Renal & Urology News - Fall 2023

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VOLUME 22, ISSUE NUMBER 4

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Diabetics’ Renal Issues Often Not DKD

© BSIP / GETTY IMAGES

More than half of kidney biopsies performed on patients with diabetes reveal a variety of other pathologies

NEW FINDINGS MAY help clinicians decide whether diabetics should undergo a kidney biopsy.

BY JODY A. CHARNOW PHILADELPHIA — Patients with diabetes mellitus who undergo kidney biopsies are often presumed to have diabetic kidney disease (DKD), but a new study presented at the American Society of Nephrology’s Kidney Week 2023 conference shows that most biopsies reveal pathologies other than DKD. The study also identified factors that associated with finding DKD vs nonDKD. Increasing hemoglobin A1c and albumin levels are associated with reduced odds of finding non-DKD on biopsy, whereas P-ANCA/MPO positivity are associated with increased odds of finding non-DKD. “We need to know as clinicians when we should really biopsy these patients

RKF Loss Ups Mortality Risk

Sparsentan

BY NATASHA PERSAUD mortality risk was observed across low Superior for LOWER RESIDUAL kidney function RKF categories, starting at a baseline (RKF) and loss of RKF correlate with renal urea clearance threshold (in mL/ IgAN, FSGS increased risks for cardiovascular and min/1.73m ) of less than 6, the investi2

non-cardiovascular mortality in patients receiving thrice-weekly maintenance hemodialysis, a new study suggests.

Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the Professor & Chief, Division of Nephrology & Hypertension Harbor-UCLA Medical Center, Torrance, California, and colleagues examined baseline RKF in 39,623 patients as well as RKF decline over 6 months in a subset of 12,169 patients. They collected data on renal urea clearance and urine volume.

A significant trend toward higher cardiovascular and non-cardiovascular

gators reported in Kidney International Reports. In subgroup analyses, noncardiovascular death risk significantly increased 79%, 31%, and 22% when baseline renal urea clearance was less than 1.5, 1.5 or higher but less than 3.0, and 3.0 or higher but less than 4.5, respectively, compared with 6 or higher. The risk for sudden cardiac death significantly increased 63% and 27% at renal urea clearances of less than 1.5 and 1.5 or higher but less than 3.0, respectively. The risk for other cardiovascular deaths significantly continued on page 19

BY JODY A. CHARNOW PHILADELPHIA — Sparsentan achieves more pronounced reductions in proteinuria in patients with immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) compared with irbesartan, according to data from separate phase 3 clinical trials presented at the American Society of Nephrology’s Kidney Week 2023 conference.

Sparsentan is a dual endothelin and angiotensin II receptor blocker.

Irbesartan only blocks the angiotensin II receptor.

In a 36-week interim analysis from the PROTECT trial, which included 404 patients with IgAN, sparsentan recipients had a 49.8% reduction in urine p ­ rotein-creatinine ratio (UPCR), whereas irbesartan recipients had a 15.1% reduction, for a significant 41% relative reduction in proteinuria in the sparsentan arm, lead investigator Brad H. Rovin, MD, of the Ohio State continued on page 19

[with diabetes], and that’s the goal of this study,” said lead investigator Shane A. Bobart, MD, a nephrologist at Houston Methodist Hospital in Texas.

As part of the Cleveland Clinic Kidney Biopsy Epidemiology Project, Dr Bobart and his collaborators identified 3503 patients who underwent biopsies of native kidneys and had ICD-10 code data available. Of these, 1271 (36.3%) had an ICD-10 code of diabetes, with biopsy findings indicating DKD alone in 462 patients (36.3%), non-DKD alone in 678 (53.3%), and both DKD and non-DKD in 105 (8.3%). Another 26 patients (2%) had either normal or non-diagnostic findings. continued on page 19

IN THIS ISSUE 9 Marijuana use ups kidney stone risk in men

10 The reality of financial toxicity in health care

13 Vitamin K found to improve calciphylaxis outcomes

13 Selenium deficiency is associated with higher death risk

15 Hemodiafiltration offers better survival than hemodialysis

18 Inflammatory bowel disease linked to CKD and AKI

25 Albuminuria may increase the likelihood of fractures

Vitamin E supplementation linked to an increased risk for NMIBC recurrence.

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FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD 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, MPH, PhD Professor & Chief of the Division of Nephrology & Hypertension at Harbor-UCLA Medical Center in Torrance, CA

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

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

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

Kenneth Pace, MD, MSc Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Vancouver, Canada

Renal & Urology News Staff Editor

Jody A. Charnow

Digital content editor

Natasha Persaud

Production editor

Kim Daigneau

Group creative director

Jennifer Dvoretz

Senior production manager

Krassi Varbanov

Vice president, sales operations and production National accounts manager Vice president, content, medical communications Chief commercial officer

Louise Morrin Boyle William Canning Lauren Burke James Burke, RPh

President, medical communications

Michael Graziani

Chairman & CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 22, Number 4. Published quarterly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). For reprint/ licensing requests, contact Customer Service at custserv@haymarketmedia.com. Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2023.

Dialysis Units Closing, But Transplants Hit Record

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n the milestone year of 2023, the Medicare End Stage Renal Disease (ESRD) Program celebrates its 50th anniversary. The program is a vital exception in Medicare coverage that includes individuals younger than 65 years. Congressionallymandated ESRD Networks were instituted in 1978 to ensure the quality of care for patients undergoing dialysis or renal transplantation. Over the years, the ESRD program has experienced remarkable growth, with a consistent rise in the number of dialysis patients and new dialysis clinics. In an unprecedented turn, however, the number of dialysis patients has recently declined, followed by the closure of hundreds of dialysis clinics nationwide in 2022 and 2023.

To put this in perspective, between 2017 and 2021, around 1,200 dialysis clinics were added, indicating a net increase of 300 to 400 clinics annually.

It is not clear whether these developments signify a decrease in the number of ESRD cases or less favorable factors such as COVID-related fatalities.

But there also have been positive developments. The number of home dialysis patients continues to rise, although challenges persist with assisted home dialysis. Furthermore, a record 25,498 kidney transplants took place in 2022, a 3.4% increase over the previous year. Efforts toward promoting health equity will be bolstered through new ESRD Quality Incentive Plans (QIP), marking a step toward more equitable kidney care provision.

Concerning trends in dialysis vascular access have emerged, however, notably an increase in the use of dialysis catheters. This trend predates the COVID pandemic and may be an unintended consequence of shared decision-making resulting in the empowerment of patients with advanced CKD and their care partners to defer dialysis transition preparation until it becomes an urgent necessity, often during an unexpected hospitalization.

Moreover, 2023 marks the second year of value-based care models in action. These voluntary models extend kidney care to encompass pre-dialysis stages of CKD, including stages 4 and 5.

Online hemodiafiltration in outpatient dialysis clinics represents a wellestablished option in many other countries but USA. The CONVINCE randomized trial, recently published in the New England Journal of Medicine, demonstrated its superior survival rates. This breakthrough might soon bridge the 20-year technology gap in US dialysis clinics, ushering in a new era of higher standards of renal treatment options.

In the face of these challenges and innovations, it is essential to acknowledge that dialysis, even in its traditional form, continues to extend the lives of many, offering hope and resilience in the face of organ failure.

As the landscape of ESRD care evolves, there is a collective commitment to addressing the uncertainties, embracing advancements, and ensuring that every person facing kidney health challenge is offered the best possible choice, care, and support.

Kam Kalantar-Zadeh, MD, MPH, PhD Professor & Chief, Division of Nephrology & Hypertension Harbor-UCLA Medical Center, Torrance, California

Contents

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VO L U M E

Nephrology 13

ONLINE

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

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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.

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

Undiagnosed CKD Highly Prevalent in HTN, CVD In a study, about two-thirds of patients with ­hypertension had undiagnosed stage 3 chronic kidney disease in the absence of type 2 diabetes Hemodiafiltration vs HD Offers Better Survival A real-world analysis revealed that hemodia­ filtration was significantly associated with a 22% lower risk for all-cause mortality.

Albuminuria Associated With Higher Fracture Risk Individuals with severe vs no or mild albuminuria had significant 37%, 31%, and 22% increased odds of hip, vertebral, or any fracture, respectively.

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Renal & Urology News 7

I S S U E

N U M B E R

ASCO Genitourinary Cancers Symposium January 25-27, 2024 San Francisco, CA Annual Dialysis Conference March 8-10 San Diego, CA European Association of Urology April 5-8 Paris, France American Urological Association May 3-6 San Antonio, TX National Kidney Foundation May 14-18 Long Beach, CA European Renal Association May 23-26 Stockholm, Sweden American Society for Clinical Oncology May 31-June 4 Chicago, IL American Transplant Congress June 1-4 Philadelphia, PA

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Prophylactic RT for High-Risk Bone Metastases Beneficial Radiation decreased the likelihood of skeletalrelated events, hospitalization, and death, according to the findings of a phase 2 trial.

Pot Use Tied to Lower Stone Risk in Men Men who used marijuana 1 to 7 times per week had significant 38% reduced odds of kidney stones compared with men who did not use marijuana, according to a study.

Microwave Ablation Is a Safe, Effective Option for SRMs Outcomes are comparable to those achieved with partial nephrectomy, researchers reported.

NMIBC Recurrence Linked to Vitamin E Patients who received vitamin E supplements, compared with those who did not, had a significant 46% increased risk for recurrence.

Aldosterone synthase inhibitors directly

lower aldosterone production and thereby may improve therapeutic efficacy for CKD. See our story on page 14

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CALENDAR

Urology

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

Vitamin K Shown to Ease Calciphylaxis Phase 2 trial results demonstrate that oral phytonadione (vitamin K1) reduces pain intensity and total lesion surface area.

FALL 2023

Departments 6

From the Medical Director Dialysis units are closing, reversing years of expansion

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News in Brief Proton pump inhibitor use shown to increase gout risk

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Renal Nutrition Update An update on managing vitamin K in CKD patients

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Ethical Issues in Medicine Patient confidentiality also applies to elevator conversations

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Practice Management The potential benefits of intelligent scheduling

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FALL 2023

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News in Brief

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

Short Takes Hyperuricemia Increases NAFLD Risk, Data Show

Black and White patients had a median

Patients with hyperuricemia are at

years and overall survival of 5.5 and 6.3

increased risk for non-alcoholic fatty

years, respectively, with no significant

liver disease (NAFLD), data show.

differences between the groups, Neeraj

progression-free survival of 2.3 and 2.9

Investigators performed a systematic

Agarwal, MD, of the University of Utah in

review and meta-analysis of 50 studies

Salt Lake City, and colleagues reported

published during 2009-2022 involving

in JAMA Network Open.

2,079,710 patients, including 719,013 increased by a significant 2.1-fold in

CV Event Risk Elevated Before AAV Diagnosis

patients with elevated vs normal serum

Individuals are at increased risk for

uric acid levels, Yang Xia, PhD, of China

cardiovascular (CV) events in the

Medical University Shenyang, Liaoning,

months preceding diagnosis of ANCA-

China, and colleagues reported in Clini-

associated vasculitis (AAV), investiga-

cal Epidemiology.

tors reported in Rheumatology.

with NAFLD. The odds of NAFLD

Using data from the Danish national

Equal Care Access Reduces mCSPC Race Disparities

patient registries, a team led by Louis

A recent study revealed similar

Hospital in Aalborg, Denmark, com-

progression-free and overall survival

pared 2371 patients with AAV and

between Black and White patients with

7113 age- and sex-matched controls

castration-sensitive prostate cancer

without AAV. Within 12 months of

(mCSPC) who had equal access to

diagnosis, the AAV group had a signifi-

treatment in a clinical trial.

cant 3-fold increased risk for any CV

Nygaard, PhD, of Aalborg University

The finding is from a secondary analy-

event and nearly 2-fold increased risk

sis of a randomized phase 3 clinical trial

for major adverse CV events (MACE),

involving 1313 patients with mCSPC

respectively, compared with the con-

taking androgen deprivation therapy

trol arm. The risks for any CV event

plus the investigational drug orteronel or

and MACE were highest at 1 month

bicalutamide. Over a median 4.9 years,

prior to AAV diagnosis.

