumors implies a more aggressive biology,” Dr. Osterman explained. “It is not possible to know whether the longer survival of asymptomatic recurrence patients after detection is related to the underlying tumor biology or to early intervention.”

The investigators speculated that fast growing tumors may have a shorter asymptomatic period during which recurrence can be detected. n

Knowledge of PCa Genetic Test Results Often Lacking CHICAGO—Understanding of personal

Factors significantly associated with

genetic test results is lacking in some

higher pre-GT KCRG included meeting

men who undergo multigene testing

HCS criteria and higher numeracy. On

for inherited prostate cancer (PCa),

multivariable analysis, family history of

according to study findings presented

meeting criteria for an HCS remained

at the American Society of Clinical

significantly predictive of higher KCRG.

Oncology Annual Meeting.

Of 101 men who responded definitively

The findings are from a study of

regarding understanding of personal

109 men who completed surveys before

GT results, 13 responded incorrectly on

and after they underwent genetic test-

mutation status. Twelve of these men

ing (GT). The pre-GT survey included

had 1 or more variants of uncertain

15 items that assessed knowledge of

significance (VUS), but reported that

cancer risk and genetics (KCRG) and 6

their test results showed a mutation.

items that assess health literacy and

That a subgroup of men did not

numeracy. The post-GT survey included

understand their test results is con-

9 items that assessed understanding GT

cerning, Dr. Giri said, because these

results. The investigators, led by Veda

men might pass misinformation to their

N. Giri, MD, an associate professor in

providers and family members. Though

the Department of Medical Oncology

many of these VUS are not in known

and Director of Cancer Risk Assessment

PCa genes, they are in genes that have

and Clinical Cancer Genetics at Thomas

other cancer risks that could be acted

Jefferson University in Philadelphia, also

upon inappropriately, leading to unwar-

categorized personal and family history

ranted screening and risk reduction

into 3 hereditary cancer syndromes

interventions if men incorrectly think

(HCS) linked to PCa.

they have a mutation. n

www.renalandurologynews.com JULY/AUGUST 2017

Renal & Urology News 13

Study: Proteomics Promising as CKD Predictor MULTIPLEX PROTEOMICS may offer promise as a way to discover novel aspects of kidney disease pathology, according to researchers.

In a study, this technique enabled Axel C. Carlsson, PhD, of the Karolinska Institutet in Stockholm, Sweden, and colleagues to identify circulating proteins associated with declining renal function. These proteins are involved in phosphate homeostasis, angiogenesis, extracellular matrix remodeling, endothelial dysfunction, and apoptosis.

The investigators assessed proteomic profiling of 80 proteins using a multiplex assay in a study involving participants in 2 studies: the Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS, 687 patients, mean age 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM, 360 men, mean age

Swedish study links 20 plasma proteins to annual eGFR decline.

78 years). The researchers used the PIVUS study as the discovery cohort and the ULSAM study for replication.

The investigators had 5-year follow-up data on estimated glomerular filtration rate (eGFR). The multiplex assay was designed primarily for assessing plasma proteins involved in cardiovascular disease (CVD) and inflammation.

In the discovery cohort, 28 plasma proteins were significantly associated with eGFR decline per year, Dr. Carlsson and his colleagues reported online ahead of print in the Clinical Journal of the American Society of Nephrology. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort after adjusting for age, sex, cardiovascular risk factors, medications, and urinary albumin-tocreatinine ratio.

Among the subset of patients free of chronic kidney disease (CKD) at baseline, CKD developed during follow-up in 231 of 660 participants in the PIVUS study and 206 of 319 patients in the ULSAM study. Eleven of the 20 proteins consistently predicted incident CKD in subgroup analyses in those with an eGFR above

60 mL/min/1.73 m2 at baseline in both cohorts.

“The vast number of proteins independently associated with decline in kidney function show CKD to be a multifactorial and highly complex disease, involving an impaired phosphate homeostasis, inflammation, apoptosis,

increased extracellular matrix remodeling, a disturbed angiogenesis, and endothelial dysfunction,” the authors concluded. “The strongest association was found for TRAIL-R2 [TNF-related apoptosis-inducing ligand receptor 2], a protein that has not been associated with eGFR decline previously.”

Impaired phosphate homeostasis “appeared to be a particularly important common pathway for the proteins associated with kidney function decline because half of the proteins were involved in this pathway, according to the functional analysis of our findings,” Dr. Carlsson’s group wrote. n

14 Renal & Urology News

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Optimal Iron Status in HD Reported Serum ferritin below 90 ng/mL and TSAT of 20% or higher achieved the best hemoglobin results

BY JODY A. CHARNOW RESEARCHERS HAVE identified what they conclude is the optimal iron status for hemodialysis (HD) patients receiving erythropoietin treatment, according to study findings presented at the European Renal AssociationEuropean Dialysis and Transplant Association 54th Congress in Madrid and published online in PLoS One. Chie Ogawa, MD, PhD, of the Maeda Institute of Renal Research in Kawasaki, Japan, and colleagues studied 208 outpatients on maintenance HD. Patients had the following means: age 58.9 years, dialysis duration 7.88 years, albumin 3.9 g/dL, and C-reactive protein (CRP) 0.06 mg/dL. The investigators measured hemoglobin levels twice monthly and serum ferritin and transferrin saturation (TSAT) monthly. They measured hepcidin, a key regulator of iron homeostasis, at baseline. The targeted hemoglobin level was 10–11 g/dL, based on Japanese guidelines. Anemia treatment consisted of erythropoietin plus low-dose iron.

Attained hemoglobin was 10.3 g/dL on a mean erythropoietin dose of 3909 IU/ week, with mean iron indices of ferritin 50.6 ng/mL, TSAT 24.7%, and total ironbinding capacity (TIBC) 243 mg/dL. Using achievement of a hemoglobin level greater than 10 g/dL as the outcome endpoint, a logistic model analysis showed that a serum ferritin level below 90 ng/mL and TSAT of 20% or higher was associated with the greatest proportion of patients achieving the study endpoint (94.4%). The area under the curve (AUC) was 0.7 for ferritin and 0.56 for TSAT. Patients with a ferritin level below 90 ng/mL had a significant 8-fold increased odds of achieving the study endpoint compared with patients who had a ferritin level of 90 ng/mL or higher.

Patients with a TSAT of 20% or higher had a significant 5.5-fold greater odds of achieving the study endpoint compared with those who had a TSAT below 20%.

Combinations compared Patients who had a combination of a serum ferritin level of 90 ng/mL or

Upcoming News

higher and TSAT less than 20% had the lowest endpoint achievement rate (26.7%) and served as the reference group. Compared with patients in the reference group, those with a serum ferritin level below 90 ng/mL and TSAT of 20% or higher had a significant 46.7-fold greater odds of achieving the endpoint. By comparison, the odds of achieving the study endpoint were increased 10-fold among patients with a ferritin level less than 90 ng/mL and TSAT less than 20% and 6.7-fold among those with a ferritin level of 90 ng/mL or higher and TSAT of 20% or higher, the investigators reported.

A linear regression model showed a positive relationship between hepcidin and serum ferritin and no relationship between hepcidin and TSAT. From their results, Dr. Ogawa and colleagues concluded that the threshold values for optimal iron status may be lower than those currently recommended in iron-level management guidelines. For example, the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guidelines recommend a TSAT above 20% and ferritin levels above 100 ng/mL in non-dialysis and above 200 ng/mL in dialysisdependent patients.

Reference value questioned Commenting on the new study, Anatole Besarab, MD, an adjunct lecturer at Stanford University in Palo Alto, California, who has published extensively on the management of anemia in patients with kidney disease, said he is unclear why the investigators chose the combination of a ferritin value of 90 ng/ mL or higher and TSAT less than 20% as reference for examining odds ratios of other ferritin/TSAT combinations, given that only 15 of the 208 patients had these values, with only a quarter achieving the desired hemoglobin outcome. He said he wonders how much the interpretation would have changed if the ferritin and TSAT values maximizing hemoglobin response were used as the reference.

