Renal & Urology News - Summer 2022 by Haymarket Media

SUMMER 2022

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VOL UME 21, IS SUE NUMBER 3

Study: Higher-Grade PCa On the Rise Upward trend in metastatic disease documented

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data from Surveillance, Epidemiology, and End Results (SEER) involving 438,432 men. GG1 cancers as a proportion of all prostate cancers declined from 47% in 2010 to 32% in 2018, he reported. GG1 at radical prostatectomy pathology also significantly declined from 31.5% in 2010 to 9.9% in 2018. Over the same period, the ageadjusted rate of GG1 disease dropped from 52 to 26 cases per 100,000. Concurrently, GG 2-5 prostate cancers increased, especially after 2014, according to Dr Borregales. GG3 increased as a proportion of prostate

PUL Use for BPH Increasing BY JODY A. CHARNOW PROSTATIC URETHRAL lift (PUL), which the FDA approved for use in 2013, now accounts for approximately one-third of all surgeries for benign prostatic hyperplasia (BPH), according to study data presented at the 2022 American Urological Association annual meeting in New Orleans, Louisiana.

The procedure was performed in 32.5% of all BPH surgeries in 2020, data show.

Analysis of de-identified and selfreported American Board of Urology case logs showed that PUL use increased from 1.6% of all BPH surgeries in 2015 to 32.5% in 2020, Samantha L. Thorogood, MD, of New York Presbyterian/Weill Cornell Medicine in New York, New York, reported on behalf of her research team. The study also identified factors associated with performing PUL, which included andrology subspecialization, higher surgeon BPH surgical volume, and non-academic practice types. “Given that PUL has been proposed as an alternative therapy to the gold standard TURP in the 2021 BPH surgical guidelines [from the American continued on page 18

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PROSTATE CANCER GRADE MIGRATION The age-adjusted incidence, per 100,000 men, of Gleason grade group (GG) 1 prostate cancer declined from 2010 to 2018, with a concomitant increase in the age-adjusted incidence of GG 2-5 cancers, as shown here. 25

■ 2010 ■ 2014 ■ 2018

20 15

BY NATASHA PERSAUD SINCE THE US Preventive Services Task Force (USPSTF) recommended against routine prostate cancer screening in 2012, prostate cancer grade at diagnosis has migrated toward higher Gleason grade groups (GGs), according to study findings presented at the American Urological Association’s 2022 annual meeting in New Orleans, Louisiana, and published recently in the Journal of the National Cancer Institute. Leonardo D. Borregales, MD, of Weill Cornell Medicine in New York, and colleagues examined 2010-2018

■

10 11

9.3

5 0

GG2

GG3

GG4

GG5

Source: Borregales L, et al. Grade migration of prostate cancer in the United States during the last decade. J Natl Cancer Inst. 2022 Mar 28:djac066. doi:10.1093/jnci/djac066

cancers from 10.7% in 2014 to 13.5% in 2018. GG4 increased from 9.6% in 2014 to 10.8% in 2018. GG5 increased from 9.3% in 2010 to 11.0% in 2018. Distant metastases as a proportion of prostate cancer diagnoses increased from 3.0% in 2010 to 5.2% in 2018,

Male LUTS May Predict Death Risk BY JOHN SCHIESZER MODERATE AND SEVERE male lower urinary tract symptoms (LUTS) may be potential markers of poor overall health and a risk factor for mortality among middle-aged and older men regardless of whether the symptoms are bothersome, a recent study suggests. “Although male LUTS have been proposed as risk factors for morbid events, the associations between LUTS and mortality should be generally considered as proxies of ill health,” corresponding author Jonne Åkerla, MD, of Tampere University in Finland, and colleagues reported in The Journal of Urology. “This indicates the importance of assessing the general health, risk factors and major comorbidities among men with LUTS.” In the Tampere Aging Male Urological Study, Dr Åkerla’s team mailed a survey that included the Danish Prostatic Symptom Score questionnaire to 3143 Finnish men (aged 50, 60, and 70 years) in 1994, with repeat continued on page 18

Dr Borregales confirmed. A 2022 study published in JAMA Network Open and a 2019 Cancer study, both using SEER data, also documented a recent increase in metastatic prostate cancers at diagnosis. continued on page 18

IN THIS ISSUE 10

Overactive bladder in men linked to visceral fat area

Active surveillance for low-risk PCa is on the rise

Radical cystectomy complication rates are declining in the US

Metastatic PCa survival up in wake of treatment advances

Albuminuria is linked to a higher risk for some cancers

Allopurinol may decrease the risk for contrast nephropathy

Encouraging results from kidney xenotransplantation reported

Late relapse of testicular cancer is a rare occurrence, according to a recent study. PAGE 21

6 Renal & Urology News

SUMMER 2022

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FROM THE EDITOR EDITORIAL ADVISORY BOARD

Xenotransplantation Reaches a Milestone

fter decades of failed attempts at transplanting kidneys from one person to another, Joseph Murray, MD, a surgeon at the former Peter Bent Brigham Hospital in Boston, achieved success in 1954 when he transplanted a kidney between identical twin brothers. Reporting on their findings in Surgical Forum in 1955, Dr Murray and his coauthors noted that the recipient had good renal function persisting after 9 months.1 “The survival of the renal homograft for this period of time with continuing good function indicates the complete lack of a rejection response by the host and demonstrates that renal transplantation is a technically feasible procedure,” they concluded. Several years later, Dr Murray performed a successful kidney transplant between non-identical twin brothers.2 Since then, development and continued improvement of immunosuppressive medications, better donor-recipient matching criteria, and other advancements have made kidney transplantation routine. In 2021, 24,670 kidney transplant procedures took place in the United States, up from 22,817 in 2020, according to the Organ Procurement and Transplantation Network. Among the most formidable challenges today, however, is the lack of kidneys for transplantation. As a result, 100,000 people in the United States are waiting for a kidney transplant, according to the National Kidney Foundation. Among the options being considered to ease the problem is xenotransplantation—the transplantation of organs or tissues from nonhuman animals into human beings. Numerous hurdles need to be resolved for this to work successfully, but investigators in 2022 reported an important milestone in the endeavor. Two separate teams—one at the NYU Langone Transplant Institute in New York City and another at the University of Alabama at Birmingham (UAB)—described how they transplanted kidneys from genetically modified pigs into brain-dead human beings with encouraging results. (See article on page 22.) “Our results add significantly to the prior knowledge generated in non-human primate models and suggest that many barriers to xenotransplantation in humans have indeed been surmounted,” the UAB team wrote in a paper in the American Journal of Transplantation.3 They also noted that “the decedent model has significant potential to propel not only the field of xenotransplantation forward but to answer a multitude of other scientific questions unique to the human condition.” Kidney transplantation is considered the optimal treatment for endstage kidney disease, but the performance of the procedure is limited by a shortage of usable kidneys.The latest reports offer hope that this impediment could disappear or at least diminish in coming years. Jody A. Charnow Editor 1. Murray JE et al. Renal homotransplantation in identical twins. Surg Forum. 1955;6:432–436. 2. Murray JE, et al. Kidney transplantation in modified recipients. Ann Surg. 1962; 156:337–355. 3. Porrett PM, et al. First clinical-grade porcine kidney xenotransplant using a human decedent model. Am J Transplant. 2022;22:1037-1053.

Medical Director, Urology

Medical Director, Nephrology

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

Kamyar Kalantar-Zadeh, MD, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine Orange, CA

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

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

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

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

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

Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD Chief Executive Officer Inova Health System Falls Church, VA Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology (ret.) Cleveland Clinic Lerner College of Medicine Cleveland Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology UC Irvine School of Medicine Orange, CA James M. McKiernan, MD John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology Columbia University College of Physicians and Surgeons New York Kenneth Pace, MD, MSc Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Vancouver, Canada

Edgar V. Lerma, MD Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA Chief Medical Officer, DaVita Inc. Denver Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Associate Professor of Medicine Wayne State University School of Medicine Detroit Vice President of Medical Affairs, DaVita Healthcare Denver

Renal & Urology News Staff Editor

Jody A. Charnow

Web editor

Natasha Persaud

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

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Renal & Urology News (ISSN 1550-9478) Volume 21, Number 3. Published quarterly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). For reprint/licensing requests, contact Customer Service at custserv@haymarketmedia.com. Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2022.

Contents

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SUMMER 2022

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ONLINE

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

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.

Metastatic PCa Survival Improved in Wake of Treatment Advances Survival increased by 1 month for every year of diagnosis after 2011 compared with 0.02 months annually from 2000 to 2008, a study found. COVID-19, OAB Link Reported Patients with COVID-19 infection are at increased risk for experiencing new or worsening overactive bladder symptoms, investigators reported. Late Relapse Rare in Testicular Cancer In a study of patients in Norway, late relapse, defined as disease recurrence more than 2 years after treatment, occurred in 1.9% of men with clinical stage I disease.