LVI Tied to Worse Overall Survival Lymphovascular invasion (LVI) in patients with surgically-treated renal cell carcinoma (RCC) is associated with lower 5-year overall survival (OS). Shown here are the 5-year OS rates according to RCC pathology.

■ LVI ■ NO LVI 100

87%

78%

80

69%

64% 60 40

41%

31%

20 0

pN0

pN1

pNx

PATHOLOGY Source: Rakic I et al. Assessing the impact of lymphovascular invasion on overall survival in surgically treated renal cell carcinoma patients: a nationwide cohort analysis. Urol Oncol. Published online August 23, 2023.

Earlier Use of Cabazitaxel for mCRPC Improves OS C

abazitaxel added to abiraterone acetate and prednisone (AAP) improves outcomes compared with AAP alone among men with metastatic castration-­ resistant prostate cancer (mCRPC), according to investigators.

In a phase 2 randomized trial that included 81 men with mCRPC, the median radiographic progression-free survival (rPFS) — the primary endpoint — was 14.8 months in the AAP-cabazitaxel arm compared with 6.4 months in the AAP. Median overall survival (OS) was 24.5 months in the AAP-cabazitaxel compared with 18.3 months in the AAP arm. In addition, a higher proportion of the AAP-cabazitaxel arm than the AAP arm had a 50% or greater decline in PSA (92.1% vs 56.1%).

“This study provides mechanistic insight into rational combinations that may improve OS and rPFS and benefit certain patients,” Susan F. Slovin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues wrote in the Journal of Clinical Oncology.

Proton Pump Inhibitor Use Linked With Gout Risk P

roton pump inhibitor (PPI) use is associated with an increased risk for gout, according to a population-based study.

Investigators propensity score matched 20,138 adults with gout and 20,138 adults without gout from the Taiwan population. In adjusted analyses, esomeprazole users had a significant 1.3-fold increased risk for gout compared with individuals who did not use PPIs, Qiang Xu, MD, of The First Affiliated Hospital of Guangzhou University of Chinese Medicine in Guangzhou, China, and colleagues reported in the International Journal of Rheumatic Diseases. Omeprazole, pantoprazole, lansoprazole, and rabeprazole had no significant effect on gout risk.

Any use of PPIs within 30 days was significantly associated with 1.7-fold increased odds of gout compared with no PPI use. PPI use within 60, 90, and 120 days was significantly associated with 1.4-, 1.3, and 1.2-fold increased odds, respectively.

BCG for Bladder Cancer Tied to Lower Dementia Risk P

atients with bladder cancer treated with bacillus Calmette-Guérin (BCG) have a lower risk of developing dementia, new findings suggest.

In a systematic review and meta-analysis of 5 studies published from 2019 to 2023 involving 45,407 patients with bladder cancer, those exposed to intravesical BCG had a 45% decreased risk of dementia compared with those not treated with BCG, MaoShui Wang, MD, of Shandong Public Health Clinical Center, Shandong University in Jinan, China, and colleagues reported in Frontiers in Aging Neuroscience. The risk for Alzheimer’s disease was a significant 43% lower. Patients aged 75 years or older and those receiving more than 6 BCG doses particularly had decreased dementia risks. The 5 retrospective studies were of high-quality and had a low risk for bias.

Previous research has suggested that intravesical BCG instillation may increase the regulatory T cell population and increase glucose utilization and thus reverse cognitive aging or reduce neuroinflammation.

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Renal & Urology News 9

Study May Explain PCa Race Disparities Researchers explored outcomes of nonmetastatic castration-resistant prostate cancer among veterans RACIAL AND ETHNIC disparities observed in prostate cancer outcomes may be due to “systemic socioeconomic inequity rather than molecular or genetic factors,” according to investigators.

The finding is the result of a retrospective observational cohort study that included 12,992 men with nonmetastatic castration-resistant prostate cancer (nmCRPC) receiving care in the equal-access Veterans Health Administration system. Black and Hispanic men had longer median times to metastasis or death (5.96 and 5.62 years, respectively) compared with White men and men of other races (4.11 and 3.59 years, respectively), Kelli M. Rasmussen, MS, of the University of Utah School of Medicine in Salt Lake City, and colleagues reported in JAMA Network Open.

“The findings of this study suggest that the availability of equal-access care may reduce and even reverse racial and

Pot Use Tied to Lower Stone Risk in Men

BY JODY A. CHARNOW MEN WHO USE marijuana regularly are less likely to report having kidney stones, according to a recent study.

An analysis of 2009 to 2018 data from the National Health and Nutrition Examination Survey (NHANES) revealed that male marijuana users had significant 28% lower odds of reporting kidney stones compared with nonusers after adjusting for multiple variables, Xin Wei, MD, of West China Hospital, Sichuan University, Chengdu, Sichuan, China, and colleagues reported in Frontiers in Pharmacology. Men who used marijuana 1 to 7 times per week had significant 38% lower odds. Those who used marijuana more than 7 times per week did not have reduced odds of kidney stones. The investigators found no association between marijuana use and kidney stones in women.

“To our knowledge, this study is the first cross-sectional study to explore the association between marijuana use and the risk of kidney stones from the

Outcomes by Race/Ethnicity A recent study of US veterans with nonmetastatic castration-resistant prostate cancer found that Black and Hispanic patients had longer median times to metastasis or death compared with White patients and those of other races. Shown below are the median times in years.

6

5.96 years

5.62 years

5

4.11 years

4

3.59 years

3 2 1 0

Black

Hispanic

White

Other

Source: Rasmussen KM, et al. Survival outcomes by race and ethnicity in veterans with nonmetastatic castration-resistant prostate cancer. JAMA Netw Open. 2023;6(10):e2337272.

ethnic disparities in patients with nonmetastatic castration-resistant prostate cancer,” the authors concluded.

Of 12 992 patients, 826 patients selfidentified as Hispanic (6%), 3671 as Black (28%), 7323 as White (56%), and 1172 of other races and ethnicities (9%), such as American Indian or Alaska Native, Asian, or Native Hawaiian or other Pacific Islander.

population-based NHANES dataset,” the authors wrote.

The study included 14,324 participants aged 20 to 59 years with a complete data on marijuana use and kidney stone history. Of these, 26% reported having used marijuana during their lifetime. The incidence rate of kidney stones was 7.8%.

With respect to study limitations, the researchers pointed out that NHANES provides cross-sectional data, so they could not explore a causal link between marijuana use and kidney stones. In addition, information about marijuana use was self-reported, with no indication of the exact type and dose of cannabis.

“The study appears to have been well done, and the data appear credible,” said David S. Goldfarb, MD, Clinical Chief of Nephrology and Director of the Kidney Stone Prevention Program at NYU Langone Health in New York, who was not involved in the current study. “I don’t think the study can really provide a plausible mechanism for the effect in men, and the lack of an effect in women.”

The finding that marijuana use beyond 7 times per week did not further reduce stone risk was “surprising,” he said.

He added, “Most of the marijuana use reported here is almost certainly smoking; it would be interesting to see if people using edibles, which has increased in the US, would have the same risk.” ■

After adjusting for patient factors and disease severity, Black and Hispanic patients had a significant 15% and 30% decreased risk for metastasis or death compared with White patients, the investigators reported. The risk did not differ significantly for men of other races and ethnicities.

Black and Hispanic patients also had a significant 20% and 36% lower risk

for all-cause mortality compared with White patients.

In addition, compared with patients who had a mild Charlson Comorbidity Index (CCI), those with a moderate or severe CCI had a significant 34% increased risk for metastasis or death.

Compared with patients who had PSA doubling time (PSADT) greater than 10 months, those with a shorter PSADT had a significant 64% increased risk for these outcomes.

“The results of our analysis not only add to evidence that differences in [prostate cancer] outcomes by self-identified race and ethnicity exist, they suggest that Black and Hispanic men may actually have considerably improved outcomes compared with men of other races or ethnicities when treated in an equal-access setting,” the authors wrote. “Concordant with that finding, Black men had a significantly lower incidence of high-risk disease as defined by a PSADT less than or equal to 10 months.” ■

Prophylactic RT for High-Risk Bone Metastases Beneficial PROPHYLACTIC RADIATION therapy

metastases in the SOC arm (29%) and 1

(RT) delivered to patients with high-

among 62 metastases (1.6%) in the RT

risk, asymptomatic bone metastases

arm, a significant difference between

decreased the likelihood of skeletal-

the groups, Dr Gillespie and colleagues

related events (SREs), hospitalization,

reported in the Journal of Clinical

and death, according to the findings of

Oncology. The investigators defined

a phase 2 clinical trial that researchers

SREs as the occurrence of pathologic

believe is the first study of its kind.

fractures, spinal cord compression,

A team led by Erin F. Gillespie, MD,

orthopedic surgery to bone and/or pal-

MPH, of Memorial Sloan Kettering

liative radiation therapy for pain.

Cancer Center in New York, enrolled 78

In addition, within the first year of

patients with 122 high-risk, asymptom-

follow-up, a significantly smaller propor-

atic bone metastases, randomly assign-

tion of patients in the RT arm than the

ing 39 to receive prophylactic RT and 39

SOC arm was hospitalized (0% vs 11%).

to receive standard of care (SOC; sys-

At a median follow-up of 2.5 years,

temic therapy or observation). Of the 78

the RT group has significantly longer

patients, 7 withdrew from trial or were

median survival compared with SOC

lost to follow-up, leaving 36 patients with

arm (1.7 vs 1.0 years).

49 bone metastases in the SOC arm and

“Given the multi-institutional nature

35 patients with 62 bone metastases in

of the study and large effect size for

the RT arm. The most common primary

reducing SRE, these findings may sup-

cancer type was lung (27%), followed by

port the consideration of RT for select

breast (24%) and prostate (22%).

patients with high-risk asymptomatic

During 1 year of follow-up, 15 SREs developed: 14 among the 49 bone

bone metastases in routine practice,” the authors concluded. ■

10 Renal & Urology News

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n FEATURE

Medicine vs Food: The Dilemma of ‘Financial Toxicity’ The cost of health care can have a life-changing impact on patients

BY JODY A. CHARNOW

S

erious illness can bring patients to financial ruin. They often have to quit their jobs to deal with their medical issues, losing both income and health insurance at a time when their out-of-pocket expenses for health care could run thousands of dollars per year.

To cope, patients may be forced to cut back on spending for food and housing and skip medication doses, forgo filling prescriptions, or discontinue treatment altogether. Patients have depleted life savings, incurred debt, and declared bankruptcy as a consequence of their illness. The economic burden imposed by health problems has been termed financial toxicity, a problem that could worsen if health insurance companies shift more costs to patients in the form of higher deductibles and copays. Some physicians believe potential financial toxicity should be included in discussions with patients about treatment plans.

“Physicians must play a central role as financial advocates for our patients,” said Courtney M.P. Hollowell, MD, chair of urology at Cook County Health in Chicago, Illinois. Cook County Health is the third largest public hospital system in the United States. It serves a particularly vulnerable segment of the population, including racial and ethnic minorities, immigrants, and the underand uninsured. “They often rely on us to provide them with information about treatment efficacy and side effects when making critical management decisions.

We order imaging, prescribe medications, provide referrals and recommend surgery — almost always without ever addressing how much all of it costs.”

Daniel D. Joyce, MD, MS, an assistant professor in the Department of Urology at Vanderbilt University Medical Center in Nashville, Tennessee, said financial

toxicity, like drug toxicity, should be included in physician-patient discussions about treatment options. “Indeed, financial toxicity has been associated with worse quality of life, symptom burden, and even survival, further supporting its inclusion in shared decision-making,” Dr Joyce said.

Worse Therapeutic Adherence Research shows that cost concerns can lead to lack of adherence to treatment.