Hemoglobin Target Attainment By Ferritin/TSAT Combinations In a Japanese study, the proportion of hemodialysis patients who achieved a hemoglobin level of 10 g/dL or higher—the study endpoint—varied according to their combination of serum ferritin and transferrin saturation (TSAT) values, as shown below. A serum ferritin value below 90 ng/mL and TSAT of 20% or higher resulted in the greatest proportion of patients achieving the study endpoint.

100

70.8%

80

78.9%

94.4%

60 40

26.7%

20 0

≥90 + <20

≥90 + ≥20

<90 + <20

<90 + ≥20

Ferritin (ng/mL)/TSAT (%) Source: Ogawa C et al. Low levels of serum ferritin and moderate transferrin saturation lead to adequate hemoglobin levels in hemodialysis patients, retrospective observational study. PLoS One. 12(6): e0179608.

In addition, Dr. Besarab pointed out that the AUC of 0.7 for ferritin found in the study is only a fair to good predictor of iron stores, as AUCs greater than 0.8 and 0.9 are needed to have a very good test and an excellent test, respectively. The AUC of 0.56 for TSAT, which was not a statistically significant predictor of the study endpoint, offers not much better than 50-50 odds that sufficient iron is available to avoid iron deficiency, he said. “This confirms that TSAT is a very poor marker of adequate iron for erythropoiesis unless the value exceeds 50%,” Dr. Besarab told Renal & Urology News. He said he believes the poor correlation between TSAT and iron availability for erythropoiesis results from a reduction in transferrin levels — and, therefore, TIBC — as transferrin is a negative acute phase reactant and underlying inflammation is common in kidney disease patients.

TIBC is the denominator of the TSAT calculation, he explained, so it is possible to have TSAT values above 20% and still have very limited iron carrying capacity in the blood.

Relatively long dialysis vintage He also pointed out that the mean hemoglobin level for the cohort was 10.3 g/dL at baseline, which is lower than the midpoint between the target

range of 10 to 11 g/dL, but quite close to that currently being achieved in the United States and other Western countries where the goal is a hemoglobin level between 10 and 11.5–12 g/dL depending on patient circumstances.

Of special note, he said, was the finding that the study cohort’s dialysis vintage was 7.88 years (and no patients who had a vintage less than 3.7 years), which is significantly greater than typically found in Western countries. In addition, the mean serum albumin level was higher (3.9 g/dL) while the mean CRP concentration (0.06 mg/dL) and the mean dose of erythropoietin (3909 IU/ week) was lower than in typical US or Western Europe dialysis units.

“These parameters point to virtual absence of significant inflammation in the studied population, with the likelihood of a very low prevalence of hyporesponsive patients,” Dr. Besarab said. “Thus the results from this study of ‘optimal iron indices’ cannot be directly extrapolated to other geographic areas where inflammation is a major issue and the mean CRP approaches 0.8–1.0 mg/dL.” The positive relationship between hepcidin and serum ferritin levels has been described by other researchers who have also concluded that, overall, hepcidin is not a better indicator of iron stores than ferritin. ■

Renal & Urology News will be providing onsite coverage of Kidney Week 2017 in New Orleans, October 31– November 5.

Go to www.renalandurologynews.com for daily reports on noteworthy studies.

www.renalandurologynews.com JULY/AUGUST 2017

Renal & Urology News 15

Targeted-Release Budesonide Improves IgAN A NOVEL targeted-release formulation of the corticosteroid budesonide (TRF-budesonide) could become the first tailored treatment for immunoglobulin A nephropathy (IgAN).

The formation is designed to deliver the drug to the distal ileum, targeting mucosal immunity before disease appears.

Due to its lower absorption, the drug may result in fewer and less severe side effects than high-dose systemic corticosteroids.

Bengt Fellström, MD, of Uppsala University Hospital in Uppsala, Sweden, led the NEFIGAN Trial to compare optimized renin-angiotensin system (RAS) blockade plus TRF-budesonide with optimized RAS blockade alone.

Of 149 IgAN patients included in the study, 48 and 51 were randomly assigned to 16 mg and 8 mg TRF-budesonide, respectively, as an adjunct to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers titrated up to maximally recommended doses.

patients with IgA nephropathy with persistent proteinuria,” Dr. Fellström said in a news release.

Adverse events occurred in similar proportions of treated and untreated patients. The researchers suggested that 2 of 13 serious adverse events were possibly related to the drug: deep vein thrombosis

in a patient receiving 16 mg and unexpected renal function decline in a patient tapered from 16 mg to 8 mg over 2 weeks.

“In my opinion, this is the most important treatment trial conducted to date for IgA nephropathy,” Robert J. Wyatt, MD, of the University of Le Bonheur Children’s Hospital in S:7”

Memphis, Tennessee, commented in an accompanying editorial. “The results will potentially change treatment strategy for an important subset of patients with IgA nephropathy.”

The study was funded by Pharmalink AB, the makers of TRF-budesonide (Nefecon). n

Patients had a 24.4% reduction in mean UPCR over 9 months, researchers reported.

Another 50 patients were randomly assigned to receive placebo. Included patients had an estimated glomerular filtration rate (eGFR) of at least 45 mL/min/1.73 m2 and a urine protein/ creatinine ratio (UPCR) above 0.5 g/g or urinary total protein of at least 0.75 g/day, indicating persistent proteinuria.

Overall, at 9 months, TRF-budesonide treatment was associated with a significant 24.4% reduction from baseline in mean UPCR, the researchers reported in the Lancet. Mean UPCR decreased by 27.3% in the 48 patients who received 16 mg/day and 21.5% in the 51 patients who received 8 mg/day. The 50 patients who received placebo had a 2.7% increase in mean UPCR. Changes in 24-hour protein excretion, urine albumin-to-creatinine ratio, and 24-hour albumin excretion were in line with UPCR results. During the study period, eGFR remained stable with TRFbudesonide, but it fell 10% with placebo.

Such a reduction in proteinuria coupled with stabilization of eGFR in IgAN patients may reduce progression to endstage renal disease. “The observed beneficial effect was additive to optimized RAS blockade and supports the use of TRF-budesonide as adjunct therapy in

10715379_DSE_JA_TABLOID_M6.indd 1

7/10/17 12:24 PM

16 Renal & Urology News

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n ASK THE EXPERTS

Focal Therapy for Prostate Cancer: An Update Patients potentially can benefit from this approach, but important challenges remain

BY JODY A. CHARNOW

David Y.T. Chen, MD

For a status report on the use of focal therapy for prostate cancer, Renal & Urology News spoke with researchers who have experience using the modality, including David Y.T. Chen, MD, Associate Professor of Surgical Oncology and Director, Urologic Oncology Fellowship Program, at Fox Chase Cancer Center-Temple Health in Philadelphia; Jonathan A. Coleman, MD, of Memorial Sloan Kettering Cancer Center in New York; and Thomas J. Polascik, MD, Professor of Surgery and Director of the Urologic Oncology Fellowship Program at Duke University School of Medicine in Durham, North Carolina.

What are the major challenges regarding focal therapy for prostate cancer?

Jonathan A. Coleman, MD

Thomas J. Polascik, MD

Dr. Chen: The main rationale to not treating the whole prostate is minimizing the known and unavoidable adverse effects that radical treatment can cause. The greatest challenge for focal therapy is confirming the accurate localization of clinically significant tumors and determining whether any clinically significant cancer is being overlooked in the rest of the prostate. Another challenge is selection: determining who is a good candidate for focal therapy and deciding on whether treatment is even needed.