Fracture Risk With SGLT2 Inhibitors Not Higher vs Other Diabetes Drugs Fracture rates in patients with CKD did not differ significantly at 180 and 365 days.

Methylprednisolone Found to Slow IgAN Progression Treatment led to a 4.8% absolute annual decline in a composite outcome of a 40% decrease in eGFR, kidney failure, or death from kidney disease.

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

AS Rate Increasing for Low-Risk PCa The proportion of men managed with active surveillance rose from 26.5% in 2014 to 59.6% in the first half of 2021, data show.

CALENDAR Editor’s note: The 2022 conference listings below include information provided by the sponsoring organizations on their websites as this issue went to press. European Association of Urology 37th Annual Congress Amsterdam, The Netherlands July 1-4 International Continence Society Annual Meeting Vienna, Austria September 7-10 Kidney Week 2022 Orlando, FL November 3-6 ASTRO 2022 Annual Meeting San Antonio, TX October 23-26 Large Urology Group Practice Association (LUGPA) 2022 Annual Meeting Chicago, IL November 10-12 Society of Urologic Oncology Annual Meeting San Diego November 30-December 2

Nephrology

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

Renal & Urology News 7

VOLUME 21, ISSUE NUMBER 3

Urology 11

SUMMER 2022

Uric Acid-Lowering Therapy May Increase CKD Risk Patients with serum uric acid levels of 8 mg/dL or less had a 24% increased risk for an eGFR less than 60 mL/min/1.73 m2. Deceased-Donor Kidneys Useful Despite Longer CIT Transplant outcomes not worse for carefully selected recipients who receive a kidney with a cold ischemia time of 36 hours or longer.

Survival among men with metastatic prostate cancer has improved markedly with

advances in medical therapy.

See our story on page 12

Departments 6

From the Editor Kidney xenotransplantation hits a milestone

News in Brief Erectile dysfunction is a risk factor for MACE

Ethical Issues in Medicine Breaches of patient confidentiality are sometimes necessary

Practice Management Study reveals a growing problem with inappropriate polypharmacy

8 Renal & Urology News

SUMMER 2022

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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 NLR Predicts Survival in Radical Cystectomy Cases

Billancourt, France, and colleagues

Patients who have an elevated neu-

REIN cohort by baseline serum urea

trophil-to-lymphocyte ratio (NLR) both

level. In adjusted analyses, serum

before and after radical cystectomy for

urea levels in the top tertile were sig-

bladder cancer have a significantly in-

nificantly associated with a significant

creased risk for death, Roy Mano, MD,

2.1-fold increased risk for CV events

of Tel Aviv Sourasky Medical Center

compared with the bottom tertile, the

and Sackler Faculty of Medicine, Tel

investigators reported.

stratified 2507 patients from the CKD-

Aviv University, Israel, and colleagues reported online in BJU International. In a study of 346 patients, the

MIBC Chemoradiotherapy Is Beneficial Long-Term

investigators found that patients with

Concomitant chemotherapy with

elevations in both pre- and postopera-

5-fluorouracil and mitomycin C added

tive NLR had a nearly 3-fold and 2.4-

to radiotherapy for muscle-invasive

fold increased risk for all-cause and

bladder cancer (MIBC) is beneficial

cancer-specific mortality, respectively,

long-term, Emma Hall, PhD, of The

compared with patients with no NLR

Institute of Cancer Research, London,

elevation.

UK, and colleagues reported online in European Urology.

Higher Urea in CKD Ups CV Event Risk

sis of the phase 3 BC2001 open-label

Elevated serum urea levels in patients

trial that included patients with T2-T4a

with nondialysis-dependent chronic

N0M0 MIBC. The 5-year cystectomy

kidney disease (CKD) predict car-

rate was 14% with chemoradiotherapy

diovascular (CV) events and death,

vs 22% with radiotherapy alone.

according to study findings presented

Chemoradiotherapy was significantly

at the European Renal Association

associated with a 46% decreased risk

59th Congress.

for cystectomy. Chemoradiotherapy

The finding is from a follow-up analy-

Ziad Massy, MD, PhD, of Ambroise Paré University Hospital, Boulogne-

also significantly improved locoregional control.

PSMs Tied to Worse RPN Outcomes Positive surgical margins (PSMs) are significantly associated with worse survival outcomes among patients undergoing robotic partial nephrectomy (RPN) for kidney cancer, according to data presented at the American Urological Association’s 2022 annual meeting. 20

18.6%

■ PSMs ■ No PSMs

7.9% 4.0%

1.6% 0

Cancer-specific Mortality

Overall Mortality

Source: Hemal S, et al. Implications of positive surgical margins following robotic partial nephrectomy. Presented at: AUA2022, May 13-16, 2022, New Orleans, Louisiana. Poster MP50-07.

Potassium Chloride May Up Hyperkalemia Risk in CKD P

atients with chronic kidney disease (CKD) who take potassium chloride (KCl) supplements to meet dietary potassium recommendations may be at increased risk for hyperkalemia, data suggest. Investigators treated 191 patients with stage 3b-4 CKD with 40 mmol KCl per day for 2 weeks, an amount equivalent to eating 4 bananas daily. Mean plasma potassium increased from 4.3 to 4.7 mmol/L, mean urinary potassium excretion increased from 72 to 107 mmol/d, and mean plasma aldosterone increased from 281 to 351 ng/L, Ewout J. Hoorn, MD, PhD, of Erasmus Medical Center, Rotterdam, The Netherlands, and colleagues reported in the Journal of the American Society of Nephrology. Hyperkalemia (plasma potassium range 5.6-5.9 mmol/L) developed in 21 (11%) of the 191 patients. “In patients with CKD stage G3b-4, increasing dietary potassium intake to recommended levels with potassium chloride supplementation raises plasma potassium by 0.4 mmol/L. This may result in hyperkalemia in older patients or those with higher baseline plasma potassium,” the authors concluded.

Erectile Dysfunction Tied to Higher Risk for MACE E

rectile dysfunction (ED) is an independent risk factor for major adverse cardiovascular events (MACE), according to study findings presented at the American Urological Association’s 2022 annual meeting in New Orleans, Louisiana. In a study of 50,291 men with ED and 379,518 control participants, investigators Udaybir Mann, MD, of the University of Manitoba in Winnipeg, Canada, and colleagues found a higher proportion of MACE among men with ED compared with the control group (9.1% vs 4.9%). Compared with the control group, men with ED had a significant 24% higher risk of MACE in propensity-weighted analyses. They defined MACE as myocardial infarction, coronary revascularization procedures, ischemic stroke, or hospitalization for heart failure.

Higher BMI in CKD Shown to Predict Lower Mortality A

mong patients with nondialysis-dependent chronic kidney disease (CKD), the risk for premature death is lower in obese than in normal-weight patients, investigators reported at the European Renal Association’s 59th Congress. In a cohort of 2420 patients in the Salford Kidney Study with a median followup of 44.3 months, the risk for all-cause mortality was a significant 12% lower for patients with a body mass index (BMI) of 30 kg/m2 or more (obese) vs 18.5-24.9 kg/m2 (normal weight), Saif Al-Chalabi, MBChB, MD, of Northern Care Alliance NHS Foundation Trust in Salford, UK, and colleagues reported. Investigators obtained the same result in a propensity-score-matched analysis comparing 414 obese and 414 normal-weight individuals. BMI did not influence the risks for CKD progression or end-stage kidney disease in either analysis. The median estimated glomerular filtration rate was 29.3 mL/ min/1.73 m2 and did not differ between BMI groups.

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Post-Kidney Transplant MACE Predicts Diminished Survival Investigators report a 2.6-fold increased risk for long-term mortality RECENTLY REPORTED study find ings provide a detailed look at how a major adverse cardiovascular event (MACE) after kidney transplantation adversely affects survival and identify which patients are at elevated risk for MACE. Data also demonstrate that patients who receive a kidney transplant

nstable angina, myocardial infarc u tion (MI), stroke, heart failure, any coronary revascularization procedure and/or any cardiovascular death. A MACE occurred in 781 patients (2.6%) within the first 12 months of transplant surgery. Unstable angina occurred in 0.2%, heart failure in 0.3%, MI in 1.1%,

Survival After MACE Kidney transplant recipients who had a nonfatal major adverse cardiovascular event (MACE) within the first year after transplant surgery, compared with those who did not, had significantly lower 1-, 3-, 5-, and 10-year survival rates, a study found. n MACE

100 80

97.4% 80.5%

94.4% 70.2%

n No MACE

90.7%

78.4%

59.5% 38.6%

40 20 0

1 Year

3 Years

5 Years

ADPKD Tied to Lower MACE Risk In a study published in Kidney International Reports, investigators found that KTRs with autosomal domi nant polycystic kidney disease (ADPKD) have a more favorable MACE-free sur vival rate than patients with diabetes and other forms of kidney disease. In an ageand sex-matched analysis, KTRs with ADPKD had a significant 29% reduced risk for MACE after kidney transplanta tion compared with those with diabetic nephropathy and those without diabetes or ADPKD, Fouad T. Chebib, MD, of Mayo Clinic in Jacksonville, Florida, and colleagues reported.