Findings from a recent survey of adult patients with cancer and cancer survivors found that financial toxicity is associated with decreased use of prescription medications and increased concern about cancer returning or getting worse, Kelly Chan, of the University of California San Diego in La Jolla, and colleagues reported in a 2022 article in

Exploratory Research in Clinical and Society Pharmacy.1 Survey responses from 609 patients revealed that those who were ever worried about paying large medical bills, compared with those who were not, had significant 4.5-fold increased odds of avoiding buying necessary prescriptions and 2.8-fold increased odds of worrying about cancer returning or getting worse.

Recent research suggests that discussions between physicians and patients about the financial burden of treatment are frequently absent. In a survey of women with early-stage breast cancer and their physicians, 55.4% of those who expressed a desire to speak with their providers about the impact of breast cancer on employment or finances reported no relevant discussion with their cancer physicians, primary care providers, social workers, or

New Drugs Especially Burdensome Men on active surveillance (AS) for low-grade prostate cancer had lower rates of New cancer drugs can substantially increase patients’ economic burden. A study published in The Journal of Urology in 2022, for example, showed that the mean first-year treatment-related out-of-pocket costs for drugs to treat advanced prostate cancer are much higher for novel hormonal therapies vs older medications.

$994

$165

Nonandrogen systemic agents

Androgen deprivation therapy (ADT)

$4246 Novel hormonal therapies Source: Joyce DD, Sharma V, Jiang DH, et al. Out-of-pocket cost burden associated with contemporary management of advanced prostate cancer among commercially insured patients. J Urol. 2022;208(5):987-996.

other ­professionals, Reshma Jagsi, MD, DPhil, of the University of Michigan in Ann Arbor, and colleagues reported in a 2018 article in Cancer.2 The survey also revealed that financial toxicity was common, with 21.5% of White, 22.5% of Asian, 45.2% of Black, and 35.8% of Latina patients reporting they had to reduce spending on food.

The Burden of Medical Debt The reality of financial toxicity is reflected in statistics on medical debt. In 2019, 23 million adults in the United States had significant medical debt, defined as more than $250, according to a Kaiser Family Foundation analysis of data from US Survey and Income Program Participation, a statistical survey conducted by the US Census Bureau. Of these, 26% owed more than $5000.3 In an analysis of 9.5 million estimated new diagnoses of cancer from 2000 to 2012 published in the American Journal of Medicine in 2018, Adrienne M. Gilligan, PhD, and colleagues found that 42.4% of patients depleted their entire life’s assets at 2 years after a cancer diagnosis and 38.2% were financially insolvent at 4 years.4 A study of claims data from January 2019 to January 2021 for 2,854,481 commercially insured adults published recently in JAMA Internal Medicine found an association between burden of chronic disease and adverse financial outcome.5 Overall, 9.6% had medical debt in collections, 8.3% had nonmedical debt in collections, 16.3% had delinquent debt, 19.3% had a low credit score, and 0.6% had a recent bankruptcy, Nora V. Becker, MD, PhD, of the University of Michigan in Ann Arbor, and colleagues reported. Among patients

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with debt in collections, the estimated amount increased with the number of chronic conditions, from $784 for patients with no chronic conditions to $1252 for those with 7 to 13 conditions.

Newer Drugs Are Especially Costly Medication costs can be a big part of patients’ economic distress. This is especially the case with newer drugs, as Dr Joyce and colleagues demonstrated in a study of 13,409 commercially insured men with advanced prostate cancer.6 Mean treatment-related outof-pocket costs for novel hormonal therapies for advanced prostate cancer in the first year of treatment was $4236, they reported recently in The Journal of Urology. By comparison, first-year treatment-related out-of-pocket costs for androgen deprivation therapy and nonandrogen systemic agents — both older conventional treatments — were $165 and $994, respectively.

Dr Joyce and his colleagues concluded that their study findings “support inclusion of a discussion regarding treatment costs as a component of shared decision making and should guide future efforts to identify and ameliorate financial toxicity in this patient population.”

A Focus on Cancer Although many types of medical problems can result in financial toxicity, much of the attention given to it comes from the cancer care community. In fact, the term financial toxicity was introduced by oncologists S. Yousuf Zafar, MD, MHS, and Amy P Abernethy, MD, PhD, at Duke Cancer Institute in Durham, North Carolina, in a 2013 article in Oncology.7 “Out-of-pocket expenses related to treatment are akin to physical toxicity, in that costs can diminish quality of life and impede delivery of the highest quality care,” they wrote.

And it was a team led by a medical oncologist at the University of Chicago Medical Center that developed and validated the Comprehensive Score for Financial Toxicity (COST) questionnaire to assess financial toxicity in patients with cancer.8,9 COST is an 11-item scale that assesses various domains of financial toxicity and distress as it relates to cancer diagnosis and treatment. It asks patients to respond to such statements as: “My out-of-pocket medical expenses are more than I thought they would be” and “I worry about the financial problems I will have in the future as a result of my illness or treatment.” Possible answers include: “Not at all,” “A little bit,” “Somewhat,” “Quite a bit,” and “Very much.”

Physicians generally are reluctant to bring up the financial aspects of medical care with patients. “One of the main reasons physicians avoid conversations about the cost of care is because providers just don’t know how,” said Dr Hollowell, who also is President of the Illinois State Urological Society in Chicago. “Physicians in training are traditionally insulated from information about the cost of the tests and treatments they order for patients. As a result, most physicians are ill-equipped to make the most cost-effective choices for patients and lack the understanding of how these decisions affect patients’ medical bills.

Additionally, lack of cost transparency, on the part of the hospital and insurance provider, can make it difficult to access accurate comparative cost information that can be meaningfully shared with the patient.”

Dr Joyce echoes that view. “Part of the difficulty is the lack of data assessing financial toxicity in patients with urologic issues,” he said. “It is challenging to provide patients accurate expectations of financial toxicity when we have limited data to inform those discussions.”

Although many patients and providers are uncertain about how to bring up finances in treatment discussions, research has shown that the majority of patients report a desire to talk to their physicians about the impact of medical costs on their lives.10 To address this reluctance and practice gap, Dr Hollowell said, the Cook County Health Cancer Center has designed an educational toolkit to assist providers with cost conversations adapted from the COST questionnaire. The answers patients provide can serve as a cost conversation guide to identify those who may warrant further discussion about the cost of care.

Shared decision-making, Dr Hollowell said, should focus on the treatment benefits of value-based care. Physicians should discourage the use of interventions that have little benefit but high costs and reduce unnecessary duplication of studies such as laboratory assessments and imaging.

“Otherwise, our patients experiencing financial toxicity are forced to make real-life, cost cutting-decisions like electing not to fill prescriptions or non-adherence to costly medications, skipping medical visits, [and] cutting back on food, clothing, and housing costs. Non-compliance can easily be mistaken for patients experiencing financial toxicity,” Dr Hollowell said.

Dr Hollowell noted that all patients seen at Cook County Health Cancer Center are routinely screened for

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f­inancial toxicity. Providers are ­encouraged to integrate financial impact into shared decision-making discussions.

“To optimize patient-centered care, I encourage providers to begin financial toxicity screening and cost conversations during the initial patient visit,” he said.

In his practice, Dr Joyce tries to incorporate treatment costs into his discussions with patients. “First, I try to get a sense of the baseline financial strain a patient is under,” Dr Joyce related.

“In my experience, this can often be straightforward to ascertain, as patients are generally open about what they can and can’t afford. Second, I seek out data that helps me better understand the outof-pocket costs associated with the treatments I prescribe. This helps me have a general idea of whether ‘treatment A’ is on average significantly more expensive for patients than ‘treatment B’.

Finally, I try to resist the urge to brush off cost concerns as ‘not my problem’ and identify resources that my patients can access to help them navigate these issues. In many cases, financial assistance programs exist that help obviate the need for management tailoring due to financial toxicity concerns.”

Food Insecurity Reduced spending on food is among the consequences of financial toxicity, and it can lead to adverse clinical outcomes. In a 2022 article in the Journal of the National Cancer Institute, Margaret Raber, DrPH, of Baylor College of Medicine in Houston, Texas, and colleagues wrote about the importance of nutrition during cancer treatment.11 They addressed the impact of food insecurity, which may be a result of cancer treatment and its impact on household finances, with data showing that it is associated with worse clinical outcomes, they noted.

“Maintaining adequate nutrition is critical to cancer therapy success,” they wrote. “Food insecurity during and after cancer treatment may undermine therapy goals and treatment success and may also add a layer of difficulty to mitigating the side effects of many cancer treatments.”

Loss of appetite, changes in olfaction and taste, and difficulty chewing and swallowing are among the adverse side effects of common cancer treatments, according to the authors. “Adapting to these changes in taste and symptoms requires flexibility in food purchasing and preparation, which is difficult while experiencing food insecurity.”

Awareness of the need for patients with cancer to maintain adequate

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­ utrition has prompted some n ­institutions to address the issue. For example, the University of Chicago Medical Center launched Feed1st in 2010 to operate food pantries at various locations around the Chicago.11 Feed1st is designed to eliminate widely known access barriers, including stigma and burden resulting from having to show proof of need and inconvenient hours of operation. Feed1st pantries distribute shelf-stable foods in various locations, such as inpatient pediatric oncology and outpatient adult oncology units and waiting areas.

A Financial Toxicity Tumor Board To deal with financial toxicity, the Levine Cancer Institute in Charlotte, North Carolina, in 2019 created what it calls the Financial Toxicity Tumor Board. The board is linked to a patient assistance program (PAP) for oncologic pharmaceutical agents. As reported in a 2021 article in JCO Oncology Practice

by Derek Raghavan, MD, PhD, and colleagues, the PAP served 1749 and 1819 patients in 2019 and 2020, respectively, saving patients approximately $55.4 million and $60.7 million in those years, respectively.12 Board members include physicians, nurses, nursing and medical administrators, the institute’s chief financial officer, financial counselors, social workers, nurse navigators, and oncology pharmacy personnel. The board meets monthly to address complex fiscal issues, identify frequent or repeated problems that require changes in standard operating procedures, and discuss in detail cases that were not handled effectively by standard patient and financial support operations, Dr Raghavan and his coauthors wrote.

To illustrate how the tumor board functions, the authors of the article described a case involving a 64-year-old patient undergoing adjuvant chemotherapy after surgery for a pancreatic tumor. Months after treatment began, the patient received notice that their insurer denied the chemotherapy claims, noting a required precertification was never obtained, according to the article.

A review of the denied claim showed that one of the drugs in the treatment regimen required precertification through the patient’s pharmacy benefits rather than the medical plan, “which was outside the norm for outpatient chemotherapy.” The insurer billed the patient $42,000 for the denied medication. The tumor board took up the case after the patient asked for assistance from the institute’s financial counseling team. A financial counselor was able to secure a

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Study Could Guide Therapeutic Choices for mCSPC Benefits of various regimens vary by disease characteristics, according to investigators RESULTS OF A recent systematic review and meta-analysis could help clinicians decide which therapeutic regimens to use for the first-line treatment of men with metastatic castration-sensitive prostate cancer (mCSPC).

The study compared triplet and doublet therapies using data from 10 phase 3 randomized controlled trials with 11,043 patients evaluating first-line treatment options for mCSPC. Investigators concluded that triplet therapy may be preferred for de novo high-volume disease and doublet therapy may be preferred for recurrent lowvolume disease, according to findings published in JAMA Oncology.

Specifically, the triplet therapy abiraterone acetate/prednisone (AAP) plus docetaxel and androgen deprivation therapy (ADT) is potentially the most efficacious treatment for men with high-volume disease and was associated with significant improvement in survival

compared doublet therapies, Irbaz Bin Riaz, MD, PhD, of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, and colleagues reported. For low-volume disease, the investigators considered androgen pathway inhibitor (API) doublet therapies to be potentially the most efficacious treatments. API doublet therapies did not differ significantly from triplet regimens.

