Renal & Urology News - Sept-Oct 2021 Issue

SE P T E MBE R /O C T OBE R 20 21

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VOL UME 20, IS SUE NUMBER 5

High BMI in mCRPC Raises Survival Odds

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BMI

>30 kg/m2

Mortality Risk

Investigators cite an ‘obesity paradox’ Alberto Martini, MD, of Vita Salute San Raffaele University, Milan, Italy, and colleagues studied 1577 patients with mCRPC who participated in the phase 3 randomized controlled ASCENT2, MAINSAL, and VENICE clinical trials. The investigators selected patients from these trials because they had similar inclusion criteria. Dr Martini’s team placed patients into 4 body mass index (BMI) categories: less than 20, 20-25, 25-30, and greater than 30 kg/m2.

To exclude possible effects attributable to a higher dose of chemotherapy (titrated according to body surface

29% decrease

© GETTY IMAGES

BY JODY A. CHARNOW OBESITY IS ASSOCIATED with better overall and cancer-specific survival among men with metastatic castrationresistant prostate cancer (mCRPC), a protective effect that investigators are calling an “obesity paradox,” according to a presentation at the American Urological Association’s virtual 2021 annual meeting.

The findings could have implications for clinical trial design and development of novel therapeutics that target certain genes that modulate fat synthesis, according to investigators.

OBESITY APPEARS PROTECTIVE in men with metastatic castration-resistant prostate cancer.

area), the investigators looked for eventual interactions between BMI and chemotherapy dose.

Of the 1577 patients, 655 died by the end of the studies. The median follow-up duration for survivors was 12 months. In adjusted analyses, obesity,

BCG May Lower Alzheimer’s Risk RCC Subtype

BY JODY A. CHARNOW MD, of the University of Washington Affects Postop BLADDER instillations of bacillus in Seattle, and colleagues found that Calmette-Guérin (BCG) to treat non- patients with any exposure to BCG Survival Rate muscle-invasive bladder cancer (NMIBC) had a significant 27% lower risk are associated with a lower risk for Alzheimer’s disease, data presented at the American Urological Association’s virtual 2021 annual meeting suggest.

In a study of 26,584 patients with high-risk NMIBC, Dimitrios Makrakis,

Any exposure to BCG decreased the risk for Alzheimer’s disease by 27%.

for Alzheimer’s disease compared with no exposure after adjusting for age, sex, race, T-stage, and Charlson Comorbidity Index. The risk decreased with increased BCG dosing. Patients who received 6 or fewer, 7 to 12, and more than 12 doses of BCG had a significant 15%, 27%, and 46% lower risk for Alzheimer’s disease, respectively, compared with those who received no BCG, Dr Makrakis reported in an oral presentation.

The finding of a dose-response relationship “strengthens the biologic continued on page 10

SURVIVAL rates at 5 years following partial or radical nephrectomy for renal cell carcinoma (RCC) vary depending on whether patients have favorable or unfavorable histologic subtypes, investigators reported at the American Urological Association’s virtual 2021 annual meeting.

“These results have implications for developing personalized therapies that target high-risk, aggressive tumors that are otherwise reasonable to manage,” Adan Becerra, PhD, of Rush University in Chicago, and colleagues concluded in a study abstract.

Using the National Cancer Database, Dr Becerra’s team identified 282,623 patients who underwent partial or radical nephrectomy from 2004 to 2017. Of these, 839 patients had unfavorable histologies (medullary cell, collecting duct, and unspecified RCC). Favorable histologies included papillary, chromophobe, cystic, and clear cell subtypes. The study population had a median follow-up continued on page 10

defined as a BMI greater than 30 kg/m2, was significantly associated with a 29% decreased risk for death compared with overweight (BMI 25-30 kg/m2) and normal weight (BMI 20-25 kg/m2).

Each 1 kg/m 2 increase in BMI was continued on page 10

IN THIS ISSUE 3 Enzalutamide found to slow progression of localized PCa 4 Metabolic syndrome after RP raises PCa death risk 4 Primary chemoablation for NMIBC shows promise 12 TURP and laser prostatectomy compared in men aged 75+ 13 5-ARI use should inform prostate biopsy decisions 20 Study challenges earlier use of androgen deprivation therapy 30 A healthful plant-based diet may lower risk for elevated PSA

Ketogenic diets may accelerate renal deterioration in CKD. PAGE 15

www.renalandurologynews.com

Contents

SEPTEMBER/OCTOBER 2021

SEPTEMBER/OCTOBER 2021

Urology 3

ONLINE

4

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

12

20

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.

NAC Underused for MIBC in Older Adults Neoadjuvant chemotherapy before radical cystectomy improves perioperative outcomes among patients aged 70 years or older.

Study Challenges ADT Use at PSA Relapse Delaying use of androgen deprivation therapy until metastasis has minimal impact on overall survival.

15

Ketogenic Diets Can Increase Renal Risks Potential dangers include accelerated loss of kidney function and exacerbation of metabolic acidosis.

15

Long-Term Kidney Transplant Outcomes Improving The 10-year graft and patient survival rates increased for patients who received deceased-donor and living-donor kidneys from 1996 to 2011.

21

Salt Substitute May Decrease Stroke Risk Patients at elevated risk for cardiovascular events who used a reduced-sodium salt had a 14% lower stroke risk.

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

Encouraging Trial Results Reported for NMIBC Primary Chemoablation Patients treated with a mitomycin-containing reverse thermal gel had a complete response rate of 65% at 3 months.

VOLUME 20, ISSUE NUMBER 5

CALENDAR Editor’s note: The listings below include dates and venues indicated by the sponsoring organizations on their websites. Some organizations have converted to all-virtual formats as a result of the pandemic. As this issue went to press, it was unclear whether other organizations will do the same.

American Society for Radiation Oncology (ASTRO) Annual Meeting Chicago, IL October 24–27 American Society of Nephrology Kidney Week Virtual November 2–7 Large Urology Group Practice Association Annual Meeting Chicago, IL November 11–13 Society of Urologic Oncology Annual Meeting Orlando, FL December 1–3

Nephrology

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

Enzalutamide vs AS Slows PCa Progression The drug increased the likelihood of a negative prostate biopsy at 1 year among men with low- and favorable intermediaterisk localized prostate cancer.

■

Renal & Urology News 1

29

AKI Tied to Arterial Stiffness Results support consideration of including arterial stiffness in risk prediction models for AKI and as a target for prevention or treatment of AKI, according to researchers.

We believe that patients will be receptive to this new

treatment option, as there is currently nothing else approved as a primary treatment therapy.

See our story on page 4

31

Departments 2

From the Medical Director Should active surveillance for prostate cancer be rebranded?

5

News in Brief FDA approves medication for pruritus in hemodialysis patients

31

Ethical Issues in Medicine Lessons from the way we deal with shopping carts

32

Practice Management Recruiting and retaining health care staff have gotten harder

2 Renal & Urology News

SEPTEMBER/OCTOBER 2021 www.renalandurologynews.com

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Should Active Surveillance for Cancer Be Rebranded?

A

n outstanding primary care physician asked me to see an 86-year-old man with elevated PSA. His rationale was that the patient is fit, has an excellent quality of life and “just doesn’t want to die from cancer.” The interaction underscores the trust physicians and patients have in our ability to detect and manage heterogeneous cancers which, depending on many variables and competing risks — known and unknown, quantifiable, and unmeasurable — may or may not be lethal.

A cancer diagnosis changes patients’ lives, a point reflected in the title of the Pulitzer Prize-winning book The Emperor of all Maladies: A Biography of Cancer by Siddhartha Mukherjee, MD. In years past, early detection was the only hope, whereas late-stage disease was nearly universally fatal in short order.

As our understanding of the diverse natural history of screened cancers has grown, active surveillance (AS) of many low-risk solid urologic tumors is now acceptable and guideline based. Finelli et al1 recently reviewed the Canadian experience in over 8500 men with low-risk prostate cancer who initially underwent a period of AS (2008-2014). While there was a near doubling in the use of AS (from 38% to 69%) as a management strategy, the researchers noted that more than half of the men sought active treatment after a median of 48 months follow-up. Importantly, only half of those men chose active treatment due to grade progression.

While retrospective analyses like these create more questions than answers, what remains clear is that once a diagnosis of cancer is made, many patients will choose treatment. This has led to past calls to rebrand nonlethal cancers. One such term, IDLE, or indolent lesions of epithelial origin, proposed almost a decade ago, remains relegated to Pubmed.2 Many justifiably fear cancer. While the idea of AS continues to slowly gain acceptance, most patients are easily moved toward treatment.

We must continue to research and educate patients on the differences between a histologic diagnosis of cancer and a biologic one, and decide if we define cancer by its beginning or by its end when creating a treatment plan. We must also work to understand and communicate the tradeoffs with our current interventions and acknowledge the limitations of “shared decision making” when there are significant knowledge differentials between patients and providers.

It’s time to acknowledge the biases patients and physicians have regarding AS for “cancer” and rebrand the concept.

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

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

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

Renal & Urology News Staff

Editor Jody A. Charnow Web editor Natasha Persaud Production editor Kim Daigneau Group creative director Jennifer Dvoretz Production manager Brian Wask

Vice president, sales operations and production Louise Morrin Boyle

National accounts manager William Canning Editorial director, Haymarket Oncology Lauren Burke

Vice president, content, medical communications Kathleen Walsh Tulley

1. Timilshina N, et al. Factors associated with discontinuation of active surveillance among men with lowrisk prostate cancer: A population-based study. J Urol. Published online ahead of print August 20, 2021.

2. Esserman LJ, et al. Addressing overdiagnosis and overtreatment of cancer: a prescription for change. Lancet Oncol. 2014;15:e234-242.

Nephrologists

Chief commercial officer James Burke, RPh President, medical communications Michael Graziani Chairman & CEO, Haymarket Media Inc. Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 20, Number 5. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). 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 © 2021.

www.renalandurologynews.com SEPTEMBER/OCTOBER 2021

■ AUA2021

Renal & Urology News 3

American Urological Association 2021 Annual Meeting

Enzalutamide vs AS Slows PCa Progression Benefit observed in men with low- and intermediate-risk clinically localized prostate cancer AMONG MEN with low- or intermediate-risk prostate cancer eligible for active surveillance (AS), those treated with enzalutamide may benefit from a significant reduction in the risk for cancer progression compared with those undergoing AS, according to findings from a phase 2 open-label exploratory study.

The study is the first to assess the efficacy and safety of a novel androgen receptor antagonist as monotherapy in patients with clinically localized low- or intermediate-risk prostate cancer, said lead investigator Neal D. Shore, MD, medical director for the Carolina Urologic Research Center in Myrtle Beach, South Carolina. Enzalutamide was well tolerated and provided significant clinical benefit compared with AS. “Enzalutamide may therefore offer an alternative treatment option in this patient population,” he said.

The trial included 227 patients (53% with low-risk and 47% with favorable intermediate-risk disease) randomly assigned to receive 160 mg/d of enzalutamide (114 patients) or to undergo AS (113 patients). Baseline characteristics were similar between study arms. Of the 227 patients, 165 (85 in the enzalutamide group and 80 in the AS arm) completed 1 year of treatment. Baseline

Negative Prostate Biopsy Rates In a phase 2 trial that included men with low- and intermediate-risk prostate cancer, those treated with enzalutamide had a significantly higher rate of negative prostate biopsies at 1 year compared with those on active surveillance. At 2 years, however, the difference in rates was not significant.

40

35.1%

n Enzalutamide n Active surveillance

30 20

14.2%

19.0% 12.0%

10 0

1 Year

2 Years

Source: Shore ND, et al. Enzalutamide in patients with localized prostate cancer undergoing active surveillance: ENACT. Presented at AUA2021. Poster MP62-17.

characteristics were similar between study arms. Of the 227 patients, 165 (85 in the enzalutamide group and 80 in the AS arm) completed 1 year of treatment.

Patients had up to 2 years of follow-up.

Enzalutamide-treated patients had a significant 46% reduction in pathologic prostate cancer progression risk and 29% decreased risk for PSA progression compared with those undergoing AS. Enzalutamide delayed PSA progression by a median of 6 months vs AS. At 1 year, a significantly higher proportion of patients in the enzalutamide group had a negative prostate biopsy

compared with the AS group (35.1% vs 14.2%). At 2 years, however, although a higher proportion of enzalutamide recipients compared with the AS group had a negative biopsy (19% vs 12%), the difference between the study arms was no longer significant. Enzalutamide recipients were 3.5 times more likely than those in the AS group to have a negative prostate biopsy at 1 year. The odds of a negative biopsy at 2 years did not differ significantly between the groups.