A fundamental problem is the absence of an easy and reliable way to assess who is responding appropriately to treatment.

When we treat the entire prostate, we expect a dramatic drop in PSA values.

If only a portion of the prostate is being treated, it is unclear how PSA will reflect the treatment effect. Magnetic resonance imaging (MRI) could be used to follow patients after focal therapy, but it is not known for certain whether changes on MRI are predictable and will be a

true measure of response to therapy.

Even if the MRI changes, the patient really needs to have a biopsy performed to prove that MRI changes match the treatment effect. At present, MRI and targeted biopsies still cannot reliably rule out the presence of clinically significant cancers elsewhere in the prostate.

Dr. Coleman: The key challenges regarding partial gland treatment for prostate cancer are the potential for undertreatment of disease, defining and verifying treatment success, and monitoring patients for new cancer occurrence or recurrence after treatment. This is a challenge for surgeons and for patient education in a situation where men’s expectations may often be unrealistic with regard to key outcomes.

it requires percutaneous needle insertion into the prostate. High-intensity focused ultrasound potentially has an advantage in being essentially noninvasive.

It focuses ultrasound energy into the prostate through the rectum without any needle punctures. Other technologies under investigation in clinical trials for use in focal therapy include laser-based ablation, brachytherapy, and photodynamic therapy.

What are the leading focal therapy modalities?

Dr. Coleman: We have done extensive preclinical research and clinical studies with several different tissue ablation technologies and have presented results demonstrating common tissue effects among many. Differences really fall in the area of application of these technologies, in terms of ease of use and reproducibility. Leading technologies may be broadly appealing because of physician comfort level, cost, and accessibility, but may not be the best for achieving the ideal outcomes sought in partial gland ablation. For example, cryotherapy has been widely used for decades. High-intensity focused ultrasound is being heavily marketed by commercial interests, but published results have suggested that clinical results have been modest. More recent data from a randomized trial using vascular targeted photodynamic therapy were highly encouraging, but this was used in a highly select group of patients with very low risk cancers.

Dr. Chen: The most common modalities in use today are cryotherapy and high-intensity focused ultrasound, both of which work by ablating tissue. Cryotherapy has been used the most for focal therapy because the technology has been around for a long time, and it is widely available.

Cryotherapy is somewhat invasive, in that

Dr. Polascik: High-intensity focused ultrasound and cryotherapy are the most commonly used focal therapy modalities.

These are the modalities with which surgeons have the most experience. They have the longest track record at this point.

With focal therapy, the continence rate is much more predictable and f­ avorable

Dr. Polascik: A major challenge in focal therapy is accurately determining the number of tumors and tumor location, size, volume, and aggressiveness, and mapping out those tumors in the 3-dimensional space within the prostate.

If you can ascertain these tumor characteristics with certainty, then treatment can be directed to the clinically significant tumors. This provides the basis for treatment. Another challenge is selecting the right patients for this type of therapy.

www.renalandurologynews.com JULY/AUGUST 2017

compared with prostatectomy. In my hands, it’s probably 99%. Surgery can’t beat that. Continence usually returns by 3 months. Potency also returns faster after focal therapy than with traditional whole-gland treatment options. Overall, based on hemiablation data, the potency recovery rate is 60% to 90%.

Have advancements in imaging modalities made focal therapy a reasonably safe option?

Dr. Chen: Most people would agree that the main advance in the last 5 years has been improvements in MRI that provide greater resolution and detail in prostate imaging. As a rough estimate, MRI probably identifies 70% of cases of prostate cancer that are clinically significant and may require treatment. Before MRI, prostate assessments have been based largely on biopsy results, which can miss cancerous tissue or provide inaccurate information about tumor burden or aggressiveness. The advent of MRIultrasound fusion has made it easier to perform targeted biopsies of suspicious areas of the prostate that are found by MRI. However, as much as MRI has improved identification of clinically significant cancer, it still has not been demonstrated that MRI is adequately sensitive to pick up all the areas of cancer that might need treatment.

Dr. Coleman: If we are talking about treatment-related patient safety, then yes. Imaging improvements have provided a better means to identify most clinically significant cancers and to target the main portions of these cancers more accurately, which is a major prerequisite for developing safe and successful techniques for tissue-sparing treatments in prostate cancer. In my opinion, further improvements are yet needed to sufficiently delineate the true extent of tumor morphology within the gland and in relation to adjacent sensitive structures (such as nerves) to improve efficacy and limit unwanted adverse effects.

Dr. Polascik: Yes. When I started performing focal cryoablation in 2006, we didn’t even routinely have multiparametric magnetic resonance imaging (MRI). I would not have predicted that we would be at this point now. Multiparametric MRI-ultrasound fusion and 3-dimensional transperineal mapping biopsy make it possible to localize and otherwise characterize tumors with a high degree of certainty, but it is not perfect.

Multiparametric MRI is going to not detect maybe 5% to 10% of clinically

significant tumors, but other new imaging modalities potentially can be used in conjunction with MRI to decrease the chances of missing a clinically significant tumor. There are targeted agents that, when injected into patients, hone in on tumor cells and cause these cells to light up on positron emission tomography, single photon emission computed tomography, or other types of functional scans. Also available are gallium scans, which can be fused with MRI or ultrasound to improve tumor localization.

Who is the optimal candidate for focal therapy?

Dr. Chen: Ideally, the candidates who might benefit from focal therapy are men who have 1 or 2 tumors that are amenable to targeted treatment. Focal therapy is based on the concept of the index tumor, the main area of cancer that needs to be treated. Some men may have multiple index tumors, and they may need whole-gland treatment.

Other men may have multiple areas of cancer, but only 1 or 2 index tumors that require treatment, and the remainder of their cancer might be indolent; perhaps these men could be candidates for focal therapy. In addition, focal therapy candidates should be patients who understand and accept the potential risks and benefits of focal therapy.

Dr. Coleman: It is important to keep in mind that the goals of partial gland ablation involve sparing much of the normal prostate tissue to preserve function, minimize effect on quality of life, and obviate the need for future interventions.

So it is logical, with the current state of technology, that these therapies are best suited to men with small-volume cancers that are not in proximity to sensitive structures and that are predominantly localized to one region of the prostate that can be confluently treated and with little risk for extraprostatic disease.

Dr. Polascik: In addition to meeting clinical criteria, such as having a moderately aggressive tumor, I consider patient expectations and personality. If a patient says he absolutely has to have the tumor out, then focal therapy is not good for him, as he needs surgery. There is some degree of uncertainty inherent in focal therapy. Surgeons ablate the known cancer, but a de novo tumor may develop in the remainder of the prostate at some point. I would consider for focal therapy a man who, if subsequently found to have an indolent tumor in an untreated area, would be okay monitoring it. n

Renal & Urology News 17

Post-RP Radiotherapy Benefits Selected Men POSTOPERATIVE radiotherapy for men who have persistently elevated PSA levels following radical prostatectomy (RP) for prostate cancer is associated with improved survival among patients with adverse pathologic characteristics, according to a new study.

In addition, persistently elevated PSA after RP is not always associated with a poor prognosis.

Giorgio Gandaglia, MD, of IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University in Milan, Italy, and colleagues studied 496 men who underwent RP and lymph node dissection at 2 referral centers from 1994 to 2014 and had persistently elevated PSA (0.1 to 2 ng/mL at 6 to 8 weeks after RP).

The group consisted of 251 men who underwent postoperative radiotherapy and 245 who did not.

The median follow-up for survivors was 110 months, the investigators reported in a paper published online ahead of print in European Urology. In all, 49 patients died from prostate cancer.

The 10-year CSM-free survival was 88%. Receipt of postoperative radiotherapy was associated with a survival benefit only among patients with a 30%

or higher CSM risk. Patients with a CSM risk less than 30% should be initially managed expectantly, according to the researchers.