“Using mixed treatment comparison methods, we provided the most up-todate evidence for performance of triplet therapy compared with API-based doublets, a question not answered in clinical trials but paramount to clinical practice and design of future clinical trials.”

Their study included 10 randomized controlled trials with 11,043 patients with mCSPC. For the overall population, data suggest that the death risk associated with darolutamide and AAP triplet therapy (either drug combined with docetaxel plus

Medicine vs Food

“As the price tags associated with cancer continue to rise and patients assume more responsibility for their treatment, it will become increasingly important for us to be able to discuss with our patients the trade-offs associated with more or less costly therapeutic options,” Matthew J. Resnick, MD, MPH, wrote in a 2019 editorial in The Journal of Urology in response to the aforementioned study by Dr Gilligan and colleagues. “Doing so will increase the likelihood that we are able to align patient preferences with treatment decision making.”13 In the same journal, Matthew Mossanen, MD, of Dana-Farber Cancer Institute in Boston, and Angela B. Smith, MD, of the University of North Carolina at Chapel Hill, wrote in a 2018 commentary, “By recognizing the importance of patient level cost in decision making, we are in a position to take practical steps to address the common and corrosive consequences of financial toxicity of cancer treatment.”14 “In the context of patient-centered cancer care, the clinician plays a central role not just in the delivery of highquality medical treatments but also in helping contain the financial burden and distress to an individual patient with cancer in the short term, and for all patients with cancer in the long term,” Pricivel M. Carrera, LLM, PhD, and

continued from page 11

retroactive and ongoing precertification for the entire course of treatment, effectively eliminating the patient’s financial responsibility.

The institute also implemented a program in which pharmacy technicians are embedded in physician office practices “to track and coordinate expensive oral medication needs for patients.” These technicians handle prior authorizations, copay assistance, free drug procurement, and directing to appropriate specialty pharmacies based on a patient’s insurance.

Calls to Action Comments in the medical literature reflect the concern about the financial consequences of health care costs to patients and the need for health care provider involvement. In their Cancer report detailing the findings of their survey of women with breast cancer and their physicians, Dr Jagsi and coauthors observed, “Efforts must now turn to confront the financial devastation that many patients face, particularly as they progress into survivorship. The first steps for clinical practice and policy are clear: all physicians must assess patients for financial toxicity and learn how to communicate effectively about it.”2

ADT) was 32% and 25% lower, respectively, compared with doublet therapy with docetaxel plus ADT), but did not differ significantly from API doublet therapy.

Among patients with high-volume disease, AAP triplet therapy was associated with a significant 28% reduction

Meta-analysis probed outcomes of doublet and triplet therapies. in death risk compared with docetaxel plus ADT doublet therapy, according to the investigators. AAP triple therapy, however, did not differ significantly from doublet API therapy (abiraterone plus ADT, enzalutamide plus ADT, and apalutamide plus ADT). In addition, AAP triplet therapy was associated with a

coauthors wrote in a 2018 article in CA: A Cancer Journal for Clinicians. “More than anyone in the multidisciplinary team of care, the oncologist may be the professional most able to integrate the diverse components of patient care.”15 Despite their possible discomfort about bringing up treatment costs with patients, physicians should make the effort because it is in the best interest of their patients, according to Dr Hollowell.

“Although physicians are often illprepared for patient-provider communication about the financial costs and burdens of treatment, patients experiencing financial toxicity report significantly worse outcomes,” he said. “As a result, discussing out-of-pocket costs related to treatment can affect not just our patients’ emotional well-being but how they respond to treatment, compliance, quality of life, and survival.”

Moreover, as Dr Joyce pointed out, financial toxicity “is a valuable patientreported outcome that places the cost of treatments in a context that clinicians are familiar and comfortable with.” ■ REFERENCES 1. Chan K, Sepassi A, Saunders IM, Goodman A, Watanabe JH. Effects of financial toxicity on prescription drug use and mental well-being in cancer patients.

Explor Res Clin Soc Pharm. 2022;14;6:100136. doi:10.1016/j.rcsop.2022.100136 2. Jagsi R, Ward KC, Abrahamse PH, et al. Unmet need for clinician engagement regarding financial toxicity after diagnosis of breast cancer. Cancer.

2018;124:3668-3676. doi:10.1002/cncr.31532

significant 46% and 53% decreased risk of disease progression compared with apalutamide plus ADT and docetaxel plus ADT doublet therapies, respectively, the investigators reported. AAP triplet therapy, however, did not differ significantly from enzalutamide plus ADT or AAP plus ADT doublet therapies with respect to disease progression Among men with low-volume disease, AAP triplet therapy was not significantly associated with improved overall or progression-free survival compared with any of the doublet therapies.

“The findings of this systematic review and meta-analysis indicate that the decision of treatment intensification with triplet therapy for patients with mCSPC must be considered carefully by accounting for the volume of disease, the timing of metastatic presentation, and API doublet options with significant survival benefit and fitness for chemotherapy,” the authors concluded. ■ 3. Rae M, Claxton G, Amin K, Wager E, Ortaliza J, Cox C. The burden of medical debt in the United States.

Kaiser Family Foundation website. Published online March 10, 2022.

4. Gilligan AM, Alberts DS, Roe DJ, Skrepnek GH. Death or debt? National estimates of financial toxicity in persons with newly diagnosis cancer. Am J Med. 2018;131(10):1187-1199.e5. doi:10.1016/j. amjmed.2018.05.020 5. Becker NV, Scott JW, Moniz MH, Carlton EF, Ayanian JZ. Association of chronic disease with patient financial outcomes among commercially insured adults. JAMA Intern Med. 182(10):1044-1051. doi:10.1001/jamainternmed.2022.3687 6. Joyce DD, Sharma V, Jiang DH, et al. Out-of-pocket cost burden associated with contemporary management of advanced prostate cancer among commercially insured patients. J Urol. 2022;208(5):987-996. doi:10.1097/JU.0000000000002856 7. Yousuf Zafar S, Abernethy AP. Financial toxicity, part I: a new name for a growing problem. Oncology.

2013;27(2):80-81.

8. de Souza JA, Yap BJ, Hlubocky FJ, et al. The development of a financial toxicity patient-reported outcome in cancer: The COST measure. Cancer.

2014;120(20):3245-3253. doi:10.1002/cncr.28814 9. de Souza JA, Yap BJ, Wroblewski K, et al. Measuring financial toxicity as a clinically relevant patientreported outcome: The validation of the Comprehensive Score for financial Toxicity (COST). Cancer.

2017;123(3):476-484. doi:10.1002/CNCR.30369 10. Alexander GC, Casalino LP, Meltzer DO. Patient-physician communication about out-of-pocket costs. JAMA. 2003; 290(7):953-958. doi:10.1001/jama.290.7.953 11. Raber M, Jackson A, Basen-Engquist K, et al. Food insecurity among people with cancer: Nutritional needs as an essential component of care. J Natl Cancer Inst. Published online September 21, 2022. doi:10.1093/jnci/djac135 12. Raghavan D, Keith NA, Warden HR, et al. Levin Cancer Institute Financial Toxicity Tumor Board: A potential solution to an emerging problem. JCO Oncol Pract.

2021;17(10):e1433-e1439. doi:10.1200/OP.21.00124 13. Resnick MJ. Editorial comment. J Urol. 2019;201(6): 1045. doi:10.1097/01.JU.0000554799.88126.46 14. Mossanen M, Smith AB. Addressing financial toxicity: The role of the urologist. J Urol. 2018;200:43-45. doi:10.1016/j.juro.2017.10.039 15. Carrera PM, Kantarjian HM, Blinder VS. The financial burden and distress of patients with cancer: ­Understanding and stepping-up action on the financial toxicity of cancer treatment. CA Cancer J Clin.

2018;68(2):153-165. doi:10.3322/caac.21443.

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Renal & Urology News 13

Kidney Week 2023, Philadelphia, PA

Vitamin K Shown to Ease Calciphylaxis Researchers also link lower plasma pyrophosphate levels in calciphylaxis to a higher mortality risk NEW RESEARCH could lead to improved treatment of calciphylaxis, including an analysis of phase 2 clinical trial data suggesting that vitamin K therapy improves outcomes and a prospective study demonstrating that plasma pyrophosphate (PPi) could be a potential treatment target.

There is no approved therapy for calciphylaxis, a serious vascular calcification disorder that predominantly occurs in patients with end-stage kidney disease (ESKD), Sagar U. Nigwekar, MD, MMSc, of Massachusetts General Hospital in Boston, who led the vitamin K trial, noted.

The double-blind randomized trial included 26 eligible adult patients on hemodialysis with calciphylaxis. Patients received oral phytonadione (vitamin K1) 10 mg or placebo twice weekly for 12 weeks. Each group had 13 patients. Use

Low Selenium Tied to Higher Death Risk DEFICIENCY IN DIETARY selenium and lower blood levels of the nutrient significantly increase the risk for all-cause mortality, especially among those with preserved kidney function and those who are overweight or moderate-to-heavy alcohol consumers, study findings suggest.

The findings are from a study of 41,423 participants in the 1999-2016 US National Health and Nutrition Examination Survey. Patients in the first quintile of dietary intake of selenium had a significant 12% increased risk for all-cause mortality after adjusting for age, sex, ethnicity, and other potential confounders compared with the third quintile (reference), Yaerim Kim, MD, of Keimyung University School of Medicine in Daegu, Korea, and colleagues reported.

In subgroup analyses, lower intake of selenium significantly increased the risk for all-cause mortality by 14% among individuals with an estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) of 60 or higher, 24% among those with a

of other vascular calcification treatments was up to physicians’ discretion.

Significantly higher proportions of patients in the phytonadione than placebo group had improvement in pain intensity (92% vs 8%) and total lesion surface area (69% vs 31%),

Oral phytonadione (vitamin K1) reduced pain intensity and total skin lesion area.

Dr Nigwekar’s team reported in a poster presentation.

All patients received intravenous sodium thiosulfate, 39% received intralesional sodium thiosulfate, and 50% received cinacalcet. No patient

body mass index of 25 to 30 kg/m2, and 27% among moderate-to-heavy drinkers. The influence of selenium blood levels on all-cause mortality was the same as for dietary selenium intake.

The investigators assessed selenium intake based on 1-day 24-hour dietary recall.

Selenium is an antioxidant with beneficial roles in human health, including metabolism and thyroid function, the investigators noted. “Based on the metabolism process, kidney function status has a potential role in the bioavailability of dietary selenium,” the investigators wrote in their study abstract.

In a recent post hoc analysis of 935 patients with hypertension aged 40 to 75 years in a Chinese folic acid intervention trial, researchers found an inverse association between baseline plasma selenium levels and rapid decline in kidney function, according to findings published in The Journal of Nutrition.

Each 10-unit increase in plasma selenium was significantly associated with 15% lower odds of a rapid decline in kidney function. The inverse association was more pronounced among patients who received folic acid.

Further, research suggests that low selenium levels in patients on hemodialysis increase their risks for death and hospitalization. ■

received etelcalcetide or bisphosphonate. “Intralesional sodium thiosulfate or cinacalcet by themselves were not associated with improvements in clinical outcomes,” the authors wrote.

Pyrophosphate Role In a separate presentation, Api Chewcharat, MD, of Massachusetts General Hospital in Boston, and colleagues reported on a prospective study showing that lower levels of PPi were significantly associated with increased mortality risk among patients with calciphylaxis. They said their findings demonstrate the potential of plasma pyrophosphate as a target for treatments aimed at improving patient-oriented and clinical outcomes in calciphylaxis.

The study enrolled 70 patients with a median age of 60 years. Most (67%) had ESKD. The researchers measured

PPi levels at study enrollment and at a 6-week follow-up visit (30 patients) and examined the association of these levels with skin lesion count, pain severity (using the Brief Pain Inventory), and 6-week mortality. The study population had a median skin lesion count of 3 and median pain severity score of 5. Median PPi levels were 568 nM at enrollment and 1155 at the 6-week follow-up.