Aspirin May Lower MACE Risk in CKD ASPIRIN MAY prevent major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD), according to study findings presented at the European Renal Association’s 59th Congress held in Paris, France, and virtually. The findings are from the International Polycap Study3 (TIPS3) study in which investigators randomly assigned 5713 individuals with and without CKD, but without previous cardiovascular (CV) disease, to receive aspirin, aspirin plus a polypill (con taining atenolol, ramipril, hydrochlo rothiazide, and simvastatin), a poly pill alone, or respective placebo. Of the 5713 participants, 983 had CKD, defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/ min/1.73 m2. The primary outcome was MACE, which included non-fatal myo cardial infarction, non-fatal stroke, or CV-related death. Secondary outcomes included all-cause mortality. The mean follow-up duration was 4.6 years.

10 Years

Source: Anderson B et al. A population cohort analysis of English transplant centers indicates major adverse cardiovascular events after kidney transplantation. Kidney Int. Published online June 15, 2022.

are at lower MACE risk compared with those who remain on dialysis. In a study of 30,325 KTRs in England published in Kidney International, a MACE occurred in 781 within the first year of transplantation surgery. KTRs who had a non-fatal MACE within that timeframe had significantly decreased patient survival compared with KTRs who did not experience a MACE at 1 year (80.5% vs 97.4%), 3 years (70.2% vs 94.4%), 5 years (59.5% vs 90.7%), and 10 years (38.6% vs 78.4%). A nonfatal MACE within the first-year of transplant surgery was significantly associated with 2.6-fold increased risk for longterm mortality, Adnan Sharif, MBChB, MD, of Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom and colleagues reported. “Non-fatal MACE within the first year, regardless of the precise timing, was a powerful predictor of increased future mortality,” the investigators wrote. “Understanding MACE rates is important for service providers, health care professionals and kidney trans plant recipients themselves.” The investigators defined MACE broadly as any hospitalization for

the age-matched general population,” Dr Sharif’s team wrote. “Adequate counselling aside, strategies to predict and/or mitigate cardiovascular risk in the setting of kidney transplantation are urgently required.”

Renal & Urology News 9

coronary revascularization in 0.4%, stroke in 0.8%, and immediate cardiac death in 0.1% within the first 12 months after transplant surgery. The investiga tors noted that these rates are lower than rates reported in North America.

Sex and Age Differences Results also showed that men had a 20% higher risk for a MACE within 12 months than women. Compared with KTRs younger than 40 years, those aged 40-49, 50-59, and 60 years or older had a 2.4-, 4.3-, and 7.1-fold greater risk for an early MACE after kidney transplantation. Recipients of deceased donor vs living donor kidneys had a 37% higher 1-year MACE risk. Previous myocardial infarction, stroke, or angina was significantly associated with a 6.9-, 4.1-, and 2.6-fold increased risk of an early MACE, respectively. Diabetes at transplantation was sig nificantly associated with a 2.2-fold increased risk for a 1-year MACE after kidney transplantation. “Successful kidney transplantation reduces cardiovascular burden com pared to remaining on dialysis, but risk remains elevated compared to

Transplantation vs Dialysis In a Korean study published in Nephrology Dialysis Transplantation, investigators examined de novo MACE in KTRs compared with patients receiving dialysis. Using the South Korean nationwide health insurance database, they matched 4156 patients without a pre-existing MACE in each of 3 groups: KTRs, dialysis recipients, and the general population. Over 4.7 years of follow-up, de novo MACE occurred in 3.7, 21.7, and 2.5 individuals per 1000 person-years in the KTR, dialysis, and general popu lation groups, respectively. De novo MACE included myocardial infarction, revascularization, and ischemic stroke. The investigators noted that these rates are lower than those reported in Western populations. KTRs had a significant 84% lower risk for de novo MACE compared with patients on dial ysis, but a similar risk compared with the general population after adjusting for underlying comorbidities such as diabetes and hypertension, Hajeong Lee, MD, of Seoul National University Hospital and colleagues reported. This finding suggests that kidney transplan tation effectively reduces the risk of MACE compared with remaining on dialysis, according to Dr Lee’s team. ■

Aspirin vs placebo was associated with a 43% reduced risk for MACE. A total of 250 primary MACE occurred: 116 among aspirin recipi ents and 134 among placebo recipients, Johannes F.E. Mann, MD, from the University of Erlangen-Nürnberg and Munich General Hospitals in Germany, reported. Among patients with CKD, there were 65 primary MACE out comes: 26 in the 502 participants on aspirin and 39 in the 481 participants on placebo. Aspirin use in those with CKD was significantly associated with a 43% reduction in MACE risk. Death from any cause occurred in 312 participants, with 82 occurring in the CKD group. Aspirin use was signifi cantly associated with a 36% decreased risk for death compared with placebo. For all participants, the aspirin-polypill combination was significantly associated with a 31% decreased risk for MACE. Among patients with CKD, the combi nation treatment was significantly associ ated with a 63% and 51% decreased risk for MACE and death, respectively. ■

10 Renal & Urology News

■ AUA 2022, New Orleans

SUMMER 2022

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American Urological Association 2022 Annual Meeting

Baseline EF Influences Potency Recovery After Nerve-Sparing RC

OAB Linked to Visceral Fat in Men

Good erectile function before surgery is a positive sign, new findings suggest

INCREASED VISCERAL fat area (VFA) is significantly associated with the presence and severity of overactive bladder (OAB) in men, data suggest. Further, excessive abdominal visceral fat accumulation alone is an important OAB risk factor, concluded a team led by Tomohiro Matsuo, MD, PhD, of Nagasaki University Graduate School of Biomedical Sciences in Nagasaki, Japan. Dr Matsuo and colleagues analyzed data from 519 participants who underwent abdominal computed tomography (CT) as part of health checks and had not been treated for lower urinary tract symptoms prior to study enrollment. Of these, 135 met criteria for OAB: 2 points or higher on question 3 (urinary urgency) of the Overactive Bladder Symptom Score questionnaire and a total score of 3 points or higher. Investigators calculated VFA, visceral fat volume (VFV), and total abdominal fat volume (TAV) from the abdominal CT scans. Patients had a mean age of 57.4 years.

who were seen between 2008 and 2014. All the men completed the International Index of Erectile Function (IIEF) at their presurgical visit and at 3, 6, 12, 18, and 24 months post-RC. Orthotopic neobladder was performed in 115 men (55%) and ileal conduit in 95 (45%). Bilateral or unilateral nerve-sparing surgery was performed in 50% of the men with neobladder and 11% of men with ileal conduit. In this cohort, ileal conduit patients were significantly older (73 vs 63 years) and had a significantly higher rate of severe ED (65% vs 44%) prior to RC. They also were significantly less likely to have no ED (17% vs 30%) prior to RC. The researchers found that 84% of men reported having severe ED at 12 months and 79% at 24 months postRC. However, among 35 men with no preoperative ED and neobladder diversion, 16.7% reported no ED at 3 months (67% had bilateral nerve sparing and 22% underwent partial nerve sparing). The largest recovery occurred from 12-24 months, with rates of no ED improving from 14% to 35%. Among men who were potent preoperatively and underwent nerve-sparing surgery, around one-third of those with orthotopic neobladder and one-fifth of those with ileal conduit reported no ED at 24 months.

BY JOHN SCHIESZER IN HIGHLY SELECTED cases, men who have good baseline erectile function (EF) can recover potency following nerve-sparing radical cystectomy (RC), according to the findings of a singlecenter, prospective nonrandomized trial presented at the 2022 American Urological Association annual meeting in New Orleans, Louisiana. “Most men undergoing RC have poor erectile function at baseline and experience further decline after surgery without recovery. However, in a select group of men with good erectile function at baseline, the use of nerve-sparing surgery allowed many to recover erectile function after surgery, and this recovery continued out to 2 years,” said study investigator Benjamin Beech, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center in New York City. RC can have significant adverse effects on quality of life (QoL). Both sexual impairment and sexual dysfunction are significant problems for men and women post-RC. Sexual dysfunction may be due to a combination of organic and surgery-related iatrogenic factors. There is a paucity of data on long-term outcomes and the impact of preoperative EF. Dr Beech and colleagues examined the natural history of EF before and after RC and examined QoL in 210 men

Recovery of erectile function (EF) after radical cystectomy depends on EF prior to surgery.