Dr Shore’s team defined pathologic progression as an increase in primary or secondary Gleason pattern by more

than 1 or a greater than 15% increase in cancer-positive cores. They defined therapeutic progression as the earliest occurrence of primary therapy for prostate cancer (prostatectomy, radiation, focal therapy, or systemic therapy).

Patients with low-risk cancer had stage T1c–T2a disease, a PSA level less than 10 ng/mL, a Gleason score 6 or less, and no nodal involvement or metastasis. Patients with intermediaterisk disease had T2b-T2c disease, a PSA level less than 20 ng/mL, Gleason score of 7 (3+4 pattern), and no nodal involvement or metastasis.

Commenting on the findings, Adam S. Feldman, MD, MPH, a urologic oncologist at Massachusetts General Hospital in Boston, who was not involved in the research, said the study cohort is notable for its relatively high proportion of patients with favorable intermediate-risk disease. As the majority of patients with favorable intermediate-risk disease opt for treatment rather than AS, enzalutamide could possibly be an alternative to radical prostatectomy or radiation, Dr Feldman said. He said he would be hesitant to place patients with low-risk or very-lowrisk prostate cancer on a drug with potential side effects when these patients may well be able to avoid treatment anyway. ■

NAC May Improve UTUC Outcomes in Older Patients NEOADJUVANT chemotherapy (NAC) prior to radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) may benefit selected elderly patients and those with locally advanced disease, new study findings suggest.

Previous studies have demonstrated that NAC prior to radical nephroureterectomy (RNU) for UTUC improves oncologic outcomes. These outcomes, however, have not previously been explored in the elderly even though the highest incidence of UTUC is among individuals aged 70 to 90 years, Nico C. Grossmann, MD, of the Medical University of Vienna in Austria, and colleagues noted.

In a multicenter study that included 170 patients, Dr Grossmann’s team found that elderly patients (defined as those older than the group’s median age of 68 years) who were eligible for

t­reatment with cisplatin-based NAC prior to radical nephroureterectomy (RNU) may experience pathologic improvements from this multimodal therapy similar to those of their younger counterparts.

All study patients had clinically nonmetastatic, high-risk UTUC treated with NAC and RNU. Of the 170 patients, 77 (45%) were older than 68 years. The median follow-up was 29 months. The younger and older groups had similar rates of pathologic objective response and pathologic complete response (51% vs 48% and 10% vs 9%, respectively).

Although overall survival was lower in the elderly group, both groups had similar recurrence-free and cancer-specific survival, according to the investigators.

“Despite the reluctance to provide systemic therapy in elderly patients,

these patients seem to benefit similarly from cisplatin-based NAC as their younger counterparts,” Dr Grossmann said. “Elderly patients who are ineligible for cisplatin treatment had the lowest response rates and are most likely to benefit from immediate RNU.”

Patients younger and older than 68 years had similar rates of pathologic response.

In a separate study of 289 patients with locally advanced UTUC—144 of whom had NAC followed by RNU and 145 who underwent RNU alone (control group)—pathologic downstaging

occurred significantly more frequently in the NAC group than the control group (69% vs 24%), Yuka Kubota, MD, of Hirosaki University Graduate School of Medicine in Hirosaki, Japan, and colleagues reported. The rate of downstaging to pT1 or less disease was significantly higher in the NAC than control group (42% vs 9%). The NAC group, which received 2 to 4 courses of either cisplatin- or carboplatin-based regimens, had a significantly lower rate of lymph node invasion (25% vs 49%). In adjusted analyses, the NAC group had a significant 41% decreased risk for death compared with the control group.

The study patients had undergone RNU at 7 hospitals from 2000 to 2020.

NAC use increased during the study period from 19% in 2006-2010 to 58% in 2011-2015 and 79% in 2016-2020. ■

4 Renal & Urology News

■ AUA2021

SEPTEMBER/OCTOBER 2021 www.renalandurologynews.com

American Urological Association 2021 Annual Meeting

Lower eGFR After RN Ups ESKD Risk A LOWER ESTIMATED glomerular filtration rate (eGFR) following radical nephrectomy (RN) is associated with more rapid progression to end-stage kidney disease (ESKD), according to investigators.

The findings “are critically important in patient counseling and surgical planning, particularly for patients with risk factors for renal deterioration,” said investigator Diego Aguilar Palacios, MD, of the Glickman Urological and Kidney Institute at Cleveland Clinic in Cleveland, Ohio, who presented study findings.

Dr Aguilar Palacios and colleagues reviewed data from 3966 patients at high risk for renal deterioration who underwent RN. The study included patients with preoperative hypertension diabetes, proteinuria, or preexisting chronic kidney disease.

The investigators defined ESKD as an eGFR less than 15 mL/ min/1.73 m2. Patients were strati-

Encouraging Trial Results Reported for NMIBC Primary Chemoablation Novel treatment tested in low-grade intermediate-risk disease

BY JODY A. CHARNOW PRIMARY CHEMOABLATION with UGN-102, an investigational mitomycin-containing reverse thermal gel, has demonstrated encouraging trial results as a possible treatment for low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR-NMIBC), according to new study findings.

“We believe that patients will be receptive to this new treatment option, as there is currently nothing else approved as a primary treatment therapy,” principal investigator William C. Huang, MD, associate professor and vice chair of urology at NYU Langone Health in New York, New York, said in an interview. “UGN-102 has the potential to be the first, non-surgical primary therapeutic treatment for patients suffering from LG IR-NMIBC, providing an alternative to repetitive surgery.”

Unlike surgery, which focuses on the removal of visible lesions, chemoablation with UGN-102 treats the entire field of urothelium exposed to the

drug, Dr Huang said. “Since we know that IR-NMIBC is often multi-focal and that microscopic disease is often present that eludes detection using standard endoscopic techniques, we may find that chemoablation is a particularly valuable strategy for managing patients with this form of bladder cancer.”

Complete response achieved by 65% of patients at 3 months, data show.

The results are from the phase 2b open-label OPTIMA II trial, which included 63 patients treated with UGN-102. They received 6 once-weekly instillations of UGN-102 in an office setting. Of these, 41 (65%) achieved a complete response (CR) at 3 months.

In this group, 39 (95%), 30 (73%), and 25 (61%) remained disease-free at 6, 9,

and 12 months, respectively, after treatment initiation. The 9-month duration of response rate (the probability that a patient will maintain a CR for at least 9 months [12 months after treatment initiation]) was 73%, the investigators reported. The medication was generally well tolerated.

Dr Huang and colleagues defined CR as negative endoscopic examination, negative cytology, and negative forcause biopsy 3 months after treatment initiation.

Major challenges exist in the current standard of care for LG IR-NMIBC, as it is a disease with a high recurrence rate (historically up to 80%) and a need for multiple repeated transurethral resection of bladder tumor procedures, Dr Huang said.

UGN-102 is similar to the mitomycincontaining agent approved for the treatment of low-grade upper tract urothelial carcinoma (Jelmyto), but they are different compounds. Both agents are made by UroGen Pharma. ■

fied by new baseline GFR (NB-GFR), defined as the final eGFR value within 3-12 months after surgery.

Within the first year after nephrectomy, 206 patients (5%) progressed to ESKD. The mean preoperative eGFR of those patients was 22 mL/min/1.73 m2. The risk of progression to ESKD increased with decreasing NB-GFR. Results showed that 15.8% and 46.9% of patients with an NB-GFR of 30-45 and 15-30 mL/min/1.73 m2 progressed to ESKD, respectively, compared with 8.7% of those with the reference NB-GFR of 45-60 mL/min/1.73 m2, the investigators reported. Patients with an NB-GFR of 30-45 and 15-30 mL/min/1.73 m2 had a significant 1.6- and 3.1-fold increased risk for ESKD. The time to progression was 71.6 and 48 months, respectively. All-cause death rates also increased with decreasing NB-GFR (34.8% and 44.7%, respectively). ■

Post-RP Metabolic Syndrome Ups PCa Death Risk

BY JODY A. CHARNOW METABOLIC SYNDROME in men following radical prostatectomy (RP) for prostate cancer is associated with an increased risk for prostate cancerspecific mortality and development of castration-resistant prostate cancer (CRPC), new findings suggest.

“If confirmed, managing metabolic syndrome components may reduce CRPC and prostate-cancer specific mortality risks in prostate cancer patients,” said Tyler R. Erickson, MS, of the Durham VA Health Care System in Durham, North Carolina, who presented study findings.

The study, which was led by Adriana C. Vidal, PhD, of Cedars-Sinai Medical Center in Los Angeles, included 4587 men who underwent RP for prostate cancer at 8 VA medical centers from 2007 to 2017. Of these, 1605 (35%) had metabolic syndrome at the time of surgery and 2982 (65%) did not. During followup, biochemical recurrence d ­ eveloped

in 30% of men, metastasis in 3.6%, and CRPC in 2.4%. Another 16% died and 1.7% died from prostate cancer.

Metabolic syndrome was significantly associated with 57% and 94% increased risks for CRPC and death from prostate cancer, respectively, after adjusting for demographic, pathologic, and other characteristics. The team found no association between metabolic syndrome and the risk for biochemical recurrence, metastasis, or allcause mortality.

The investigators defined metabolic syndrome as the presence of 3 of 5 components: hypertension (systolic blood pressure [BP] greater than 130 mm Hg or diastolic BP greater than 85 mm Hg), obesity (body mass index greater than 30 kg/m2), high triglycerides (150 mg/ dL or higher), low high-density lipoprotein (less than 40 mg/dL), and diabetes.

“The study generates an interesting hypothesis that metabolic syndrome does not impact the risk of d ­ eveloping

biochemical recurrence or metastasis after radical prostatectomy, but does increase the risk of developing castration-resistant metastatic disease and the risk of death from prostate cancer,” said urologic oncologist Keyan Salari, MD, PhD, co-director of the Prostate Cancer Genetics Program at Massachusetts General Hospital, who was not involved in the study. “This suggests there may be metabolic factors at play in promoting the transition from the castration-sensitive to castrationresistant disease state.”

Dr Salari added, “If the findings are confirmed in additional studies, this would provide a strong rationale for aggressively treating components of metabolic syndrome in patients with metastatic prostate cancer with the goal of preventing progression to castration resistance. Further investigation of the mechanism of this observed effect might also lead to new therapeutic strategies for this disease state.” ■

www.renalandurologynews.com SEPTEMBER/OCTOBER 2021

Renal & Urology News 5

News in Brief

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

Short Takes Undiagnosed CKD Common in Preeclampsia Cases

279 patients treated with BCG. Of

A nephrology work-up may be war-

these, 225 (80.6%) received a single

ranted for women who experience

BCG strain and 54 (19.4%) were treat-

preeclampsia during pregnancy

ed with multiple BCG strains. The over-

because these patients have a high

all recurrence and progression rates

prevalence of undiagnosed chronic

were 30.8% and 13.6%, respectively.

kidney disease (CKD), investigators

A propensity score matched analysis

concluded in a report published in

revealed no significant difference in

Nephrology Dialysis Transplantation.

these rates between the groups.

and colleagues retrospectively studied

In a retrospective study of 282 by preeclampsia, Gianfranca Cabiddu,

FDA Denies Approval for Novel Anemia Drug

MD, of Brotzu Hospital in Cagliari,

The FDA has denied approval of roxa-

Italy, and colleagues found a 19%

dustat for the treatment of anemia

prevalence of newly diagnosed CKD

of chronic kidney disease in both

at each center, much higher than an

non-dialysis dependent and dialysis-

expected prevalence of 3% among

dependent patients.

pregnancies at 2 centers complicated

women of childbearing age.

Roxadustat, which is being developed

by FibroGen, is an oral hypoxia-inducible

Switching BCG Strains Does Not Affect Outcomes

factor prolyl hydroxylase inhibitor that

Switching bacillus Calmette-Guérin

endogenous erythropoietin production.

promotes erythropoiesis by increasing In a Complete Response Letter

(BCG) strains during maintenance therapy for patients with nonmuscle-

to F­ ibroGen regarding its New Drug

invasive bladder cancer does not af-

Application for roxadustat, the FDA

fect outcomes compared with use of

stated that the application could not

a single strain, researchers reported

be approved in its present form and

online in Urology.

requested an additional clinical study be

Evren Süer, MD, of Ankara University

conducted in both non-dialysis depen-

School of Medicine in Ankara, Turkey,

dent and dialysis-dependent patients.