Among the 245 patients who did not receive postoperative radiotherapy, those in pathologic grade group 4 or higher had a nearly 7-fold higher risk of CSM than those in pathologic grade 3 or lower.

Pathologic grade group and pathologic stage independently predicted CSM. In multivariable analysis, a pathologic grade group of 4 or higher was associated with a significant 2.7-fold higher risk of CSM compared with a pathologic grade group of 3 or less. A pathologic tumor stage of T3b/4 versus T2-pT3a was associated with a significant 2.3-fold higher risk of CSM. The association between CSM-free survival and PSA at 6 to 8 weeks differed by the baseline risk of CSM, as defined by pathologic characteristics. The effect of increasing PSA was evident only in patients with a CSM risk of 10% or more. “Increasing PSA levels should be considered as predictor of mortality exclusively in men with worse pathologic characteristics,” the investigators concluded. n

All-Cause Hospitalizations Soar Among Patients With Gout ALL-CAUSE HOSPITALIZATIONS among

A total of 789.8 million all-cause

patients with gout in the United States

hospitalizations occurred during the

have increased by 410% from 1993

22-year period. Patients with gout

to 2014, a rate much higher than in

accounted for 9,741,598 of these hos-

the US population as a whole, accord-

pitalizations. All-cause hospitalizations

ing to a new study presented at the

among gout patients increased from

2017 Annual European Congress of

167,441 in 1993 (64.2 hospitalizations

Rheumatology in Madrid.

per 100,000 ­person-years) to 854,475

The increase in gout patient hospitaliza-

in 2014 (267.9 hospitalizations per

tions may reflect, in part, better recogni-

100,000 person-years), an increase of

tion and coding of co-morbidities, inves-

410%, Dr. Singh’s group reported in a

tigators Gurkipal Singh, MD, of Stanford

poster presentation. By comparison, all-

University, and colleagues explained.

cause hospitalizations in the general US

Dr. Singh’s team analyzed all inpatient hospitalizations in the Nationwide Inpatient Sample (NIS) from 1993 to

population rose from 33.7 million in 1993 to 35.4 million in 2014, a 4.8% increase.

In 2014, gout patient hospitalizations

2014. The NIS is a stratified random

accounted for more than 4.6 million

sample of all US community hospitals

hospital days for a total national cost

that includes information on all patients,

of $42.6 billion, according to the

regardless of insurance coverage.

investigators. n

18 Renal & Urology News

JULY/AUGUST 2017 www.renalandurologynews.com

Intensive BP Lowering Benefits CKD Patients Study reveals reductions in the risk of major cardiovascular events and death of the University of Utah in Salt Lake City, and colleagues reported. Targeting lower SBP reduced cardiovascular events in CKD patients aged 75 and older, similar to the original SPRINT findings.

The intensive group with CKD was 28% less likely to die from any cause.

Patients without CKD from the original SPRINT who were treated to the lower target had a 27% lower risk of mortality.

© TERRY VINE / GETTY IMAGES

BY NATASHA PERSAUD INTENSIVE LOWERING OF systolic blood pressure (SBP) to less than 120 mm Hg may further reduce the risk of cardiovascular events and death among patients with mild to moderate chronic kidney disease (CKD) and hypertension, according to a new study.

The latest findings, published online in the Journal of the American Society

In a study, intensive lowering of systolic blood pressure in hypertensive patients with CKD was associated with a 28% decrease in the risk of all-cause mortality.

of Nephrology, are from subgroup analyses of patients with pre-existing CKD (estimated glomerular filtration rate [eGFR] 20–59 mL/min/1.73m2) from SPRINT (Systolic Blood Pressure Intervention Trial). The investigators randomly assigned participants to an SBP target of less than 120 mm Hg (intensive group; 1330 patients) or less than 140 mm Hg (standard group; 1316 patients). By design, those with diabetes or substantial proteinuria above 1 gram per day were excluded.

CKD patients appeared to have benefits similar to those without CKD from the original SPRINT trial. After a median follow-up of 3.3 years, 112 intensive-group and 131 standard-group participants experienced the primary composite cardiovascular outcome (nonfatal myocardial infarction, decompensated heart failure, acute coronary syndrome, stroke, or cardiovascular-related death).

The intensive group had a 19% lower risk of the composite outcome than the standard group, Alfred K. Cheung, MD,

“Therefore, our findings present the best available evidence to date in favor of intensive SBP reduction as a means to improve survival in patients with CKD and hypertension who are plagued with very high mortality rate,” the investigators wrote.

End-stage renal disease or a 50% or greater decrease in eGFR occurred in 15 and 16 patients in the intensive and standard groups, respectively. The intensive group had a slightly higher annual rate of eGFR decline (0.47 vs.

0.32 mL/min/1.73 m2 per year). All told, intensively lowering blood pressure did not slow kidney disease progression.

“In people with CKD, lowering systolic blood pressure beyond the conventional goal reduced the risks of heart disease and death, but slightly hastened the decline in kidney function that often accompanies aging,” Dr. Cheung said in a news release.

George L. Bakris, MD, director of the ASH Comprehensive Hypertension Center at University of Chicago Medicine,

who was not involved in the study, offered a different interpretation of the findings.

“The observational data presented are very important. Renal SPRINT supports the concept that more aggressive lowering of blood pressure reduces allcause mortality” Dr. Bakris told Renal & Urology News. “It is well known that people with stage 3b and 4 CKD have a 4- to 8-fold greater cardiovascular risk than people with stages 1 and 2. If blood pressure reduction was important, as it has been shown in many other trials, there should have been a greater benefit in the intensive group. There was a greater benefit in further reduction in all-cause death but not the primary endpoint or other cardiovascular event.”

He noted that the study was not sufficiently powered for a “hard renal endpoint.” Intensive blood pressure lowering did not further slow CKD progression, which confirms many previous reports of no additional slowing of GFR decline at blood pressures below 130 mm Hg. Although the overall rate of serious adverse events did not differ significant between groups, the intensive group was more likely to experience hypokalemia, hyperkalemia, and acute renal failure. The adverse effects associated with intensive treatment are worrisome, Dr. Bakris said.

Of concern, he said, was a higher incidence of acute kidney injury (AKI) in the intensive group. “This needs careful scrutiny and evaluation, especially based on the loose definition of AKI. The changes in potassium are not difficult to anticipate, but the AKI requires far more attention. Aggressively lowering blood pressure is well known to reduce GFR more than a mild reduction in pressure among people with low GFRs below 45 mL/min/1.72m2. However, there needs to be careful evaluation of who really developed AKI, what their volume status was, and over what time course.”

Dr. Bakris cautions clinicians to be aware that blood pressure is often measured differently in clinics and may appear higher than in SPRINT trial.

“The method of measuring blood pressure in this study, while correct, is not typically used in practice and yields systolic readings that are at least 7 to 10 mm Hg lower than in usual clinical practice.” ■

Study: ED Risk Higher in Gout Patients NEW STUDY findings support an association between gout and an increased risk of erectile dysfunction (ED).

Naomi Schlesinger, MD, of Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, and colleagues used the Health Improvement Network, an electronic medical record database in the United Kingdom, to identify 2290 new cases of ED among 38,438 patients with gout (mean age 63.6 years) and 8447 ED cases among 154,332 individuals without gout matched to the gout cases by age, enrollment time, and body mass index. The median follow-up time was 5 years. In multivariate analysis, the risk of incident ED was a significant 15% higher among the gout patients than the comparison group, Dr. Schlesinger’s team reported at 2017 Annual European Congress of Rheumatology in Madrid.

When the investigators restricted their analyses to gout patients receiving antigout treatment (31,227 patients), gout was associated with a 29% increased risk of incident ED.

Erectile dysfunction is 15% more likely to develop in men who have gout.

