Renal & Urology News - Spring 2022

SPRING 2022

■

■

■

VOLUME 21, IS SUE NUMBER 2

■

■

■

www.renalandurologynews.com

Darolutamide Ups Survival in mHSPC Phase 3 study results demonstrate benefit of adding darolutamide to ADT plus docetaxel

© BACKGROUND IMAGE: STEVE GSCHMEISSNER / SCIENCE PHOTO LIBRARY / GETTY IMAGES

IMPROVED OUTCOMES WITH DAROLUTAMIDE The ARASENS trial showed that combining darolutamide with ADT and docetaxel improves outcomes of patients with metastatic hormone-sensitive prostate cancer compared with placebo plus ADT and docetaxel. Compared with the placebo group, the darolutamide group had a:

32.5% Lower risk for death *Castration-resistant prostate cancer

64%

21% Lower risk for pain progression

Lower risk for CRPC*

Source: Smith MR, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. Published online February 17, 2022.

New Insights Into nmCRPC NEW FINDINGS from a study of the prevalence and natural history of nonmetastatic castration-resistant prostate cancer (nmCRPC) may provide a benchmark to gauge potential benefits of novel imaging and therapies for prostate cancer, investigators reported at the 2022 Genitourinary Cancers Symposium.

Investigators identified a real-world Canadian cohort diagnosed with nmCRPC from 2007 to early 2018 prior to the introduction of novel antiandrogen agents, such as enzalutamide, apalutamide, and darolutamide. The cohort included 2045 patients with a castration level of testosterone (less than 1.7 nmol/L) who experienced rising PSA (beyond 2.0 nmol/L with a

25% or more increase from the nadir) to a median 3.0 ng/L and met criteria for nmCRPC. The annual prevalence of nmCRPC was 8% of men with prostate cancer prescribed androgen deprivation therapy (ADT), Amanda Elizabeth Hird, MD, of the University of Toronto in Ontario, Canada, reported on behalf of her team. Overall, metastasis developed in 20% of men after a median of 31.1 months.

The median time to metastasis and from metastasis to all-cause death was 20.0 and 8.3 months, respectively.

A total of 984 patients (48.1%) had received upfront hormonal therapy, 584 (28.5%) had received initial radiation continued on page 14

BY JODY A. CHARNOW ADDING darolutamide to androgen deprivation therapy (ADT) and docetaxel improves overall survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC), compared with ADT plus docetaxel alone, new research suggests.

These findings, from the phase 3 ARASENS trial, were presented at the ASCO Genitourinary Cancers Symposium 2022 and published concurrently in the New England Journal of Medicine.

“Based on the results of ARASENS, we conclude that darolutamide in combination with ADT and docetaxel should become the new standard of care for the treatment of patients

Gene Mutations in RCC Vary By Metastatic Site INVESTIGATORS have identified genetic alterations associated with patterns of metastasis in patients with renal cell carcinoma (RCC), according to a presentation at the 2022 Genitourinary Cancers Symposium.

“Renal cell carcinoma from primary and distant metastatic sites have differential molecular features,” lead investigator Rana R. McKay, MD, of the University of California San Diego in La Jolla, said in an interview.

“Understanding the molecular underpinning of organotropism will help inform personalized therapy strategies in patients with renal cell carcinoma.”

During an oral presenta tion, Dr McKay cited previous studies demonstrating that site of metastasis is prognostic for overall survival (OS) in patients with RCC. For example, one study showed that pancreas, adrenal, and lung metastases were associated with improved OS, whereas bone and brain metastases were associated with continued on page 14

with mHSPC,” Matthew R. Smith, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, said during a presentation at the meeting.

The ARASENS trial included 1305 patients with mHSPC randomly assigned to receive darolutamide at 600 mg twice daily (651 patients) or placebo (654 patients), each in combination with ADT and docetaxel.

The treatment arms had similar demographics and clinical characteristics at baseline. The median age of patients in both groups was 67 years.

The vast majority of patients — 85.7% in the darolutamide arm and 86.5% in the placebo arm — had metastatic disease at initial diagnosis. continued on page 14

IN THIS ISSUE 5

Diabetes found to up major bleeding risks from renal biopsy

11

Management of small renal masses differs by race

19

In-hospital acute kidney disease linked to worse outcomes

20

RCC outcomes not worse with minimally invasive PN

21

Frailty increases complication risks after sling surgery

21

Pre-kidney transplant costs are increasing rapidly

26

Prior prostate radiation therapy has no effect on BCG efficacy

Urology group practices are thought to have an advantage under MIPS. PAGE 28

Contents

www.renalandurologynews.com

SPRING

2022

■

ONLINE

11

this month at renalandurologynews.com 20

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

21

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

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

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

Small Renal Mass Management Varies By Race The natural history of SRMs is similar in Black and White patients, but Black patients are more likely to undergo radical nephrectomy.

RCC Outcomes Not Worse With Minimally Invasive PN A minimally invasive vs open partial nephrectomy is not associated with increased risk for port-site incisional or peritoneal seeding.

Frailty Ups Risks After Sling Surgery A study of 54,112 women aged 66 years or older found that frailty increased the likelihood of complications, repeat procedures, and death.

14

Conservative Care for Advanced CKD Falls Short In a study, use of acute care services was common toward the end of life and intensified for a subset of patient.

18

Poor Nutrition at Dialysis Start Ups Mortality Odds New findings suggest special attention be paid to diet as patients approach dialysis, investigators say.

19

In-Hospital AKD Tied to Adverse Outcomes Data reveal higher risks for heart failure hospitalizations, death, and major adverse kidney events.

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

Diabetes May Complicate Renal Biopsy The presence of diabetes in patients undergoing percutaneous renal biopsy increases the risk for major bleeding.

CALENDAR Editor’s note: The 2022 conference listings below include information provided by the sponsoring organizations on their websites as this issue went to press.

American Urological Association Annual Meeting New Orleans, LA May 13-16 European Renal Association 59th Congress Paris, France May 19-22 American Transplant Congress Boston, MA June 4-8 Canadian Urological Association Annual Meeting Prince Edward Island, Canada June 24-27 American Society of Clinical Oncology Annual Meeting Chicago, IL June 3-7

Nephrology

Job Board

26

Renal & Urology News 1

VOLUME 21, ISSUE NUMBER 2

Urology 5

SPRING 2022

Reduced Kidney Function Raises SCD Risk Investigators zeroed in on the association in a study of 9687 individuals in the general population.

Our results seem to support the view that

lowering circulating urate levels plays a role in improving kidney function in kidney transplant recipients.

See our story on page 18

27

Departments 2

From the Medical Director The emergence of value-based models in kidney care

4

News in Brief Same-day discharge feasible after RARP

27

Ethical Issues in Medicine Physicians have a duty to stop medical misinformation

28

Practice Management The impact of MIPS on urology practices

2 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Implications of Value-Based Models in Kidney Care

P

resident Richard Nixon signed into law the Social Security Amendments of 1972, which included creation of the National End Stage Renal Disease (ESRD) Program.

This legislation authorized Medicare entitlement for dialysis therapy coverage under Parts A and B of Medicare without the age requirement of 65 years or older. Some consider the ESRD program the first and last socialist medicine initiative in the country. With subsequent legislation, dialysis therapy has emerged as one of the most statutorily regulated Medicare programs, with designated ESRD Network Organizations acting as the federal government’s oversight bodies to ensure quality and safety of the delivery of ESRD services.

Along with the resultant growth of dialysis industry, medical organizations issued practice guidelines in the late 1990s recommending earlier rather than later dialysis transition (when the estimated glomerular filtration rate [eGFR] reaches 15 mL/min/1.73 m2 or lower). During the first 2 decades of the 21st century, however, there has been a trend toward increasingly earlier dialysis transition, with almost a quarter of patients now having an eGFR value above 15 mL/min/1.73 m2 on dialysis therapy initiation.

In July 2019, the US Presidential Executive Order known as the “Advancing American Kidney Health Initiative” was issued. One of its goals is a 25% reduction in the ESRD rate by 2030, a target to be achieved by adding strong financial incentives for health care providers to manage the care of patients with advanced chronic kidney disease (CKD) as well as ESRD. The idea is to encourage clinicians to provide care that delays the need for dialysis and perform more preemptive kidney transplants. These so-called value-based models are being operationalized as of 2022 and include the “Kidney Care First” and “Comprehensive Kidney Care Contracting” initiatives.

At this writing, it is not clear how dialysis initiation should be delayed in patients with CKD. The most likely scenarios include more effective nutritional management of CKD using low-protein and plant-dominant diets, along with adjunct pharmacotherapy for fluid management, anemia, acidosis, potassium and phosphorus load, and symptom management such as pruritus. Just how effective such an integrated multimodal approach can be in delaying dialysis is unknown. And when dialysis becomes necessary, clinicians might want to consider a more conservative approach, such as increasing the frequency of dialysis incrementally or using dialysis only as needed.

Going forward, nephrologists and dietitians will be eager to apply and enhance their knowledge in their attempt to improve kidney care so patients can avoid or delay dialysis.

Kam Kalantar-Zadeh, MD, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine, Orange, CA Twitter/Facebook: @KamKalantar

Medical Director, Urology

Medical Director, Nephrology

Robert G. Uzzo, MD, MBA, 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, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine Orange, CA

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

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

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

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

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center Memphis

Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD Chief Executive Officer Inova Health System Falls Church, VA Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology (ret.)

Cleveland Clinic Lerner College of Medicine Cleveland Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology UC Irvine School of Medicine Orange, CA 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 Kenneth Pace, MD, MSc Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Vancouver, Canada

Edgar V. Lerma, MD 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. Denver Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Associate Professor of Medicine Wayne State University School of Medicine Detroit Vice President of Medical Affairs, DaVita Healthcare Denver

Renal & Urology News Staff Editor

Jody A. Charnow

Web editor

Natasha Persaud

Production editor Group creative director Production manager Vice president, sales operations and production National accounts manager Editorial director, Haymarket Oncology Vice president, content, medical communications Chief commercial officer President, medical communications Chairman & CEO, Haymarket Media Inc.

Kim Daigneau Jennifer Dvoretz Brian Wask Louise Morrin Boyle William Canning Lauren Burke Kathleen Walsh Tulley James Burke, RPh Michael Graziani Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 21, Number 2. Published quarterly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). For reprint/licensing requests, contact Customer Service at custserv@haymarketmedia.com. Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2022.

4 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

News in Brief

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

Short Takes FDA Approves Product to Aid Renal Imaging The FDA has approved NephroScan™

replacement therapy from 2781 US counties.

All-cause mortality rates standard-

(kit for the preparation of technetium

ized by age among patients with

Tc 99m succimer injection) for use

ESKD ranged from 45 to 1022 per

as an aid in the scintigraphic evalua-

1000 person-years across counties,

tion of renal parenchymal disorders in

Kylie K. Snow, MPH, of Rollins School

adults and pediatric patients including

of Public Health, Emory University,

term neonates.