AS for Intermediate-Risk PCa Active surveillance for men with both favorable and unfavorable intermediate-risk prostate cancer increased from 2010 to 2016, according to a study of data from the National Cancer Database.

6.8%

7

■ 2010 ■ 2016

PERCENTAGE

6 5

4.6%

4 3 2

1.6%

2.1% 0.9%

1 0

2.0%

Overall

Favorable

Unfavorable

Source: Agrawal V et al. Active surveillance for men with intermediate risk prostate cancer. J Urol. 2021;205:115-121.

Drug Approved for Pruritus in Patients on Hemodialysis D

ifelikefalin (Korsuva), a kappa opioid receptor antagonist, has received FDA approval for the treatment of moderate to severe pruritus in patients undergoing hemodialysis (HD). The FDA based its approval on data from the pivotal phase 3 KALM-1 and KALM-2 trials as well as data from an additional 32 clinical studies.

The KALM-1 and KALM-2 trials evaluated the efficacy and safety of difelikefalin in 851 patients 18 years of age and older undergoing HD who had moderate to severe pruritus. Patients were randomly assigned to receive difelikefalin 0.5mcg/kg intravenously 3 times per week after each dialysis session or placebo for 12 weeks.

Results from the KALM-1 trial showed that 40% of difelikefalin-treated patients had an improvement of at least 4 points in the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) score at week 12 compared with 21% for placebo. In the KALM-2 trial, 37% of difelikefalin-treated patients achieved a 4-point or greater improvement in WI-NRS score vs 26% for placebo.

NAC vs AC for Node-Positive UTUC Improves Outcomes F

or patients with node-positive upper tract urothelial carcinoma (UTUC), neoadjuvant chemotherapy (NAC) followed by radical nephroureterectomy is more clinically beneficial than RNU followed by adjuvant chemotherapy (AC), investigators reported online in Urologic Oncology.

Keisuke Shigeta, MD, of Keio University School of Medicine in Tokyo, Japan, and colleagues identified 89 patients with UTUC and clinical nodal involvement who received NAC before radical nephroureterectomy (RNU) or upfront RNU followed

by AC. The 1- and 2-year recurrence-free survival rates were 67.9% and 47.0%, respectively, in the NAC group compared with 43.9% and 24.6%, respectively, in the AC group. The 1- and 2-year cancer-specific survival rates were 80.5% and 64.2%, respectively, in the NAC arm compared with 68.2% and 48.2%, respectively, in the AC arm. These between-group differences were statistically significant.

Cinacalcet Does Not Increase Risk for Severe GI Bleeding C

inacalcet use does not increase the risk for severe gastrointestinal (GI) bleeding in patients on hemodialysis (HD) that leads to hospitalization or death, according to results from a study published in Pharmacoepidemiology and Drug Safety.

Of 48,437 patients, 2498 experienced nonfatal and 72 fatal GI bleeding events.

Investigators matched each case to 4 controls for analysis. Compared with no cinacalcet use, any use, current use, and past use were associated with 4% increased, 3% decreased, and 22% increased odds for GI bleeding leading to hospitalization or death, respectively, but the differences were not statistically significant, Jiannong Liu, PhD, of Hennepin Healthcare Research Institute in Minneapolis, Minnesota, and colleagues reported.

“The results do not suggest an elevated risk of gastrointestinal bleeding resulting in hospitalization or death for hemodialysis patients exposed to cinacalcet,” Dr Liu’s team concluded.

10 Renal & Urology News

SEPTEMBER/OCTOBER 2021 www.renalandurologynews.com

Metastasectomy for mUC Does Not Up Survival METASTASECTOMY for patients with metastatic urothelial cancer (mUC) does not significantly improve overall survival (OS), according to a recent study.

Using the National Cancer Database, a team led by Raj Satkunasivam, MD, of Houston Methodist Hospital in Houston, Texas, identified 11,601 patients diagnosed with mUC from 2004 to 2016. Of these, 817 underwent metastastectomy and 10,784 who did not. The investigators matched 556 patients in each group by propensity score. In this matched group, the median OS was 9.1 months for those who underwent metastasectomy and 7.7 months for those who did not, Dr Satkunasivam and colleagues reported in Urologic Oncology. The 2-year OS survival rates were 16.7% and 14.4%, respectively. The 5-year rates were 6.2% and 4.9%, respectively.

These between-group differences were not statistically significantly.

No survival benefit found regardless of the treatment for the primary tumor.

In subgroup analyses, metastasectomy had no survival benefit regardless of whether patients received systemic therapy or radical surgery to the primary tumor, clinical N stage, and primary location of the primary tumor (bladder vs upper tract), according to the investigators.

The study found that the overall utilization rate of metastasectomy in mUC was 7% and did not change significantly over time (5.38% in 2004 and 7.19% in 2016).

“Although our study did not show a benefit on OS for metastasectomy in mUC, smaller retrospective studies demonstrated a potential benefit in patients with a good response to systemic therapy and low volume disease,” Dr Satkunasivam and colleagues wrote. “Those with higher volume metastatic disease, visceral or bone metastasis, or poor response to systemic are unlikely to benefit from metastasectomy in mUC with regards to OS.” ■

High BMI in mCRPC continued from page 1

s­ignificantly associated with a 4% decreased risk for death.

Higher BMI also was associated with reduced cancer-specific mortality (CSM). Obesity was significantly associated with a 35% decreased risk for CSM compared with overweight and normal weight. Each 1 kg/m2 increase in BMI was significantly associated with a 6% decreased risk for CSM. Dr Martini and colleagues found no interaction between BMI categories and docetaxel dose.

He explained that the protective effect of obesity might be attributed to some oncogenes that are downregulated as a result of obesity. For example, among patients with metastatic k ­ idney

RCC subtype continued from page 1

duration of 4.6 years. The 5-year survival rates were significantly higher for patients with favorable rather than unfavorable histology (75% vs 39%).

In a propensity score matching analysis that adjusted for confounding by patient, treatment, tumor, and hospital factors, unfavorable histologies overall were significantly associated with a 75% increased risk for dying within 5 years compared with favorable histologies. Medullary cell, collecting duct, and unspecified RCC were significantly associated with 82%, 65%, and 71% increased risks for dying within 5 years, respectively.

The increased risks for 5-year mortality associated with unfavorable histolo-

BCG and Alzheimer’s risk continued from page 1

­ lausibility” of an association between p BCG and reduced Alzheimer’s disease risk, he said.

The investigators identified study patients using Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Of the 26,584 patients, 13,477 received BCG. During a median followup of 39 months, 2192 patients (8.2%) were diagnosed with Alzheimer’s disease.

Sustained neuroinflammation is a key feature of Alzheimer’s disease. In a mouse model of Alzheimer’s disease, BCG immunization, which stimulates systemic immune modulation, resulted in improved cognition and reduced inflammation, Dr Makrakis and colleagues noted.

cancer, obesity is associated with downregulation of the FASN oncogene, which is implicated in fatty acid synthesis. Further research is needed in the context of prostate cancer to better elucidate this phenomenon, he said.

The latest findings could be useful when designing clinical trials, such as

for stratifying patients based on BMI categories, Dr Martini said. The findings also highlight a need to better understand prostate cancer as a disease

because this could lead to new ways to manage it. “The fact that some oncogenes might be downregulated in cases of obesity can help identify novel potential therapeutic targets,” said Dr Martini, adding that ongoing studies are examining a molecule that inhibits FASN. Commenting on the study, Stephen J. Freedland, MD, professor of surgery and director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Medical Center in Los Angeles, who was not involved in the new research but has studied the relationship between obesity and prostate cancer, said another possibility is that obese men do not experience the muscle-wasting and weight loss that can accompany latestage cancer and are thus in better health than those who do. ■

gies were independent of tumor characteristics, “suggesting that unfavorable histologies are mechanistically different than favorable histologies,” according to the investigators.

The latest findings add to mounting evidence of different treatment outcomes associated with various histologic subtypes of RCC. In a study of patients with intermediate-high-risk and highrisk RCC published online September 4, 2021, in Urology, Joshua Ikuemonisan, MD, of the University of Minnesota in Minneapolis, and colleagues found that patients with chromophobe RCC had significantly better overall and cancerspecific survival following nephrectomy relative to those with clear cell RCC, whereas those with the sarcomatoid subtype had significantly worse overall and cancer-specific survival.

Compared with patients who had clear cell RCC, those with chromophobe RCC had a 42% decreased risk for death from any cause and a 53% decreased risk for death from prostate cancer. Overall and cancer-specific survival did not differ significantly between patients with papillary RCC and those with clear cell RCC. In a study of 3331 patients who underwent partial or radical nephrectomy for RCC, Yasmin Abu-Ghanem, MD, of The Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel, and colleagues found that patients with clear cell RCC had a 5-year recurrencefree survival rate of 78% compared with 86% and 91% for those with papillary and chromophobe RCC, respectively, according to study findings published in European Urology Oncology. ■

In a separate study of a racially diverse cohort of 1290 patients with NMIBC receiving treatment at the Montefiore Health System from 1984 and 2020, those who received bladder instillations of BCG had a significant 59% decreased risk for Alzheimer’s disease and other dementias compared with those who did not, after adjusting for age, race and ethnicity, and comorbidities, Joseph I. Kim, MD, of Albert Einstein College of Medicine in Bronx, New York, and colleagues reported in a poster presentation.

The association was strongest among patients who received both induction and additional maintenance rounds of BCG instillation. These patients had a significant 77% decreased risk for Alzheimer’s disease and other dementias compared with patients who did

not receive BCG. Patients who received BCG induction alone had a nonsignificant 49% decreased risk, they reported.

The new findings add to those of previous studies linking BCG therapy and a reduced risk for Alzheimer’s disease in patients with bladder cancer.

For example, in a study of 1371 patients with bladder cancer (1134 men and 237 women) Ofer N. Gofrit, MD, of Hadassah-Hebrew University Medical Center in Jerusalem, Israel, and colleagues found that Alzheimer’s disease developed in 2.4% of patients treated with BCG and 8.9% of those not treated with BCG during a postoperative followup period of 8 years. Compared with BCG-treated patients, those not treated with BCG had a significant 4.8-fold increased risk for Alzheimer’s disease, the researchers reported in PLoSOne. ■

Improved survival is not related to higher chemotherapy doses, researchers report.

www.renalandurologynews.com SEPTEMBER/OCTOBER 2021

■ AUA 2021

Renal & Urology News 11

American Urological Association 2021 Annual Meeting

Outcomes of BCG-Unresponsive NMIBC Compared ONCOLOGIC OUTCOMES appear to be no worse for selected patients who choose bladder-sparing therapy instead of radical cystectomy (RC) for nonmuscle-invasive bladder cancer (NMIBC) unresponsive to intravesical bacillus Calmette-Guérin. But treatment failure rates are high, and many patients ultimately require RC, investigators reported.

In a study of 60 patients who chose initial RC and 89 patients who chose bladder-sparing therapy, 5-year metastasis-free survival was 80% vs 73% and 5-year cancer-specific survival was 82% vs 69%, respectively, with no significant differences between the groups, Yair Lotan, MD, and colleagues from the University of Texas Southwestern Medical Center in Dallas, and colleagues reported. Patients opting for bladdersparing therapy had an estimated 5-year

treatment for an organ-confined disease, meaning that patients face the potential for serious systemic side effects, even death in rare cases. Use of pembrolizumab also requires very close

coordination between medical oncology and urology because urologists are still responsible for surveillance.”

Nadofaragene firadenovec had a similar complete response rate to pembroli-

zumab in a recent phase 3 single-arm trial, but as an intravesical agent, it does not have the same limitations as pembrolizumab and thus would be preferred in many he said. ■News Renalcases, & Urology

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cystectomy-free survival rate of only 38%, however. Having more than a single line of bladder-sparing therapy before RC was significantly associated with an increased risk of pT3 or higher disease or positive lymph nodes: 44% for 2 or more lines vs 14% for 1 line vs 15% for initial RC, the investigators reported.