“This population-based study suggests an increased risk of erectile dysfunction among gout patients, supporting a possible role for hyperuricemia and inflammation as independent risk factors for erectile dysfunction,” Dr. Schlesinger’s team concluded in their study abstract.

The study adds to growing evidence of a link between gout and ED. Previously, Dr. Schlesinger and colleagues reported on a cross-sectional study of men aged 18 to 89 years showing that a significantly higher proportion of ED cases in men with than without gout (76% vs 51%), according to a paper published in the Journal of Rheumatology (2015;42:1893-1897).

In a report in the European Journal of International Medicine (2015;26:691695), researchers in Taiwan showed that ED was 1.2 times more likely to develop in men with gout than in those without the condition. ■

20 Renal & Urology News

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Women Less Likely to Have AVFs When Starting HD

BY NATASHA PERSAUD WOMEN, especially black women, are less likely than men to initiate hemodialysis (HD) with an arteriovenous fistula (AVF) for vascular access, according to a new study.

The study, based on data from the US Renal Data System (USRDS), included

187,577 HD patients older than 18 years who received predialysis nephrology care and initiated HD from January 1, 2006 to September 30, 2009. In the overall unadjusted cohort, 18.2% of women reported an AVF as initial access for HD compared with 25.8% for men, Mariana Markell, MD, and colleagues

at SUNY Downstate School of Medicine in Brooklyn, New York, reported online in Hemodialysis International. The odds of starting HD with an AVF were 31% lower for women overall compared with men; the odds were 34% lower for black women and 30% lower for nonblack women.

Dr. Markell’s team observed a gender gap across all 18 end stage renal disease (ESRD) networks, with AVF use ranging 20% to 46% lower for women. New York and the upper Midwest exhibited the greatest disparities, and Southern California, the Pacific Northwest, and Alaska, the least. According to the investigators, international data from DOPPS (Dialysis Outcomes and Practice Patterns Study) 1996–2012 also has shown lower prevalence of AVF use in women.

“Gender disparities have long been overlooked in the nephrology community for unclear reasons,” Dr. Markell told Renal & Urology News. “Our finding that marked geographic variation exists in the gender disparity regarding use of fistula on initiation of hemodialysis is concerning on several levels.”

Compared with men, women had 31% lower odds of initiating HD with an AVF. AVF is the preferred vascular access for HD due to its lower rate of infection, lower risk of complications and thrombosis, and reduced costs compared with arteriovenous graft and tunneled catheter. Women are purported to have smaller vessel diameter, but some studies suggest that the overall difference in vessel size between men and women is not significant. Other studies the investigators cited point to more vascular access-related procedures, worse AVF maturation, or more salvage operations among women.

“It is hard to explain the observed geographic variations in fistula placement, if vessel size alone were the ultimate arbiter of fistula placement,” Dr. Markell said. “The presence of marked geographic differences in gender disparity suggests that some aspect of bias, either on the part of [the] referring physician, patient, or surgeon may be playing a role, or surgical technique issues, referral patterns or transition to care factors may be contributing.”

She speculated that chronic kidney disease severity may be recognized later in women due to the use of estimated glomerular filtration rate formulas based on lower muscle mass.

Surgical bias regarding AVF maturation ability in women versus men is another possible factor. n

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www.renalandurologynews.com JULY/AUGUST 2017

Renal & Urology News 21

n SPECIAL FEATURE

To Divest or Not to Divest?

Evaluating Practice Options Now is a good time to take stock of your practice and reflect on short- and long-term goals

BY ROBERT PROVENZANO, MD, FACP, FASN, MARK HOVERMANN, MBA, AND LANNY TEETS

growing e­ xpenses, many have at least considered — if not seriously contemplated — divesting their practices.

Nephrologists are not alone. The traditional practice of medicine is falling by the wayside as providers across the board look to adapt to a new practice environment. The question is how physicians will survive and what factors should be considered in evaluating the current marketplace and next steps.

© BULL’S EYE / GETTY IMAGES

Challenges to independent practice

Editor’s note: This article is the first of a 3-part series.

P

racticing medicine in today’s healthcare environment is not for the faint of heart.

Historically, successful practices were predicated on providing high-quality patient care; that is, being great physicians. Slowly but surely, over the past 25 years, operating and maintaining the necessary business infrastructure has evolved dramatically, outpacing physicians’ limited time and ability to manage it properly. Sadly, this new reality may put our passion for practicing medicine at risk, increasing physician frustration and burnout.

This is not because we are bad doctors; it is simply that we may not be the best business people. Not surprisingly, as payment models shift, and physicians face lower reimbursements amid

Several developments are motivating physicians to consider different business models to practice medicine, including the shift away from fee-for-service to value-based payments. These changes, initiated largely by new federal laws and increasingly complex regulations, are requiring the medical community to: • Invest in costly electronic health records to satisfy meaningful use requirements. According to new data from the Medical Group Management Association, physicianowned multispecialty practices spent more than $32,500 per full-time physician on information technology equipment, staff, maintenance and other related expenses in 2015.

• Engage in the physician quality reporting system.

• Implement the Medicare Access and CHIP Reauthorization Act (MACRA).

• Contemplate new integrated care agreements, including accountable care organizations (ACOs) and endstage renal disease seamless care organizations (ESCOs).

Nephrologists are particularly vulnerable to changes in Medicare since the federal program is the primary payer of kidney care. As such, not keeping

up with new requirements can have outsized financial consequences as these programs shift from offering incentives focused on boosting physicians’ participation to penalizing providers who don’t meet certain requirements. For example, MACRA carries significant reimbursement implications over the next several years, with possible penalties of up to 9% of Medicare Part B revenue for nonparticipation or poor performance. This year, about 171,000 providers are subject to a downward payment adjustment under Medicare for failing to demonstrate meaningful use.

Thriving in this new healthcare environment demands both significant capital investment and the ability to navigate increasingly complex reporting requirements and financial arrangements. These factors, combined with a new generation of nephrologists with different expectations for their work-life balance, are prompting many nephrologists to seek a new way of doing business, including joining larger organizations.

Robert Provenzano, MD

Laying a foundation for the future According to the Physicians Advocacy Institute (PAI), the number of employed physicians grew by 46,000 nationwide from 2012 to 2015, with the percentage of hospital-employed physicians increasing almost 50% from July 2012 to July 2015.

The trend is expected to continue.

Uncertainty clouds many aspects of healthcare today, including how to cover uninsured Americans. However, the federal government and private insurers are aligned in their focus to better manage care for patients with chronic kidney disease and end-stage renal disease. These patients consume a disproportionate share of resources, to

Mark Hovermann, MBA

Lanny Teets

22 Renal & Urology News

JULY/AUGUST 2017 www.renalandurologynews.com

Study Supports Sevelamer Use

Divesting

Better survival seen when the drug is added to or replaces calcium-based binders

the tune of more than $30 billion a year.

Regardless of what happens with the Affordable Care Act, integrated care and risk-based agreements are here to stay.

In addition to the significant capital investment required, these new payment arrangements pose other challenges for many doctors, the majority of whom have little to no formal training in business or business principles. After all, historic fee-for-service reimbursement models did not require physicians to have a sophisticated understanding of the business of practice. Further, payment structures employed by the federal government and private insurers increasingly favor integrated health systems, making it more difficult for independent physicians to compete.

BY NATASHA PERSAUD HEMODIALYSIS (HD) patients with hyperphosphatemia who receive sevelamer as an adjunct to, or substitution for, calcium-based phosphate binders have lower mortality, a new study finds.

Calcium-based binders such as calcium carbonate and calcium acetate have been associated with arterial calcification. However, previous trials have not consistently shown benefit from switching from calcium-based binders.

Furthermore, in real-world practice, the non-calcium, resin-based binder sevelamer frequently is taken in conjunction with calcium-based binders.