Atlanta, Georgia, and colleagues

NephroScan is a sterile, single-dose

reported in Kidney360.

kit for the preparation of technetium Tc Tc 99m succimer binds to the cortical

Frailty May Up Vascular Access Thrombosis Risk

region of kidneys, and in conjunction

Frail patients on hemodialysis (HD) are

with gamma scintigraphy or single pho-

at elevated risk for vascular access

ton emission computed tomography, is

(VA) thrombosis, according a study

used to image the renal cortices.

published in the American Journal of

99m succimer injection. Technetium

Kidney Diseases.

ESKD Patient Death Rates Vary By County

centers in Taiwan, frail patients had a

In the United States, 18.9% of the

significant 2.3-fold higher risk for VA

variation in death rates among pa-

thrombosis compared with robust pa-

tients with end-stage kidney disease

tients, a team led by Chih-Cheng Wu,

(ESKD) is attributable to county-level

MD, of National Taiwan University in

factors such as demographics and

Taipei, reported. The investigators as-

health care spending, according to a

sessed frailty using the Fried scoring

recent study.

method, assigning 1 point for each of

Using 2010-2018 data from the

In a study of 761 patients at 9 HD

the following if present: weight loss,

US Renal Data System, investigators

exhaustion, low activity level, low grip

identified 1,515,986 adults (aged

strength, and slow walking speed. A

18-84 years) who initiated renal

score of 3 to 5 indicated frailty.

Racial Divide in CPR Use In a study of patients experiencing cardiac arrest at dialysis centers, Black patients had significant 57% lower odds of receiving CPR from staff members compared with White patients, according to a recent study. Here are the percentages of patients, by race, who did not receive CPR.

BLACK: 15%

WHITE: 9%

OTHER: 12%

Source: Pun PH, et al. Facility-level factors and racial disparities in cardiopulmonary resuscitation within US dialysis clinics. Kidney360. Published online March 11, 2022. doi:10.34067/KID.0008092021

Hyperuricemia May Be Linked to SHPT in Patients With CKD H

yperuricemia may contribute to development of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD), possibly independent of renal function, investigators suggest.

Among 922 patients with stages 3 or higher CKD not on dialysis, SHPT and hyperuricemia occurred in 70% and 62.4%, respectively. The group with vs without SHPT had significantly higher mean levels of serum uric acid (7.2 vs 6.6 mg/ dL) and a significantly higher prevalance of hyperuricemia (66% vs 33%), Rosilene M. Elias, MD, and colleagues from Hospital das Clinicas HCFMUSP in São Paulo, Brazil, reported in International Urology and Nephrology. In multivariable analyses, hyperuricemia remained independently associated with SHPT.

Study: Same-Day Discharge After RARP Is Safe, Feasible S

ame-day discharge (SDD) following robot-assisted radical prostatectomy (RARP) is feasible and safe, with complication and readmission rates comparable to those of inpatient RARP, data reported at the 2022 Genitourinary Cancers Symposium suggest.

The findings are from a systematic review and meta-analysis of data from 14 studies (8 prospective and 6 retrospective cohort studies) with a pooled population of 3795 patients, including 2348 (61.9%) who underwent inpatient RARPs and 1447 (38.1%) who underwent SDD RARPs. Compared with the inpatient RARP group, patients who had SDD RARPs did not differ significantly with respect to grade 3 or higher Clavien-Dindo complications, 90-day readmission rates, or unscheduled emergency department visits, Michael Uy, MD, of McMaster University in Hamilton, Ontario, Canada, and colleagues reported. Cost savings per patient ranged from $367 to $2109 in US dollars. Overall satisfaction rates were high (87.5%-100%).

Patients With Cancer Are At Higher Risk for Kidney Failure P

atients with cancer have a higher risk for kidney failure requiring replacement therapy (KFRT), and that risk differs by cancer type, a new study finds.

Using the Korean National Health Insurance Service database, investigators examined KFRT risk among 824,365 Korean patients with cancer compared with 1,648,730 patients without cancer matched by age, sex, estimated glomerular filtration rate (eGFR), diabetes status, and hypertension status.

KFRT was required for 1.07 patients with cancer compared with 0.51 patients without cancer per 1000 person-years, Soo Wan Kim, MD, PhD, Chonnam National University Medical School, Korea, and colleagues reported in the American Journal of Kidney Diseases. Cancer was significantly associated with a 2.3-fold increased risk for KFRT, in a fully adjusted model. Among patients with chronic kidney disease (CKD), those with vs without cancer had a significant 1.4fold increased risk for KFRT. Among patients with proteinuria, cancer was associated with a significant 1.3-fold increased risk for KFRT.

www.renalandurologynews.com

SPRING 2022

Renal & Urology News 5

Diabetes May Complicate Renal Biopsy Recent study reveals an increased risk for major bleeding complications and need for transfusion THE RISK FOR MAJOR bleeding complications after percutaneous renal biopsy is higher among patients with than without diabetes, according to a new Japanese study.

All percutaneous renal biopsies in Japan are performed in the hospital. In a nationwide inpatient database of 76,302 Japanese patients who underwent percutaneous renal biopsy, major bleeding complications occurred in 678 patients (0.9%), including 622 (0.8%) with red blood cell (RBC) transfusion within 7 days and 109 (0.1%) with invasive hemostasis requiring transcatheter arterial embolization or nephrectomy. Of the cohort, 8245 had diabetes mellitus.

Major bleeding complications (3.1% vs 0.6%), including requiring RBC transfusion (2.9% vs 0.66%), transfusion of more than 1 L (1.6% vs 0.1%), and invasive hemostasis (0.3% vs 0.1%)

was significantly more common in the group with vs without diabetes. In multivariate analysis, the diabetes group had a 2.4-fold increased risk for major

Researchers report results from their study of 76,302 Japanese patients. bleeding complications and a 2.4- and 1.9-fold increased risk for transfusion and invasive hemostasis, respectively, corresponding author Hideo Yasunaga, PhD, of The University of Tokyo in Japan, and colleagues reported in Kidney International Reports.

Multiagent or insulin for diabetes treatment was significantly associated

Cardiovascular Calcification Increases Death Risk in ESKD CALCIFICATION IN cardiac valves and

not be overlooked and can be used

aorta portends worse survival and

for risk assessment in maintenance

progresses faster in patients with end-

HD patients,” Dr Cao and colleagues

stage kidney disease (ESKD), according

wrote. “Moreover, it can help identify

to a recent study.

patients who are appropriate for

In a study of 434 patients receiving hemodialysis (HD), 27.2% of patients displayed mitral valve calcification

intensive medical treatment to reduce cardiovascular events.”

In a second study, researchers

(MVC) and 31.8% aortic valve calci-

examined progression of aortic calci-

fication (AVC) on echocardiography.

fication in 150 patients with stage 4-5

The group with vs without cardiovas-

chronic kidney disease transitioning to

cular calcification had significantly

dialysis or transplantation or continuing

higher all-cause and cardiovascular

conservative care. The median abdomi-

mortality rates, Ning Cao, MD, of

nal aortic calcification (AAC) score

General Hospital of Northern Theater

significantly increased from 4.8 before

Command, Liaoning, China, and col-

renal replacement therapy or conser-

leagues reported in BMC Nephrology.

vative care to 8.0 at 3 years after the

The presence of MVC and AVC was

transition, with no difference among

significantly associated with 1.5- and

treatment modalities, Roosa Lankinen,

1.4-fold increased risks for all-cause

MD, of University of Turku, Finland,

mortality and 2.3- and 2.4-fold

and colleagues reported in Kidney and

increased risks for cardiovascular mor-

Blood Pressure Research.

tality, respectively. Left atrial dimen-

The annual rate of AAC increase was

sion also significantly correlated with

significantly associated with a 1.4-fold

all-cause and cardiovascular death.

higher risk for mortality and, in trans-

Cardiovascular calcification on

plant recipients, a longer time on the

routine echocardiography “should

transplant waiting list.

■

with a 1.6-fold increased risk for major bleeding complications compared with single-agent treatment.

The patients with diabetes tended to be older, male, and steroid users with acute kidney injury (AKI), chronic kidney disease (CKD), or rapidly progressing glomerulonephritis (RPGN).

In multivariable analysis, older age, female sex, AKI, CKD, or RPGN, and steroid use each were associated with higher risks of major bleeding. Diabetes remained a risk factor after adjustment for patient and hospital characteristics and in a sensitivity analysis considering anemia, according to the investigators.

Dr Yasunaga’s team acknowledged that the study was limited by a lack of information on needle gauge, glucose control, timing of discontinuation and resumption of antithrombotic agents, and some other relevant factors.

The researchers concluded that “nephrologists should carefully judge whether the anticipated benefits outweigh the relatively high risk of major bleeding complications when considering [percutaneous renal biopsy] for patients with diabetes.”

In an accompanying editorial, Emilio D. Poggio, MD, of Glickman Urological and Kidney Institute at Cleveland Clinic in Cleveland, Ohio, and colleagues wrote that they “strongly support the practice of [percutaneous renal biopsy] in patients with diabetes when a secondary diagnosis is suspected, and identification of that disease would alter management with the hopes of reducing the progression to end-stage kidney disease. As in all patients with or without diabetic kidney disease, we recommend aggressively managing modifiable risk factors to reduce the risk of bleeding.” ■

Study Finds Continuous Rise in mPCa

California’s Keck School of Medicine in Los Angeles, and colleagues reported in JAMA Network Open. Among men aged 75 years or older, mPCa incidence significantly decreased 1.5% annually from 2004 to 2011, but significantly increased 6.5% annually from 2011 to 2018.

The rise in mPCa occurred despite a significant concurrent reduction in overall PCa diagnoses, according to the investigators.

“Although the reasons behind this recent rising incidence of mPCa are multifactorial, it is unlikely to be due to a true change in cancer biology in such a short period,” the authors wrote.

“Factors such as environmental exposures or germline variations leading to changes in epidemiological signatures of cancers take substantially longer.

Rather, changes in clinical policy and/ or practice such as screening strategies and use of diagnostic imaging are much more likely to explain such short-term changes in cancer epidemiological trends.”

Regardless of the cause, Dr Desai and colleagues noted, the finding of a rising incidence of mPCa by itself does not imply that screening practices should be changed. “The overall risk vs benefit of PSA-based screening is extremely complex and must take into account various other factors that impact the overall health of the community.” ■

METASTATIC PROSTATE cancer (mPCa) incidence continues to increase in the US, a trend temporally associated with changes in guidelines from the US Preventive Services Task Force (USPSTF), according to the latest data.

The USPSTF recommended against routine PSA screening of men older than 75 years in 2008 and all men in 2012, but revised their recommendation in 2018, advising personalized decision-making for screening men aged 55 to 69 years.