In an interview with Renal & Urology News, study investigator Jeffrey Howard, MD, PhD, noted that clinician judgment and patient priorities and preferences factor into these complex treatment decisions. Maintaining an intact bladder in the hopes of avoiding RC is important to some patients, he said, but it comes with a very high burden of ongoing treatment, including cystoscopies as often as every 3 months, frequent catheterizations for intravesical treatments, office biopsies, and operating room procedures.

“It varies a lot from patient to patient whether the benefits of bladder-sparing treatment outweigh the costs, including living with the anxiety of developing progressive disease,” Dr Howard said.

The FDA approval of systemic pembrolizumab was “big news,” but the drug does have shortcomings, Dr Howard noted. “It is a systemic

75C, 63M, 63Y

Study examines bladder-sparing therapy vs radical cystectomy.

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12 Renal & Urology News

■ AUA 2021

SEPTEMBER/OCTOBER 2021 www.renalandurologynews.com

American Urological Association 2021 Annual Meeting

NAC Underused for MIBC in Older Adults Study demonstrates improved survival and perioperative outcomes in patients aged 70 years or older NEOADJUVANT chemotherapy (NAC) before radical cystectomy — the gold standard treatment for muscleinvasive bladder cancer (MIBC) — is underused in older patients with cT24a MIBC despite evidence that they benefit from the treatment, new study findings suggest.

“In elderly patients undergoing cystectomy, use of NAC results in comparable perioperative outcomes as well as survival to cystectomy alone,” investigator Natasza Posielski, MD, of Virginia Mason Medical Center in Seattle, Washington, concluded in an oral presentation. “Patients of advanced age who are candidates for radical cystectomy should be offered NAC.” Guidelines from the National Comprehensive Cancer Network recommend that patients with cT2-4a receive neoadjuvant cisplatin-based

NAC vs No NAC Patients aged 70 years and older benefit from neoadjuvant chemotherapy (NAC) prior to radical cystectomy for muscle-invasive bladder cancer, according to a study. Here are some of the perioperative outcome rates.

12 10 8

n NAC n No NAC

10.6% 8.6%

7.7%

6

4.9%

4 2

1.5%

0

30-day readmission

30-day mortality

chemotherapy before radical cystectomy (RC).

Using the National Cancer Database 2006 to 2017, her team identified 70,911 adults with cT2-4a MIBC, including 43,683 who were aged 70 years or older.

The 90-day readmission rates were

is highly prevalent among patients

28% for the no-CKD group compared

undergoing radical cystectomy (RC) for

with 32.6% and 43.2% for those with

bladder cancer and is associated with

CKD stages 3 and 4, respectively, the

adverse oncologic and perioperative

investigators reported.

outcomes, a study revealed.

“CKD is associated with a higher

Patients with CKD stage 4 were more likely to have adverse pathology com-

likelihood of non-organ confined disease

pared with the other groups. The pro-

and lymph node metastases and post-

portion of patients with pT3 or greater

operative transfusion as well as 90-day

disease and positive lymph nodes

readmissions,” first author Charles

was 68.2% and 45.5%, respectively,

Nguyen, MD, said in an oral presentation.

among the patients with CKD stage

Dr Nguyen and his colleagues at the

4 compared with 37.5% and 24.8%,

University of Southern California’s Keck

respectively, for those with CKD stage

School of Medicine in Los Angeles

3 and 28.9% and 18.8%, respectively,

studied 1214 patients undergoing RC.

for those without CKD.

Of these, 722 had no CKD (estimated

On multivariable analysis, an eGFR less

glomerular filtration rate [eGFR] greater

than 30 mL/min/1.73 m2 was signifi-

than 60 mL/min/1.73 m2), 448 (36.9%)

cantly associated with approximately

had CKD stage 3 (eGFR 30-59 mL/

7-fold increased odds of extravesical or

min/1.73 m ), and 44 (3.6%) had

node-positive disease, 2.1-fold increased

CKD stage 4 (eGFR less than 30 mL/

odds of 90-day readmission, 2.4-fold

min/1.73 m ). The researchers calcu-

increased odds for 90-day complica-

lated eGFR using the Modification of

tions, and 2.1-fold increased odds for

Diet in Renal Disease study equation.

perioperative blood transfusion. ■

2

2

90-day mortality

Source: Posielski N, et al. Use of neoadjuvant chemotherapy in elderly patients with muscle invasive bladder cancer: a population-based study, 2006-2017. Presented at: AUA2021 Virtual Experience held September 10-13, 2021.

Poster MP13-14.

CKD Associated With Worse Radical Cystectomy Outcomes CHRONIC KIDNEY disease (CKD)

3.1%

Of these older patients, 14,018 underwent RC alone.

After propensity weighting, the proportion of patients receiving NAC prior to RC was significantly lower among patients aged 70 years or older c­ ompared

TURP, LP Compared in Men 75+ COMPARED WITH laser prostatectomy (LP) procedures, transurethral resection of the prostate (TURP) is generally associated with higher complication rates but lower reoperation rates in older men and men with multiple comorbidities, according to new study findings.

“Clinicians often hesitate to perform TURP in the multimorbid and elderly population, as they may be more prone to perioperative complications,” David Bouhadana, MD, of McGill University in Montreal, Quebec, Canada, and colleagues wrote. “Compared to LP, TURP was associated with higher complication rates for the multi-morbid and elderly cohorts overall but a lower hazard of reoperation, supporting its durability.”

Using the New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS) and the California Office of Statewide Health Planning and Development 2005-2016 databases, investigators analyzed short- and longterm outcomes after TURP and LP in

with those younger than 70 years: 7.2% vs. 20.9%. Older age independently predicted significant 48% lower odds of receiving NAC before RC. Many elderly patients are not offered NAC because of concerns regarding physiologic reserve and postoperative complications, according to Dr Posielski.

Yet perioperative outcomes in the older group were significantly better in those receiving NAC. Compared with the noNAC group, those receiving NAC had a shorter length of hospital stay (8.5 vs 9.6 days), lower rate of readmission within 30 days (8.6% vs 10.6%), reduced 30-day mortality rate (1.5% vs 3.1%) and 90-day mortality rate (4.9% vs 7.7%), and higher overall survival rate (43.8% vs 37.5%). The NAC group had significant 34%, 38%, and 28%, reduced odds of longer hospitalization, and 30and 90-day mortality, respectively. ■

the populations typically underrepresented in trials: 29,806 patients aged 75 years and older and 12,815 patients with a Charlson Comorbidity Index (CCI) of 3 or greater. LP encompassed laser coagulation, vaporization, and enucleation of the prostate.

After propensity score matching, older men who underwent TURP vs LP had significant 7% increased adjusted odds for 90-day hospital readmission and emergency room visits, Dr Bouhadana’s team reported. Men with multiple comorbidities had significant 8% decreased odds for these outcomes with TURP. Patients with more complex risk profiles may have opted for LP, they pointed out. They also noted that not all men with a CCI of 3 or greater are necessarily frail.

With respect to 90-day complications, older men who underwent TURP vs LP had significant 28% increased odds of hematuria. The multimorbid group had significant 17% decreased odds of urinary tract infection following TURP. TURP was associated with significant 20% and 19% lower adjusted odds of reoperation after 6 months compared with LP in the older and multimorbid populations, respectively.

Men with multiple comorbidities had significant 53% increased adjusted odds of urethral stricture developing within 6 months of TURP. ■

www.renalandurologynews.com SEPTEMBER/OCTOBER 2021

Renal & Urology News 13

KSS Safe, Effective for High-Risk UTUC Study challenges EAU guidelines indicating that radical nephroureterectomy is the best treatment

BY NATASHA PERSAUD KIDNEY-SPARING surgery (KSS) may be safe and effective in controlling upper tract urothelial carcinoma (UTUC) in patients who are followed closely, including those with high-risk disease, researchers reported.

The gold standard treatment for UTUC is radical nephroureterectomy (RNU), Nora Hendriks, a PhD candidate at the University of Amsterdam in Amsterdam, the Netherlands, and colleagues explained. Criteria to qualify for kidney-sparing surgery (KSS), however, have become less strict in consecutive guidelines, allowing more patients to opt for segmental ureter resection, ureterorenoscopy, or percutaneous tumor resection instead of RNU, she said.

In her team’s retrospective review of 180 patients with histopathologically confirmed nonmetastatic UTUC,

Kidney Stone Risk Affected

by Heredity A FAMILY HISTORY of kidney stone disease may predict earlier onset of kidney stones and an increased risk for recurrent kidney stones, with differences between maternal and paternal genetic inheritance.

Any family history of kidney stone disease imparts an increased severity of urinary stone disease, Rei Unno, MD, PhD, of Nagoya City University Graduate School of Medical Sciences in Aichi, Japan told Renal & Urology News. The presence of a maternal relative with kidney stones may predict earlier onset of urolithiasis, she said.

Her team’s analysis of prospectively collected data from the Japanese Registry for Stones of the Kidney and Ureter (ReSKU) found that 603 of 1566 patients (38.5%) had a family history of urolithiasis. On multivariate analysis, any family history was significantly associated with 62% increased odds of recurrent stone events, 84% increased odds of first stone onset at or before the age of 30 years, and 54% increased odds of bilateral stones.

metastasis-free survival, cancer-specific survival, and overall survival rates over approximately 125 months were all significantly higher for patients who were treated with KSS compared with RNU.

Metastasis-free, cancer-specific, and overall survival are higher vs RNU. Even high-risk patients treated with KSS outside the scope of current European Association of Urology (EAU) guidelines had improved survival outcomes, Hendriks reported. In the study, 74.2% of the KSS group were considered high risk, compared with 93.8% of the RNU group. High-risk f­eatures

A patient who had a first-degree relative with stone history had significant 58% increased odds of stone recurrence and 42% increased odds of first stone onset. Having both a first- and a seconddegree relative with stone history significantly associated with 2.2-fold increased odds for a recurrent stone event, 3.3fold increased odds for early onset, and 1.9-fold increased odds of bilateral stones. Having a paternal or maternal relative with stone history significantly associated with 93% and 72% increased odds of recurrence and 1.5- and 2.9-fold increased odds of early onset, respectively.

“There is an association between mitochondrial dysfunction and kidney stone disease,” Dr Unno explained.

“Maternal inheritance of abnormal mitochondrial DNA could contribute to the early stone development in patients with positive maternal family history of stones.” Maternal dietary habits have been shown to transmit to children more strongly than paternal dietary habits, she added.

“As there are many drivers associated with urolithiasis, we consider those with maternal relatives or multiple family members with kidney stone disease warrant closer follow-up, improvement of their diet, and aggressive stone prevention techniques to reduce the risk of urolithiasis,” Dr Unno said. ■

were similarly distributed within both groups, including high-grade disease, invasive disease, tumor size larger than 2 cm, multifocality, hydronephrosis, cystectomy, and high-grade urothelial carcinoma of the bladder.

In an interview, Hendriks said, “This begs the question: Is current risk stratification based on clinical variables stated in EAU guidelines correctly discriminating between high-risk and low-risk disease?”

Among high-risk patients, the RNU group had significantly higher intravesical and ipsilateral recurrence-free survival.

The differences in intravesical recurrence rate were likely partly influenced by a post-RNU regimen of intravesical mitomycin C, which started in 2017, she noted.

The ipsilateral finding might reflect tumor seeding down the tract in the KSS group, Hendriks noted, or a longstanding tumor. In the KSS group, 84.3%, 10.1%,

and 5.6% underwent ureterorenoscopy, segmental ureter resection, and percutaneous tumor resection, respectively.

Estimated glomerular filtration rate (in mL/min/1.73 m2) was comparable at baseline for both the RNU and KSS group (57.02 vs 53.52, respectively).

There were no significant differences at 2 (51.18 vs 44.75) and 5 years (51.03 vs 45.29) after intervention.

As UTUC is a rare disease and EAU guidelines are still quite young and partly based on low-quality evidence, a health care team’s experience is essential for disease management and to attain favorable results from kidneysparing procedures, Hendriks said.