Hirotaka Komaba, MD, of Tokai University School of Medicine in Isehara, Japan, and colleagues examined data from DOPPS (Dialysis Outcomes and Practice Patterns Study) phases 3 (2005–2008) and phase 4 (2008–2011) in 12 countries. Of 12,564 patients with hyperphosphatemia taking calcium-based phosphate binders, 2606 subsequently received sevelamer hydrochloride or sevelamer carbonate as either add-on or alternative therapy.

In the initial 4 months of treatment, mean serum phosphorus levels in patients receiving sevelamer fell by 0.3 mg/dL, followed by slower declines,

according to results published online ahead of print in the Clinical Journal of the American Society of Nephrology.

Serum levels of calcium and parathyroid hormone did not change meaningfully.

To assess survival, the investigators matched 2501 sevelamer-treated patients with 1 or more patients not treated with

Sevelamer use was associated with a 14% lower risk of death, according to a study. sevelamer with similar estimated risks of death. Patients treated with sevelamer had a 14% lower risk of death than patients not receiving sevelamer.

“Our results extend the findings from recent observational studies showing the survival benefit of phosphate-lowering therapy … and provide a new rationale for using sevelamer as a switch or addon therapy in patients on hemodialysis being treated with calcium-based phosphate binders,” Dr. Komaba and colleagues wrote.

The authors noted that several possible mechanisms could explain why

sevelamer was associated with improved survival. “The most plausible mechanism is that the improved control of serum phosphorus, along with decreases in the calcium load, was associated with attenuation of vascular calcification and thereby led to improved cardiovascular outcomes,” they stated.

The investigators also discussed additional possibilities, including reductions in malnutrition, fibroblast growth factor 23, uric acid levels, low-density lipoprotein levels, and/or advanced glycation end products.

In a discussion of study limitations, the authors stated that they could not completely exclude the possibility that unmeasured confounders contributed to the survival benefit of sevelamer. “Although the extensive DOPPS database and detailed longitudinal data collection allowed us to perform a comprehensive analysis using a sequential stratification method, we cannot exclude residual confounding by unmeasured confounders that might affect both sevelamer prescription patterns and patient outcomes.” In addition, the team noted that sevelamer hydrochloride and sevelamer carbonate have different profiles with regard to their effect on metabolic acidosis, which might affect survival. n

Ferritin Spike After Starting HD May Up Mortality

BY NATASHA PERSAUD MAJOR INCREASES in serum ferritin within the first 6 months of starting maintenance hemodialysis (HD) may increase the risk of death, a new study finds.

Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the University of CaliforniaIrvine School of Medicine in Orange, California, and colleagues used 2007–2011 data from an administrative database to study the change in serum ferritin in quintiles from the first to second quarter after HD initiation for 93,979 outpatients. Compared with patients who had relatively stable serum ferritin (100 ng/mL decrease to less than 100 ng/mL increase per quarter), patients who experienced an abrupt rise of 400 ng/mL or more per quarter had a 7%, 17%, 26%, and 49% higher risk of all-cause mortality when baseline serum ferritin levels were less than 200, 200 to less than 500, 500 to less than 800, and 800 ng/mL or greater, respectively.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 clinical practice guidelines for anemia recommend intravenous (IV) iron administration in HD patients with serum ferritin levels at or below 500 ng/mL. “These findings suggest that a more cautious approach in selecting patients needing IV iron treatment may be appropriate,” Dr. Kalantar-Zadeh and his team stated in the American Journal of Nephrology (2017;46:120-130).

The mortality risk associated with a rise in serum ferritin was robust regardless of IV iron dose, according to the investigators. Iron saturation, a marker of iron deficiency or overloading, also appeared to have no independent effect on mortality. An serum ferritin increase of 100 ng/mL per quarter or more was associated with an increased death,risk whether iron saturation rose or fell.

Using multivariable models, the team adjusted for malnutrition-inflammation

cachexia syndrome (MICS), IV iron, erythropoiesis-stimulating agent (ESA) doses, as well as sociodemographic factors.

Study strengths include the size and contemporary nature of the cohort and adjustment for numerous covariates related to malnutrition and inflammation, the authors noted. With regard to limitations, the investigators pointed out that direct inflammatory markers, such as C-reactive protein and interleukin-6 were not available. “Although they adjusted for a number of potential inflammatory markers, residual confounding with inflammatory status may exist, they stated. “This residual confounding may also explain the lack of better survival observed in patients with decreased serum ferritin after adjustment for malnutrition and inflammation markers.” In addition, a relatively small proportion of patients (3.6%) never received IV iron over 6 months after HD initiation. n

continued from page 21

Choosing a partner Times of change are challenging, but there are viable options for partnerships that will put nephrologists on a sustainable path for the future. Physicians should consider partners who are not only better equipped to participate in integrated care models but who can also more easily absorb administrative costs to comply with regulatory and reporting requirements. Having access to a larger infrastructure allows administrative experts to manage contracts and reporting requirements, helping physicians, who may already be spread thin, to continue to focus on their top priority: caring for their patients.

Healthcare will always be local, and patients will always need nephrologists to meet their needs wherever they are.

However, today’s environment requires nephrologists to evaluate how best to partner. Now is a good time to take stock of your practice and reflect on short- and long-term goals. This exercise will not only help doctors address future challenges, but it will also better position them to identify solutions. In future articles, we will describe different practice options, as well as how to evaluate them in light of your personal and financial priorities.

With increased competition and costs, you can’t afford not to. n Robert Provenzano, MD, is vice president for medical affairs at DaVita Kidney Care in Denver. He also is on the editorial advisory board of Renal & Urology News. Mark Hovermann, MBA, is Senior Director, Corporate Development, and Lanny Teets is Director, Transactions & Growth Initiatives, at Nephrology Practice Solutions.

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RP for High-Risk PCa Rises Sharply Over a 10-year period, radical prostatectomy use increased steadily while radiotherapy use declined THE PROPORTION of men with high-risk localized prostate cancer undergoing radical prostatectomy (RP) increased dramatically from 2004 to 2013, such that by the end of the study period, RP and external beam radiation therapy (EBRT) were used with similar frequency in this patient population, new findings suggest.

In an analysis of data from 127,391 patients with high-risk localized prostate cancer (PCa) in the National Cancer Database (NCDB), a team led by Scott E. Eggener, MD, of the University of Chicago, found initial use of RP increased from 26% to 42%, whereas initial use of EBRT decreased from 49% to 42%, according to a report published in Prostate Cancer and Prostatic Diseases (2017; published online ahead of print). Compared with men treated in 2004, those treated in 2013 were 51% more likely to undergo RP. Of a total of 127,391 men in the study, 45,978 (36%) received RP. Increasing PSA at diagnosis was associated with decreasing use of RP. For example, 41% of men with a PSA level of 4.1–10 ng/mL underwent RP compared with 29% of men who had a PSA level of 20 ng/mL or higher. Patients with a

Radical Surgery for High-Risk Localized Prostate Cancer Surges A study of initial treatment modalities for high-risk localized prostate cancer showed a dramatic increase in the use of radical prostatectomy (RP) and decreased use of external beam radiation therapy (EBRT) from 2004 to 2013. Shown here are the proportions of cases treated with these modalities. n RP n EBRT

49%

50

30

42%

42%

40

26%

20 10 0

2004

2013

Source: Weiner AB, Matulewicz RS, Schaeffer EM, et al. Contemporary management of men with high-risk localized prostate cancer in the United States. Prostate Cancer Prostatic Dis. 2017; published online ahead of print.

biopsy Gleason score of 8–9, with or without any primary Gleason 5 patterns, had a significant 19% decreased likelihood of RP use compared with patients who had a Gleason score of 6 or less.