Investigators observed the trend when they analyzed data from 836,282 PCa cases in the Surveillance, Epidemiology, and End Results (SEER) 18 registry. They identified 26,642 men (56.5%) aged 45 to 74 years and 20,507 (43.5%) men aged 75 years or older diagnosed with metastatic PCa from 2004 through 2018.

Among men aged 45 to 74 years, mPCa incidence was stable from 2004 to 2010 (-0.4% annually), but significantly increased 5.3% annually from 2010 to 2018, Mihir M. Desai, MD, MPH, of the University of Southern

6 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

Anaphylaxis Risk With IV Iron Differs By Product

BY NATASHA PERSAUD INTRAVENOUS (IV) iron use overall is associated with a very low risk for anaphylaxis, but iron dextran and ferumoxytol are associated with a higher risk compared with iron sucrose, according to new research.

Investigators compared the risks for anaphylaxis among 5 IV iron products using data from 167,925 new users of IV iron older than 65 years receiving Medicare Part D. The adjusted rates for anaphylaxis per 10,000 administrations were 9.8 cases for iron dextran, 4.0 cases for ferumoxytol, 1.5 cases for ferric gluconate, 1.2 cases for iron sucrose, and 0.8 cases for ferric carboxymaltose.

Compared with iron sucrose, iron dextran and ferumoxytol were significantly associated with 8.3- and 3.4-fold increased odds for anaphylaxis, respectively, Chintan V. Dave, PharmD, PhD, of Rutgers University, New Brunswick, New Jersey, and colleagues reported in the Annals of Internal Medicine.

Hospitalization for anaphylactic reactions occurred only among patients receiving iron dextran or ferumoxytol.

Anaphylaxis with CPR, hypotension, or epinephrine also occurred at higher rates among patients receiving iron dextran or ferumoxytol.

High-molecular-weight iron dextran was withdrawn from the US market in 2014. Anaphylaxis risk with low-molecular-weight iron dextran was also increased.

“Clinically, factors guiding the choice of parenteral iron preparation should include not only the risk for anaphylaxis but also medical history, clinical indication, setting, dose, number and duration of administrations needed, risk for other adverse events, and cost,” Dr Dave’s team wrote.

In a second study of 12,237 patients (mean age 51 years) with iron deficiency published in JAMA Network Open, Joseph Shatzel, MD, of OHSU Knight Cancer Institute, Portland, Oregon, and colleagues found a low 3.9% rate of adverse events from IV iron use.

The adverse event rate was significantly higher among patients who received premedication such as corticosteroids and antihistamines compared with those who did not (38.6% vs 1.7%).

Severe adverse reactions were extremely rare. The study identified only 2 documented epinephrine administrations, both associated with iron dextran use, according to the investigators.

The risk for infusion reactions differed significantly among IV iron ­products:

4.3% with iron sucrose, 3.8% with iron dextran, 1.8% with ferumoxytol, and 1.4% with ferric carboxymaltose.

Among patients with a history of infusion reactions, readministration with the same IV iron formulation was significantly associated with a higher reaction rate especially with (68%) than without

(32%) premedication, compared with an alternate IV iron formulation with (21%) than without (5%) premedication.

“Although further investigation is warranted to determine the ideal approach of readministration of iron in those who experience an infusion reaction,” the investigators concluded,

“our data suggests that rechallenging patients with IV iron, perhaps with an alternate formulation and not preceded by sedating antihistamines, would be both safe and effective. Overall, IV iron continues to hold an undeniably essential role in the management of iron deficiency.” ■

www.renalandurologynews.com

SPRING 2022

Renal & Urology News 7

Pediatric ESKD Racial Gap Persists Into Adulthood

BY NATASHA PERSAUD A 30-YEAR observational cohort study of children with childhood-onset kidney failure found that Black patients are disadvantaged in all aspects of kidney transplantation into adulthood compared with White patients, according to investigators.

Black patients have a significantly higher overall mortality rate and lower graft survival rate compared with White patients. Black patients also are less likely to undergo preemptive transplantation. Researchers speculate that socioeconomic factors might contribute to the disparities.

“Our analysis demonstrated that Black patients faced more economic challenges as evidenced by a greater likelihood of living in areas of low median household income, having Medicaid as primary payer, or having no health insurance, all of which could present barriers to transplant access

and limit the chance of preemptive transplantation,” they wrote.

Using 1980-2017 US Renal Data System (USRDS) data, Susan R. Mendley, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of

8 Renal & Urology News

SPRING 2022

ESKD race disparities continued from page 7

Health in Bethesda, Maryland, studied 28,337 children — 24% Black and 76% White — diagnosed with ESKD before age 18 years.

Compared with White patients, Black patients had a significantly lower unadjusted 30-year overall survival rate (39% vs 57%) and significantly lower

www.renalandurologynews.com

rate of preemptive transplantation (23.6% vs 13.4%), the investigators reported in the Journal of the American Society of Nephrology.

Compared with White patients, Black patients had a significant 45% higher risk for all-cause mortality, a 31% lower rate of first transplant, and a 39% lower rate of second transplant, Dr Mendley’s team reported. A significantly lower proportion of Black patients had a living

donor for a first (26.0% vs 49.2%) or second kidney transplant (15.4% vs 35.1%).

After their first transplant, Black patients received 11% fewer total lifetime transplants compared with White patients, according to the investigators. A significantly higher proportion of Black than White patients never received a transplant (23.6% vs 13.4%).

Among transplanted patients, graft survival was shorter in Black than White

patients (median 6.1 vs 10.3 years). Graft survival was 20% and 24% lower after the first and second transplant, respectively, for the Black population.

The risk for mortality was 38% and 23% higher after the first and second transplant, respectively, for Black patients, the investigators reported. These trends largely persisted across defined eras from 1980 through 2017 with no meaningful improvement in outcomes

www.renalandurologynews.com

over time despite medical and technical advancements. The investigators could not assess how 2014 changes in the Kidney Allocation System may have affected outcomes.

Transplantation was associated with a 72% decreased risk for death over a lifetime for patients with childhood-onset ESKD, Dr Mendley and colleagues reported. Yet time with a functioning allograft was significantly shorter for Black

than White patients who began renal replacement therapy in childhood: 57% vs 83% of follow-up time, respectively.

In a simulation, investigators found that equalizing transplant number, graft survival, and time with a functioning transplant would reduce Black excess mortality from 45% to 34%.

“This indicates that 35% of the excess mortality between Black and White patients would be eliminated if the

SPRING 2022

t­ ransplant experience was the same in each racial group, but 65% of the survival differential would remain from other mediators independent of transplantation,” Dr Mendley’s team wrote.

Transplant waiting time, graft survival, and access to subsequent transplants may all contribute to the disparity in time with a functioning graft, the investigators noted. They suggested that social determinants of health

Renal & Urology News 9

and the consequences of structural racism likely play important roles. A greater proportion of the Black than White population had a low median household income of less than $34,000 (56.2% vs 11.1%) and Medicaid as primary insurance (48.3% vs 32.9%). The study lacked more granular information on socioeconomic status, comorbidities, and body mass index, limiting interpretation of the findings. ■

10 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

HRQOL Predicts Post-RP Outcomes in High-Risk PCa MEN WITH GOOD health-related quality of life are more likely to have favorable outcomes following radical prostatectomy (RP) for high-risk prostate cancer, researchers reported at the 2022 Genitourinary Cancers Symposium.

In a propensity-score matched analysis of 636 patients with high-risk prostate

cancer, the biochemical recurrence-free survival rate at 5 years was significantly higher among those who had a preoperative global health status (GHS) of 70 or higher vs lower than 70 on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-

C30), Thilo Westhofen, MD, of LudwigMaximilians-University Munich in Germany reported on behalf of his team. The metastasis-free survival rate at 5 years was also significantly higher among patients with a good GHS at baseline: 86% vs 68%, respectively.

The groups were well matched by age,

PSA, pT stage, Gleason grade, positive surgical margin rate, and lymph node involvement. A multivariate analysis confirmed that a GHS of 70 or more independently predicted a 40% and 49% decreased risk for biochemical recurrence and metastasis, respectively, according to researchers. ■

www.renalandurologynews.com

SPRING 2022

Renal & Urology News 11

Small Renal Mass Management Varies by Race ALTHOUGH THE NATURAL history of small renal masses (SRMs) is similar in Black and White patients, Black patients are more likely to undergo radical nephrectomy and to have worse survival, investigators reported at the 2022 Genitourinary Cancers Symposium.

In the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry, 410 patients elected active surveillance (84% White, 16% Black) and 335 chose primary intervention. At a median 12.5 months, 66 of the 410 patients on active surveillance underwent delayed intervention for

progressive disease or other reasons.

Within the active surveillance cohort, investigators found no racial differences in age, comorbidities, or tumor size. The median overall growth rate of the renal masses also did not differ significantly between Black and White patients: 0.04 vs 0.1 cm/year, Joseph

G. Cheaib, MD, MPH, of The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, reported on behalf of his team.

Tumor size was comparable between patients with primary or delayed intervention. Black patients, however, had a significant 68% lower likelihood of delayed intervention compared with White patients. Black patients also were significantly more likely to undergo radical nephrectomy: 24.6% vs 10.4%, Dr Cheaib’s team reported. Pathologic stage and grade were similar between groups. Papillary histology, however, was significantly more frequent among Black patients: 34.1% vs 19.9%.

In the intervention group, 31 patients died. Black patients had a significant 2.5-fold increased risk for death.

The differences in histology, surgical approach, and survival between Black and White patients with SRMs masses are puzzling, according to the investigators.

Black vs White patients less likely to have delayed intervention.

Further socioeconomic and molecular analyses will help elucidate biological differences and identify strategies to improve outcomes among patients with SRMs, Dr Cheaib’s team concluded in the study abstract.

The current study adds to a growing literature on factors influencing SRM management.

In a previous study published in 2019 in Urology, Kevin A. Nguyen, MD, and colleagues found that Black race was independently associated with 56% increased odds of active surveillance at initial management for SRMs compared with White race. That finding was based on an analysis of 59,189 patients in the National Cancer Database.

In a paper published in 2013 in BJU International, Andreas Becker, MD, and colleagues reported their findings from a study of 26,468 patients with SRMs in the Surveillance, Epidemiology, and End Results (SEER) database showing that Black patients were 23% more likely than other races to be managed non-surgically. Among patients treated surgically, Black patients were 20% less likely to undergo partial nephrectomy. ■

12 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

Prostate MRI Less Likely for Black Men Geographic differences, socioeconomics, and structural racism identified as contributing factors

KTRs at High Risk for Graft Loss ID’d INVESTIGATORS have identified 2 distinct populations of kidney transplant recipients (KTRs) at high risk for graft loss, with risk factors at baseline suggesting approaches to management.

Among 5752 solitary kidney transplants performed 2006-2018, graft loss occurred in 21.6% of patients, including 9.6% with graft failure and 12.0% with death with a functioning graft (DWFG).