“We believe these findings are clinically relevant and can help with preoperative counseling for men facing radical cystectomy and can also inform the decisions of surgeons around nervesparing surgery,” Dr Beech said. The strengths of the current study include the prospective collection of patient-reported outcome measures conducted repeatedly over the short to medium-term post-operative period. Limitations included a focus on EF specifically, which does not account for other components of overall sexual function, such as desire, orgasmic function, and satisfaction. Eric Klein, MD, chair of the Glickman Urological & Kidney Institute at Cleveland Clinic in Ohio, where he is professor of surgery in the Lerner College of Medicine, said it is important to have serial monitoring and long-term follow-up in this patient population. “There is older literature supporting this concept, both with respect to not compromising cancer control and return of erectile function,” Dr Klein said. “Nerve sparing is the right thing to do in appropriately selected patients.” “Nerve sparing is a major aspect of radical prostatectomy, but within pelvic uro-oncology it has received less attention as a part of the technique for radical cystectomy,” said Zachary Dovey, MD, assistant professor, general urology, robotics and uro-oncology at Mount Sinai Queens and Icahn School of Medicine at Mount Sinai, New York, New York. “This study confirms the important finding that, when oncologically safe, nerve sparing is feasible and can maintain EF in the postoperative period.” Neobladder for appropriately selected patients, especially using the robotic approach, is increasingly performed in high-volume pelvic uro-oncology centers as the chosen modality of urinary diversion for the surgical treatment of muscle-invasive bladder cancer, Dr Dovey said. The study by Dr Beech’s group is clinically relevant because of its prospective nature with repeated surveillance. ■

Excessive visceral fat accumulation alone is an important OAB risk factor, data show. Compared with the men without OAB, the men with OAB had significantly higher mean VFA (113.5 vs 72.1 cm2), VFV (3299.6 vs 1829.1 cm3), and VFV/TAV (0.50 vs 0.32). VFV/TAV at a cutoff value of 0.409 had a sensitivity and specificity for OAB of 74% and 73%, respectively. On multivariable analysis, a VFV/TAV of 0.409 was independently associated with 4.5-fold increased odds for OAB. Recent research suggests that metabolic syndrome is an important factor in the development of lower urinary tract symptoms, Dr Matsuo and colleagues noted. A recent study of women demonstrated that excessive visceral fat accumulation, which can trigger metabolic syndrome, is associated with OAB presence and severity. No such research has been conducted with men, who are considered more susceptible to the effects of visceral fat than women, according to the investigators. ■

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SUMMER 2022

Renal & Urology News 11

AS Rate Increasing for Low-Risk PCa Study identifies a concomitant decline in the use of radical prostatectomy and radiation therapy THE PROPORTION OF men with low-risk prostate cancer (PCa) managed initially with active surveillance (AS) more than doubled from 2014 to mid2021 in the United States, with a concomitant decrease in the use of active treatments, according to investigators. Matthew Cooperberg, MD, of the University of California, San Francisco, and colleagues examined data from the AUA Quality (AQUA) Registry, which was launched by the AUA in 2013 to help urology practices understand and improve their quality of care and streamline reporting as mandated by the Centers for Medicare and Medicaid Services. Data are obtained directly from a range of electronic health record systems at participating practices. By mid-2021, the registry included data from 1945 urologists at 349 practices across the United States. The investigators analyzed data from 20,809 men with low-risk PCa and known primary treatment. The

Complications Following RC Are Declining RADICAL cystectomy (RC) complications overall appear to be decreasing in the United States, investigators reported. Using the 2006-2018 American College of Surgeons’ National Surgical Quality Improvement Program (NSQIP) database, investigators identified 11,351 RC cases. Mean hospital length of stay (LOS) significantly decreased from 10.5 to 9.8 to 8.6 days, across the 3 contemporary eras: 20062011, 2012-2014, and 2015-2018, respectively, likely reflecting improvements in perioperative care, Kevin Chua, MD, of Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, reported on behalf of his team. The readmission rate held steady at 20.0%, 21.3%, and 21.0%, respectively. The 30-day mortality rate also remained unchanged at 2.7%, 1.7%, and 2.0%, respectively.

Rapid Rise in Active Surveillance An analysis of data from 20,809 men with low-risk prostate cancer and known primary treatment revealed that the use of active surveillance (AS) more than doubled from 2014 to mid-2021, with concomitant decreases in the use of radical prostatectomy (RP) and external beam radiation therapy (EBRT). 60

■ 2014 ■ Mid-2021

50 40 30 20 10 0

26.5%

59.6%

29.7%

15.8% RP

28.2%

20.9%

EBRT

Source: Cooperberg M, et al. Active surveillance for low-risk prostate cancer: Time trends and variation in the AUA Quality (AQUA) Registry. Presented at: AUA2022, May 13-16, 2022. Poster MP43-03.

patients had a median age of 65 years at diagnosis. The proportion of men managed with AS rose from 26.5% in 2014 to 59.6% in the first half of 2021, Dr Cooperberg and colleagues reported in a poster presentation. During that same period, the proportion of men treated with radical

The rate of any postoperative complication significantly decreased from 56.5% in 2006-2011 to 50.6% in 2015-2018, Dr Chua reported. The rate of major complications within 30 days of RC did not change significantly. Sepsis rates remained high. Deep incisional surgical site infections, however, decreased from 1.9% to 0.8%. Pulmonary embolism significantly decreased from 3.0% to 1.5%. The rate of minor complications within 30 days of RC significantly declined from 46.4% in 2006-2011 to 41.0% in 2015-2018. Superficial surgical site infections significantly decreased from 6.5% to 4.6% and transfusions from 34.2% to 31.7% over the 12-year span. But the rate of urinary tract infections stayed the same. “An analysis of the contemporary era shows continued decrease in LOS after RC and a decrease in overall complications,” Dr Chua and colleagues concluded in a study abstract. “This may reflect beneficial effects of changes in perioperative bladder cancer management such as increased use of neoadjuvant chemotherapy, enhanced recovery after surgery protocols and laparoscopic/robotic techniques.” ■

prostatectomy decreased from 29.7% to 15.8% and the proportion who received external beam radiation therapy decreased from 28.2% to 20.9%. The proportion of patients with lowrisk PCa managed with AS ranged from 4% to 78% at the practice level and 0% to 100% at the provider level.

Overall, AS rates were not meaningfully different between Black and White patients (39.4% and 39.8%, respectively). On logistic regression, age, year of diagnosis, and provider volume of lowrisk disease were strongly associated with AS receipt, whereas race and practice volume of low-risk disease were not, according to the investigators. “AS rates are improving but are still suboptimal, and variation across providers is excessive,” the investigators concluded. The latest findings are consistent with those of previous studies. In a paper published in JAMA, Brandon A. Mahal, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues reported that the use of AS or watchful waiting (WW) for men with low-risk PCa increased from 14.5% in 2020 to 42.1% in 2015. During the same period, use of RP declined from 47.4% to 31.3% and use of radiation therapy decreased from 38.0% to 26.6%. ■

Kidneys from Donors With COVID-19 Safe to Transplant TRANSPLANTING KIDNEYS from COVID-

prior to surgery, whereas 7.3% received

19-positive deceased donors appears

1 dose and 25.5% were not vaccinated.

to be safe, according to researchers.