The patient population had a median follow-up of 4.4 years. The median overall survival for men was 8.3 years for men who received no treatment, 9.9 years for those treated with EBRT plus androgen deprivation therapy (ADT),

and 5.7 years for those who received ADT alone. Median survival was not reached for men treated with RP. The 10-year overall survival was 41% for no treatment, 77% for RP, 49% for EBRT plus ADT, and 24% for ADT alone.

Compared with RP, no treatment was associated with a 3-fold higher risk of death. EBRT with ADT and ADT alone were associated with a 1.6and 3.4-fold increased risk of death, respectively.

A number of possible reasons could explain an increase in the use of RP for high-risk localized PCa, the authors noted. Findings from population-based studies have suggested an improved cancer-specific survival benefit with RP compared with radiation. “Although these studies were limited by their retrospective design and unmeasured confounding variables, they were likely influential on patients and physicians,” said Adam Weiner, MD, a urology resident at Northwestern University in Chicago, the study’s primary author.

Strengths of the study include the large and diverse patient population captured in the NCDB, which, unlike other datasets, such as the Surveillance, Epidemiology and End Results (SEER) database, provides valuable information on ADT use and the order in which treatments were received to accurately discern initial treatments. The NCDB, however, is a hospital-based cancer registry, not population-based. “The data from the NCDB should be interpreted as generalizable to hospitals similar to those included in its registry,” the authors noted. n

Review Supports Sodium Thiosulfate Use for Calciphylaxis

BY NATASHA PERSAUD A NEW SYSTEMATIC review supports the use of sodium thiosulfate (STS) for treating calciphylaxis, also known as calcific uremic arteriolopathy (CUA)—in patients with advanced chronic kidney disease.

The review, which included 45 case reports and multi-case reports describing a total of 358 patients who received STS for calciphylaxis, found that 70% of patients experienced improvement in skin lesion cicatrisation or pain relief without death, Daqing Hong, MD, PhD, of Sichuan Provincial People’s Hospital in Chengdu, China, and colleagues reported in Nephrology. The efficacy of STS therapy was 84.4% in case reports and 67.0% in multi-case reports, the researchers noted. The efficacy found in the new study was higher than observed in previous reports, and the investigators noted that other factors, such as dialysis improvements, may have contributed to the relatively higher response rate. More

than a third of patients (37.6%) died even with continuous use of STS. “Calciphylaxis remains a serious complication and carries high mortality,” Dr. Hong and colleagues concluded. “Our study has reinforced the promising role of STS as an efficient therapy for calciphylaxis. Although the

Efficacy was 84.4% in case reports and 67.0% in multi-case reports, study finds. study was unable to assess the efficacy of sodium thiosulfate used alone in the treatment of calciphylaxis, it may represent an emerging component of most therapeutic strategies to treat this devastating condition.”

STS was variably administered. A majority (70.3%) had intravenous (IV)

injection, with the remaining receiving combined IV injection and oral tablets, intraperitoneal injection, or infusion during dialysis. Patients often received STS, an antioxidant and calcium-chelating drug, concomitantly with other medications.

The researchers found no significant differences in efficacy among the routes of administration. STS was given an average 3 times a week and doses ranged from 5 to 25 g.

The most common adverse events were nausea and vomiting, sepsis, and metabolic acidosis. Sepsis occurred in more patients who received STS intravenously (20%).

The patients had a mean age of 58 years, and 96.1% of them were on dialysis for a median of 44.5 months. Most patients (87.4%) were on long-term hemodialysis. Nearly three-quarters of patients were female. According to the investigators, these factors may represent risk factors. Additional, prospec-

tive studies are needed to determine optimal therapy for calciphylaxis. The authors further suggested that a registry of calciphylaxis patients would yield valuable data.

The largest of the studies looked at

by Hong’s group was an investigation led by Sagar U. Nigwekar, MD, that included 172 maintenance HD patients (mean age 55 years) who had calciphylaxis and were treated with STS. Of these, 85% completed STS treatment. Among surveyed patients, calciphylaxis resolved completely in 26.4%, improved markedly in 18.9%, improved in 28.3%, and did not improve in 5.7%, according to findings published in the Clinical Journal of the American Society of Nephrology (2013;8:1162-1170). The 1-year mortality rate in STS-treated patients was 35%. The authors concluded that “this study suggests that STS is reasonably safe in the treatment of CUA in maintenance HD patients.” n

www.renalandurologynews.com JULY/AUGUST 2017

Renal & Urology News 25

ED May Predict Parkinson’s Disease The neurodegenerative disorder was 52% more likely to develop among men with erectile dysfunction ERECTILE DYSFUNCTION (ED) is associated with a higher risk for the development of Parkinson’s disease, according to a new study.

In a population-based retrospective cohort study, researchers led by Tengfu Hsieh, MD, of Taichung Tzu Chi Hospital in Taiwan, compared 3153 men newly diagnosed with ED with 12,612 randomly selected men without ED (controls) matched by propensity score.

The incidence rate of Parkinson’s disease was significantly higher in the ED group than the control group (3.44 vs. 1.64 per 1000 person-years), the investigators reported in the Journal of Clinical Neurology (2017;13:250-258).

The ED patients had a 52% higher risk of Parkinson’s disease, after adjusting for age and comorbidities. When stratified by age and Charlson Cormorbidity Index Score, the ED group had a 38% higher risk of Parkinson’s disease. Men with organic ED had a 43% higher risk of Parkinson’s disease.

Compared with controls, ED patients with diabetes or hypertension had a 2.8 times and 2.2 times higher risk of Parkinson’s disease, respectively.

For the study, the investigators analyzed data from the Taiwan National

Health Insurance (NHI) program. The mean ages of the ED and control groups were 56.7 and 53.4 years, respectively.

Investigators followed patients from their index date (when ED was diagnosed) to the date of Parkinson’s disease diagnosis, withdrawal from the NHI program, or the end of 2012, whichever occurred first. The mean follow-up times for the ED and control groups were 5.0 and 6.8 years, respectively.

ED plus diabetes or hypertension further increased Parkinson’s risk.

In a discussion of study limitations, the authors noted that diagnoses of ED, Parkinson’s disease, and comorbid conditions were dependent on ICD-9 CM codes, “so the presence of coding errors should be considered.” In addition, the NHI database does not contain information on daily activity, dietary habits, body mass index, tobacco use, and education, which also may be risk factors for Parkinson’s disease, they noted.

The new study adds to growing evidence of a link between ED and future development of Parkinson’s disease.

In a paper published in the American Journal of Epidemiology (2007;166:14461450), researchers reported on a study demonstrating an association between ED and later development of Parkinson’s disease. The study included 32,616 men who participated in the Health Professionals Follow-up Study who were free of Parkinson’s disease at baseline in 1986 and, in 2000, completed a questionnaire that asked about ED in different time periods. Among men who reported their erectile function prior to 1986, 200 were diagnosed with Parkinson’s disease during the period from 1986 to 2002. Men with ED before 1986 were 3.8 times more likely to develop Parkinson’s disease during follow-up than men with very good erectile function.

Effect of age at ED onset On multivariable analysis, men with first onset of ED prior to 1986 when they were aged 60 years or more, 50–59 years, and younger than 50 years had a 2.7, 3.7, and 4.0 times higher risk of Parkinson’s disease relative to men without ED.

In another study, researchers at University College London found that ED was among the prediagnostic features that can be detected years before Parkinson’s disease is diagnosed. The study, published in The Lancet Neurology (2015;14:57-64), compared 8166 individuals with Parkinson’s disease and 46,755 without the disease (controls). At 5 years before diagnosis, patients who went on to develop Parkinson’s disease had a 30% higher incidence of ED versus controls.