The KTRs had a mean age of 53.8 years.

The top causes of graft failure were alloimmunity (38.7%), glomerular diseases (18.6%), and renal tubular injury (13.9%), Mark D. Stegall, MD, of William J. von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota, and colleagues reported in Transplantation Direct. More than three-quarters (79.4%) of the alloimmune losses were associated with antibody-mediated damage. Renal tubular injury comprised recurrent episodes of acute tubular necrosis due to infection (39.0%), recurrent/chronic hypovolemia (14.3%), a severe episode of acute tubular injury (16.9%), and

vs 9.9%), with Black men having significant 38% lower odds of receiving this imaging, the investigators reported in JAMA Oncology. Receipt of prostate MRI among men of other races was similar to that of White men.

Mediators of Racial Disparity In a mediation analysis, Dr Leapman’s team determined that 24% of the racial disparity in prostate MRI use between Black and White patients was attributable to geographic differences, 19% to residence in high-poverty neighborhoods, 19% to racialized residential segregation, and 11% to low individual socioeconomic status (defined as dual eligibility for Medicare and Medicaid).

Clinical and pathologic factors were not significant mediators of racial disparities, the researchers reported.

“This research suggests that targeted actions to address race-based differences in prostate MRI use should incorporate a focus on spatial factors as c­ ardiorenal syndrome (15.6%). Major causes of DWFG included malignancy (20.0%), infection (19.7%), and cardiac disease (12.6%) with risk factors of older age, pretransplant dialysis, and diabetes as the cause of kidney failure.

According to competing risk incidence models, patients aged 55 years and younger had significantly higher rates of graft failure due to alloimmune causes compared with older patients.

Recipients with vs without diabetes had significantly higher rates of nonalloimmune graft loss.

According to Dr Stegall’s team, the data indicate that there are 2 populations of high-risk KTRs that can be identified at baseline: Young recipients without diabetes who lose their allograft due to alloimmunity and older recipients with diabetes prone to DWFG and graft failure due more often to a mixture of nonalloimmune causes.

“Some of the possible approaches [to prevent allograft failure] include improved management of diabetes, including bariatric surgery; calcineurin-inhibitor free immunosuppression, which has been shown to improve a combined endpoint of patient and graft survival at 7 y; and the avoidance of pretransplant dialysis via preemptive kidney transplantation,” Dr Stegall and colleagues wrote. ■

analysis. Therefore, we cannot account for factors external to those identified, such as other built environment variables or other manifestations of systemic racism, which introduce the possibility of missed mediation.”

In an editorial accompanying the new report, Michael Poulson, MD, MPH, of Boston University School of Medicine, lauded the research as a “model for accurate and robust study of racial disparities in the context of the discriminatory landscape from which they were built.”

Prostate MRI improves prostate cancer detection and can enhance decision-making.

well as upstream social determinants of health,” Dr Leapman’s team wrote.

In a discussion about study limitations, the researchers noted that the model they constructed “is inherently constrained by the candidate mediators that were selected for this retrospective

Societal Structural Change Needed “Solutions to racial disparities are attainable through actionable reparative actions aimed at righting the wrongs of history and narrowing the racial wealth gaps created by the discriminatory history of the US,” Dr Poulson wrote.

“Not all solutions to health care disparities are solved in the hospital. Many must come from changes to the societal structure in which we all live.” ■

Bacterial Supplement in mRCC May Improve CPI Outcomes RESULTS FROM a small study suggest

Research at City of Hope in Duarte,

that a live bacterial supplement might

California, said in a press release.

improve outcomes in patients receiv-

Dr Pal’s team tested whether use of

ing checkpoint inhibitor (CPI) immuno-

CBM588 could improve CPI response

therapy for advanced kidney cancer,

by increasing the relative abundance

possibly by increasing the abundance

of Bifidobacterium species in the gut.

of certain beneficial bacteria.

Previous studies have shown that

Data from an open-label phase 1 trial demonstrate that use of a live strain

Bifidobacterium species are associated with enhanced clinical benefit from CPIs.

of Clostridium butyricum (CBM588)

Dr Pal and colleagues studied 30

orally in combination with the CPIs

treatment-naive patients with mRCC

nivolumab/ipilimumab significantly

who had clear cell and/or sarcomatoid

improved progression-free survival

histology and intermediate- or poor-

(PFS) in patients with metastatic renal

risk disease. They randomly assigned

cell carcinoma (mRCC) compared with

patients 2:1 to receive nivolumab/

nivolumab/ipilimumab alone, investiga-

ipilimumab with or without daily oral

tors reported in Nature Medicine.

CBM588, respectively. PFS was

“These results can help improve treat-

significantly longer among the CBM588

ment options for patients with kidney

recipients compared with those not

cancer and is an important foundational

receiving the bacterial supplement

step to bring about more effective

(12.7 vs 2.5 months). CBM588 was

targeted therapies for cancer treatment,”

significantly associated with an 85%

the study’s senior author Sumanta K.

decreased risk for progression.

Pal, MD, a professor in the Department of Medical Oncology & Therapeutics

The bacterial supplement is being developed by Osel, Inc. ■

© BFK92 / GETTY IMAGES

BLACK PATIENTS with localized prostate cancer are less likely than White patients to undergo prostate magnetic resonance imaging (MRI) during initial diagnosis, a disparity due largely to geographic variation, socioeconomic disadvantage, and structural racism, according to a new study.

Prostate MRI improves prostate cancer detection and can enhance clinical decision-making, research shows.

Using 2011-2015 data from the US Surveillance, Epidemiology, and End Results (SEER)-Medicare database, Michael S. Leapman, MD, of the Yale School of Medicine in New Haven, Connecticut, and colleagues identified 39,534 men who receied a prostate MRI within 6 months of localized prostate cancer diagnosis. The group included 3979 Black patients (10.1%), 32,585 White patients (82.4%), and 2970 patients of other races (7.5%).

A smaller percentage of Black than White men had a prostate MRI (6.3%

14 Renal & Urology News

SPRING 2022

Darolutamide in mHSPC continued from page 1

The researchers found that darolutamide significantly decreased the risk of death by 32.5% compared with placebo.

Overall Survival The overall survival rate at 4 years was 62.7% in the darolutamide arm and 50.4% in the placebo arm. The survival benefit associated with darolutamide was consistent across prespecified subgroups, Dr Smith reported.

In addition, darolutamide significantly delayed the development of castration-resistant prostate cancer (CRPC) and time to pain progression.

The median time to CRPC was 19.1 months in the placebo arm and was not reached in the darolutamide arm.

Darolutamide recipients had a significant 64% lower risk for CRPC. The median time to pain progression was 27.5 months in the placebo arm and was not reached in the darolutamide arm. Darolutamide therapy was significantly associated with a 21% lower risk for pain progression.

The 2 study arms had a similar incidence of treatment-related adverse events (TRAEs). The incidence of grade 3/4 TRAEs was 66.1% in the darolutamide arm and 63.5% in the placebo arm. The

Gene mutations in RCC continued from page 1

inferior OS. “These data suggest that site of metastatic involvement may reflect divergent biologic underpinnings driving heterogeneous clinical behavior,” Dr McKay told attendees.

Using a commercially available assay, Dr McKay’s team performed exome and transcriptome sequencing on RCC tissue specimens obtained from the kidney and distant metastatic sites. A total of 657 samples from 653 patients (70.6% male) underwent molecular profiling.

New nmCRPC insights continued from page 1

therapy, and 478 (23.4%) underwent radical prostatectomy. The median time from primary treatment to nmCRPC was 6 years, she said The crude median time from nmCRPC diagnosis to death from any cause was 37.6 months, Dr Hird reported.

Using regression analysis, the investiga­tors identified the f­ollowing

www.renalandurologynews.com

with PEACE-1, this study provides clear evidence that a triplet combination that includes standard hormonal therapy, chemotherapy, and a next generation androgen signaling inhibitor, produces meaningfully better outcomes than a chemotherapy plus standard hormonal therapy doublet.”

The PEACE-1 trial demonstrated that adding abiraterone acetate plus prednisone to ADT plus docetaxel improved survival in patients with de novo

mHSPC compared with ADT plus docetaxel alone. Investigators reported results at the 2021 European Society for Medical Oncology Congress.

The 3-drug combination studied in ARASENS is a standard of care that can be offered to patients, Dr Beer said. “I also think that the evidence for 3-drug combinations is strongest in the highestrisk patients, particularly patients with newly diagnosed metastatic disease.”

He pointed out that neither ARASENS nor PEACE-1 compared the triplet to a doublet of standard hormonal therapy plus a next-generation androgen signaling inhibitor. “This leaves us with several competing standards of care,” Dr Beer said. “The appropriate choice of therapy remains individualized and may include a hormonal therapy doublet or a chemotherapy containing triplet.

But for patients we used to treat with a chemotherapy containing doublet, it is now clear that a third drug, a nextgeneration androgen signaling inhibitor, improves outcomes, particularly in high-risk patients.”

“The findings are very important,” said Amar U. Kishan, MD, chief of genitourinary oncology and vice chair of clinical and translational research at the University of California, Los Angeles, where he is an assistant professor in the Department of Radiation Oncology.

While the ENZAMET trial, which

Compared with the kidney, several genes at selected metastatic sites were mutated at higher rates, including the PBRM1 and KDM5C genes. The mutation rates in the PBRM1 gene were 59.5%, 59.1%, and 45.9% in bone, endocrine glands (adrenal glands, pancreas, and thyroid glands), and lung, respectively, compared with 33.8% in the kidney, Dr McKay’s team reported.

For the KDM5C gene, the mutation rates were 27.8%, 29.2%, and 35.3% in endocrine glands, lymph nodes, and soft tissue, respectively, compared with 9.3% in the kidney.

Further, compared with kidney specimens, bone metastases had a significantly higher proportion of tumors classified as “angio/stromal” (42.2% vs 15.4%; p < 0.0001), whereas liver metastases had a higher proportion of the “complement/ Ω-oxidation” subgroup (60.7% vs 14.1%).

Results also showed that PD-L1 and PD-L2 gene expression is higher in lung, pleural, and bone metastases.

“These findings define molecular features that differentiate primary and distant metastatic sites of disease in patients with renal cell carcinoma,” Dr McKay concluded.

most common TRAE was neutropenia (33.7% and 34.2%, respectively).

‘A Major Contribution’ “The ARASENS study is major contribution to the field,” said Tomasz M. Beer, MD, Professor of Medicine and Grover C. Bagby Chair of Prostate Cancer Research at Oregon Health & Science University (OSHU) in Portland, and chief medical officer of the Center for Early Detection Advanced Research at the OHSU Knight Cancer Institute. “Together

The darolutamide and placebo study arms had a similar incidence of TRAEs.

­ redictors of faster time to prostate p cancer death: older age, ADT use with primary treatment, higher PSA at nmCRPC diagnosis, and higher grade group.