By 4 weeks after transplant surgery,

At an American Urological Association

no recipient had tested positive for

press conference, Alvin Wee, MD, MBA,

COVID-19 on polymerase chain reaction

program director for kidney transplan-

assays, the study found. There was no

tation at Glickman Urologic and Kidney

change in postoperative management,

Institute at Cleveland Clinic in Ohio,

including immunosuppression.

reported results from 55 patients (36

Delayed graft function occurred in

men and 19 women) who received

19.6% of the recipients, which the

kidneys from 34 deceased donors

investigators attributed to more dona-

who tested positive for COVID-19 from

tion after cardiac death (59%) and longer

February to October 2021. Donor

cold ischemia time. At a mean 3.5

selection criteria evolved to the point

months of follow-up, all grafts were func-

that only COVID-19-positive donors

tional. They observed no transmission

without significant primary or second-

of COVID-19 through transplantation.

ary kidney injury were selected. The

Kidneys from COVID-19-positive

average Kidney Donor Profile Index

donors are safe to transplant and

was 36.9.

recipient outcomes are not different

Among recipients, 67.3% completed standard 2-dose COVID-19 vaccination

from regular donors, the investigators noted in their study abstract. ■

12 Renal & Urology News

■ AUA 2022, New Orleans

SUMMER 2022

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American Urological Association 2022 Annual Meeting

Metastatic PCa Survival Improved In Wake of Treatment Advances Reductions in cancer-specific and overall mortality reported

COVID-19, OAB Link Reported PATIENTS WITH COVID-19 infection

ADVANCES IN TREATMENT circa 2009-2011 have led to increases in survival for men with metastatic prostate cancer (PCa), according to investigators. Using the Surveillance, Epidemiology, and End Results (SEER) database, investigators identified 21,558 men with metastatic PCa diagnosed from 2000 to 2008 and 30,063 men diagnosed after 2011. The eras occurred before and after FDA approval of novel therapies such as abiraterone and cabazitaxel. Median overall survival was significantly longer for men diagnosed after 2011 compared with 2000-2008 (37 vs 30 months), Camilo Arenas Gallo, MD, of Case Western Reserve University, Cleveland, Ohio, reported for his team. Survival increased by 1 month for every year of diagnosis after 2011 compared with 0.02 months annually from 2000 to 2008. Receiving a diagnosis of metastatic prostate cancer after 2011 compared with the earlier era was significantly associated with 20% lower all-cause

mortality and 25% lower cancer- specific mortality. “Survival among men with metastatic prostate cancer has improved markedly with advances in medical therapy,” Dr Gallo said in an interview. “The therapeutic arsenal has grown dramatically over the past decade.”

‘The therapeutic arsenal has grown dramatically over the past decade.’ These include drugs with different mechanisms of action, such as upfront chemotherapy (cabazitaxel, approved in 2010), androgen biosynthesis inhibitor (abiraterone, 2011), pure androgenreceptor signaling inhibitor (enzalutamide, 2012), radionuclide therapy (radium-223, 2013), and cellular-based immunotherapy (sipuleucel-T, 2013), he said. He acknowledged that their

study was limited to 2000-2018, so it did not capture more recently approved therapies, such as 177Lu-PSMA-617 (approved in 2022). “There is still much room for improvement, as metastatic prostate cancer continues to claim more than 34,000 American men’s lives per year,” Dr Gallo said. Prior work demonstrates that many approved therapies for metastatic prostate cancer are adopted slowly, according to Dr Gallo. This is due to numerous factors, including cost and reluctance by patients and providers to utilize unfamiliar treatments with complex side effects. “Practicing urologists, who may be the first to encounter patients with advanced prostate cancer, are encouraged to educate patients on options that can improve survival. It is important for us to be a part of these conversations. Medical professionals must also continue to advocate for insurers to cover the cost of advanced therapies once their efficacy has been demonstrated.” ■

Rezˉum for BPH Safe, Effective in Real-World Study REAL-WORLD DATA confirm that Rez̄um therapy, a minimally invasive procedure that uses water vapor to ablate prostate tissue, is safe and effective for treating benign prostatic hyperplasia (BPH) over a wide range of prostate volumes, including glands 80 mL or larger, according to a presentation at the 2022 American Urological Association annual meeting in New Orleans, Louisiana, and published online ahead of print in Urology. The findings are from a large multicenter prospective registry study of 229 patients with a mean age of 67.3 years treated with the procedure. The group included 83 patients with prostate volumes of 80 mL or larger. The mean prostate volume was 71.5 mL (range 20-160 mL). Patients received a mean of 11 injections (range 4-28). The mean duration of the procedure was 4.8 minutes (range

1.5-14). The mean duration of post- procedure catheterization was 9.8 days. Patients’ International Prostate Symp tom Score (IPSS) decreased from 22 at baseline to 15.8, 10.3, and 9.3 at 1, 3, and 12 months, respectively, lead investigator Dean Elterman, MD, of University Health Network, University of Toronto, Canada, reported. The IPSS quality of life (QoL) score improved from a baseline of 4.4 to 2.2 and 1.5 at 3 and 12 months, respectively. The peak flow rate (Qmax) increased from 8.7 mL/s at baseline to 13.9 mL/s at 3 months. Postvoid residual volume values improved by 63%, 51%, and 61% at 1, 3, and 12 months. Results showed no significant changes in International Index of Erectile Function (IIEF)-15 score and Male Sexual Health Questionnaire (MSHQ) score for function or bother. The investigators conducted a subgroup analysis of the patients

with glands 80 mL or larger (mean 104.6 mL). The mean duration of the procedure was 5.9 minutes and mean duration of post-procedure catheterization was 11.8 days. The IPSS declined significantly from a baseline score of 20.9 to 15.8, 9.0, and 8.4 at 1, 3, and 12 months, respectively. IPSS QoL score improved from a baseline of 4.2 to 1.8 and 1.4 at 3 and 12 months, respectively. Qmax increased significantly from 9.2 mL/s at baseline to 14.3 mL/s at 3 months. Dr Elterman and colleagues observed no significant change in IIEF-15 scores, MSHQ function, or bother. No Clavien-Dindo events of grade 3 or higher occurred, according to the investigators. ■

are at increased risk for developing new or worsening overactive bladder (OAB) symptoms, data suggest. Ly Hoang Roberts, MD, of Oakland University, Royal Oak, Michigan, and colleagues noted they were the first US group to identify de novo genitourinary symptoms, such as frequency, urgency, nocturia, and pain/ pressure, in individuals with prior COVID-19 infection. They termed this condition COVID-19 associated cystitis (CAC). Among the BLAST COVID study group, 1895 individuals responded to a survey assessing their OAB symptoms before and after the start of the pandemic, including 605 individuals who were infected with the COVID-19 virus. The vast majority of the study group were female (81.7%) and White race (85.8%). Black (4.1%), Asian (3.8%), and Hispanic (1.4%) individuals formed the minority. Approximately one-third of patients with COVID-19 reported a clinically significant 1-unit increase in symptoms on the International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB) at 2 months after infection compared with before the pandemic, Dr Roberts reported. For 1 in 5 of these patients, OAB symptoms were new. Comparing the pre-pandemic period to the present day, 35.7% of participants with prior COVID-19 infection and 15.7% of uninfected participants reported a 1-unit increase in symptoms on the ICIQ-OAB. Infected patients had significant 3.0-fold increased odds of new or worsening OAB symptoms. COVID-19 antibody levels did not correlate with OAB symptoms, Dr Roberts reported. She noted that patients with CAC are being followed

Disclosure: The investigators report being consultants to Boston Scientific, which markets Rez̄um.

prospectively to assess the progression of OAB symptoms. ■

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SUMMER 2022

Fracture Risk With SGLT2 Inhibitors Not Higher vs Other Diabetes Drugs Fracture rates in CKD patients did not differ significantly at 180 and 365 days

Renal & Urology News 13

Eating Nuts Tied to Lower CKD Risk NEW RESEARCH links consumption

SOME CLINICAL trials have linked sodium-glucose cotransporter-2 (SGLT2) inhibitors to a higher risk for skeletal fractures. In contrast to this research, a new study finds that SGLT2 inhibitors pose no greater fracture risk in patients with chronic kidney disease (CKD) compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, diabetes drugs with no known association with fracture risk. Investigators compared 37,449 new users of a DPP-4 inhibitor and 38,994 new users of an SGLT2 inhibitor aged 66 years or older from Ontario, Canada. A total of 342 skeletal fractures occurred within 180 days and 689 fractures within 365 days. Fracture risk at 180 days and 365 days after drug initiation did not differ significantly between the DPP4-inhibitor and SGLT2 inhibitor groups (0.46% vs 0.44% and 0.96% vs 0.84%, respectively), Andrea Cowan, MD, of Western University, London, Canada, and colleagues reported in the Clinical Journal of the American Society of Nephrology. Fracture risk also did not vary by kidney function (estimated glomerular filtration rate more than 30 mL/ min/1.73 m2). Users of these diabetes

SGLT2 inhibitors are no more likely than DDP-4 inhibitors to cause fractures in CKD patients, according to a recent study.

medications had comparable risks for falls, hypotension, and hypoglycemia. Patients with CKD are vulnerable to fractures due to CKD mineral bone disorder. Dr Cowan’s team noted that in short-term studies, the SGLT2 inhibitors dapagliflozin and canagliflozin (but not empagliflozin) have been associated with hyperphosphatemia, secondary hyperparathyroidism, and increased bone turnover.