Among the 21% of patients who died by the 6-week follow up, PPi levels at enrollment were a significant 66% lower compared with patients who were alive. In adjusted models, each 100 nM decrease in PPi at enrollment was significantly associated with a 25% increased risk of 6-week mortality, Dr Chewcharat and colleagues reported. A decrease in PPi levels over the 6-week period since enrollment was significantly associated with increased 12-week mortality. ■

Undiagnosed CKD Highly Prevalent in HTN, CVD UNDIAGNOSED EARLY chronic kidney

as the absence of a CKD diagnosis code

disease (CKD) is highly prevalent among

any time before and up to 6 months after

patients with hypertension and cardio-

the second eGFR measurement (index

vascular disease in the absence of type

date). The analysis included 4 cohorts

2 diabetes (T2D), new findings suggest.

based on ICD diagnosis codes: patients

Early diagnosis of CKD and active

with hypertension but not T2D; patients

management can slow disease progres-

with hypertension or atherosclerotic car-

sion and improve outcomes, but the

diovascular disease (ASCVD) but not T2D;

prevalence of undiagnosed early-stage

patients with hypertension or heart failure

CKD in patients with comorbidities

but not T2D; and patients with T2D.

other than T2D has not been reported, according to investigators.

In the absence of T2D, the proportion of patients with undiagnosed stage

Using the US TriNetX database,

3 CKD was 68.4% in patients with

Navdeep Tangri, MD, of the University

hypertension, 68.7% in patients with

of Manitoba in Winnipeg, Canada, and

either hypertension or ASCVD, and

colleagues studied 209,876 patients

68.6% among patients with hyperten-

(94,441 with T2D, median age 70

sion or heart failure, the investigators

years; 114,435 with hypertension and

reported in a poster presentation. All of

no T2D, median age 73 years).

these proportions were greater than for

All patient had 2 consecutive estimated glomerular filtration rate (eGFR, in mL/

patients with T2D (51.7%).

“Recording a CKD diagnosis in these

min/1.73 m ) measurements of 30 or

high-risk patients is crucial to ensure

higher but less than 60 (stage 3 CKD)

that they can receive appropriate and

recorded 91-730 days apart from 2015

timely treatment that could slow disease

to 2020. They defined undiagnosed CKD

progression,” the authors concluded. ■

2

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Kidney Week 2023, Philadelphia, PA

Novel AS Inhibitor May Slow CKD Progression A NOVEL selective aldosterone synthase (AS) inhibitor may improve the ability to slow chronic kidney disease (CKD) progression, researchers reported.

In a phase 2 clinical trial that included 714 patients with CKD with or without type 2 diabetes, a team led by Katherine R. Tuttle, MD, of the University of Washington in Seattle, compared the effects of the AS inhibitor at various doses (3, 10, and 20 mg) plus placebo or combined with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin. The primary endpoint was the change in the urine albumin-creatinine ratio (UACR) from baseline to week 14.

“Aldosterone synthase inhibitors directly lower aldosterone production and thereby may improve therapeutic efficacy for CKD,” she said.

Hyponatremia Present in 2% of US Adults AN ESTIMATED 6 million people in the United States, or 2% of the adult population, have hyponatremia, data show.

The prevalence is higher among women than men (2.53% vs 1.55%), and increases with age (from 1.41% of those aged 18-29 years to 5.72% of those aged 80 years or older), David A. Woolley, of the University of Oregon in Eugene, and Bhupinder Singh, MD, of Nephcentric LLC in Phoenix, Arizona, reported. The researchers used pooled 1999-2020 data from 55,731 participants in the National Health and Nutrition Examination Survey (NHANES). They defined hyponatremia as a serum sodium level below 135 mmol/L. Based on 2022 US census data, they estimated that 5,944,024 US adults had hyponatremia.

The researchers predicted that as the US population ages, the prevalence of hyponatremia will increase.

NHANES is a nationally representative cross-sectional survey of the noninstitutionalized civilian US population. ■

Among patients who received the AS inhibitor with background empagliflozin, those who received the 3, 10, and 20 mg dose of the AS inhibitor had a 19%, 46% and 40% reduc-

tion in UACR, respectively, whereas the patients who received the AS inhibitor placebo had an 11% r­ eduction. The AS inhibitor was generally well tolerated with no unexpected safety findings.

Dr Tuttle concluded that “aldosterone synthase inhibition is a promising new therapy that may add benefit to SGLT2 inhibition for CKD with or without type 2 diabetes.” ■

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Hemodiafiltration vs HD Offers Better Survival HEMODIAFILTRATION is associated with improved survival compared with hemodialysis, according to findings from a real-world analysis of data from 85,222 adult patients.

The study population included 46,961 on hemodialysis and 38,261 on hemodiafiltration at EMEA NephroCare Clinics from 2019 to 2022. The study population had a mean age of 62.3

years, and was 60% male. The median follow-up was 22.6 months.

Compared with patients receiving hemodialysis, those treated with hemodiafiltration had a significant 22% lower

risk for death from any cause, Yan Zhang, PhD, of Fresenius Medical Care Deuthschland GmbH in Bad Homburg, Hessen, Germany, and colleagues reported in a poster presentation. ■

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SABR Effective for Inoperable Renal Cell Carcinoma

BY JOHN SCHIESZER STEREOTACTIC ABLATIVE body radiotherapy (SABR) is safe and effective treatment for older patients who have primary renal cell carcinoma (RCC) but are not suitable candidates for surgery, according to a recent study.

The new findings are from the phase 2 prospective, nonrandomized TransTasman Radiation Oncology Group (TROG) FASTRACK II trial (ClinicalTrials.gov ID: NCT02613819).

Besides an exceptional cancer control rate for relatively large cancers (average 4.7 cm), there were no cancer-related

deaths and only modest renal function decline after treatment, said lead investigator Shankar Siva, MBBS, PhD, a radiation oncologist who presented the findings at the American Society for Radiation Oncology (ASTRO) 2023 Annual Meeting. There is a significant unmet need for curing patients with tu-

mors of these sizes, and these new findings point to the potential of radiation therapy to address that need, he said.

“Our trial benchmark for success was a control rate of greater than 80%, and we were pleasantly surprised that there was a 100% control rate, which is unprecedented in cancers of this size,”

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said Dr Siva, of the Peter MacCallum Cancer Centre in Melbourne, Australia.

He noted that older patients with primary RCC have unique challenges that make it difficult to treat them surgically.

“We are able to offer a new novel standard of care,” Dr Siva said. “This is the largest trial of a nonsurgical curative option in patients with primary RCC.” The trial included 70 patients with a median age of 77 years. All had in-

operable, high-risk kidney tumors or ­declined surgery. The median follow-up was 42 months. The majority of patients were male (70%) and the median body mass index was 32 kg/m2. The median Charlson comorbidity score was 7; the median RENAL complexity score was 8.

SABR was delivered in 1 or 3 sessions at 7 Australian centers and 1 in the Netherlands. Treated tumors on ­average were 4.7 cm. Of the 70 patients,

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23 who had tumors smaller than 4 cm received a single fraction of radiation and 47 who had tumors larger than 4 cm received 3 fractions. No patient experienced local failure or died from their cancer. Dr Siva said. Freedom from distant failure was 99% at 1 and 3 years.

Overall survival was 99% at 1 year after SABR and 82% at 3 years.

Adverse events (AEs) were relatively modest, with no grade 4 or 5 toxicities

Renal & Urology News 17

observed. However, 7 patients (10%) experienced grade 3 AEs, most commonly transient abdominal pain (3 patients). In this study, 51 patients (73%) had a grade 1/2 treatment-related event and 11 patients (16%) experienced no AEs. The average estimated glomerular filtration rate declined by 10.8 mL/min/1.73 m 2 at 1 year and 14.6 mL/min/1.73 m2 at 2 years after treatment, indicating mild-to-moderate kidney stress, the investigators reported. Only 1 patient required dialysis following treatment. Kidney function decreased modestly, leveling off after 2 years. “Most of these patients did not have a curative option,” Dr Siva said.

Commenting on the TROG trial, Ellen Kim, MD, MPH, Director of Clinical Informatics in the Department of Radiation Oncology at DanaFarber Cancer Institute in Boston, Massachusetts, noted the trial is relatively small, with only 70 patients.

However, patients were recruited from 8 centers over nearly 4 years. “When available, SABR should certainly be considered for medically inoperable patients with this disease,” Dr Kim said. ■

Longer HHD May Increase Survival THRICE-WEEKLY extended home hemodialysis (HHD) is associated with better survival and other outcomes compared with in-center conventional hemodialysis (ICHD), data suggest.

Patients undergoing thrice-weekly extended HHD had a significant 40% lower risk for death in adjusted analyses compared with those receiving ICHD, Ercan Ok, MD, of Ege University School of Medicine in Izmir, Turkey, and colleagues reported in Kidney International Reports.

Dr Ok’s team propensity score matched 349 patients starting thriceweekly extended HHD with 1047 concurrent ICHD patients. The mean duration of dialysis sessions were 418 minutes in the extended HHD group compared with 242 minutes in the ICHD group. All-cause mortality rates in the extended HHD and ICHD groups were 3.76 and 6.27 per 100 patientyears, respectively, a significant difference between the groups. ■

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IBD May Raise Risk of Chronic Kidney Disease

Microwave Ablation Is a Safe, Effective Option for SRMs

INFLAMMATORY bowel disease (IBD) may increase the risks of chronic kidney disease (CKD) and acute kidney injury (AKI), even in patients without a genetic predisposition, according to a recent study.

Xianhui Qin, MD, of Nanfang Hospital, Southern Medical University, in Guangzhou China, and colleagues examined data from 417,302 patients from the 2006-2010 UK Biobank, including 2940 patients with ulcerative colitis and 1261 patients with Crohn’s disease. During a median follow-up period of 12.5 years, patients with IBD had a 57% and 96% increased risk for new-onset CKD and AKI, respectively, compared with patients with diseases other than IBD after adjusting for age, sex, and race, the investigators reported in the American Journal of Preventive Medicine. The associations were stronger among younger vs older patients.

Crohn’s disease was significantly associated with a 38% and 62% increased risk for new-onset CKD and AKI, respectively, in fully adjusted models, the investigators reported. Ulcerative colitis was significantly associated with a 29% and 71% increased risk, respectively.

Outcomes are similar to those achieved with partial nephrectomy

Crohn’s disease is linked to a significant 38% increased risk of new-onset CKD. Genetic risk score for kidney diseases – assessed by the presence of 263 single nucleotide polymorphisms – did not influence the associations between IBD and kidney health, according to Dr Qin’s team.

The IBD-associated risks for CKD and AKI decreased to 32% and 70%, respectively, after investigators further adjusted for biological (eg, body mass index, estimated glomerular filtration rate, albuminuria, diabetes, hypertension, and high cholesterol), behavioral (eg, smoking, alcohol, exercise, and diet), and socioeconomic factors as well as mental health and self-rated health.

Poor self-rate health appeared to be the strongest mitigating factor, but the investigators could not account for all possible variables. ■

BY JOHN SCHIESZER MICROWAVE ABLATION (MWA) is a safe and effective alternative to partial nephrectomy (PN) for the treatment of small renal masses (SRMs), with both modalities associated with similar oncologic and renal function outcomes, according to study findings published recently in Urologic Oncology.

“Our study confirmed that in experienced hands microwave ablation can be an effective tool in preventing local recurrence for masses less than 4 cm, with no significant difference in the change in renal function after the procedure compared to the partial nephrectomy cohorts,” said lead investigator Jennifer Mason Lobo, PhD, Associate Professor of Biomedical Informatics at the University of Virginia in Charlottesville.

Dr Lobo and colleagues analyzed retrospective data from 2009 to 2015 and prospective data since 2015 from a single-institution database. The study included 80 patients who underwent PN and 126 who had MWA. Patients had a median age of 55 and 67 years, respectively. Although preoperative renal function was better in patients receiving PN and those with smaller tumors, the investigators found no significant differences in the change of renal function following the procedures.