“Given that the study period was prior to the introduction of [androgen receptor axis-targeting therapies] for nmCRPC and prior to the more widespread use of novel imaging modalities to detect metastasis, this study provides a historical reference for the approximate prevalence and

Overall, metastasis developed in 20% of men after a median time of 31.1 months. expected disease trajectory for patients with nmCRPC,” the investigators concluded.

In a separate study of nmCRPC presented at the meeting, Shawn Malone,

compared enzalutamide plus androgen suppression and androgen suppression, did include a substantial proportion of patients on either arm who received docetaxel, ARASENS “is the first published randomized trial to uniformly use androgen suppression plus docetaxel on both the standard arm and the experimental arm,” he said.

“The large improvement in overall survival as well as time to castration resistance is a critically important finding, as is the fact that overall adverse event rates were not significantly increased with the addition of darolutamide,” Dr Kishan said.

In general, the triple combination of darolutamide plus ADT and docetaxel “certainly meets the bar to consider it a new standard of care,” but some caveats should be considered, Dr Kishan said.

For example, it remains unclear whether the findings are generalizable to men with M1c disease, recurrence mHSPC, and/or poor performance status. Nearly 80% of the patients had M1b disease and 85% had de novo mHSPC, and study participants overall “were quite fit with a high performance status.”

Moreover, ARASENS investigators did not analyze treatment effect according to disease burden, so “we cannot discuss the benefits [of the triple combination] in men with high vs low burden of disease.” ■

New findings could inform personalized therapeutic strategies, investigators say.

The patients from whom tissues samples were obtained had a median age of 62 years. The most common histology was clear cell RCC (77.5% of cases), followed by papillary (9.6%), chromophobe (4.6%), medullary (1.2%), collecting duct (0.9%), and mixed (6.2%). ■

MD, and colleagues found that PSA testing and imaging studies were underused in a real-world setting for the management of of nmCRPC, particularly among patients at high risk for metastatic disease.

“Infrequent monitoring impedes proper risk stratification, disease staging, detection of treatment failure, and/ or metastases, resulting in delays with necessary treatment intensification of life prolonging therapies,” they concluded in a poster presentation. ■

18 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

Early Dialysis Initiation Associated With Lower Risks for Death, MACE Recent finding from an observational study contrasts with previous research

Allopurinol May Improve KT Outcomes URATE-LOWERING treatment with

EARLY INITIATION of dialysis may modestly reduce the risks for death and major adverse cardiovascular events (MACE), an observational study finds.

But the tradeoff may be in quality of life.

Among 10,290 patients with advanced chronic kidney disease (median age 73 years; 36% women) in the National Swedish Renal Registry, 3822 started

Lowest death risk observed when dialysis started at an eGFR of 15-16. dialysis, 4160 died, and 2446 had a MACE (a composite of cardiovascular death, nonfatal myocardial infarction, or non-fatal stroke). Investigators examined dialysis initiation in this cohort at estimated glomerular filtration rates (eGFR; in mL/min/1.73 m2) from 4 to 19 in increments of 1.

Mortality displayed a U-shaped curve with eGFR, with the lowest death risk at eGFR 15-16. Compared with dialysis initiation at eGFR 6-7, initiation at eGFR 15-16 was significantly associated with a 5.1% lower absolute risk for death within 5 years, Edouard L. Fu, MD, PhD, of Leiden University Medical Center, Leiden, The Netherlands, and colleagues reported in BMJ. “This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up,” Dr Fu’s team wrote. “However, dialysis would need to be started four years earlier.” For most patients, this purported survival benefit would not outweigh the burden of more years spent on dialysis, according to the investigators.

The lowest absolute risk for MACE was 3.3% when dialysis was initiated at an eGFR of 13-14, using an eGFR of 6-7 as a reference.

The investigators adjusted analyses for multiple relevant factors, such as laboratory values and comorbidities. However,

the study lacked information on nutritional status or muscle mass, uremic symptoms, volume status, and quality of life or physical activity. The team also noted that optimal eGFR to start dialysis may differ between hemodialysis and peritoneal dialysis; up to 39% of patients in Sweden start with peritoneal dialysis.

“Our results further suggest that in the absence of symptoms or strong indications, initiation of dialysis may be postponed until lower eGFR values are reached (intent to defer), without a large increase in mortality or cardiovascular events,” according to Dr Fu’s team.

The new findings differ from those of some previous reports, including one in Hemodialysis International in 2021. That report, which provides details of a study involving 676,196 adult patients initiating hemodialysis between 2006 and 2014, found that patients who started hemodialysis early (eGFR 13 or higher) had a significant 93% increased risk for all-cause mortality compared with those who started late (eGFR less than 8.7). ■

allopurinol may help maintain graft function in kidney transplant (KT) recipients with elevated serum uric acid levels, a new study suggests.

In the ADOPTR (Allopurinol Drug use on GFR and Proteinuria in Renal Transplantation Recipients) study, researchers randomly assigned 124 KT recipients to receive allopurinol (300 mg once daily) or matched placebo. Mean serum uric acid levels significantly decreased from 6.98 mg/dL at baseline to 6.00 mg/dL at 24 weeks in the allopurinol group, but did not change significantly in the placebo group, Özlem Usalan, MD, and colleagues from Gaziantep University School of Medicine, Gaziantep, Turkey, reported in Transplant Immunology. In the allopurinol group, mean estimated glomerular filtration rate (eGFR; according to the Modification of Diet in Renal Disease study equation) significantly increased from 68.05 to 71.97 mL/

Poor Nutrition at Dialysis Start Ups Mortality Odds PATIENTS WITH POOR or declining nutritional status during dialysis initiation are at higher risk for death for up to 5 years afterward, according to investigators.

“This calls for special attention to be paid to diet and adequate treatment of comorbidities as patients approach dialysis, in order to optimize survival after dialysis start,” Sara Blumberg Benyamini, PhD, of Wolfson Medical Center in Holon, Israel, and colleagues reported in the Journal of Renal Nutrition.

They also observed, “Our study also suggests the importance of improving the nutritional status during the first months in dialysis. Dietary intervention at this time, during the first 3 months on dialysis, might improve survival during the 3 years following RRT commencement.”

The investigators calculated an Integra­tive Clinical Nutrition Dialysis Score (ICNDS) for 297 patients at dialysis initiation and 1, 2, and 3 months later. For each patient, they ranked 7 parameters — serum albumin, creatinine, and urea, cholesterol, dialysis

adequacy, C-reactive protein (CRP), and post-dialysis weight change — on a scale from 1 (abnormal) to 5 (meets guideline recommendations) and tallied the score. Weight change and albumin levels each accounted for 25% of the ICNDS, and the remaining 5 parameters each made up 10%. A low

Findings suggest special attention be paid to diet as patients approach dialysis.

ICNDS was less than 75 and a high ICNDS 75 or more.

Patients with a low vs high ICNDS at baseline had 2.5- and 1.5-fold increased odds of all-cause death at 1 and 5 years, respectively. Deterioration of nutritional status within the first 3 months of dialysis (indicated by a negative vs positive ICNDS slope) was significantly associated with 1.7-fold increased odds of mortality within 3 years — even

among those with favorable nutritional status at baseline.

Patients with a low ICNDS at dialysis initiation were significantly older and had a higher prevalence of diabetes, cardiovascular disease, and malignancy. They also had higher CRP levels. According to the investigators, protein-energy wasting and inflammation, together known as malnutritioninflammation complex syndrome, likely explains the differences between the low and high ICNDS groups.

“We suggest a multidisciplinary approach that includes attention to diet and provision of adequate treatment for comorbidities in the period before initiation of dialysis, with the aim of increasing the ICNDS during the transition to [RRT],” Dr Benyamini’s team wrote. “This then might improve survival odds after dialysis initiation.”

The authors acknowledged a number of study limitations. For example, it had a relatively small sample size and was conducted at a single dialysis center, “thereby limiting the possibility of generalizing these findings.” ■

min/1.73 m2 and mean urinary albumin to creatinine ratio (UACR) significantly decreased from 325.14 to 319.29 mg/g. No meaningful kidney function changes occurred in the placebo group. C-reactive protein levels increased significantly over 24 weeks in the placebo group but not the allopurinol group.

“Our results seem to support the view that lowering circulating urate levels plays a role in improving kidney function in kidney transplant recipients,” Dr Usalan’s team concluded.

They acknowledged that elevated uric acid levels may reflect metabolic acidosis or other conditions, and not just hyperuricemia. Routine prophylaxis of asymptomatic hyperuricemia is not recommended in current guidelines.

Previous studies have yielded conflicting results on the use of allopurinol in patients at various stages of chronic kidney disease.

Limitations of the study include its small sample size and short duration of follow-up, the investigators noted. ■

www.renalandurologynews.com

SPRING 2022

Renal & Urology News 19

In-Hospital AKD Tied to Adverse Outcomes Data reveal higher risks for heart failure hospitalizations, death, and major adverse kidney events

BY NATASHA PERSAUD ACUTE KIDNEY disease (AKD) is increasingly recognized as a state that requires medical attention to avoid adverse outcomes. AKD reflects nonrecovery from acute kidney injury (AKI) persisting for 7-90 days or enduring subclinical alterations in kidney function without an AKI diagnosis, according to the Acute Disease Quality Initiative (ADQI). Recent studies on patients hospitalized with heart failure, cirrhosis, and critical illness find that AKD often leads to major adverse kidney events (MAKEs) and death.

Heart Failure In Kidney International Reports, investigators reported outcomes from 7519 patients admitted for acute decompensated heart failure (ADHF), of whom AKI and AKD occurred in 9% and 21.2%, respectively. Within the AKI group, 39.4% of patients progressed to AKD as defined by ADQI criteria.

In the group without prior AKI, AKD developed in 19.4% of patients.

AKD was significantly associated with 32%, 30%, and 20% increased risks for all-cause death, MAKEs, and heart failure hospitalization, respectively, during 5 years of follow-up,

corresponding author Chih-Hsiang Chang, MD, of Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taipei, Taiwan, and colleagues reported. MAKEs included end-stage kidney disease requiring long-term renal replacement therapy (RRT), new-onset chronic kidney disease (CKD), and death.

Dr Chang’s team developed prediction models that identified patients at high risk of any-stage AKD and stage 3 AKD or mortality. According to the investigators, it is an easy-to-use tool that can effectively predict the risk of AKD after ADHF and aid in early AKD diagnosis and intervention. The scoring system requires additional validation.

“Our scoring system is an easy-to-use tool that can effectively predict the risk of AKD after ADHF and thus aid in early AKD diagnosis and intervention,” the authors wrote.