After surgery, it is crucial to implement a stringent, clearly defined follow-up protocol including regular ureterorenoscopy, cystoscopy, and computed tomography-urography. ■

5-ARI Use Should Inform Prostate Biopsy Decisions CURRENT USE OF 5-alpha reductase

At their institution, 143 men were tak-

inhibitors (5-ARI) is another reason to

ing 5-ARIs at the time of prostate biopsy

perform a biopsy for prostate cancer

and 910 men were not. Demographic

(PCa), according to investigators.

characteristics appeared similar

“While not emphasized in common

between groups, but men taking 5-ARIs

risk calculators, pre-diagnostic use

had a significantly higher median pros-

of 5-ARI should be considered when

tate volume (51.1 vs 43.4 mL) and non-

deciding to biopsy,” lead investigator

significantly higher median PSA values

James T. Kearns, MD, of Levine

(8.2 vs 6.4 ng/mL). At PCa diagnosis,

Cancer Institute in Charlotte, North

5-ARI users were significantly more likely

Carolina, said in an interview. “The

to have a higher clinical T stage com-

use of 5-ARIs reduces PSA by approxi-

pared with nonusers: 12.7% vs 8.7% had

mately 50%, and I do believe it is asso-

cT2 and 4.2% vs 0.9% had cT3-4, respec-

ciated with a delay in the diagnosis of

tively, Dr Kearns and his colleagues

prostate cancer.”

reported in a poster presentation. More

A 2019 retrospective study published

5-ARI users than nonusers were stratified

in JAMA Internal Medicine revealed an

into National Comprehensive Cancer

association between 5-ARI use and

Network high-risk (30.3% vs 25.9%)

delayed diagnosis of PCa and worse

and intermediate-risk (50.5% vs 43.0%)

oncologic outcomes. Dr Kearns and his

categories, respectively.

colleagues at the institute compared

“These findings suggest that 5-ARI

clinical characteristics and treatments

[use] is an important risk factor to be con-

between 5-ARI users and nonusers at

sidered at referral and highlight the need

prostate biopsy and PCa diagnosis to

to optimize diagnostic care for 5-ARI

identify possible risk factors.

users,” the researchers concluded. ■

www.renalandurologynews.com SEPTEMBER/OCTOBER 2021

Renal & Urology News 15

Ketogenic Diets Can Increase Renal Risks Accelerated loss of kidney function is among the potential dangers of high protein intake

BY JOHN SCHIESZER HIGHER-PROTEIN ketogenic (keto) diets may hasten kidney failure and cause other medical problems in patients with kidney disease, according to the most comprehensive review yet of these diets.

Keto diets are low in carbohydrates and high in fat, with disagreement over whether the diets are high in protein, according to study coauthor Shivam Joshi, MD, clinical assistant professor of medicine at the NYU Grossman School of Medicine in New York, New York. The average keto diet consists of 1.2-2.0 g/kg/d of protein, Dr Joshi said, adding that he and his colleagues consider this technically to be a high amount. Supporters of keto diets, however, consider this protein intake to be normal or average, possibly because the typical American diet already consists of 1.2-1.5 g/kg/d of protein, Dr Joshi said.

The review, which was published in Frontiers in Nutrition, demonstrated that the possible long-term risks of the keto diet include heart disease, cancer, diabetes, kidney stones, Alzheimer’s disease, and other diseases.

Keto diets, which can result in ketosis, may be especially unsafe for women who are pregnant or may become pregnant, with strong data suggesting that

keto diet, patients may worsen their acidosis and thereby require more medication to treat it, Dr Joshi said.

“Some diets have the potential to exacerbate underlying kidney disease, or the complications of kidney disease, whereas other diets can help ameliorate the progression of kidney disease, the complications of kidney disease, and, in some cases, the causes of kidney disease, like diabetes and hypertension,” Dr Joshi said.

low-carb diets are linked to a higher risk of neural tube defects in infants even if mothers take folic acid.

“By definition, keto diets are very high in fat and protein, and that is challenging for long-term renal health,” said study coauthor Neal Barnard, MD, an adjunct professor of medicine at the George Washington University School of Medicine in Washington, D.C., and president of the Physicians Committee for Responsible Medicine.

Strain on Diseased Kidneys In patients with any reduction in kidney function due to diabetes, hypertension, or infection, high protein intake accelerates loss of kidney function, Dr Barnard said. “A keto diet can really strain already troubled kidneys,” he said.

The review confirmed that high animal fat consumption is associated with increased risks for albuminuria and chronic kidney disease (CKD).

“Nephrologists see many patients who are looking for ways to lose weight, and many also have diabetes, hypertension, and atherosclerosis. Evidence shows that ketogenic diets can lead to further harm and should not be recommended,” Dr Barnard said. “A healthful diet of vegetables, fruits, whole grains,

Possible long-term risks of a ketogenic diet include heart disease, cancer, diabetes, and kidney stones.

and legumes, appropriately planned will lead to healthier long-term weight control, in addition to helping preserve kidney function to the extent possible.”

Impact on Metabolic Acidosis Dr Joshi said the keto diet has the potential to exacerbate metabolic acidosis. A common treatment for metabolic acidosis is sodium bicarbonate, which can have side effects such as worsening edema and elevated blood pressure. By increasing the potential acid load with a

Keto Diets and Type 1 Diabetes Because keto diets include concentrated fats, meat, poultry, fish, eggs, and cheese, they have been associated with increased diabetes risk. These foods often are high in saturated fat, cholesterol, chemical contaminants, and other potentially inflammatory compounds.

When the researchers looked at adults with type 1 diabetes, they found studies suggesting both favorable and unfavorable outcomes. One small study suggested the keto diet could improve blood glucose control in patients with type 1 diabetes, but it triggered more frequent and extreme hypoglycemic episodes.

The investigators concluded that the only well-supported use for keto diets is to reduce seizure frequency in some individuals with drug-resistant epilepsy. ■

© JASMIN MERDAN / GETTY IMAGES

Long-Term Kidney Transplant Outcomes Improving LONG-TERM GRAFT and patient survival following receipt of a kidney transplant have been improving, according to the authors of a recently published review article.

Among patients who received a deceased-donor transplant, the 10-year graft survival rate increased from 42.3% for patients who received a transplant during 1996-1999 to 53.6% for those who received a transplant from 20082011. During these same time intervals, the 10-year patient survival rates increased from 60.5% to 66.9%.

These improvements have occurred despite increases in recipient age, body mass index, frequency of diabetes, length of time on dialysis, and donor age and percentage of donations after circulatory death, as well as a higher proportion of recipients with a previous kidney transplant, Sundaram Hariharan, MD, of the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania, and

coauthors reported in the New England Journal of Medicine.

Survival outcomes also improved among recipients of kidneys from living donors. From 1996-1999 to 2008-2011, the 10-year graft survival rate increased from 53.6% to 69.6% and the 10-year patient survival rate increased from 75.3% to 81.3%.

Trend observed in both deceased-donor and living-donor transplant recipients The authors wrote that the observed improvement in long-term outcomes has been attributed to a decrease in clinical acute rejection rates as well as surveillance for viral infections, effective antiviral prophylaxis, and prudent use

of paired-exchange transplants for candidates with incompatible living donors.

Dr Hariharan and coauthors examined outcomes from individuals who received kidney transplants during 6 periods: 1996-1999, 2000-2003, 20042007, 2008-2011, 2012-2015, and 20162019. The total number of transplants from living and deceased donors increased from 45,008 during 19961999 to 76,885 during 2016-2019. The increase was due mostly to the number of transplants from deceased donors, which increased from 29,823 during 1996-1999 to 53,139 during 2016-2019.

The number of transplants from living donors increased from 15,185 to 23,746 during the same time period.

The authors lauded the December 2020 passage of the Immunosuppressive Drug Coverage for Kidney Transplant Patients Act, which indefinitely extends Medicare coverage of immunosuppressive ­medications for kidney trans-

plant recipients who do not have other coverage. They also noted that the COVID-19 pandemic might have positive consequences for the care of kidney transplant recipients. “A silver lining of the Covid-19 pandemic,” they wrote, “may be the incorporation of telemedicine into routine care to facilitate access to transplantation and post-transplantation care, particularly for older patients and those in underserved and geographically remote communities.”

They concluded, “Improvements in long-term survival after kidney transplantation has been gratifying, despite unfavorable changes in donor and recipient risk factors. Continuation of this trend will require a multipronged approach that addresses coexisting conditions before transplantation, health literacy, access to caregivers, and, especially among racial and ethnic minority and young transplant recipients, adherence to therapy.” ■

20 Renal & Urology News

SEPTEMBER/OCTOBER 2021 www.renalandurologynews.com

Study Challenges ADT Use at PSA Relapse Waiting until metastasis to start treatment has minimal impact on overall survival, investigators found OVERALL SURVIVAL is not meaningfully prolonged for patients with biochemically recurrent (BCR) prostate cancer who receive continuous androgen deprivation therapy (ADT) at the time of PSA relapse rather than metastasis, according to investigators.

“Metastasis-free survival and overall survival of men with BCR who delay hormone therapy is long. This underscores the need to reevaluate when to start primary ADT in this patient population,” Catherine Handy Marshall, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and her colleagues team concluded in a report published online in The Journal of Urology.

Dr Marshall’s team studied 806 highrisk patients (mean age 61 years; 16% Black) from Johns Hopkins Hospital and Walter Reed National Military

Medical Center in Bethesda, Maryland, who experienced BCR after radical prostatectomy and delayed ADT initiation until metastasis. From the time of local treatment, median metastasis-free

Long survival time observed for men with biochemical recurrent PCa who delay ADT. survival (MFS) was 144 months and 192 months for men with a PSA doubling time of less than 6 months and less than 10 months, respectively, the investigators reported. Median overall survival (OS) from the time of local treatment was 168 and 204 months, respectively.

Older age, higher pathologic T stage,

Study: Biomarkers May Predict COVID-19 Death Risk in KTRs AMONG KIDNEY TRANSPLANT recipi-

The 60-day survival rate was as high

ents (KTRs) infected with SARS CoV-2,

as 92% among patients without eleva-

those who have elevations in biomark-

tion in any of the 3 biomarkers, but the

ers of inflammation, cardiac injury, and

rate declined to 77% among those with

coagulation appear more likely to die.

elevation of at least 1 of the biomarkers.

In a French nationwide registry of

The 60-day survival rate declined to 58%

494 KTRs with COVID-19 during the first

and 40% among patients with elevations

wave of the pandemic, 101 (20%) died.

in 2 and 3 biomarkers, respectively.

Patients with levels of serum creatinine

Several studies in the adult general

above 150 μmol/L, C-reactive protein

population have found an association

above 50 mg/L, procalcitonin above

between elevation of cardiac injury,

0.3 mg/L, hs-troponin I above 20 ng/L,

coagulation, and inflammatory biomark-

lactate dehydrogenase above 280

ers and COVID-19-related mortality, the

UI/L, and D-dimer above 1500 UI/L

investigators noted.

were at increased risk for COVID-19related mortality.

On multivariate analysis, only procalcitonin and troponin I remained

“If independently validated, the use of biomarkers may help to guide therapeutic decision making in transplant patients,” Dr Caillard’s team concluded.

independently associated with a signifi-

Of the 494 KTRs (approximately 5%

cant 3.7- and 2.9-fold increased risk for

dual organ transplants) with COVID-19,

mortality, respectively, Sophie Caillard,

83% were admitted to the hospital

MD, PhD, of the Strasbourg University

and 30.6% of these were sent to an

Hospital in Strasbourg Cedex, France,

intensive care unit. Mechanical ventila-

and colleagues reported in Kidney

tion was required by 26% of the cohort.

International Reports. Subgroup analy-

Overall, acute kidney injury occurred in

ses additionally identified D-dimer as a

57.8%, and renal replacement therapy

prognostic biomarker.

was initiated in 15.6%. ■

higher Gleason sum, and faster PSA doubling time were all associated with higher likelihood of death.

Dr Marshall and her collaborators compared their results with MFS and OS times from pivotal trials of highrisk patients with nonmetastatic castration-resistant prostate cancer who were treated with surgery, radiation, or primary ADT alone. Estimated median MFS was 136 vs 110 months in the apalutamide and placebo arms, respectively, of the SPARTAN trial, and 127 vs 103 months in the darolutamide and placebo arms, respectively, of the ARAMIS trial. Estimated median OS was 169 vs 154 months in the apalutamide and placebo arms, respectively, of the SPARTAN trial and not reached in the ARAMIS trial. OS times from these trials are comparable to those from the current study.