Possible mechanisms With respect to possible mechanisms to explain a link between ED and Parkinson’s disease, Dr. Hsieh’s team noted that ED is among the manifestations of parasympathetic cholinergic failure, and the findings of previous studies suggest that many non-motor symptoms and autonomic dysfunction could be early signs of preclinical stages of Parkinson’s disease. Testosterone levels also might have a role. Lower testosterone levels, they noted, are an important component of ED, and previous studies have shown that testosterone deficiency is frequently found in men with Parkinson’s disease compared with age-matched controls. n

Kidney Acceptance Varies By Transplant Center TRANSPLANT CENTERS vary in their willingness to accept offers of deceased-donor kidneys for transplantation, according to a new study.

Acceptance is more likely at centers that perform greater numbers of transplants and less likely at centers with more minority waitlisted patients, researchers reported.

“Our results have implications for patients, providers, researchers, and policy makers,” Anne M. Huml, MD, of Case Western Reserve University in Cleveland, and colleagues wrote in an online report in the Clinical Journal of the American Society of Nephrology.

“Waitlisted patients should be aware of how the offer process works and may consider selecting transplant centers on the basis of their acceptance practices.”

Additionally, they said their results “will allow transplant providers to compare their rates of and reasons for offer refusal with national rates and reasons.”

The study cohort consisted of 178,625 patients waitlisted for a deceased-donor kidney transplant and 31,230 deceased donors. Deceaseddonor kidneys were offered a median of 7 times before being accepted for transplantation, Dr. Huml’s group reported.

The most common reasons for refusing an offer were donor-related factors such as age or organ quality (45%) and transplant center “bypass,” such as minimal acceptance criteria not being met (44%).

After adjusting for characteristics of waitlisted patients, the researchers found that male and Hispanic patients were less likely to have an offer accepted than female and white patients, respectively.

The likelihood of kidney acceptance varied across transplant centers (interquartile ratio 2.28). Offers to highervolume centers were more likely to be accepted for transplant. The odds of kidney acceptance increased by 10% for each 100 transplants performed. Offers to transplant centers with more black

and Hispanic patients on the waiting list were less likely to be accepted for transplant. The odds of kidney acceptance decreased by 17% for each 10% increase in the number of black patients waitlisted and decreased by 19% for each 10% increase in the number of Hispanic patients waitlisted.

Higher-volume centers are more apt to accept offers of a kidney from a deceased donor.

“We found that deceased-donor kidneys are typically offered and declined many times before being accepted for transplantation,” Dr. Huml and colleagues stated. “Such refusals differ by patient and donor characteristics and may contribute to racial and ethnic disparities in access to transplantation.”

In an editorial accompanying the new report, Sumit Mohan, MD, MPH, and Mariana C. Chiles, MPH, of Columbia University in New York, noted that although shared decision making may not be feasible or even appropriate when a kidney is offered, “patients deserve to know how aggressive their transplant center will be in accepting kidneys for transplantation.”

Patients also should be informed if their wait times to receive a kidney are likely to be longer because of a transplant program philosophy or if their ability to receive a timely transplant or get transplanted at all will be impeded by regulatory pressures or concerns, the editorial noted. “Patients who have the ability to choose between transplant centers may find this a more meaningful decision point than other metrics currently being provided.”

The editorial writers said Dr. Huml’s team should be congratulated for an important analysis of organ offer data. n

26 Renal & Urology News

JULY/AUGUST 2017 www.renalandurologynews.com

Practice Management Providers can negotiate better payer contracts by demonstrating superior care and identifying reimbursement problems BY TAMMY WORTH these differentiate their practice from others in their area, Zetter said. “There may be procedures that you provide that your competition doesn’t,” he said.

“Or maybe you provide a higher quality of care or have better outcomes. That is where you will have leverage.”

Review reimbursements When renegotiating contracts, providers also should look at where they are having issues with insurers. Zetter recommends analyzing all reimbursement data for claims submitted for previous 2 years. In cases where a payer consistently causes hurdles for the practice or is not paying their contracted rates, providers have some leverage when they go into negotiations. They also may have a basis for requesting retroactive payment on those claims.

“You should have reimbursement rates in your practice management system that will tell you if you are being paid appropriately or not,” Zetter said.

If providers use outside vendors to manage their revenue cycle, these vendors should be verifying payments with their copy of the providers’ reimburse-

Contracts should provide enough time to submit claims and include deadlines that ensure timely payments of claims.

Analyze services When figuring out where to hone negotiations, it makes sense to start with the largest payers. Contract rates typically will be set at a certain percentage above Medicare reimbursement, and providers may have some wiggle room to increase that slightly. Practices that can show payers they are worth higher rates will have an easier time negotiating increased reimbursement rates, according to David Zetter, founder and senior consultant at Zetter HealthCare, of Mechanicsburg, Pennsylvania. Providers need to analyze which procedures and services constitute a large portion of their practice, and how

ment fee schedules. If the vendors do not have them or are not verifying payment rates, they are not doing their job fully.

Evaluating language Jones said providers should be alert for language that is “payer favored,” especially with respect to amendments.

Any amendments a payer makes to a contract should be agreed upon, in writing, by both parties. Payers should not be making unilateral changes, and having mutual amendment language will guard against this.

The contract also should include a provision that a practice is notified

© SKYNESHER / GETTY IMAGES

D

epending upon Congress’ actions in the coming year, the insurance industry may be an entirely new landscape in 2018. But that does not mean providers should be satisfied with payers’ rates and terms.

Familiarity with current contracts and knowing how to negotiate better ones will be crucial to boosting income.

When working with clients, Jaimee Jones, Associate Director of Managed Care for Innovative Practice Services at McKesson Specialty Health in The Woodlands, Texas, said she always starts by giving them homework. She has them go through files to ensure that the entirety of their managed care contracts are in their possession, including amendments and rates.

“It’s important for them to understand their current reimbursement, have a comfort level with the terms in their agreement and to identify what the pain points are in moving forward to renegotiation,” she said.

She even recommends creating a quick reference document that includes terms and rates of all contracts, plan contacts, and other relevant information.

When negotiating contracts, providers should be alert for language that favors the payers.

regarding policy changes, including those affecting fee schedules, reimbursement rate changes, preauthorization, and other requirements that could cause administrative burden to the practice and be considered material in nature. Many contracts only require notification of policy changes on the payer’s website, which providers may not be monitoring. It is also prudent to include language stating that any changes a payer makes to a contract give providers a right to renegotiate the contract.

Finally, providers should look at claim filing and payment deadlines.

They should be provided enough time to submit claims. Contracts should include payment deadlines that ensure timely payments of claims and reasonable dispute timelines so that resolutions do not drag out indefinitely.

Most payer contracts are evergreen, meaning that providers probably have been happy to let them roll over without any effort on their part. But when providers opt to negotiate contracts, they should review the terms of the current ones. Depending on language in existing agreements, a practice could be held to a window of time in which they can request renegotiation; for instance, the request may be required to be submitted with 60, 90,

or 120 days advance notice prior to the contract renewal date.

1-year contracts Unless there are rate escalators built into a multi-year agreement, Jones encourages practices to contract for 1-year terms so they have an opportunity to return to the table frequently. The key is having calendar reminders of when anniversary dates for contract renewals are coming up, since most contracts will keep renewing year after year.

“If [practices] perform a rates review annually, they can look at those numbers and analytics because their payer mix can and will change over time,” Jones said. “Different employers might be choosing different payers, a practice’s Medicare and Medicaid business may shift up or down…so keeping abreast of their payers is important as it relates to overall practice reimbursement.”

If payers balk at 1-year terms, make sure to include rate inflators. If a practice has a 3-year contract, for instance, it should include rate inflators for years 2 and 3. When those are implemented, providers will need to run annual reports to ensure the rates are escalated on time. n Tammy Worth is a freelance medical journalist based in Blue Springs, MO.