Identified risk factors for any AKD included female sex, AKI, AKI severity, diabetes, CKD, laboratory values including creatinine, hemoglobin, albumin, and B-type natriuretic peptide, and cumulative dosage of inotropes and intravenous loop diuretics. Age, blood urea nitrogen, and

­ utpatient loop diuretic prescription o were additional predictors for stage 3 AKD (defined as a serum creatinine level 3.0 times baseline, an absolute serum creatinine increase of 4.0 mg/ dL or more, or RRT after 7 days and within 90 days).

“Until evidence-based quality metrics are established, we should stick with a repertoire of common sense strategies for high-risk patients after ADHF: careful volume status and l­aboratory

AKI stage 2 and 3, ascites, and obesity are among the risk factors for AKD. assessments, vigilant m ­ edication reconciliation, dietary counseling, ­ careful titration of heart failure medications, and removal of aggravating (true) nephrotoxic factors,” Dr Chang and colleagues wrote. “Nephrologists should also assume an expert role in managing potential metabolic derangements from heart failure therapies (e.g., hyper/hypokalemia and dysnatremias), along with offering reassurance

to patients and team members when small changes in [serum creatinine] are detected after therapy titrations.”

Cirrhosis In the Journal of Hepatology, another team of investigators reported that AKD (also defined by ADQI criteria) developed in 32% of 6250 patients hospitalized with cirrhosis who had community- or hospital-acquired AKI. The risk for mortality at both 90 and 180 days was a significant 1.4-fold higher for patients with vs without AKD. Compared with patients who did not have AKD, patients with AKD and AKD non-recovery were at significantly higher risk for short- and longer-term mortality, Kavish R. Patidar, DO, of Indiana University School of Medicine, Indianapolis, Indiana, and colleagues wrote.

De novo CKD occurred in a significantly higher proportion of the AKD vs no AKD group: 64.0% vs 30.7%. The investigators found that AKD was independently associated with a 2.5-fold increased risk for de novo CKD. Dr Patidar’s team identified several independent risk factors for AKD. AKI stage 2 or 3 and communityacquired AKI were significantly

Study: HRQOL in Advanced CKD May Vary By Sex

BY JOHN SCHIESZER HEALTH-RELATED quality of life (HRQOL) in patients with chronic kidney disease (CKD) may differ between men and women, according to a recent study.

At the start of the study, which enrolled 1421 patients aged 65 years or older with advanced CKD but not on dialysis, women had lower average physical and mental HRQOL scores compared with men. These scores, however, declined approximately twice as fast in men as in women during a 4-year study period, Nicholas C. Chesnaye, PhD, and colleagues reported in the Clinical Journal of the American Society of Nephrology.

Better understanding of sex-specific HRQOL over the course of pre-dialysis CKD and the potential mechanisms underlying any differences may provide insights into a patient’s health and other needs, according to the i­nvestigators.

“It could also aid sex-specific clinical monitoring, and the [kidney replacement therapy] decision making process,” said Dr Chesnaye, who is in the department of medical informatics at the University of Amsterdam and the Amsterdam Public Health Research Institute in The Netherlands.

New findings may offer insights into a patient’s health and other needs.

Multinational Study Population The investigators analyzed questionnaire responses from the European Quality Study on Treatment in Advanced Chronic Kidney Diseases (EQUAL).

The study included patients receiving routine medical care in Germany, Italy,

the Netherlands, Poland, Sweden, and the United Kingdom.

The researchers analyzed answers to the 36-Item Short Form Survey at 3 to 6 month intervals between April 2012 and September 2020. Dr Chesnaye’s team evaluated 5345 HRQOL measurements from 485 women and 936 men.

At baseline, patients had a mean age of 76 years and eGFR of 17 mL/min per 1.73 m2. Compared with men, women were older, more likely to be widowed, and had lower levels of education. They had higher body mass index and higher values of serum calcium, cholesterol, and potassium as well as lower levels of hemoglobin, lower albumin-creatinine ratio and higher baseline eGFR. Women had a mean physical component score of 42 and mental component score of 60. Men had mean scores of 55 and 69, respectively. During the study period, physical and mental component scores declined significantly

faster in men (by 2.5 and 2.7 points per year, respectively) compared with women (by 1.1 and 1.6 points per year, respectively).

The finding that women perceive an overall poorer HRQOL compared with men is consistent with what has been found in patients on dialysis and in several studies in patients with nondialysis dependent CKD. “The few longitudinal studies exploring the role of sex on HRQOL trajectories over time in advanced stage CKD found, in contrast to our own results, no difference in the rate of HRQOL decline between men and women,” Dr Chesnaye said.

Sex-Specific Determinants The current study showed that decreasing kidney function occurred at a faster rate in men than women, according to the study. Higher phosphate and lower hemoglobin levels and the presence of preexisting diabetes were associated

20 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

RCC Outcomes Not Worse With Minimally Invasive PN PARTIAL NEPHRECTOMY for renal cell carcinoma (RCC) with a minimally invasive approach is not associated with worse oncologic outcomes compared with an open procedure, a recent study suggests.

In fact, minimally invasive modalities resulted in a lower risk for recurrence and death from any cause, investigators reported in Urologic Oncology.

The finding supports previous reports suggesting that minimally invasive surgery is not associated with increased risk for port-site incisional or peritoneal seeding, they noted.

“There have been a few anecdotal arguments that minimal invasive renal surgery is not safe and puts patients at

a higher risk of tumor recurrence,” said lead investigator Reza Mehrazin, MD, associate professor of urologic oncology at the Icahn School of Medicine at Mount Sinai in New York, New York.

“This multicenter study shows that this is not true.”

Dr Mehrazin and colleagues studied a cohort of 2440 patients who underwent partial nephrectomy at 2 urban quaternary referral centers and identified 190 patients who underwent an open partial nephrectomy (OPN) and 190 propensity score-matched patients who underwent a minimally invasive partial nephrectomy (MIPN), either laparoscopic or robotic-assisted. The median follow-up duration was ­significantly

longer in the OPN than the MIPN group (59 vs 23 months).

Cancer recurrence was significantly more common in the OPN group than the MIPN group (10% vs 3.2%),

Dr Mehrazin’s team reported. The surgical approach did not predict location of recurrence. Time to recurrence did not differ significantly between the

OPN and MIPN groups (23.8 and 26.3 months, respectively), according to the investigators. On multivariable analysis, however, OPN was significantly associated with a 3.9-fold increased risk for recurrence compared with MIPN. In addition, the all-cause mortality rate was significantly higher in the OPN group (10.5% vs 2.6%).

“There likely remains some patient selection bias that is unaccounted for in the statistical analysis,” the authors wrote. “Nevertheless, the design of this study is concrete, and the outcomes should warrant reconsideration of the current opinion that OPN and MIPN result in equivalent long-term oncological outcomes.” ■

In-hospital AKD

use within 7 days of AKI onset were not associated with AKD. For cirrhosis patients with AKI, the investigators urged early nephrology consultation with follow-up and frequent lab monitoring and medication adjustments based on kidney function during and after hospitalization to help prevent AKD.

persisting for longer than 7 days — occurred in 403 patients (24.9%).

Mark Andonovic, MD, of the Uni­ ver­sity of Glasgow, Glasgow, UK, and colleagues observed significantly higher mortality rates in the ICU (16.1% vs 6.2%) and in the hospital (26.1% vs 11.6%) among patients with AKD compared with AKI that recovered. Longterm survival did not differ significantly between groups.

MAKEs occurred in a significantly higher proportion of the AKD group (54.2%) than the AKI group (41.9%).

By component, a decline in estimated glomerular filtration rate (eGFR) of more than 30% from baseline (50.4%

vs 41.9%), a doubling in serum creatinine (26.4% vs 18.8%), and initiation of long-term RRT (2.8% vs 0.6%) occurred in significantly more of the AKD group. AKD was significantly associated with 1.3-fold increased odds for MAKEs, the investigators found.

With respect to AKD risk factors, baseline eGFR of 30-60 or less than 30 mL/min/1.73 m2 was significantly associated with 1.4- and 2.0-fold increased odds for progression to AKD, respectively, the investigators reported.

Male sex and admission due to sepsis were significantly associated with 1.3and 1.4-fold increased odds for AKD, respectively. ■

is experiencing their disease and how to improve any suffering,” she said.

the 2 groups had been more similar, the outcome might have been different.”

May Be ‘Missing the Mark’ “The patient lives with the disease. If we aren’t helping them live better with their disease, then we are missing the mark. We need to see more studies that are done like this and take a longitudinal perspective. Data like these really help us when we want to set up our care models.”

Stephen Seliger, MD MS, an associate professor in the Division of Nephrology at the University of Maryland School of Medicine in Baltimore, said the design of the new study makes it impossible to measure many confounding variables. “The authors point out that there were important differences in medical comorbidities between men and women, and I think it explains a lot,” Dr Seliger said. “Women were more likely to be taking antidepressants.

They were also heavier and had higher potassium and cholesterol levels. So, if

Critical Insights Yelena Drexler, MD, assistant professor of clinical medicine in the Katz Family Division of Nephrology and Hypertension at the University of Miami in Florida, said patients who have a high burden of comorbidities and CKD-related complications may have significantly better outcomes with a deeper understanding of sex differences regarding patient-reported outcomes. “This study provides critical insights into the intersection between sex differences and the changes in patients’ perception of their quality of life over time,” Dr Drexler said. “Future research should explore the impact of interventions targeting the potentially modifiable factors identified in this study, and whether such interventions might attenuate the sex disparities in outcomes among patients with CKD.”■

continued from page 19

a­ssociated with 9.4- and 1.6-fold increased odds for AKD, respectively.

Pre-existing CKD and elevated serum albumin at the time of AKI were significantly associated with 3.1- and 1.4fold increased odds of AKD, respectively. For every 1 mm Hg decrease in mean arterial pressure at the time of AKI, the odds of AKD significantly increased 1%. Ascites and obesity were significantly associated with 1.6and 1.5-fold increased odds of AKD. Etiology of cirrhosis, presence of diabetes or hypertension, and vasopressor

HRQOL in advanced CKD continued from page 19

with lower physical and mental scores in men, but to a lesser extent in women.

Higher serum phosphate, lower hemoglobin, and the presence of preexisting diabetes were associated with lower physical scores.

Dr Chesnaye noted that CKD is highly prevalent in adults over age 65, and with life expectancies rising, efforts to improve HRQOL in this patient population are badly needed.

“Participants in our international cohort were prospectively included when their eGFR dropped below the pre-defined level of 20 mL/min/1.73 m2, thus minimizing the risk of survivor bias,” he said. “Our study is also subject to several limitations. We were unable to capture the complex interplay between demographic, psychosocial, and biological factors not collected by our study.”

Critical Illness In eClinicalMedicine, a product of The Lancet Discovery Science, researchers examined MAKEs and mortality outcomes among 5334 patients in intensive care (ICU), of whom 1620 (30.4%) had de novo AKI. AKD — defined as AKI Nephrologist Jennifer S. Scherer, MD, assistant professor of medicine at NYU Langone Health in New York, New York, said she was surprised by the stark differences in HRQOL between women and men. “With chronic diseases, we have to look at how the patients feel every day,” Dr Scherer

Over a 4-year period, physical and mental HRQOL deteriorated more rapidly in men. said. “The study’s outcome is a patientreported outcome, so we are getting important data about how people feel as a result of their disease.”