“Microwave ablation is the ablation modality used at the University of Virginia due in part to lower sedation requirements and shorter procedure times relative to other ablation modalities,” Dr Lobo said. “Our team wanted to compare oncological and renal function outcomes for small renal mass patients treated with microwave ablation and partial nephrectomy.”

Cumulative progression-free survival rates at 36 months were similar between the cohorts (90% for PN and 91% for MWA), the researchers reported. Among patients with SRMs smaller than 3 cm, the PN cohort had 3 recurrences (8.3%) and the MWA cohort had 2 (3.2%).

Among patients with 3-4 cm SRMs, the PN cohort had 2 recurrences (4.6%) and the MWA cohort had 6 (9.4%).

Complications developed in 35 patients: 12 (27.3%) and 8 patients (22.2%) in the PN cohort with SRMs 3-4 cm

and less than 3 cm, respectively, and 7 (10.9%) and 8 (12.9%) in the MWA cohort with SRMs 3-4 cm and less than 3 cm, respectively.

Among patients with SRMs smaller than 3 cm, high-grade complications developed in 0 and 2 (3.2%) patients in the PN and MWA cohorts, respectively.

Among patients with 3-4 cm SRMs,

acteristics such as age or comorbidities.

In addition, the study lacked adequate statistical power to analyze relationships between tumor complexity, local recurrence, and treatment modality due to the small number of recurrences.

Jeffrey A. Cadeddu, MD, Professor of Urology and Distinguished Chair in Minimally Invasive Urologic Surgery

MWA vs PN In a study, microwave ablation and partial nephrectomy for renal masses smaller than 4 cm achieved similar cumulative progression-free survival rates at 36 months.

100

91%

90%

Microwave Ablation

Partial Nephrectomy

80 60 40 20 0

Source: Qiu J et al. Comparison of microwave ­ablation and partial nephrectomy for T1a small renal masses. Urol Oncol.

Published online August 17, 2023.

high-grade complications occurred in 4 (9.1%) and 3 (4.7%) patients in the PN and MWA cohorts, respectively.

Preoperative renal function was significantly lower in patients undergoing MWA for both tumor sizes, but there was no significant difference in the postoperative change in renal function between the cohorts for SRMs up to 4 cm.

“Our study supports microwave ablation as a safe nephron-sparing option for patients, including those that might not be surgical candidates,” Dr Lobo said.

The median follow-up for patients with SRMs smaller than 3 cm was 35.9 months for PN and 25.6 months for MWA; the median follow-up for patients with 3-4 cm SRMs was 36.1 months and 27.3 months, respectively.

The median time to recurrence for patients with SRMs smaller than 3 cm was 119.1 months for PN and 76.1 months for MWA. The median time to recurrence for patients 3-4 cm SRMs was 72.0 and 91.9 months, respectively.

The authors note that the patient cohorts were not matched for key char-

at UT Southwestern Medical Center in Dallas, Texas, said longer follow-up of these patients is required to support MWA being an accepted ablation modality compared with cryoablation and radiofrequency ablation. “It adds to the experience with microwave energy, which is still immature relative to the 2-decade experience with cryoablation and radiofrequency ablation,” Dr Cadeddu said. “These results are encouraging, and I believe that microwave ablation will be a reasonable alternative, but not oncologically or functionally better than these other ablation technologies.”

Keith Quencer, MD, Associate Professor of Interventional Radiology at Oregon Health and Sciences University in Portland, said the study is part of a growing body of research comparing PN and ablation. “As in this study, no great difference in outcomes can be found between these 2 treatment modalities,” Dr Quencer said. “Patient preference and local expertise should therefore play a large role in triage of patients to interventional radiology or urology.” ■

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Diabetics’ renal issues continued from page 1

The most common diagnoses among patients with non-DKD were focal segmental glomerulosclerosis (FSGS, 23.6%), global glomerulosclerosis, not otherwise specified (NOS, 12.8%), acute tubular injury (8.9%), immunoglobulin A (IgA) nephropathy (8.0%), ANCA vasculitis (7.4%), and membranous nephropathy (4.9%).

When the investigators compared patients with non-DKD alone with those who had both DKD and nonDKD, they found that global glomerulosclerosis NOS occurred more frequently in the non-DKD alone group (13.9% vs 5.7%). Oxalate nephropathy and post-infectious glomerulonephritis were more common in the DKD and non-DKD group than in the non-DKD

RKF loss, mortality risk continued from page 1

increased 59% at a renal urea ­clearance less than 1.5. The investigators adjusted for case-mix, ultrafiltration rate, and multiple laboratory values.

Adjustment for ultrafiltration rate slightly attenuated the association between low renal urea clearance and high cause-specific mortality, Dr Kalantar-Zadeh’s team reported. The highest serum potassium level reached did not explain the excess mortality.

The faster RKF declined, the greater the mortality risks. In case-mix adjusted analyses, the risk for sudden cardiac death, other cardiovascular mortality, and non-cardiovascular

Sparsentan for IgAN, FSGS continued from page 1

University Wexner Medical Center in Columbus, reported in an oral presentation.

In addition, the proportion of patients who had complete remission (urine protein excretion less than 0.3 g/d) was significantly greater in the sparsentan group than in the irbesartan group (31% vs 11%).

A final analysis at 110 weeks showed that sparsentan maintained its superior antiproteinuric effect, Dr Rovin said.

From baseline to 110 weeks, kidney function, as determined using estimated glomerular filtration rate (eGFR), declined in both treatment arms, but significantly less in the sparsentan group: 5.8 vs 9.5 mL/min/1.73 m2 in the irbesartan group. The chronic eGFR

alone group (4.8% vs 0.9% and 11.4% vs 3.5%, respectively), the investigators reported.

On multivariable analysis, each 1% increase in hemoglobin A1c and 1 g/mg increase in albumin-to-creatinine ratio were significantly associated with 32% and 22% reduced odds of a biopsy finding of non-DKD vs DKD alone, respectively, the investigators reported in a poster presentation. Biopsy findings of P-ANCA/MPO positivity and any positive serology were significantly associated with 4.0- and 3.1-fold increased odds of non-DKD alone, respectively.

“These findings will help provide additional information to clinicians on when they should really consider biopsying patients with diabetes to find other causes of kidney disease,” Dr Bobart said.

­ ortality significantly increased by m 14%, 24%, and 19%, respectively, when renal urea clearance declined by 3.0 compared with 1.5 over 6 months.

Findings are from a study of 39,623 patients starting thrice-week HD.

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The latest investigation adds to existing research on the topic, including a study of 321 patients with diabetes who underwent kidney biopsy at a center in New Delhi, India. On multivariable analysis, female gender, absence of diabetic retinopathy,

Biopsies revealed DKD alone in only 36.3% of patients with diabetes. absence of h ­ ypertension, and duration of diabetes of 24 months or less independently predicted non-DKD, according to findings published in International Urology and Nephrology (2022;54:1303-1309).

for sudden cardiac death and non-cardiovascular mortality, respectively.

“Future clinical trials are warranted to demonstrate the benefits of interventions to preserve RKF, such as an incremental hemodialysis and/or emerging renoprotective pharmacotherapies, and whether these interventions improve high mortality in patients undergoing hemodialysis,” Dr Kalantar-Zadeh’s team wrote.

The investigators used urine output as another measure of RKF. Mortality risk trended higher across urine volume categories lower than 900 mL/d.

Faster decline in urine volume over 6 months correlated with increased risks

Important, Useful New Insights In an accompanying editorial, John T. Daugirdas, MD, of the University of Illinois College of Medicine in Chicago, commented that the study provides “important and useful new insights.” He noted that

slope (from week 6 onward) favored sparsentan, with eGFR declining by 2.7 mL/min/1.73 m2 per year compared with 3.8 mL/min/1.73 m2 per year in the irbesartan group, a significant difference of 1.1 mL/min/1.73 m2.

Sparsentan was well tolerated and had a safety profile similar to that of irbesartan, Dr Rovin reported.

“I think we can consider sparsentan as a foundational therapy for Ig[A] nephropathy on which we can add immunosuppressive therapy as needed,” Dr Rovin said.

In the phase 3 DUPLEX trial, which included 371 patients with FSGS, patients treated with sparsentan had a 50% reduction in proteinuria from baseline compared with a 32% reduction with irbesartan, said Michelle N. Rheault, MD, of the University of Minnesota Medical School in

Minneapolis, who presented study findings. In a 36-week interim analysis, a higher proportion of the sparsentan arm than the irbesartan arm achieved the FSGS partial remission endpoint (FPRE; 42% vs 26%). Sparsentan recipients were a significant 55% more likely to achieve FPRE compared with irbesartan recipients. A difference between the study arms was maintained in the final analysis at 108 weeks (37.5% vs 22.6%) with sparsentan recipients a significant 60% more likely to achieve FPRE. The investigators defined the FPRE as a UPCR of 1.5 g/g or less and a greater than 40% reduction from baseline. “This FSGS partial remission endpoint has been associated with hard kidney outcomes in other studies of patients with FSGS,” Dr Rheault said.

Further, a higher proportion of the sparsentan group than the irbesartan

Renal & Urology News 19

In a study of 371 men with diabetes mellitus published in the Journal of the American Society of Nephrology (2013;8:1718-1724), biopsy findings showed that 37% of patients had DKD alone, 36% had non-DKD alone, and 27% had both.

Among patients with non-DKD alone, 22% had FSGS, 18% had hypertensive nephrosclerosis, 17% had acute tubular necrosis (ATN), 11% had IgA nephropathy. In the DKD plus nonDKD group, 43% had ATN, 19% had hypertensive nephrosclerosis, 13% had FSGS, and 7% had IgA nephropathy.

Multivariate analyses demonstrated that longer duration of diabetes was associated with a greater likelihood of DKD and a lower likelihood of non-DKD. Duration of diabetes for 12 years or more was the best predictor of DKD alone. ■

i­nfection-related mortality would have been a valuable addition.

“The exact mechanism whereby RKF is associated with a lower death risk remains incompletely defined, but it is most likely related to reduced serum levels of potential uremic toxins rather than to lower ultrafiltration rates or to lower incidence rates of severe hyperkalemia,” Dr Daugirdas wrote. “Even small amounts of RKF can substantially lower serum levels of higher molecular weight toxins such as beta-2-microglobulin5 and protein-bound uremic toxins, which are not well removed by hemodialysis.

Future exploration of the role of RKF and urine volume on hard outcomes should ideally include measurement of serum levels of such uremic toxins.” ■

group achieved complete remission: 18.5% vs 7.5%, she reported.

The annual eGFR chronic slope (week 6 to 108) declined less in the sparsentan arm than irbesartan arm

Investigators report findings from the phase 3 PROTECT and DUPLEX trials.

(-4.8 vs -5.7 mL/min/1.73 m2) but the 0.9 mL/min/1.73 m2 difference was not significant. Even so, she noted that the magnitude of the difference is clinically meaningful as it could delay the need for renal replacement therapy.

Sparsentan “is a very reasonable option for patients with FSGS,” she said. ■

24 Renal & Urology News FALL 2023

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NMIBC Recurrence Linked to Vitamin E Investigators published findings from the double-blind, randomized SELENIB trial

Frailty May Increase CV Risk in CKD BOTH PRE-FRAIL and frail patients with nondialysis chronic kidney disease (CKD) have increased risks for cardiovascular (CV) events and death, according to a recent study.

“Our findings suggest that frailty status may be a unique cardiovascular risk factor for patients with CKD,” Mary Hannan, PhD, NP, of University of Illinois Chicago and colleagues reported in the American Journal of Kidney Diseases. “This is of critical importance given the high prevalence of pre-frailty and frailty in our cohort and its association with cardiovascular risk and death.”

Among 2539 adults in the Chronic Renal Insufficiency Cohort (CRIC) Study, 12% were frail, 51% were prefrail, and 37% were non-frail.