In a news release from the American Society of Nephrology, Dr Cowan said the study reassures patients and doctors that SGLT2 inhibitors “are not associated with an increased risk of fracture in patients with chronic kidney disease.” The authors said that, to their knowledge, their study is the first of its kind to specifically examine fracture risk in patients with CKD. With regard to study limitations, the investigators said that to preserve statistical power, they were unable to stratify their analysis by SGLT2 inhibitor type. Another limitation was the 1-year time frame. Fracture risk due to SGLT2 inhibitor use may take longer than a year to manifest. In an accompanying editorial, Mirela Dobre, MD, MPH, of Case Western Reserve University in Cleveland, Ohio, encouraged continued research. “The report by Cowan et al. adds to the growing body of evidence related to the safety of SGLT2is; however, it should encourage continued basic and clinical studies to determine with more certainty their potential risk of fractures, especially in individuals with advanced CKD (eGFR less than 30 ml/min per 1.73 m2).” ■

Methylprednisolone Found to Slow IgAN Progression TREATMENT WITH methylprednisolone reduces the risk for disease progression in patients with IgA nephropathy (IgAN) and proteinuria of 1 g per day or greater who are receiving optimal supportive therapy, but it carries an excess risk for infection, investigators reported in JAMA. In the Therapeutic Effects of Steroids in IgA Nephropathy Global (TESTING) randomized trial, a 6- to 9-month course of the oral glucocorticoid methylprednisolone significantly reduced the risk for the primary outcome by a significant 47% compared with placebo, according to Hong Zhang, MD, PhD, of Peking University First Hospital, Beijing, China, and colleagues. The primary outcome was a composite of a 40% decrease in estimated glomerular filtration rate (eGFR), kidney failure, or death due to kidney disease. The study enrolled 503 patients, three-quarters of whom were Chinese.

They had a mean age of 38 years and a mean eGFR of 61.5 mL/min/1.73 m2. The primary outcome occurred in 74 of 257 patients (28.8%) receiving oral methylprednisolone and 106 of 246 patients (43.1%) receiving placebo over a mean 4.2 years of followup. Treatment led to a 4.8% absolute annual decline in the composite outcome, Dr Zhang’s team reported. At baseline, patients’ eGFR was 20 to 120 mL/min/1.73 m2. The annual rate of eGFR decline was 2.50 vs 4.97 mL/ min/1.73 m 2 per year in the methylprednisolone vs placebo group, respectively. The first 136 patients randomly assigned to oral methylprednisolone received 0.6-0.8 mg/kg/d to a maximum of 48 mg/d, with tapering by 8 mg/d/mo. The investigators identified an excess of serious infections and subsequently reduced the dose to 0.4 mg/kg/d to a maximum of 32 mg/d,

with tapering by 4 mg/d/mo. They also administered sulfamethoxazoletrimethoprim to all remaining patients as prophylaxis against pneumocystis pneumonia. Full-dose and reduceddose methylprednisolone were significantly associated with a 42% and 73% lower risk for the composite outcome, respectively. Dr Zhang and colleagues reported that time-averaged mean 24-hour urine protein excretion was significantly lower in the methylprednisolone than placebo group (1.70 vs 2.39 g/d) but the benefit decreased over time and was no longer observed at 36 months. Serious adverse events, such as excess hospitalizations and infections, occurred more frequently with methylprednisolone vs placebo (10.9% vs 2.8%), mostly with the full-dose regimen, the investigators reported. Four infection-related events led to death in the methylprednisolone group. ■

of nuts 1-6 times per week with a lower risk of chronic kidney disease (CKD) and all-cause mortality. Among 6072 adults who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES) and completed food frequency questionnaires, 284, 273, 594, 46, and 6 adults had CKD stage 1, 2, 3, 4, and 5, respectively. The remaining 4869 participants had no CKD. Compared with no nut consumption, eating nuts 1-6 times per week (but not more than once daily) was significantly associated with 33% lower odds of developing CKD and 37% lower odds of all-cause mortality among those with CKD, Ying Yao, MD, and colleagues of Tongji Hospital, Wuhan, China, reported in the American Journal of Nephrology. Increasing nut consumption also was significantly associated with lower all-cause mortality in the nonCKD population. No reductions in cardiovascular mortality risk were observed in a fully adjusted model. Nuts contain many nutrients and healthy compounds, including unsaturated fatty acids, vegetable protein, fiber, phytosterols, vitamins, minerals, and phenols, the investigators explained. However, nuts are also rich in protein, potassium, and phosphorus, which are restricted in advanced CKD. According to Dr Yao’s team, whether nuts should be incorporated into nutritional therapy for nondialysis-dependent CKD requires further study. They also noted that different nut types may have different effects. Some types may be more suitable for patients with CKD. “In general, ‘1–6 times per week’ rather than a higher frequency might be an appropriate choice, in which nuts could continue their good work without causing any complications,” the investigators wrote. “More rigorously designed studies are needed to confirm this conclusion.” ■

14 Renal & Urology News

SUMMER 2022

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Uric Acid-Lowering May Raise CKD Risk Findings do not support initiating this therapy to prevent development of chronic kidney disease URIC ACID-LOWERING therapy is associated with a higher risk for newonset chronic kidney disease (CKD) among patients with baseline serum uric acid levels of 8 mg/d or less, a new study finds. The therapy did not change the risk for individuals with higher baseline serum uric acid levels. “These findings do not support the initiation of uric acid-lowering therapy as a means to prevent the development of CKD,” investigators concluded. Among 269,651 patients (94% male) with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/ min/1.73 m2 and no albuminuria treated at US Veterans Affairs health care facilities from 2004 to 2019, a total of 29,501 patients (10.9%) started uric acid-lowering therapy. The vast majority (99.7%) received allopurinol. Of the full cohort, 21.7% eventually experienced an eGFR

decline to less than 60 mL/min/1.73 m2, 25.5% new-onset albuminuria, and 0.2% end-stage kidney disease (ESKD). After propensity-score matching, use vs nonuse of uric acid-lowering therapy was associated with a significant 15% higher risk of eGFR decline to less

Higher risk observed in patients with uric acid levels of 8 mg/dL or less at baseline. than 60 mL/min/1.73 m2 and a significant 5% higher risk of albuminuria in the overall cohort, Csaba P. Kovesdy, MD, of Memphis VA Medical Center in Tennessee, and colleagues reported in JAMA Network Open. Allopurinol

Dysnatremias in ESKD Linked to Higher In-Hospital Mortality HYPERNATREMIA AND hyponatremia in

Sample. The racial composition was

hospitalized patients with end-stage kid-

39.2% White and 34.9% Black. The

ney disease (ESKD) are associated with

study population was 54.72% male and

higher in-hospital mortality and longer

45.28% female.

hospital length of stay (LOS), investiga-

Compared with patients who did not

tors concluded in a poster presented at

have hypernatremia, those with the

the National Kidney Foundation’s 2022

condition were significantly older (66.5

Spring Clinical Meeting in Boston.

vs 61.5 years) and significantly more

After adjusting for age, sex, race,

likely to be Black (38.1% vs 34.8%).

and comorbidities, hypernatremia and

Compared with patients who did

hyponatremia were significantly associ-

not have hyponatremia, patients with

ated with a 2.0- and 1.8-fold increased

hyponatremia were significantly older

risk for in-hospital death compared with

(63 vs 61 years), significantly more

patients without these conditions, Calvin

likely to be female (49.1% vs. 44.8%),

Ghimire, MD, of McLarin Flint Hospital in

and significantly less likely to be Black

Flint, Michigan, and colleagues reported.

(27.2% vs 35.9%).

Female patients had significantly lower

“Prevention of dysnatremia remains

in-hospital mortality and shorter LOS

vital and patient education remains a

compared with male patients.

cornerstone to achieve it,” Dr Ghimire’s

Patients with hypernatremia and

team wrote.

hyponatremia had a significantly longer

They also observed, “Effectiveness of

LOS than patients without these condi-

managing underlying comorbidities and

tions (11.6 vs 5.7 days and 8.9 vs 5.4

renal replacement methods to maintain

days, respectively).

normal sodium level as per the require-

The findings are from a study of

ment remains an unsolved mystery to

643,555 index hospitalizations for

prevent worse clinical outcomes and

ESKD identified in the National Inpatient

mortality.” ■

use did not decrease the risk for ESKD. Among individuals with baseline serum uric acid levels of 8 mg/dL or less, uric acid-lowering therapy was significantly associated with 24% and 7% increased risks for an eGFR less than 60 mL/min/1.73 m2 and albuminuria, respectively. The investigators did not find these associations among those with higher baseline serum uric acid levels. “Our findings of higher risk of incident CKD and albuminuria in patients with less severe elevations of serum uric concentration treated with urate lowering therapy may appear surprising, as we hypothesized that the lowering of uric acid levels would be beneficial owing to the detrimental effects of uric acid on various metabolic and cardiovascular processes,” the authors wrote. They also noted that the findings “support results of recent large

randomized clinical trials that found no benefit of allopurinol in delaying progression of established CKD.” Dr Kovesdy’s team said their study “is notable for its large size, national representativeness, and availability of comprehensive information on a broad array of clinical data.” They also acknowledged that their study was observational and retrospective, and thus open to confounding. “While we accounted for major known confounders of the development of kidney disease, residual confounding remains possible, such as the doses of various potentially nephrotoxic medications or the severity of cardiovascular disease or other comorbidities.” In addition, their analysis included mostly male US veterans, so it is unclear whether their results apply to women or nonveterans, they noted. ■