While the study has limitations, Dr Scherer said most studies focus on disease-centered outcomes. “We have to refocus our research on how the patient

Recurrence risk found to be higher with open partial nephrectomy.

www.renalandurologynews.com

SPRING 2022

Renal & Urology News 21

Pre-Kidney Transplant Costs Rising Rapidly Efforts to expand kidney waiting list access may accelerate increases in spending MEDICARE spending through the Organ Acquisition Cost Center (OACC) for kidney transplantation evaluation and waiting list management have risen by a median of 4.4% annually per transplant from 2012 to 2017, according to a recent study.

During that time frame, Medicare’s share of OACC costs increased from $0.95 billion to $1.32 billion, which was 3.7% of total Medicare spending through its end-stage kidney disease (ESKD) program, Xingxing S. Cheng, MD, MS, of Stanford University in Stanford, California, and colleagues reported in JAMA Network Open.

Median OACC costs per kidney transplantation increased from $81,000 in 2012 to $100,000 in 2017.

Policy reforms aimed at expanding the kidney waiting list could result in substantial increases in OACC expenditures, according to the researchers.

The investigators observed that the existence of a transplant waiting list

OACC Spending Increasing Medicare reimburses transplant programs for costs attributable to kidney transplantation evaluation and waiting list management through the Organ Acquisition Cost Center (OACC).

A recent study has documented a rapid increase in OACC expenditures from 2012 to 2017.

$0.95 billion

2012

$1.32 billion

2017

Medicare share of OACC costs

$81,000

2012

$100,000

2017

Median OACC costs per kidney transplant

Source: Cheng XS, et al. Trends in cost attributable to kidney transplantation evaluation and waiting list management in the United States, 2012-2017. JAMA Netw Open. Published online March 10, 2022.

is evidence that a shortage of kidneys and not a shortage of patients eligible for transplantation limits the volume of kidney transplantation in the United States.

“Measures solely to increase waiting list access, unaccompanied by measures to improve organ availability, are

unlikely to succeed in increasing the number of kidney transplants,” they wrote. “Our findings suggest that such measures may also have the unintended consequence of diminishing efficiency and substantially increasing the OACC and overall costs of the Medicare ESKD program.”

Allopurinol, Febuxostat Found Frailty Ups Similarly Effective for Gout Flares Risks After ALLOPURINOL AND FEBUXOSTAT are

­anti-inflammatory prophylaxis with

similarly effective in controlling flares in

­colchicine, nonsteroidal ­anti-inflammatory

patients with gout, including those with

drugs, or glucocorticoids. After the

stage 3 chronic kidney disease (CKD),

maintenance phase, no study drug dose

according to trial results published in

adjustments were allowed, and all anti-

the New England Journal of Medicine.

inflammatory treatments were discontinued except in the event of gout flare.

In the double-blind CSP594

Results showed that 36.5% of the allo-

Comparative Effectiveness in Gout:

purinol group and 43.5% of the febuxo-

Allopurinol versus Febuxostat trial, investigators randomly assigned 940

stat group experienced the primary out-

patients with hyperuricemia to receive

come of 1 or more gout flares during the

allopurinol or febuxostat at titrated

observation phase — a 7% difference

doses to achieve a serum urate target of

that met a criterion for noninferiority,

6 mg/dL or lower (or 5 mg/dL or lower

James R. O’Dell, MD, of Veterans Affairs

if tophi were present). Approximately

(VA) Nebraska-Western Iowa Health

a third of patients in both groups had

Care System in Omaha, Nebraska, and

stage 3 CKD (30-59 mL/min/1.73 m

colleagues reported. Among patients

using the Modification of Diet in Renal

with stage 3 CKD, allopurinol also proved

Disease study formula for estimated

noninferior to febuxostat with 31.9%

glomerular filtration rate). The allopurinol

vs 45.3% experiencing a gout flare,

and febuxostat groups received daily

respectively, the investigators reported.

2

doses of 100 and 40 mg, respec-

In both the allopurinol and febuxostat

tively, to start, then therapies were

groups, 80% of patients — including

titrated until attainment of target uric

those with stage 3 CKD — achieved

acid levels or maximal dose. Patients

and maintained target serum urate

also received guideline-directed

levels at 1 year. ■

Sling Surgery FRAILTY INCREASES the risk for complications, repeat procedures, and death after sling surgery in women, a new study finds.

Using 2014-2016 Medicare data, investigators stratified 54,112 women aged 66 years and older who underwent sling surgery (with or without concomitant prolapse repair) by frailty status. The Claims-based Frailty Index (CFI) described 4 categories: not frail (CFI less than 0.15), pre-frail (0.150.25), mildly frail (0.25-0.35), and moderately-severely frail (0.35 or more). Of the cohort, 4.8% patients were mildly frail and 0.4% were moderately to severely frail.

On multivariate analysis, the relative risk for 30-day complications was significantly increased 1.8- and 2.5fold among mildly and moderately to severely frail patients, respectively, compared with patients who were not frail, Michelle E. Van Kuiken, MD, and colleagues from the University of California, San Francisco reported in

Dr Cheng and colleagues noted that the median 4.4% annual increase in OACC costs per transplant is higher than that of Medicare’s expenditures per patient with ESKD, which rose by 2.6% annually during the same study period.

The investigators calculated that for a median-sized transplantation program, costs per transplantation significantly increased $4400 annually, $1900 per 10-point increase in local price index, and $3100 per 100 patients listed “active” on the waiting list.

Patient factors appear to be the main drivers of rising costs. From 2012 to 2017, transplantation hospitals experienced increases in kidney waiting list volume, kidney waiting list active volume, and comorbidity burden, according to the investigators. The study also revealed that greater kidney transplantation volume offset costs. For a median-sized program, mean OACC costs per transplantation significantly decreased $3500 for every 10 transplants performed. ■

The Journal of Urology. Moderately to severely frail women experienced high rates of urinary tract infections (UTI; 15.7%), cardiovascular complications (19.9%), and pulmonary complications (9.4%). The relative risk for UTIs was significantly increased 1.7- and 2.4-fold in the mild and moderate-severe frailty groups, respectively.

Frailty also significantly increased the risk for repeat sling surgery, urethral bulking, sling revision, or urethrolysis procedures for persistent incontinence or obstructed voiding within 1 year by 1.4-fold, the investigators reported.

In addition, the relative risk for 1-year mortality was significantly increased 3.4and 6.7-fold among the mildly and moderately-severe frail groups, respectively, compared with the no-frailty group.

“Our findings underscore the importance of considering and measuring frailty in the preoperative setting, as an emerging body of evidence demonstrates the negative association that frailty has on the risk of postoperative complications,” Dr Van Kuiken’s team wrote.

Frailty was independently associated with these increased risks even after adjusting for age, Charlson comorbidity index, and concomitant pelvic organ prolapse repair, “demonstrating the value of assessing frailty independently,” according to the researchers.■

26 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

Reduced Kidney Function Raises SCD Risk Recent findings ‘open up new avenues for future research,’ according to investigators EVEN MILDLY or moderately reduced kidney function is associated with an increased risk for sudden cardiac death (SCD) in the general population, independent of other important SCD risk factors, according to a recent report.

“The high incidence of SCD worldwide together with the devastating consequences and the sudden aspect of this event show the importance of identifying modifiable risk factors for SCD, such as kidney function, and of identifying these subgroups at risk,” Anna C. van der Burgh, BSc, of Erasmus Medical Center, University Medical Center Rotterdam, The Netherlands, and colleagues reported in the Clinical Kidney Journal. “Our study suggests an increased SCD risk with lower levels of eGFR in middleaged and elderly individuals from the general population, even without

Alprostadil May Protect Against CIN ALPROSTADIL may lower the risk for contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention (PCI).

Xiaogang Liu, MD, of Tianin Chest Hospital in Tianjin, China, and colleagues randomly assigned 1146 patients undergoing PCI to an alprostadil plus hydration group and a control group that received hydration only. They classified patients into groups at low, moderate, and high

CKD, only when using serum cystatin C measurements.”

In a study that included 9687 participants with a mean age of 65.3 years and median follow-up of 8.9 years, each 10 mL/min/1.73 m2 decrease in

The link, observed in the general population, is independent of other risk factors. estimated glomerular filtration rate (eGFR) based on cystatin C measurements was significantly associated with a 23% increased risk for SCD after adjusting for age, sex, history of coronary heart disease, hypertension, and diabetes, and other potential confounders.

When evaluating kidney function using both serum cystatin and ­creatinine measurements, each 10 mL/ min/1.73 m 2 decrease in eGFR was significantly associated with a 17% increased risk for SCD. Based on serum cystatin C measurements, an eGFR less than 60 mL/ min/1.73 m2 was significantly associated with a 2.1-fold increased risk for SCD compared with an eGFR above 90 mL/ min/1.73 m2, according to the investigators. The 10-year absolute risks for SCD rose from 1.0% to 2.5% when comparing an eGFR of 90 to 60 mL/min/1.73 m2.

“Our findings could be clinically relevant, as they open up new avenues for future research,” van der Burgh and colleagues concluded. “This includes further investigation of the pathophysiological mechanisms underlying the association between kidney function and SCD. Unravelling these unknown

mechanisms could identify potential therapeutic targets, which is crucial as SCD is often the first manifestation of underlying [cardiovascular disease].”

Study strengths include a large number of participants from a populationbased cohort study with middle-aged and elderly individuals, which includes a population at high risk for SCD, the investigators noted. In addition, the prospective population-based design along with a high participation rate reduced the likelihood of selection bias, making the results applicable to the general population.

The study also had limitations. The investigators had only a single assessment of eGFR using cystatin alone and both creatinine-cystatin measurements available. In addition, the study included mainly White individuals older than 45 years, so the generalizability of their results to other populations might be limited. ■

BCG Efficacy Unaffected by Prostate RT PRIOR RADIATION treatment for prostate cancer does not increase the risk for bladder cancer recurrence following bacillus Calmette-Guérin (BCG) induction for high-risk nonmuscle-invasive bladder cancer (NMIBC), investigators reported at the ASCO Genitourinary Cancers Symposium 2022.

“Despite known associations with history of radiation and worse oncologic outcomes in bladder cancer, our study provides preliminary evidence that BCG intravesical therapy in high-grade NMIBC remains effective in patients with prior prostate radiotherapy,” said Adri M. Durant, MD, of Mayo Clinic Arizona in Phoenix, who presented the

findings. “With high BCG failure rates and current BCG shortages, this data provides reassurance that BCG therapy is being appropriately allocated to this population.”