At baseline, patients received 1 point for each frail criterion they met, including slow gait, exhaustion, muscle weakness, weight loss, and low physical activity. Non-frail was defined as a score of 0, pre-frail as a score of 1-2, and frail as a score of 3-5. Estimated glomerular filtration rate (eGFR), per protocol, ranged

Vitamin E increased NMIBC recurrence risk increased by 46%, researchers reported.

United Kingdom, randomly assigned 65 patients to receive selenium and vitamin E placebo; 71 to receive vitamin E and selenium placebo; 69 to receive selenium and vitamin E; and 65 to receive both placebos.

Patients had a median overall follow-

from 20 to 70 mL/min/1.73m2 based on a race-free creatinine-cystatin formula.

The risk for atherosclerotic events (including myocardial infarction, peripheral artery disease, and stroke) was a significant 1.8- and 2.0-fold higher for pre-frail and frail patients, respectively, compared with the non-frail group, according to the investigators.

The risk for new-onset heart failure was a significant 1.4- and 2.2-fold higher for pre-frail and frail patients, respectively.

The risk for CV death significantly increased 1.8- and 3.0-fold for the prefrail and frail groups, respectively, whereas the risk for non-CV death significantly increased 1.8- and 2.5-fold. The risk for all-cause mortality was a significant 1.8- and 2.5-fold higher for the prefrail and frail groups, respectively.

Frail adults were more likely to be older, female, and unmarried and to have lower eGFR, more proteinuria, and higher rates of diabetes, hypertension, and/or cardiovascular disease. Yet their baseline medical condition did not fully account for their excess risks.

“Although frail individuals in our cohort had a higher prevalence of cardiovascular risk factors at baseline, the associations between frailty and risk for an atherosclerotic event, incident heart failure, and cardiovascular death remained robust even after adjustment for risk factors,” Dr Hannan’s team pointed out. ■

up of 5.5 years, with a follow-up of more than 5 years for 228 patients (84%). The main outcome was recurrence-free interval (RFI) on an intention-to-treat basis.

Median treatment duration was 1.5 years.

The investigators observed no significant difference in RFI with selenium vs no selenium. Patients who received vitamin E, however, had a significant 46% increased risk for recurrence compared with patients who did not receive vitamin E, Dr Bryan and colleagues reported in JAMA Network Open. The investigators observed no significant differences in progression-free interval or overall survival time with either supplement.

“These findings suggest that vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required,” Dr Bryan and his collaborators concluded.

The researchers acknowledged study limitations, “including the fact that

patient accrual fell below the intended 515 due to an unexpectedly high proportion of ineligible patients, the elderly age of the patient population with accompanying comorbidities and medication, and the proposed trial duration.” Trial funding was withdrawn in 2010, resulting in the decision to end recruitment and treatment in 2011, Dr Bryan and colleagues noted. Thus, patients received much less selenium and vitamin E than intended.

The SELENIB trial is not the first to show a lack of beneficial effect of selenium and vitamin E supplementation in preventing cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed that dietary supplementation with 400 IU daily of vitamin E significantly increased the risk for prostate cancer among healthy men. A secondary analysis of SELECT demonstrated that selenium or vitamin alone or combined had no significant effect on bladder cancer incidence. ■

Renal Impairment Need Not Stop Axitinib Use for mRCC RENAL IMPAIRMENT does not

(ORR) between patients who had renal

adversely affect the efficacy of the

impairment and those who did not.

axitinib therapy for metastatic renal cell

Dr Minami’s team classified patients

carcinoma (mRCC), a study of real-

according to pretreatment renal

world data suggests.

function: receiving dialysis; estimated

“Although there are currently no

glomerular filtration rate (eGFR, in

established evidence-based guidelines

mL/min/1.73 m2) less than 30; eGFR

for the management of these patients

30 or higher but less than 45; eGFR

[with renal impairment], the present

45 or higher but less than 60; and

results indicate that clinicians do not

60 or higher. Median ­PFS was 6, 12,

need to avoid the administration of

14, 14, and 11 months, respectively.

axitinib to mRCC patients with impaired

After adjusting for treatment-related

renal function in consideration of the

confounders, the investigators found

risk of progression to end-stage renal

that renal function was not a significant

disease,” Keita Minami, MD, of Sapporo

prognostic factor for PFS.

City General Hospital in Sopporo,

ORR rates were 38%, 20%, 18%,

Japan, and colleagues reported in

23%, and 22%, respectively. The

Urologic Oncology.

median TTF was 5, 9, 9, 10, and

The finding is based on post hoc analyses of a Japanese multicenter cohort

7 months, respectively.

The median overall survival (OS) times

study of 477 patients with mRCC who

were 43, 28, 42, 39, and 21 months,

received axitinib. Investigators found

respectively. The worse OS among

no significant difference in progression-

patients with an eGFR of 60 or higher

free survival (PFS; the primary study

may be due to a large number of patients

outcome), time to treatment failure

with IMDC poor-risk disease in that

(TTF), and objective response rate

group, according to the investigators. ■

© BSIP / GETTY IMAGES

BY JODY A. CHARNOW VITAMIN E supplementation is associated with an increased risk for disease recurrence following treatment for nonmuscle-invasive bladder cancer (NMIBC), whereas selenium supplementation has no effect on the risk, according to investigators. Neither vitamin E nor selenium was associated with disease progression or overall survival.

The findings are from the SELENIB trial, which researchers believe is the first trial to investigate the use of selenium and vitamin E for preventing recurrence and progression in patients with newly diagnosed NMIBC. The trial included 270 patients with a mean age of 68.9 years who underwent transurethral resection for newly diagnosed NMIBC. A team led by Richard T. Bryan PhD, of the Bladder Cancer Research Centre at the University of Birmingham’s Institute of Cancer and Genomic Sciences in the

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Renal & Urology News 25

Albuminuria Associated With Higher Fracture Risk ALBUMINURIA MAY increase the risk for fragility fractures in patients with chronic kidney disease (CKD), new study findings suggest.

In a study of 2.72 million community-dwelling adults in Alberta, Canada who had a least 1 creatinine and albuminuria measurement from April 1, 2008 to March 31, 2019, individuals with severe albuminuria had significant 37%, 31%, and 22% increased odds of hip fracture, vertebral fracture, and any fracture, respectively, compared with those who had no or mild albuminuria, investigators Sandra M. Cooke-Hubley, MD, MPH, MSc, of Memorial University in St. Johns, Newfoundland, Canada, and colleagues reported in Kidney International Reports. Patients with moderate albuminuria had significant 25%, 20%, and 18% greater odds of hip, vertebral, and any fracture, respectively.

“This study demonstrates the important role of albuminuria as a risk f­ actor for fragility fracture in CKD and may help inform risk stratification and prevention strategies in this high-risk population category,” the investigators concluded.

Severe albuminuria was associated with a 37% increased risk of hip fracture.

The investigators defined no or mild albuminuria as an albumin-creatinine ratio (ACR) less than 30 mg/g, proteincreatinine ratio (PCR) less than 150 mg/g, and trace or negative dipstick findings. They defined moderate albuminuria as ACR 30-300 mg/g, PCR 150500 mg/g, and 1+ dipstick, and severe albuminuria as ACR above 300 mg/g, PCR greater than 500 mg/g, 2+ dipstick or more. In all, 94% of patients had no or mild albuminuria, 4.7% had moderate albuminuria, and 1.3% had severe albuminuria.

Dr Cooke-Hubley and colleagues also examined the risk for fragility fracture by estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and KDIGO risk categories. The relationship between eGFR and any type of fracture showed a U-shaped association. Compared with patients who had an eGFR of 60-89, those with an eGFR of 90 or higher had significant

21% greater odds of fracture. Patients with an eGFR of 45-49 had significant 6% lower odds, whereas those with an eGFR of 30-44 and 15-29 had significant 5% and 17% increased odds, respectively. Patients in the KDIGO moderate, high-, and very high-risk categories had significant 3%, 12%,

and 25% increased odds of any type of fracture compared with those in the low-risk category. The investigators observed similar trends for spine, pelvic, and hip fracture.

“We propose that albuminuria may be a prognostic indicator for incident fracture risk in the population with

CKD, and that the KDIGO risk categories which combine albuminuria and eGFR can also be used to prognosticate fracture risk,” the authors wrote.

“These findings underscore the importance of using albuminuria in addition to eGFR when evaluating metabolic bone health and fracture risk.” ■

26 Renal & Urology News FALL 2023

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Renal Nutrition Update Update on the management of vitamin K levels in patients with chronic kidney disease BY LINDSEY ZIRKER, MS, RD

Green leafy vegetables are a good source of vitamin K1, or phylloquinone.

dysbiosis and reduce vitamin K production from gut bacteria. Warfarin use is also associated with increased calcification and lower vitamin K levels • Uremia possibly due to reduced vitamin K cycle enzyme activity Vascular calcification is a significant concern in those with CKD, impacting as many as 79% of those with non-­ dialysis-dependent CKD. Poor vitamin K status has been linked to an increased risk of calcification in

Although tests to directly measure vitamin K levels are available, use of indirect measures may be a more reliable way to assess vitamin K status.

Causes of Low Vitamin K Studies across of patients with CKD stages 3-5 those on hemodialysis and peritoneal dialysis have found significant numbers of patients with vitamin K deficiency or subclinical deficiency. There are several suggested causes for low vitamin K levels in these populations:2 • Low intake related to over-restrictive traditional renal diet (specifically potassium restriction) • Medications such as omeprazole and antibiotics that contribute to

CKD. There are multiple pathways proposed for this correlation, such as altered activity and function of smooth muscle cells and reduced production of matrix Gla protein that leads to increased calcification activity as well as reduced ability to inhibit calcification.

Thus, it is suggested that low vitamin K2 may contribute to increased risk of atherosclerosis, calcification, higher bone breaks, and bone disease.5 Given the high frequency of vitamin K deficiency and correlation with

serious issues, assessing vitamin K status and deficiency risk and improving vitamin K status is a worthy consideration in CKD patients.

Assessment There are various options for assessing vitamin K status, albeit some are not easily available. Additionally, adequate amounts of intake or supplementation are not well established in the CKD population. Consequently, a multidisciplinary approach and clinical judgment should play a significant role in any vitamin K intervention.

Direct measurements of vitamin K are one approach, but lipid levels and smoking status may obscure results.

Indirect methods may provide a more reliable option. These include measuring osteocalcin, matrix Gla protein, and dephosphorylated-­carboxylated MGP (dp-cMGP). Osteocalcin and matrix Gla protein, however, have limitations in patients with advanced secondary hyperparathyroidism due to bone resorption and for those with later stages of CKD due to more retention of osteocalcin fragments. Measuring dpcMGP may be more reliable, but testing may not be as readily available.6 In the absence of testing, use of clinical judgment combined with a review of deficiency risk factors can assist in ­assessing

vitamin K status. Vitamin K2 supplementation, especially with MK-7, shows mixed results with regard to reducing calcification and improving cardiac related outcomes, although increased intake seems to consistently show benefit.

Researchers postulate that higher vitamin K doses for longer periods of time than allowed in studies may be needed to see results.1 It is also worth considering, as it is with many vitamins, dietary sources of vitamin K have a synergistic effect with supplementation that contributes to improved outcomes.

In light of this, dietitians can play a key role in supporting physicians and other nephrology providers in assessing vitamin K status, supporting gut health to ensure optimal K2 production as well as digestion and absorption of nutrients, and liberating patients from the restrictions of a traditional renal diet that evidence continues to show is not heart-healthy and creates more fear and confusion for patients with CKD.7 ■ Lindsey Zirker, MS, RD, is a renal dietitian and Director of Clinical Services for the Kidney Nutrition Institute in Titusville, Florida. She specializes in autoimmune kidney disease and advanced practice medical nutrition therapy for people with kidney disease.

REFERENCES 1. Grzejszczak P, Kurnatowska I. Role of vitamin K in CKD: Is its supplementation advisable in CKD patients?