Endometrial CA Ups Risk for UTI, CKD

factors and those treated with chemotherapy and/or radiation, may be an important part of ongoing survivorship care after endometrial cancer.” The study population, which investigators identified using the Surveillance, Epidemiology, and End ResultsMedicare linked database (2004-2017), compared 44,386 women diagnosed with endometrial cancer with a control group of 221,219 women without a cancer history matched by age, race or ethnicity, and state of residence. In the endometrial cancer cohort, 65% of women had localized disease. Among women with endometrial cancer, the risk of most urinary outcomes tended to be higher among women who were older at cancer diagnosis, according to the investigators. For example, compared with women aged 66-69 years, those aged 70-74, 75-79, 80-84, and 85 years or older had a significant 1.06-, 1.25-, 1.42-, and 1.51-fold increased risk for lower UTI, respectively, and 1.22-, 1.47-, 1.82-, and 2.10fold increased risk for CKD, respectively, Dr Anderson’s team reported. The study identified racial and ethnic differences among women with endometrial cancer. For example, compared with White women, Black women had a 1.58- and 1.72-fold higher risk for CKD and renal failure, respectively, and Hispanic women had a 1.17-fold higher risk for lower UTIs. ■

WOMEN WITH endometrial cancer are at increased risk for urinary problems, including lower urinary tract infection (UTI) and chronic kidney disease (CKD), according to a recent study. An analysis of 265,605 women aged 66 years or older showed that women diagnosed with endometrial cancer had a 2.36-fold increased risk for lower UTI compared with women who did not have a history of cancer, Chelsea Anderson, PhD, MPH, of the Gillings School of Global Public Health at the University of North Carolina in Chapel Hill, and colleagues reported in Cancer Epidemiology, Biomarkers, & Prevention. They also had a 1.85- and 2.28-fold increased risk for CKD and kidney failure, respectively, and a 2.22fold increased risk for urinary stones. “Results of the current study suggest that older women with endometrial cancer have a higher risk of several urinary outcomes than similarly aged women without a cancer history,” the authors wrote. “Timely identification and treatment of these conditions, especially among those with preexisting risk

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SUMMER 2022

Renal & Urology News 15

COVID-19 Conversations With Older CKD Patients Inadequate

Race Affects ADPKD Care, Study Finds

Limited discussions about vulnerability and advance care planning reported

INVESTIGATORS HAVE identified racial and ethnic disparities in autosomal dominant polycystic kidney disease (ADPKD) outcomes. “Compared with White patients, Black and Hispanic patients with ADPKD have earlier age of onset of kidney failure and less access to kidney transplantation,” Rita L. McGill, MD, of the University of Chicago in Illinois and colleagues concluded in a paper published in the Clinical Journal of the American Society of Nephrology. National and local resources need to focus on education and outreach, and they need to clarify these systemic disadvantages to achieve health equity for all patients.

CLINICIANS SHOULD make a greater effort to engage older patients with chronic kidney disease (CKD) in discussions about the risks they face from COVID-19 and the effect of the illness on treatment options, researchers concluded in an article in the Clinical Journal of the American Society of Nephrology. The investigators based that conclusion on interviews with 39 patients aged 70 years or older with advanced CKD, 17 care partners, and 20 clinicians from Boston, Portland, Maine, San Diego, and Chicago from August to December 2020. “Although clinicians perceived greater vulnerability among older patients CKD and more readily encouraged homebased modalities during the COVID-19 pandemic, their discussions of vulnerability, advance care planning, and conservative management remained limited, suggesting areas for improvement,” Thalia Porteny, PhD, MSc, a postdoctoral scholar at the REACH Lab at Tufts University in Medford, Massachusetts, and colleagues concluded. The investigators found that many patients “learned about their high vulnerability to COVID-19 from the media, and some expressed that they would have preferred to discuss their heightened risk with clinicians.”

Favorable View of Telemedicine The interviews also revealed a generally favorable view of telemedicine. “As we think about the future, our findings suggest an openness to telemedicine, as participants perceived this form of care to be convenient; it also gave care partners the ability to participate in clinical encounters when in-person care was restricted,” the authors wrote. Clinicians are well positioned to discuss challenging new risks with

Unanswered Questions “I think the most surprising finding was that few clinicians directly discussed how COVID reshaped risks for patients

with CKD, and patients had unanswered questions about COVID and the impacts on their kidney disease,” study investigator Keren Ladin, PhD, MSc, an associate professor at Tufts and director of the REACH Lab, said in an interview with Renal & Urology News. She also observed, “The findings illustrate that patients are generally satisfied with treatment decisions and perceive them to be quite safe, irrespective of whether they selected in-center or a home-based treatment. Undoubtedly, this reflects the tremendous efforts of kidney clinicians to adapt to higher precautions in the clinic and dialysis center, and communication with patients about the efforts in place to keep them safe.” Adapting decision-making and treatment recommendations to reflect new understanding of COVID-19-related risks offers patients the opportunity to better understand and weigh the risks and benefits, Dr Ladin said.

Clinician consultations with older CKD patients about COVID-19 come up short, study finds.

patients, even under conditions of significant uncertainty and emerging information, she noted. Nephrologists can be more open to recommending home-based modalities, especially when risks of in-center modalities increase. “Although this was true for peritoneal dialysis, clinicians were still hesitant to recommend or discuss conservative management. This offers an important opportunity for improvement, as a balanced description of treatment options, including discussion of risks, benefits, and implications for quality of life is critical to shared decision-making,” Dr Ladin said. Nephrologist Alexander Chang, MD, an assistant professor of clinical research and co-director of the Kidney Health Research Institute at Geisinger Medical Center in Danville, Pennsylvania, said his team has been discussing these issues at length over the past year. “I’ve noticed myself that the pandemic was an effective way to introduce the topic of home dialysis modalities to my patients, with some success in getting them to consider home modalities as the first option if possible,” Dr Chang said. He said he agrees that the pandemic may have encouraged clinicians and patients to think more about home dialysis modalities, but the true impact remains unclear. “The burnout issue and the ‘great resignation’ with staffing challenges may have also limited the ability of providers in getting patients on home dialysis, as that requires experienced dialysis nurses available to educate and train patients as well as availability of surgeons familiar with peritoneal dialysis and operating room time during the pandemic,” Dr Chang said. Panduranga Rao, MBBS, Richard D Swartz Collegiate Professor of Nephrology at the University of Michigan in Ann Arbor, said he predicts an increase in the use of home dialysis, perhaps peritoneal dialysis more so than home hemodialysis, in coming years due to a confluence of factors. “We could be seeing a new era in home dialysis, especially given the innovations in dialysis hardware which would make it more appealing, less intimidating and less burdensome even to the elderly patient,” Dr Rao said. ■

Black and Hispanic patients found to have less access to kidney transplantation. Among 41,485 adults aged 30 years or older with ADPKD in the 20002018 US Renal Data System, 77% were White, 13% were Black, and 10% were Hispanic. Black and Hispanic patients experienced kidney failure at significantly younger ages than White patients (55 and 53 years vs 57 years), Dr McGill’s team reported. Yet, in adjusted analyses, Black and Hispanic patients had significant 67% and 50% decreased odds of preemptive kidney transplantation and 39% and 22% decreased odds of transplantation after dialysis initiation, respectively, compared with White patients. Living donor transplants occurred in just 7% and 15% of Black and Hispanic patients compared with 27% of White patients. Results showed 20% and 22% of Black and Hispanic patients were placed on a transplant waiting list prior to kidney failure, respectively, compared with 38% of White patients. The median time from waitlisting to transplantation was 28 and 24 months for Black and Hispanic patients, respectively, compared with 15 months for White patients. Nephrology care prior to kidney failure, private insurance, employment, and higher income increased the odds of both preemptive transplantation and transplantation after dialysis initiation, the investigators reported. ■

16 Renal & Urology News

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Protocol Biopsies for Low-Risk KTRs at 1 Year May Be Unjustified T-cell-mediated rejection detected in only a small fraction of patients

Second Bx in LN More Revealing IN PATIENTS WITH lupus nephritis

NEW DATA SHOW a low likelihood of borderline and T-cell-mediated rejection (TCMR) in 1-year protocol kidney graft biopsies in stable low-risk kidney transplant recipients (KTRs) without proteinuria, donor-specific HLA antibodies (DSA), or acute rejection, investigators reported at the 2022 American Transplant Congress in Boston. Among 1601 non-HLA-sensitized KTRs with a protocol biopsy at 1 year in the national transplant centers of Finland and Norway during 2004-2017, subclinical acute TCMR (Banff i2t2v0 or higher) occurred in 2.0% of patients and borderline TCMR or higher (Banff i1t1 or higher) occurred in 12%. Among 1018 KTRs with no history of acute rejection, proteinuria, or DSA, and adequate graft function at 1 year (serum creatinine less than 150 µmol/L or 1.7 mg/dL), TCMR was detected in only 0.1% and subclinical TCMR or higher in only 5.1% at 1 year, Ilkka Helanterä, MD, PhD, of Helsinki University Hospital in Finland, reported on behalf of his team. In contrast, among the 116 patients with de novo DSA, subclinical TCMR occurred in 9.5% and borderline

TCMR or higher in 34%. Half of patients with de novo DSA experienced a previous acute rejection. Among all 355 patients with acute rejection within the first year (prior to the protocol biopsy), TCMR occurred in 7.9% and borderline TCMR or higher in 32%.