Badder cancer is not more likely to recur in patients with high-risk NMIBC, data show.

The retrospective study included 199 patients who received at least 1 induction course of BCG for NMIBC. Of these,

23 patients had a history of prostate radiotherapy, 17 had a prior radical prostatectomy, and 159 had no prostate cancer history. The 1-year bladder cancer recurrence rates in these patients were 39.1%, 29.4%, and 42.8%, respectively. The rates of progression to MIBC were 8.7%, 0%, and 6.9%, respectively; the rates of progression to metastatic disease were 4.3%, 5.9%, and 6.9%, respectively. None of the differences in these rates among the groups were statistically significant.

Study limitations included the retrospective design, the small number of patients treated with radiation, and the lack of full radiation histories, such as dose and length of treatment. ■

risk for CIN as ascertained using the Mehran risk score. Among patients with moderate and high risk, alprostadil recipients had significant 65.7% lower odds of CIN compared with controls, the researchers reported in Angiology.In the low-, moderate-, and high-risk groups, the incidence of CIN in the control and alprostadil group was 2.9 vs 2.6%, 11.4 vs 4.9%, and 19.1 vs 7.7%, respectively.

Alprostadil’s protective effect may be related to an anti-inflammatory response, the authors concluded. ■

Cystectomy vs Trimodal Treatment for MIBC OVERALL survival appears comparable after radical cystectomy (RC) and trimodal therapy (TMT) for muscleinvasive bladder cancer among patients who receive chemotherapy, except in the case of higher-stage disease, according to investigators.

Among 2048 patients (aged 40 to 79 years) with cT2-3 N0 M0 urothelial carcinoma in the 2006-2015 National Cancer Database, 1812 patients were treated with

multiagent neoadjuvant chemotherapy and RC with lymphadenectomy (RC arm) and 236 were treated with transurethral resection of bladder tumor (TURBT), multi-agent chemotherapy, and 3D conformal radiation therapy (TMT arm). The median follow-up was 29 months.

After propensity-score adjustment, overall survival did not differ significantly between the RC and TMT arms, Boris Gershman, MD, of Beth Israel

Deaconess Medical Center, Boston, Massachusetts, and colleagues reported in Urologic Oncology. Among patients with cT3 disease, however, the risk for all-cause mortality was a significant 58% lower for patients who underwent RC vs TMT. Survival did not differ by age or comorbidity burden.

The database lacked information on tumor characteristics and completeness of TURBT, which is a study limitation. ■

www.renalandurologynews.com

SPRING 2022

Renal & Urology News 27

Ethical Issues in Medicine Physicians have a professional obligation to combat medical misinformation in the interest of the public good BY DAVID J. ALFANDRE, MD, MSPH

Akin to an Epidemic So-called infodemiologists have begun approaching the problem of misinformation from an epidemiologic vantage point by preventing it from going “viral.”1 They conceptualize misinformation as analogous to an infectious disease outbreak that must have its origin, virulence, transmission patterns, and potential “treatments” rapidly identified, along with a need to inoculate people against these deceptions. When misinformation, like an epidemic, is

Health care professionals’ trusted position in society provides them with a valuable platform to inform the public. They are licensed by their state and often boarded by a professional society who have professional obligations to their patients and the public to disseminate evidence-based information.

Call Out Misinformation Promotion of the public good and a commitment to integrity and competence is central to the ethics of the health care profession. These obligations include avoiding the release or propagation of mis- and dis-information, calling misinformation out when they see it, and not promoting it either with their patients or on social media outlets.

Rather than a clear right or wrong duality to scientific debates, there is often a slowly evolving consensus about what we clearly know from what we do not. Society must protect legitimate scientific discourse, free expression, and openness to new ideas, but significant professional consequences are justifiable when spreading misinformation that is not firmly grounded in evidence especially when it has real and serious public health implications.

Some health care professionals’ goal in sharing what could be considered

The COVID-19 pandemic exposed how easy it is for non-authoritative sources to spread wrong and possibly dangerous medical information. not promptly identified and contained, it spreads so rapidly within a population that it takes far greater effort and resources to counteract.

While public health professionals, scientists, and journalists are all working to deliver healthier “media diets” that serve accurate, reliable information to the public, health care professionals are sometimes operating at both the public and individual patient level to ensure good healthy practices for their patients.

misinformation may be rooted in a desire to respect patient autonomy and individual liberty and avoid coercion.

In this case, misinformation should be distinguished from legitimate shared decision-making, the latter being when there is reasonable debate about a range of acceptable medical options.

For example, because there is sufficient empirical data that SARS-CoV-2 vaccination is associated with a very small risk of self-limited myocarditis, it could

© WILDPIXEL / GETTY IMAGES

T

he COVID-19 pandemic has stressed the health care system and the public like no other event in the last century. Responding to the public’s needs for clear, authoritative, continually evolving information has required an extraordinary commitment from public health authorities, elected officials, scientists, and other health care professionals. Regrettably, misinformation from a variety of sources has challenged an effective response to the information needs of the public. Although misinformation is not a new phenomenon, social media and other internet outlets have expanded the potential for disreputable, nonauthoritative sources to achieve an outsize immediate effect on the public.

be part of a shared decision-making conversation. The same could not be said for infertility and vaccination, as no such data exist for that association. Although the risk of COVID-19associated myocarditis is greater than the risk of vaccine-associated myocarditis, vaccine-associated adverse events remain a concern for some patients.

Again, for some patients, the public health benefits may be greater than the individual ones — the largest benefit for some patients may be the reduction in community disease burden leading to less strain on their local health care system. When hospitals are not overwhelmed, everyone benefits.

Medical Organizations Speak Out After a series of events that involved promotion of COVID-19 misinformation from health care professionals, the Federation of State Medical Boards as well as professional societies and the American Board of Medical Specialties all released public statements that its members’ board certification could be sanctioned or their license could be suspended or revoked if they are involved in disseminating misinformation to their patients or the public. This was an important step to demonstrate to the public and remind all health care professionals of their professional

obligations to provide high-quality evidence-based information to the public.

The statements from professional societies and state medical boards were not intended to quell legitimate scientific debate or the free exchange of ideas among health experts, but rather to prohibit the dissemination of information that lacks a clear evidence base and is contrary to the efforts of halting the pandemic.

Although physicians are patient advocates first and must continue to promote individual liberty, there are circumstances when their public health role is relevant and important.

Physicians must continue to act in the best interest of all members of their community. ■ David J. Alfandre, MD, MSPH, is a health care ethicist and an Associate Professor in the Department of Population Health at the NYU School of Medicine in New York. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the VA National Center for Ethics in Health Care or the US Department of Veterans Affairs.

REFERENCE 1. Scales D, Gorman Jamieson KH. The COVID-19 infodemic—Applying the epidemiologic model to counter misinformation. N Engl J Med. 2021;385:678681. doi:10.1056/NEJMp2103798

28 Renal & Urology News

SPRING 2022

www.renalandurologynews.com

Practice Management Study characterizes effect of Medicare’s merit-based incentive payment system on urology practices BY JOHN SCHIESZER were in APMs, and 20.6% were in independent practice.

Group Practices Score Higher Urologists had an overall MIPS score of 86.9 on a scale of 0 to 100. Scores on 4 MIPS domains were 82.5 for quality, 88.9 for promoting interoperability, 74.4 for cost, and 37.3 (on a 0-to-40 scale) for improvement activities. Urologists in group practices and APMs had higher scores than individual urologists in all categories except cost. Urologists who graduated medical school more recently were more likely to be in group practices or APMs. Younger urologists tended to have higher MIPS scores.

Geographic Differences In addition, the study showed practice patterns varied among the geographic sections of the United States as defined by the American Urological Association. Urologists in the southeastern and western sections of the United States were more likely to be in an individual practice, whereas group practice was more common in the northeastern section. APMs were dominant in the New York and New England sections.

Daniel Barocas, MD, MPH, a professor of urology at Vanderbilt University Medical Center in Nashville,

Urologists in group practices had higher MIPS scores than individual urologists in all categories except cost, investigators found. the MIPS database for performance year 2018. At that time, physicians were encouraged to voluntarily participate in the new system. MIPS became mandatory for all Medicare-participating physicians in 2019. Of the cohort, 47.0% participated in group practices, 32.4%

On The Web

Tennessee, said the goal of the MIPS program is to reduce incentives for “doing more” and increase incentives for providing better care. “The principle is sound. Health care expenditures currently account for about 18% of gross domestic product in the US, and

© JOSE LUIS PELAEZ / GETTY IMAGES

U

rologists in group practices or an alternative payment model (APM) score higher across categories within Medicare’s merit-based incentive payment system (MIPS) compared with those in individual practices, according to a study published recently in Urology Practice.

The study provides a glimpse into how the switch from a traditional feefor-service to MIPS, which is a valuebased care model, might affect the treatment landscape in urology, which serves large numbers of Medicare recipients. Under MIPS, physicians who exceed defined performance measures earn a payment bonus, whereas those who underperform receive a payment penalty.

“The COVID pandemic has altered the landscape more than anyone could have imagined,” said lead author Ridwan Alam, MD, MPH, of the James Buchanan Brady Urological Institute at Johns Hopkins University School of Medicine in Baltimore, Maryland.

“However, if we can study and understand policy changes more readily, it puts us in a better position to protect not only the interests of our patients but also our urologists.”

For the study, Dr Alam and colleagues analyzed data from 9055 urologists in

Urologists in group practices may have an edge over independent urologists under MIPS.

the growth rate of health care expenditures is higher than the growth rate of the GDP, so that 18% is predicted to grow to almost 20% by 2028 if we don’t change things,” Dr Barocas said.

Large vs Small Practices It remains unclear how smaller practices will fare under the MIPS program compared with larger practices. “Since practices must compete for the incentive payments, which come at the cost of penalties for other practices, the smaller practices with less infrastructure support may be at a disadvantage,” Dr Barocas said.

Mara R. Holton, MD, vice chair of the health policy committee for the Large Urology Group Practice Association (LUGPA), said the new system is unfortunately marginally relevant, with arbitrary criteria that create a bureaucratic and administrative burden without making any discernible improvements in patient care.

“Ultimately, this has very significant implications for access in rural areas, which often cannot support larger

practices,” Dr Holton said. “This might then well contribute to consolidation into more central locations or incorporation into hospital systems, which can support the infrastructure necessary to attest to these metrics.”

Worse Access to Care Possible There is growing appreciation that independent practices are a critical site for innovation, efficient delivery of care, lower-cost delivery of care, and maintenance of access to care, according to Dr Holton. The new system may be well intended, but it paradoxically may have the ultimate effect of creating barriers to care.

“It remains to be seen if these can be constructed in such a way that takes into account input from clinical stakeholders so that pathways can be constructed that can be instituted across different clinical settings and provide meaningful value to patients,” Dr Holton said. ■ John Schieszer is a freelance medical writer based in Seattle, Washington.

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