Kidney Blood Press Res.2021;46(5):523-530. doi:10.1159/000526611 2. Cozzolino M, Mangano M, Galassi A, Ciceri P, Messa P, Nigwekar S. Vitamin K in chronic kidney disease. Nutrients. 2019;11(1):168. doi:10.3390/ nu11010168 3. Bus K, Szterk A. Relationship between structure and biological activity of various vitamin K forms. Foods.

2021;10(12):3136. doi:10.3390/foods10123136 4. Ren R, Liu J, Cheng G, Tan J. Vitamin K2 (Menaquinone-7) supplementation does not affect vitamin Kdependent coagulation f­actors activity in healthy individuals. Medicine (­Baltimore). 2021;100(23):e26221. doi:10.1097/MD.0000000000026221 5. Levy DS, Grewal R, Le TH. Vitamin K deficiency: an emerging player in the pathogenesis of vascular calcification and an iatrogenic consequence of ­therapies in advanced renal disease. Am J Physiol Renal Physiol. 2020;319(4):F618-F623. doi:10.1152/ajprenal.00278.2020.

6. Evenepoel P, Claes K, Meijers B, et al. Poor vitamin K status is associated with low bone mineral density and increased fracture risk in end-stage renal disease. J Bone Miner Res. 2019;34(2):262-269. doi:10.1002/jbmr.3608 7. Biruete A, Jeong JH, Barnes JL, Wilund KR. Modified nutritional recommendations to improve dietary patterns and outcomes in hemodialysis patients.

J Ren Nutr. 2017;27(1):62-70. doi:10.1053/j. jrn.2016.06.001

© ALEX POTEMKIN / GETTY IMAGES

V

itamin K gets significant attention with regard to its impact on clotting factors. However, a growing body of evidence suggests a link between vitamin K status and calcification and bone and heart health.

This is noteworthy considering that cardiac events continue to be the leading cause of death for those with CKD.1 Considering vitamin K status may provide additional options for preventing complications and understanding their underlying causes.

Vitamin K is actually a collection of fat-soluble cofactors that activate vitamin K-dependent proteins (VKDP) primarily dealing with bone and vascular health (including blood clotting and preventing calcification). Vitamin K1, or phylloquinone, is found abundantly in green leafy vegetables. Vitamin K2, or menaquinone (MK), is produced by intestinal bacteria and found in fermented foods like cheese and natto (fermented soybeans), and liver.2 There are several known types of MK, and their effects may differ. For example, supplementation with MK-4, which can be converted from phylloquinones, increases prothrombin time/international normalized ratio (PT-INR), whereas MK-7 does not seem to have this impact.2,3,4

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Renal & Urology News 27

Ethical Issues in Medicine Elevator ethics: Health care providers should avoid discussing specific patients among themselves BY DAVID J. ALFANDRE, MD, MSPH

Modeling Professionalism Although the ethical principle of confidentiality is central when traveling in elevators, the value of modeling professionalism deserves consideration as well. Some observational studies have

found that unprofessional behavior in elevators is almost as common as breaches of patient confidentiality.1 Elevators are public spaces where health care professionals’ behavior can have as significant an impact as when they are engaged in patient care. The public’s experience of a health care provider’s unprofessional behavior can damage the integrity of both the local institution where they receive care and the health care profession in general. For example, the public’s trust in the profession can be damaged when a health care professional disparages another colleague or is demeaning of the quality of care in the organization where they work.

Patients Take Priority Elevators aren’t just ethical minefields.

They bring people together. It confines us in a cramped space for a short time, forcing us in some cases to interact and engage with strangers. Although it’s common to keep our heads down (or perhaps just staring up at the floor numbers), some people appreciate an elevator’s ability to create community.

I recall a moment earlier in my career when I was taking a crowded elevator up to my office on the 16th floor in the hospital. On the 8th floor, the doors

© PHOTO_CONCEPTS / GETTY IMAGES

A

lot can happen in a hospital elevator. Perhaps that is why elevator scenes are so popular in television and movies. The geometry of that enclosed space creates interesting possibilities between human beings. Over years of my career and many elevator rides, I’ve observed a wonderfully interesting and broad range of behaviors and incidents that have informed my life and medical practice. The situations with ethical dimensions are worth exploring.

The most common elevator event with a decidedly ethical dimension is the discussion of patient care by health care providers. Their professional obligation to maintain and protect patient confidentiality limits what can be said in the confines of an elevator, so much so that most hospital elevators now have signs clearly prohibiting discussion of patient care. This expectation is probably clear to most providers, and in my experience is most likely to be followed when these professionals and the public are in the elevator together. What may be more common is the willingness of hospital and clinic staff to discuss the care of specific patients when patients or members of the public are not present. Even in those cases, however, patient care should not be discussed.

The ethical principle of confidentiality demands not just keeping patient information private and secure, but also to only divulge the minimum amount of information necessary to people on a need-to-know basis. So even if I have a hospital ID around my neck doesn’t mean I am entitled to hear about the patient on the 8th floor with the post-procedure complication. What if I could deduce who that patient was based on the clinical description? What if that patient was my family member or friend? In either case, I’m not privy to that information.

Health care providers need to protect patient privacy even on elevators.

than a culture than only leads from the top, here was a prime example of how anyone in the organization can be an exemplary leader and show patients and other employees what makes their organization great.

The patient’s takeaway from that experience might be that every employee in the organization cares about what’s good for patients and ensures that patients are always the focus of their efforts. That’s a more powerful message than one found

Elevators are public spaces in which the behavior of health care professionals can have as significant an impact as when they are engaged in patient care. opened and a transporter attempted to wheel a patient onto the crowded elevator. Most of us stood there dumbfounded. Before any of us even had time to react or say, “Can you wait for the next one?” a custodial staff member leaped off the elevator to make room and proclaimed, “Patients come first!”

This was undoubtedly true, but what made it remarkable was that the mission of the institution could be so clearly embodied by a single person in the health care organization. Rather

on any billboard, magazine advertisement, or internet search. What do I do now when a patient needs to get on a crowded elevator? I make room by getting off the elevator and take the stairs because I want to be as exemplary as that employee taught me to be years ago.

Finally, the elevator remains one of the few tightly enclosed spaces where we share our lives with strangers, albeit briefly. Some patients who have come to the hospital or clinic in recent weeks continue to wear masks even though

the institution no longer requires it of patients or staff. So even if I may no longer wear my mask in the elevator, I always carry an extra mask in my white coat or briefcase in case I have to share the elevator with a masked patient who asks me to wear one. No, masks aren’t required, but out of respect for patients’ preferences in a place they come to get well, I make sure I can honor that request and put on my mask while we share that space together.

Elevators are a unique space we share together in our work and personal life.

A lot happens waiting for them and in them that relates to our ethical behavior. If we pay attention, we may get the chance to do good. ■ David J. Alfandre, MD, MSPH, is a health care ethicist and an Associate Professor in the Department of Population Health at the NYU School of Medicine in New York. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the VA National Center for Ethics in Health Care or the US Department of Veterans Affairs.

REFERENCE 1. Ubel PA, Zell MM, Miller DJ, et al. Elevator talk: observational study of inappropriate comments in a public space. Am J Med. 1995;99:190-194. doi:10.1016/s0002-9343(99)80139-9

28 Renal & Urology News

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www.renalandurologynews.com

Practice Management I

t may be possible to improve clinical practice efficiency and patient satisfaction and prevent errors that impact administrative workloads through so-called “intelligent scheduling.” Scheduling tools that use datadriven algorithms can automate administrative tasks and improve patient interactions in ways that traditional appointment booking capabilities previously could not.

Enhanced Physician Utilization “Specialty organizations using an intelligent scheduling solution have seen an average increase of 5%-10% in physician utilization, with gastroenterology, orthopedic and musculoskeletal, urology, and multi-specialty practices each maintaining between 87%-98% physician utilization rates,” said Jeff Gartland, CEO of Relatient, an intelligent patient scheduling and engagement technology company.

New algorithm-based scheduling tools use a rules-based solution that streamlines the complexity of managing provider rules and preferences.

They also create a simplified scheduling experience for staff and patients.

An intelligent scheduling platform is configured across a network of providers and practice locations to create a

practices are becoming increasingly more complex as patients demand more autonomy with their care and better digital experiences,” Gartland said. “Meanwhile, providers themselves want more streamlined operations that will ensure they’re working at the top of their license, while filling appointments according to their preferences.”

No-shows cost the health care industry billions annually. Unbalanced physician schedules can create long appointment wait times for patients and unfilled appointment slots. Managing schedules in a centralized manner may lead to improved staff productivity and close gaps in care. Intelligent scheduling configures rules and preferences that are specifically customized by each individual provider. “In specialty practices, we know that providers have very unique needs and preferences depending on the types of procedure, patient visit reason, and more,” Gartland said.

It is estimated that approximately 90% of provider organizations rely on internal staff knowledge when it comes to scheduling rules. Gartland said this poses a risk when staff turnover occurs and historical knowledge is lost. “By building these rules directly within the scheduling system, administrators can ensure they are booking the specific

‘Day-to-day analytics can help drive optimal scheduling performance, such as identifying opportunities to improve provider utilization...’ centralized, real-time view of physician appointment availability, whether they work at a single office or across multiple locations.

Scheduling is the backbone of a health care organization, yet many practices use scheduling systems that rely heavily on manual, analog operations like binders, spreadsheets, or historical knowledge, Gartland said. It is the staff who normally have the best knowledge for managing provider rules and preferences. “These scheduling

appointments or patient types exactly aligned to how providers want their schedules structured,” he said.

Specific rules can be directly applied in an intelligent scheduling system.

This can pave the way to significant improvements in revenue. Clinicians can have their schedules aligned and structured in a manner that improves care while saving time. “Administrators can ensure they are booking the specific appointments, such as a vasectomy versus ureteroscopy, or patient types, such

© ANDREYPOPOV / GETTY IMAGES

‘Intelligent scheduling’ offers the promise of improved medical practice efficiency and patient satisfaction BY JOHN SCHIESZER

Intelligent scheduling of appointments can increase practice revenue.

as new versus existing, Medicare versus private insurance, etc.,” Gartland said.

Adopting online scheduling of appointments can be beneficial. Traditional scheduling tools and even many native electronic health records capabilities do not adequately account for complex and evolving provider needs and preferences, Gartland said. “True intelligent scheduling tools don’t stop after an appointment is scheduled. Day-to-day analytics can help drive optimal scheduling performance, such as identifying opportunities to improve provider utilization and also track KPIs [key performance indicators] for patient acquisition, appointment volume, and more,” Gartland said.

Quality of Scheduling Matters Automating basic tasks such as appointment reminders, managing a wait list, and smartly overbooking can drastically reduce the burden on staff while maintaining appointment volume. The majority of providers say that quality of scheduling is one of the most important factors for patient experience. “Likewise, 61% of patients have reported skipping doctors’ appointments due to challenges associated with scheduling, including having to schedule through a phone call instead of online,” Gartland said. “As more and more scrutiny is applied to the

scheduling process, there are also a lot more consumer demands that need to be taken into consideration.”

In the current work environment with an acute shortage of workers, learning the digital and analog processes and managing provider rules and preferences can be daunting for new employees. An intelligent scheduling system can diminish staff training time by 50%, Gartland said. Over time, not only does this improve operations at the organization, but also may help staff find more fulfillment in their work, which is a leading factor in staff retention.

Matt Hollingsworth, CEO and cofounder of Carta Healthcare, said intelligent scheduling is an example of an AI application in health care that will be quickly and more safely adopted than other applications. “Initially, the system may not be able to perform a scheduling role similar to a human’s role,” Hollingsworth said. “Like a new employee, it will need to be observed and trained by a human.” Integrating this type of administrative intelligence in health care is vital, as it frees up clinicians and healthcare workers to spend their time instead providing face-toface care to patients. ■ John Schieszer is a freelance medical journalist based in Seattle, Washington.