In an accompanying editorial, David VanderWeele, MD, PhD, and Maha Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center at the Northwestern University Feinberg School of Medicine, in Chicago, Illinois, agreed that the risks of early ADT in men with biochemically recurrent prostate cancer may not outweigh the benefits.

“These data provide context for patients with BCR and providers on whether to undergo ADT for years despite unproven benefit and quality of life impact,” they wrote. “New imaging may help or further add to the controversy, since BCR patients may have metastases on newer imaging. Until definitive data are available, men with BCR should be counselled regarding the lack of data to support ADT benefit in nonmetastatic BCR.” ■

Finerenone’s Benefits Span CKD Spectrum

data from of data from 13,026 patients in the FIDELIO-DKD and FIGARODKD randomized trials. CKD severity was defined according to categories of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR).

The primary endpoint was time to first occurrence of a composite of cardiovascular (CV) death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The secondary endpoint was time to first occurrence of a composite of kidney failure, decrease in eGFR by 57% or more, or renal death.

Over a median of 3.0 years of follow-up, the composite CV endpoint occurred in a lower proportion of patients receiving finerenone compared with placebo: 12.7% vs 14.4%, according to investigators. Finerenone reduced the risk for the CV outcome by a significant 14%.

The composite renal endpoint also occurred in a smaller proportion of patients receiving finerenone vs placebo: 5.5% vs 7.1%. Finerenone reduced the risk for the renal outcome by a significant 23%.

Hyperkalemia was more common with finerenone than placebo: 14.0% vs 6.9%. Discontinuation of treatment due to hyperkalemia occurred in 1.7% of the finerenone and 0.6% of the placebo group. ■

FINERENONE REDUCES the risk for cardiovascular and renal outcomes in patients with type 2 diabetes who have mild to advanced chronic kidney disease (CKD) and those with diagnosed diabetic kidney disease, investigators announced at the 2021 congress of the European Society of Cardiology.

The nonsteroidal mineralocorticoid receptor antagonist (MRA) carries an increased risk for hyperkalemia.

“The FIDELITY analysis demonstrates that finerenone reduced the risk of cardiovascular and kidney outcomes compared with placebo across the spectrum of chronic kidney disease in patients with type 2 diabetes,” study author Gerasimos Filippatos, MD, of the National and Kapodistrian University of Athens Medical School in Greece stated in an ESC congress press release. “The cardiovascular benefits of the drug were consistent across eGFR and UACR categories, indicating that treatment should be initiated in the early stages of renal disease.”

In FIDELITY, a prespecific metaanalysis combining individual patient

www.renalandurologynews.com SEPTEMBER/OCTOBER 2021

Renal & Urology News 21

Salt Substitute May Decrease Stroke Risk Large trial reveals cardiovascular benefits of using a salt containing 25% potassium chloride

A STUDY of individuals at elevated risk for cardiovascular events found that use of a salt substitute with reduced sodium levels instead of regular salt decreased the risk for stroke without increasing the likelihood of serious adverse effects, according to investigators.

In the randomized Salt Substitute and Stroke Study (SSaSS), participants who used a salt substitute (75% sodium chloride and 25% potassium chloride) had a significant 14% lower risk for stroke — the trial’s primary outcome — compared with those who used regular salt (100% sodium chloride), Bruce Neal, MB, ChB, PhD, of the George Institute for Global Health at the University of New South Wales in Australia, and colleagues reported in the New England Journal of Medicine.

Users of the salt substitute also experienced a significant 13% decreased risk for major cardiovascular events and 12% decreased risk for death from any cause.

The rate of serious adverse events due to hyperkalemia was not significantly higher with salt substitute use.

Dual Combo for Advanced RCC Cleared THE FDA HAS approved pembrolizumab in combination with lenvatinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). The agency based its approval on data from the multicenter, open-label, randomized phase 3 CLEAR (Study 307)/KEYNOTE-581 trial, which evaluated the efficacy

Fewer CV Events With Salt Substitute Use In a randomized trial that included 20,995 rural Chinese residents, use of a salt substitute lowered the risk for stroke, major cardiovascular (CV) events, and death compared with the use of regular salt. Shown here are the event rates per 1000 person-years.

60 40

49.09% 29.14%

n Salt substitute n Regular salt

56.29% 39.28%

33.65%

44.61%

20 0

Stroke

Major CV events

Deaths

Source: Neal B, Wu X, Feng R, et al. Effect of salt substitution on cardiovascular events and death. N Engl J Med. Published online ahead of print on August 29, 2021.

The study included 20,995 persons who lived in 600 rural villages throughout China. Participants had a history of stroke or were aged 60 years or older and had poorly controlled blood pressure. Of the study population, 72.6% had a history of stroke, and 88.4% had a history of hypertension. Individuals had a mean age of 65.4 years. The mean duration of followup was 4.74 years. The study excluded

individuals if they or others living in their household had a potential contraindication to the salt substitute used in the trial (such as use of a potassium supplement, use of a potassium-sparing diuretic, or known serious kidney disease).

The rates of stroke, major cardiovascular events, and death (in events per 1000 person-years), all higher in saltsubstitute group than the regular-salt

group, were 29.14 vs 33.65, 49.09 vs 56.29, and 39.28 vs 44.61, respectively.

The investigators defined major cardiovascular events as a composite of nonfatal stroke, nonfatal acute coronary syndrome, or death from vascular causes.

The rates of definite, probable, or possible hyperkalemic events were 3.35 and 3.30, respectively, a nonsignificant difference between the groups.

In an acknowledgment of study limitations, the authors noted that potassium “was not measured serially, and elevated potassium levels might have been missed in some participants.” Further, only a single preparation of a salt substitute was used in the trial, “so graded decreases in sodium intake, which might have induced graded responses, were not evaluated.”

“The results of the SSaSS appear impressive,” the journal’s deputy editor Julie R. Ingelfinger, MD, wrote in an accompanying editorial. “If the strategy is feasible over time, the salt-substitute approach might have a major public health consequence in China, and possibly, elsewhere.” ■

Serious CV Events Tied to Low BMD LOW BONE mineral density (BMD) may increase the risk for major adverse cardiovascular events and progression of coronary artery calcification among patients with predialysis chronic kidney disease (CKD), new study findings suggest.

In a prospective cohort study that included 1957 patients with predialysis CKD, the lowest tertile of total hip BMD was significantly associated with a nearly 2.2-fold increased risk for major adverse cardiovascular events (MACE) compared with the highest tertile after

adjusting for age, sex, smoking, diabetes, systolic blood pressure, and other potential confounders, Hyoungnae Kim, MD, of Soonchunhyang University Seoul Hospital in Seoul, Korea, and colleagues reported in the Clinical Kidney Journal. The investigators also found the association of MACE with BMD at the femur neck, but not with BMD at the lumbar spine.

In a subgroup of 977 patients with repeat measurements of coronary artery calcification (CAC) at year 4 of the study, higher total hip BMD was

significantly associated with 25% decreased odds for CAC progression.

Baseline CAC scores of 100 to 400 and higher than 400 were significantly associated with 3.0-fold and 5.9-fold increased risks for MACE compared with no CAC at baseline, according to the investigators.

Dr Kim and colleagues measured BMD using dual-energy X-ray absorptiometry and CAC using coronary computed tomography scans. MACE occurred in 115 patients during a median follow-up of 4.2 years. ■

and safety of pembrolizumab plus lenvatinib compared with sunitinib.

“This is a significant milestone for newly diagnosed patients with advanced renal cell carcinoma and introduces a promising combination option in the first-line setting,” study investigator Robert Motzer, MD, of Memorial Sloan Kettering Cancer Center in New York, said in a press release issued by Merck and Eisai, the makers of pembrolizumab and lenvatinib, respectively. ■

Urate-Lowering Therapy May Cut Gout Flare Risk CONTROLLING asymptomatic hyperuricemia with urate-lowering therapy (ULT) may decrease the likelihood of gout flares, according to an analysis of real-world data from Japan.

A retrospective study of 19,261 patients with serum uric acid levels of 8.0 mg/ dL or higher found that patients with either gout or asymptomatic hyperuricemia who achieved levels of 6.0 mg/dL or lower with ULT had fewer occurrences

of gout flare compared with those whose serum uric acid level remained above 6.0 mg/dL, Ruriko Koto, MMSc, of Teijin Pharma Limited in Tokyo, and colleagues reported in the Annals of the Rheumatic Diseases. Patients with asymptomatic hyperuricemia and those with gout who were on ULT and had serum uric acid levels of 6.0 mg/dL or less but higher than 5 mg/dL had a significant 55% and 35% decreased risk for gout flare compared

with untreated patients whose serum uric acid levels were 8.0 mg/dL or higher.

The researchers identified study patients using the JMDC Claims Database, which contains information from health insurance associations that include only limited data from individuals aged 65 years or older and no data from those aged 75 years or older, “so our findings cannot be generalized to the entire Japanese population.” ■

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SEPTEMBER/OCTOBER 2021 www.renalandurologynews.com

Wide BMI Fluctuations in CKD Linked to Worse Outcomes

Exercise May Postpone PCa Progression

High variability in body mass index found to increase risks for death, MI

EXERCISE MAY DELAY biochemical progression of localized prostate cancer while improving cardiorespiratory fit­ ness, according to the results of the small randomized ERASE clinical trial.

“The findings of this study indicate that exercise may be an effective inter­ vention for improving cardiorespira­ tory fitness and suppressing the pro­ gression of prostate cancer for patients undergoing active surveillance,” a team led by Kerry S. Courneya, PhD, of the University of Alberta in Edmonton, Alberta, Canada, reported in JAMA Oncology.

For the trial, investigators randomly assigned 52 men (mean age 63.4 years) on active surveillance for localized lowor intermediate-risk prostate cancer to a usual care group or a high-intensity interval training (HIIT) group. Each group had 26 patients.

Men in the HIIT group were asked to complete 12 weeks of thrice-weekly supervised aerobic sessions on a tread­ mill including eight 2-minute intervals at 85% to 95% peak oxygen consump­ tion. The usual-care group maintained their usual exercise levels.

Compared with the usual-care group, the HIIT group experienced signifi­ cantly improved peak oxygen con­ sumption (the study’s primary outcome) — which rose by 0.9 mL/kg/min in the HIIT group and decreased by 0.5 mL/ kg/min in the usual care group, the investigators reported.

From baseline to post-intervention, the mean PSA level declined from 6.1 ng/mL at baseline to 5.7 ng/mL following intervention in the HIIT group, whereas it increased from 8.3 to 8.6 ng/mL in the usual-care group, resulting in a significant adjusted between-group mean difference of –1.1 favoring the HIIT group, according to Dr Courneya’s team. The mean PSA velocity decreased from 1.1 to 0.1 ng/ mL per year in the HIIT group and from 1.3 to 1.2 ng/mL per year in the usual-care group, resulting in a signifi­ cant adjusted between-group mean dif­ ference of –1.3 ng/mL per year favor­ ing the HIIT group. The investigators adjusted between-group differences for baseline values of the outcomes and resistance exercise behavior.

Dr Courneya’s team found no signifi­ cant changes in PSA doubling time or testosterone level. ■

replacement therapy, 2% had an MI, and 3% had a stroke. Compared with individuals who had the least BMI variability, those with the greatest vari­ ability had a 66% higher risk for death, 20% higher risk for kidney replacement therapy, and 19% higher risk for an MI or stroke.

© INHAUSCREATIVE / GETTY IMAGES

BY JOHN SCHIESZER PATIENTS WITH chronic kidney dis­ ease (CKD) and wide body mass index (BMI) variability are at elevated risks for death, myocardial infarction, and stroke as well as an increased likeli­ hood for requiring kidney replacement therapy, according to a recent study.

A recent study highlights the importance of unstable metabolic status, a researcher said.

Previous studies have demonstrated that BMI variability or metabolic parameter variability is associated with a higher risk for heart disease in the general population. Investigators in South Korea examined whether BMI variability may affect the prognosis of patients with kidney dysfunction.

The retrospective observational study, published in the Journal of the American Society of Nephrology, included 84,636 patients with CKD who were listed in a national health screening database.

Patients had a mean age of 68 years and median BMI of 24.6 kg/m2. At baseline, all the individuals had persistent pre­ dialysis CKD (defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 or dipstick albu­ minuria of 1 or higher), and had 3 or more health screenings before the base­ line visit. The analysis included factors such as sex, waist circumference, cur­ rent smoking history, alcohol intake, regular physical activity, diabetes mel­ litus, income status and other factors.

After a median follow-up of 4 years, 6% of patients died, 4% needed ­kidney

Study investigator Sehoon Park, MD, of the Kidney Research Institute at Seoul National University, said a high BMI is traditionally considered a risk factor for adverse cardiovascular dis­ ease (CVD) and mortality in the gen­ eral population. However, this did not appear to apply to patients with CKD, as baseline BMI was inversely associ­ ated with major adverse outcomes.

Assess BMI Trends “The major point which was surpris­ ing was that the significance remained both in those with an increasing trend of body mass index and in those with a decreasing trend,” Dr Parks said. “This highlights the importance of unstable metabolic status, which would be more important than obesity or increasing body mass index, even though a higher BMI is one of the most widely acknowl­ edged bad metabolic health statuses in the general population.”

Variabilities in certain metabolic syndrome components were also sig­ nificantly associated with the prognosis of patients with CKD not on dialysis.

Those with a higher number of meta­ bolic syndrome components with higher BMI variability had a worse prognosis.

Clinicians should ask, record, and assess the trends of BMI and metabolic health parameters at regular clinic visits, according to the researchers.

“Focusing on a single time point may miss important clinical risk factors associated with the prognosis of CKD patients,” Dr Parks said. “A high vari­ ability state of body mass index or met­ abolic parameters should be carefully assessed. We believe the findings can be generalizable for Western countries, including North America, as unstable metabolic health status also appears to be associated with worse prognosis.”

Explore BMI Changes Holly Kramer, MD, MPH, a professor of public health sciences and medi­ cine at Loyola University in Maywood, Illinois, said the study findings are not surprising because BMI fluctuations may indicate other serious comorbid conditions. “You have to look at depres­ sion and other issues,” Dr Kramer said.

“Nutritional parameters are an excel­ lent way to access a patient’s wellbeing.”

Dr Kramer, who is a past president of the National Kidney Foundation, said the study underscores the impor­ tance of asking patients about appetite and how they feel mentally. “If you are seeing large fluctuations in their body weight that may mean something is not stable in their life and it could be social problems and not medical problems.

Looking at trajectories of body weight can give you information and lead to queries about issues,” Dr Kramer said.

Some patients may be using food as an emotional crutch or in some cases they may not have access to food, she said.

She added, “If you don’t look at their weight, you might not find out that the wife died and did all the cooking.”

It is well established that bariatric surgery improves metabolic param­ eters, but Dr Kramer said it is necessary to investigate further the effects that big drops in weight among patients with CKD have on their risk for CVD, the leading cause of mortality in this patient population. ■

www.renalandurologynews.com SEPTEMBER/OCTOBER 2021

Researchers: 78% of Men Who Have Metastatic PCa Die From It Another 17% die from noncancer causes such as cardiovascular disease

Renal & Urology News 29

AKI Tied to Arterial Stiffness ACUTE KIDNEY INJURY (AKI) is independently associated with arterial

METASTATIC PROSTATE cancer (PCa) is the cause of death for approximately three-quarters of men who have it, according to a recent study.

Additional causes of death in these men include other cancers and medical conditions other than cancer.

“These findings may provide insight into how men with metastatic [PCa] should be counseled regarding future health risks and highlight the importance of multidisciplinary care for such patients,” a team led by Omar Alhalabi, MD, of the University of Texas MD Anderson Cancer Center in Houston, reported in JAMA Network Open.

Using data from the Surveillance, Epidemiology, and End Results (SEER) program database, the investigators studied 26,168 men diagnosed with metastatic PCa from January 1, 2000, to December 31, 2016. Of these, 16,732 (63.9%) died during follow-up. Most deaths (59%) occurred within 2 years of diagnosis.

The mean age at death was 74 years.

Of the total number of deaths following a diagnosis of metastatic PCa, 13,011 (77.8%) were from PCa, 924 (5.5%) were from other cancers, and

2797 (16.7%) were from noncancer causes, Dr Alhalabi and colleagues reported. Noncancer causes of death include cardiovascular and cerebrovascular diseases and chronic obstructive pulmonary disease (COPD).

Men with metastatic PCa had a significant 34%, 31%, and 19% higher mortality rate from cardiovascular disease,

In a study of 26,168 men with metastatic PCa, 59% died within 2 years of diagnosis. cerebrovascular disease, and COPD, respectively, compared with the agematched US male population in adjusted analyses, according to the investigators.

Men younger than 50 years at the time of diagnosis of metastatic PCa had a higher overall risk for death within 2 years after diagnosis compared with men younger than 50 years without metastatic prostate cancer, Dr Alhalabi’s team reported.

White patients and Asian and Pacific Islander patients had a significantly increased risk for death by suicide, whereas Black patients and American Indians and Alaska Native patients did not.

In an accompanying editorial, Samuel W. D. Merriel, MSc, of the University of Exeter Medical School in Exeter, UK, and coauthors noted that, as the study investigators observed, most men with metastatic PCa die from it instead of other possible causes of death, “reinforcing the need for innovations to promote early-stage diagnosis. The recent developments and implementation of new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage, although some metastatic disease at the time of diagnosis will likely still occur.”

The editorialists also commented, “Their finding of increased suicide rates among Asian or Pacific Island patients and White patients with metastatic prostate cancer is a surprise and should be investigated further, considering that such deaths are potentially preventable.” ■

stiffness, according to investigators.

Their study of 613 participants in SPRINT (Systolic Blood Pressure Intervention Trial) revealed that each 1 m/s increase in carotid-femoral pulse wave velocity (PWV) — the gold standard for measuring arterial stiffness — was significantly associated with a 32% increased risk for AKI in a fully adjusted model, corresponding author Anna Jovanovich, MD, of the University of Colorado’s Anschutz Medical Campus in Aurora, and colleagues reported in the Clinical Journal of the American Society of Nephrology.

Compared with a carotid-femoral PWV below the median (10.4 m/s), a value of 10.4 m/s or higher was significantly associated with a nearly 13.3-fold increased risk for AKI. “Our results support consideration of including arterial stiffness into risk prediction models for AKI and as a target for prevention or therapeutic treatment of AKI,” the authors concluded.

“However, further inquiry in larger and more diverse populations, including healthy individuals and those with

HHD Failure Tied to Higher Death Risk

diabetes, are needed to validate these

HOME hemodialysis (HHD) treatment failure is associated with increased mortality, a new study finds.

Of 19,306 patients receiving hemodialysis in the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry from 2005 to 2015, a total of 2457 started on or transitioned to HHD and 577 returned to in-center hemodialysis (ICHD) at some point.

In both univariate and multivariate analysis, HHD treatment failure (defined as transition from HHD to incenter hemodialysis) was significantly associated with 3.9, 3.3-, and 2.3-fold increased risks for all-cause mortality in the first 30 days, 30-90 days, and 90 days or more, respectively, compared with continued HHD, David J. Semple, PhD, of Auckland District Health Board in Auckland, New Zealand, and colleagues reported in the American Journal of Kidney Diseases. When ICHD was the first modality, treatment failure was

race, sex, smoking category, history

significantly associated with a 1.9-fold increased mortality risk compared with continued HHD. HHD return (after a period of ICHD and HHD) was associated with 1.1-fold increased mortality risk compared with continued HHD. A competing risk analysis showed that withdrawal from dialysis was a significant cause of early mortality within 90 days after return to ICHD from HHD. Both withdrawal from dialysis and cardiovascular death significantly accounted for late mortality.Other significant independent predictors of death included older age, late dialysis referral, smoking, non-glomerular cause of kidney failure, and major comorbidities.

Dr Semple’s team wrote that “the need to transition from HHD to ICHD should now prompt an examination of the patient’s overall health trajectory and, where appropriate, increased support and consideration of advanced care planning.”

Patients who resume HHD after a period of ICHD may have technical, vascular access, or social issues, rather than clinically significant changes in health status and frailty, the investigators suggested.

In a discussion of study strengths, the authors noted that their analysis “includes all HHD and ICHD patients in Australia and New Zealand from the study period with data derived from a robust and clinically relevant registry (ANZDATA). Patient inclusion is therefore unbiased and representative of true clinical practice, and patients typically excluded in many prospective studies have been included in the analysis. As such, the generalizability of these results to other patient populations is increased.”

The causes of HHD treatment failure were not available for this study, precluding further meaningful analysis, according to the investigators. ■

hypothesis-generating findings.”

The investigators adjusted for age, of cardiovascular disease, number of antihypertensive medications, estimated glomerular filtration rate, and other potential confounders.

SPRINT was a randomized trial comparing the effect of intensive blood pressure treatment to standard treatment on cardiovascular outcomes in 9361 hypertensive participants without diabetes.

Study strengths included use of data from a large multicenter trial, “which allowed us to account for many important confounders.” The authors acknowledged, however, that the study is limited in its generalizability because it only included participants in SPRINT, who were older, hypertensive, nondiabetic adults at high risk for cardiovascular disease. ■

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SEPTEMBER/OCTOBER 2021 www.renalandurologynews.com

High PSA Less Likely With a Healthy Diet Investigators find a protective effect of high consumption of healthful plant-based foods plant foods and healthful plant foods (such as whole grains, vegetables, fruits, nuts, legumes, tea, and coffee), respectively. The men had a median age of 54 years and a median PSA level of 0.9 ng/ mL. Of these men, 69 (4.9%) had a PSA level of 4 ng/mL or higher.

Compared with men in the lowest quartile of hPDI score, those in the highest quartile had a significant decreased probability of having an elevated PSA (4 ng/mL or higher) after adjusting for multiple variables, with an odds ratio of 0.47.

The investigators found no significant association between PDI score and PSA level. The authors said the finding may be attributable to the limitations of the NHANES database, which lacks information regarding changes in participants’ dietary behavior.

Dr Mouzannar’s team said their study is the first to evaluate the association between a graded plant-based diet index and PSA levels in men without prostate

A new study links diet and PSA levels.

cancer. Still, the study had limitations.

Data obtained using food-frequency questionnaires are subject to both selfserving and recall bias, they pointed out. What’s more, NHANES data are cross-sectional and do not include serial PSA measurements and medications or

Kidney Transplantation Reduces KDI Possibly Beneficial in Cardiovascular Risk in LN ADPKD Cases

KIDNEY transplantation improves cardio-

patients with LN-ESRD are likely similar

vascular (CV) outcomes in patients with

as in patients with all-cause ESRD,

lupus nephritis (LN), but many patients

primarily related to the prevention of

fail to receive it, a new study finds.

accelerated progression of atheroscle-

Of 5963 waitlisted patients with

rosis which is known to occur with the

LN and end-stage kidney disease

alternative of remaining on dialysis,” the

(LN-ESKD) in the US Renal Data System

investigators explained.

(USRDS) from 2000 to 2016, only 3209

Recipients older and younger than

(54%) received a kidney transplant dur-

40 years had a significant 62% and

ing the study period. Kidney transplan-

73% reduction in atherosclerotic event

tation was associated with a significant

risk, respectively. Recipients of living

69% lower risk of nonfatal and fatal

and deceased donor kidneys had a

CV events compared with no trans-

significant 79% and 76% reduction in

plantation, April Jorge, MD, of Harvard

atherosclerotic event risk, respectively.

Medical School and Massachusetts

White recipients had a significant 88%

General Hospital in Boston, and col-

reduction in atherosclerotic risk. For

leagues reported in Arthritis Care &

Black patients, the result did not reach

Research. Specifically, it was associ-

significance. Black patients repre-

ated with significant 87% and 70%

sented 48% of waitlisted and 43% of

lower risks of myocardial infarction and

transplanted patients.

cerebrovascular accidents (ischemic

“Our findings highlight the importance

stroke and transient ischemic attack),

of identifying barriers to transplantation

respectively.

in this population, as improved access

“The mechanisms of CV risk reduction with kidney transplantation among

could reduce CV morbidity,” Dr Jorge’s team stated. ■

PRELIMINARY DATA from a retrospective case series suggest that ketogenic dietary intervention (KDI) is safe, feasible, and potentially beneficial for patients with autosomal dominant polycystic kidney disease (ADPKD), investigators reported online in the Clinical Kidney Journal.

The data are from a study that recruited 131 patients with ADPKD who tried self-initiated KDIs in the past. Of these, 74 tried ketogenic diets, 52 tried time-restricted diets, and 5 tried caloric restriction diets. Patients followed these diets for an average of 6 months.

KDIs included variations of ketogenic diets, time-restricted diets, and caloric restriction.

“Since KDIs are widely used in the general population for numerous potential health benefits, we reasoned that PKD patients might already have tried self-initiated KDIs.” The study was designed “to collect first real-life observations of ADPKD patients about safety, feasibility, and

comorbidities that may alter PSA values.

In addition, participants with a higher hPDI may have confounding factors associated with a healthy lifestyle that could influence PSA levels.

“Even with these limitations, our study is relevant to the present literature because it provides a large sample size and investigates the potential association between dietary intake and PSA level,” Dr Mouzannar and colleagues wrote.

In a study presented recently at the American Urological Association’s virtual 2021 annual meeting, Stacy Loeb, MD, of NYU Langone Health in New York, and colleagues demonstrated that greater consumption of a plant-based diet, especially one that consists of a high intake of healthful plant-based foods, is associated with a reduced risk for aggressive prostate cancer. Patients in the highest quintile of overall plant-based food consumption had a significant 19% decreased risk of dying from prostate cancer compared with those in the lowest quintile. ■

possible benefits of KDIs in ADPKD as part of a translational project pipeline,” they noted.

Results showed that 86% of patients reported that KDIs had improved their overall health and 67% described improvements in ADPKD-associated health issues, a team led by Thomas Weimbs, PhD, of the University of California, Santa Barbara, and colleagues reported. In addition, 64% of those with hypertension reported improvements in blood pressure. On average, participants reported 9.1 kg of weight loss, reducing their body mass index by 3.1 points, Dr Weimbs and colleagues reported.

The authors acknowledged study limitations, including the retrospective design that “could have facilitated biased data reports attracting more participants with positive rather than negative experiences.” In addition, participants might have altered aspects of their lifestyle other than diet that might have affected results, they noted.

“Our observations indicate that KDIs might not have negative but rather positive outcomes in PKD,” the authors wrote. “Thus, it suggests that prospective clinical trials utilizing more standardized diets are warranted to elucidate the specific impact of KDIs on well-being, blood pressure, weight, renal function and [total kidney volume] of PKD patients.” ■

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CONSUMPTION of a diet rich in healthy plant-based foods is associated with a reduced likelihood of having an elevated PSA level, new research suggests.

“This finding may be incorporated into the shared-decision making process with patients to promote healthier lifestyle choices to reduce the likelihood of prostate biopsy and potential treatment-related morbidity,” a team led

by Ali Mouzannar, MD, of the Miller School of Medicine at the University of Miami in Florida, concluded in a paper published in Urology.

Dr Mouzannar and colleagues analyzed 2003-2006 data on demographics, diet, and PSA levels from 1399 men who participated in the National Health and Nutrition Examination Survey (NHANES) database. They calculated a plant-based diet index (PDI) and healthful plant-based diet index (hPDI) based on responses to food frequency questionnaires. A higher score on PDI and hPDI indicates greater ­consumption of

www.renalandurologynews.com SEPTEMBER/OCTOBER 2021

Renal & Urology News 31

Ethical Issues in Medicine I

was finishing loading my groceries into the car last week when I was presented with the regular challenge for any suburban grocery shopper. Do I leave the shopping cart by the car or do I return it to the designated cart area 75 feet away? Those who have read my previous columns may remember that grocery stores are of particular interest to me for elucidating complex ethical dilemmas. Last summer, when there were widespread discussions for how to fairly allocate life-saving resources like ICU beds and ventilators, I wrote how grocery stores’ use of priority queues for certain customers could illuminate principles of equitable resource allocation frameworks: Who gets first access to a scarce resource and why.

The shopping cart question may be less charged, but when presented with this challenge, it still begs the question, what is the right thing to do?1 The answer to this question is particularly important because if we can understand more clearly what drives us to do the right thing in a low-stakes setting like a grocery store parking lot, it may provide some helpful insights when deciding more important questions as a health care professional.

has ever walked through a parking lot knows that plenty of people do not follow this norm.

Is it simply that people are selfish and choose not to be helpful? We are probably more likely to feel that way when a cart is blocking the parking space we are trying to pull into, but this claim of a moral failing is perhaps an unfair indictment and an oversimplification.

There are numerous reasons why we might find ourselves choosing to leave a cart behind. Some may not return a cart because they have left a small child in their car seat. Others might have a disability or avoid returning the cart only when it is pouring rain or oppressively hot. Some people might believe that it is someone else’s job to return the carts.

A number of social science studies have helped us to understand complex human choices when presented with similar norm-challenging scenarios.2 In general, when people see that others have already disrupted norms, they are less likely to follow the norm as well.

In one study, participants were 3 times more likely to violate a parking lot’s “No Trespassing” sign if they saw that many others had already violated the “No Bike Parking” sign. Other studies

In many cases, how we decide to care for our colleagues and our patients will not be dictated by a rule, but rather by a norm.

The easy and “cocktail party” answer to this question is to simply return the shopping cart because that is the prosocial thing to do. There are no laws that require us to return the cart — we won’t be arrested if we choose not to oblige. However, we are social beings who live in communities that require people to cooperate with one another.

When we shop at stores, convention, and not rules, can compel us to return the cart to its receptacle area. So even if we should return the cart, anyone who

with similar findings suggest that while there will be outliers who always follow or ignore norms, the majority of us are likely to be influenced by the good or bad behavior of others.

Which brings us back to the central importance of norms in life and in medicine. Ethics asks us to critically reflect on our judgments to determine the right thing to do. When Dr. Martin Luther King in his 1963 sermon concluded that to be a good neighbor was to be altruistic, he asked us to be

© TADAS KAZAKEVICIUS / GETTY IMAGES

To return or not return: What the shopping cart dilemma can teach us about doing the right thing BY DAVID J. ALFANDRE, MD, MSPH

What people do with a shopping cart after using it reflects what drives them to do what is right.

willingly obedient to unenforceable obligations.3 He reminded us that rules and laws — “enforceable” obligations that have legal consequences — are not necessarily sufficient for us to do the right thing. They are often just the floor beneath which we cannot go, but they do not necessarily inspire us to do good for those around us.

What then can the lone shopping cart teach us about our obligations as health care professionals? In many cases, how we decide to care for our colleagues and our patients will not be dictated by a rule, but rather by a norm. A code of ethics, an oath at medical school graduation, or an ethics committee opinion are all generally advisory, aspirational, and unenforceable. We choose to do the right thing for numerous reasons: it makes us feel good to help even if it means more work; we were taught that way by a respected mentor or colleague; we think the world will be a little better off even if we’re never recognized for it; or we remember that we are part of an honorable profession that relies on public trust and embodies a willingness to be obedient to unenforceable obligations.

Whatever the reason, these normative decisions deserve our continued

attention. We may all be susceptible to occasional moral failings because we are human. I will admit that I do not always return the shopping cart, but the last time I was in that situation I felt a stronger obligation to do so because the person next to me was returning his cart. I hope my decision was not simply to avoid a minor public shame, but to try to be part of a community of people who try to be their best. We may not always succeed, but trying is always the right thing to do. ■ 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.

REFERENCES 1. D’Costa K. Why don’t people return their shopping carts? Sci Am. April 26, 2017.

2. Keizer K, Lindenberg S, Steg L. The spreading of disorder. Science. 2008;322(5908):1681-1685. doi:10.1126/science.1161405 3. King ML Jr. On being a good neighbor. Draft of Chapter III. Available at The Martin Luther King, Jr. Research and Education Institute, Stanford University.

32 Renal & Urology News

SEPTEMBER/OCTOBER 2021 www.renalandurologynews.com

Practice Management T

he continuing COVID-19 pandemic is hastening the retirement of many health care providers. The United States now faces acute shortages of physicians, nurses, and medical assistants, putting medical practices in an unprecedented situation.

New data published by the Association of American Medical Colleges (AAMC) revealed there could be an estimated shortage of 54,100 to 139,000 physicians in both primary and specialty care by 2033. The association’s sixth annual study, The Complexities of Physician Supply and Demand: Projections from 2018-2033, was conducted prior to the COVID-19 pandemic.

The analysis included supply and demand scenarios and was updated with the latest information on trends in health care delivery and the state of the health care workforce. From 2018 to 2033, the US population is projected to grow by 10.4% from about 327 million to 361 million. The US population under age 18 is projected to increase by 3.9%, while the population aged 65 or older is projected to grow by 45.1% by 2033, according to the report.

“The baby boomers need the help now and they are living longer,” said Frank F. Brabec, MBA, founder and CEO of Brabec Healthcare Management Inc.,

of people said, ‘Okay I am done now.’

As a result, there is less supply and more demand, and now we see hospitals are offering more in terms of compensation,” said Brabec, who is also an independent consultant for the Medical Group Management Association (MGMA).

The analysis showed that more than 2 out of 5 currently active physicians will be aged 65 or older within the next decade. Physician shortages were already apparent before the pandemic.

A public opinion poll conducted in September 2019 by Public Opinion Strategies for the AAMC found that 35% of voters said they had trouble finding a doctor in the past 2 or 3 years.

This was a 10-point jump from when the question was asked in 2015.

“I think people are leaving in droves,” said Dave Carpenter, CEO of Minnesota Urology, the largest independent urology medical group in the upper Midwest. “There are more people leaving health care because this whole pandemic has scared them.”

Candidates in Short Supply Finding physicians can be especially challenging this year because fellowship programs during the pandemic slowed down. “So, there are fewer candidates to draw from,” Brabec said.

A slowdown in fellowship programs during the pandemic has added to difficulties in hiring physicians, according to a consultant.

Indio, California. “So they are going to stay in that space and need health care for a long period of time. We are not keeping up. There is a need to ramp up for the increasing demand.”

Older Physicians Calling It Quits The pandemic has accelerated the number of clinicians retiring, he said.

The trend is most pronounced in certain regions of the country, with rural areas in the most critical situation. “A lot

“There was already a shortage of doctors and nurses. With the pandemic, 80,000 nursing students were unable to train last year due to money, space, and personnel, and that is going to leave a mark.”

In a May 6 MGMA Stat poll, 88% of health care leaders responded that they are having difficulty recruiting medical assistants, and several studies showed that large percentages of nurses are either considering or planning to leave

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Attracting and retaining health care providers has become more challenging because of the COVID-19 pandemic BY JOHN SCHIESZER

Medical practices have had to take creative measures to recruit new doctors.

their position. “You can feel the ground moving under our feet. Workers have leverage now when it comes to where and how they work. Many new employees are requesting hybrid work ­models,” Carpenter said.

Never before has there been such a focus in health care on finding and retaining workers, according to Carpenter. “When you’ve got 40% turnover, you may be spending close to a million dollars in terms of hard and soft costs,” said Carpenter, who is a current member of the board of directors for the Large Urology Group Practice Association.

During the first 6 months of this year, Carpenter was meeting virtually with other urologic practices about recruiting and training employees. It is now necessary to shift wages for positions that present recruitment challenges.

“Signing bonuses to attract candidates are becoming the norm. However, being fair to existing employees is also important. If you have loyal workers, you have to be careful when navigating recruitment incentives,” Carpenter said.

It is common for practices to pay $500 to $1,500 signing bonuses depending on the position and the demand for a particular specialty. At some medical practices, staff members who refer

somebody for a position will receive $500 if that person is hired and stays for 6 months. “We are shaking the trees, going to schools to try to get clinical assistants.

The problem is there are fewer of them coming out of school,” Carpenter said.

Novel Approaches to Staff Retention Loan forgiveness is common as are a host of other perks. A medical practice in the Midwest recently bought a beach house in Florida as a tool for acquiring and retaining good staff.

“The employees can reserve and use the beach house for a certain number of days based on their number of years of tenure and level of seniority,” Carpenter said. “Everyone is looking for novel approaches.”

Brabec said the biggest problem he sees in many medical practices is that they do not define their mission.

Subsequently, the staff just think their day is a bunch of tasks and they get a paycheck. “It is much easier to retain employees when they feel like they are part of a team, like a baseball team.

They have to feel they matter, and so it means they have to be listened to,” Brabec said. ■ John Schieszer is a freelance medical writer based in Seattle, Washington.