Study included 1601 KTRs who had 1-year protocol biopsies in Finland and Norway. Among the 115 patients with proteinuria of more than 10 mg/dL, TCMR occurred in 4.3% and borderline TCMR or higher in 22%. Among 248 patients with suboptimal graft function (serum creatinine exceeding 1.7 mg/dL), TCMR occurred in 3.6% and borderline TCMR or higher in 20%. “Whether the detected incidence of TCMR (including borderline) justifies taking protocol biopsies in all patients, or only in targeted patients, has to be evaluated based on local practices and

circumstances,” Dr Helanterä said in an interview. A recent study published in the American Journal of Transplantation (2022;22:761-771) found that even borderline TCMR correlates with graft loss. Following a first TCMR event, persistent or subsequent TCMR events later occurred in at least half of recipients. Dr Helanterä said he believes transplant centers should have standard practices to deal with TCMR findings in the biopsies. An optimal treatment regimen for TCMR has yet to be defined. In a recent systematic review and meta-analysis, also published in the American Journal of Transplantation (2022;22:772-785), Julie Ho, MD, of the University of Manitoba in Winnipeg, Canada, and colleagues found that TCMR treatment varied. “While pulse steroids and enhanced maintenance immunosuppression are mainstays of TCMR therapy, the low observed histological response rates and known complications of high dose glucocorticoids suggest that improved TCMR management strategies and RCTs evaluating novel drugs for TCMR treatment are urgently required,” Dr Ho’s team wrote. ■

(LN), findings from a second vs first kidney biopsy better predict the risk for end-stage kidney disease (ESKD), investigators reported in Lupus Science & Medicine. Andrea Doria, MD, of the University of Padua in Padova, Italy, and colleagues compared first and second biopsy findings from 92 patients with lupus nephritis. Clinicians ordered a second kidney biopsy after patients experienced nephritic flares (30.4%), proteinuric flares (50%), or lack of complete renal response to therapy (19.5%). The times between the first and second biopsies were 5.1, 4.6, and 4.1 years for the nephritic flare, proteinuric flare, and poor renal response groups, respectively. Half of patients had a switch in LN class at the second biopsy, typically from non-proliferative to proliferative classes. Class IV disease remained stable in over 50% of cases. ESKD developed in 25 patients (27.2%), including 60.7% of the nephritic flare group. At second biopsy, the nephritic flare group had significantly lower estimated glomerular filtration rate, significantly higher

Deceased-Donor Kidneys Useful Despite Longer CIT

serum creatinine, and more class IV

RECIPIENTS OF carefully selected deceased-donor kidneys with a cold ischemia time (CIT) of 36 hours or longer do not have worse transplant outcomes compared with those who receive kidneys with a shorter CIT, according to study findings presented at the 2022 American Transplant Congress in Boston, Massachusetts. Consequently, investigators concluded, transplantation of kidneys with a CIT of 36 hours or more should be considered by regional centers in places with limited direct national flights, a factor that can increase organ transport time. “The changes in kidney allocation have increased the logistical complexity of getting the grafts into patients,” lead investigator Lyle J. Burdine, MD, PhD, a transplant surgeon at the University of Arkansas for Medical Sciences in Little Rock, said in an interview with Renal & Urology News. The result has been

2 or more, chronicity index greater

an increase in the number of donor kidneys with prolonged CIT arriving at his transplant center. The finding that a CIT of 36 hours or more does not adversely affect transplant outcomes could expand the pool of acceptable kidneys to offer patients and potentially shortens the waiting time for a transplant. A kidney transplant would free patients from dialysis, improve their lives, and enable them to return to work, an important consideration given the very limited financial and health care resources of the patient population that his center serves, Dr Burdine noted. Dr Burdine and colleagues conducted a retrospective study of 117 kidney transplant recipients who received deceased-donor kidneys from 2018 to 2020. The investigators divided patients according to the CIT of the kidneys they received: 30-35.99 and

36+ hours. Each group had 54 patients. Mean creatinine levels at 12 months — the study’s primary endpoint — did not differ significantly between the groups (2.07 and 1.78 mg/dL in the CIT 30-35.99 and 36+ groups, respectively), the investigators reported in a poster presentation. Both groups had similar rates of rejection, consistent with previously published rates for kidney transplantation, they noted. Results also revealed that patients who received immunosuppression with calcineurin inhibitors had significantly lower creatinine levels at 12 months compared with those who did not (1.69 vs 2.96 mg/dL). On multivariable analysis, the investigators found no association between CIT and creatinine at 12 months when controlling for possible impactful predictors, such as age, kidney donor profile index, and BK virus status. ■

disease than the other 2 groups. At second biopsy, activity index of than 4, and 24-hour proteinuria level of 3.5 g/d or more significantly predicted a 20%, 41%, and 22% increased risk for ESKD, respectively, Dr Doria’s team reported. The investigators found that glomerular activity and tubular chronicity correlated the most with ESKD risk. No histologic or laboratory results from the first biopsy predicted ESKD, although arterial hypertension did. “Because an increased [activity index] at second biopsy signified an increased risk in ESKD, this highlights the importance of performing a second kidney biopsy in patients with suboptimal/no response or flaring LN as a tool for long-term risk stratification, regardless of LN class [change],” Dr Doria’s team wrote. ■

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r elatively low uptake of pre-biopsy MRI during our study period and there was insufficient data to support a significant effect of biomarkers or increased incidence of risk factors of high-grade [prostate cancer] such as obesity,”

Dr Borregales and colleagues noted in a study abstract. “Further research is needed to examine the downstream effects of these changes in [prostate cancer]-specific mortality.” In an interview, senior investigator Jim C. Hu, MD, MPH, of NewYorkPresbyterian’s Lefrak Center for Robotic Surgery, agreed that the USPSTF 2012 recommendations are “obsolete.” He said the challenge with the current grade C USPSTF recommendation of individualized choice for PSA testing at ages 55 to 69 years is that it is based on age criteria from the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial. “Currently, we don’t have level 1 guidance for PSA screening in younger men, Black men, and those with a significant family history of prostate cancer,” he said. As for advice to urologists, Dr Hu said, “Men should have a baseline PSA test in their 40s to determine the future frequency of PSA testing based on [individual] risk stratification.” ■

In addition, the investigators observed a 2.2-fold increased risk of death among men with frequent urgency incontinence. This particularly strong association suggests that urinary urgency has a significant impact on health and functional status in aging men, possibly reflecting the effects of long-term neurologic and vascular disease, they explained. “While the association between LUTS and mortality is largely explained by the comorbidities in men with LUTS, the fact that the association remained even after adjustment for age and comorbidity shows that other, currently unidentified factors increasing the risk of death are also involved,” the authors wrote. In a discussion of study limitations, the investigators noted that there were no bladder diaries, so they were unable

to further characterize the association between urinary frequency and mortality and whether daytime frequency and nocturia were due to global/nocturnal polyuria or possibly reduced bladder capacity or even caused by a mixed etiology. Short-term studies suggest treatment of male LUTS improves quality of life, but there are no randomized trials that have examined the impact of treating LUTS on morbidity or mortality, according to the investigators. The roles of daytime frequency and nocturia as mortality risk factors independent of symptom severity indicates they may be useful markers. Studies such as these “highlight the importance of managing LUTS, and also to facilitate studies to understand the underlying process, which can lead to improved strategy for treating

LUTS,” Amy Zhang, PhD, an associate professor in the department of urology at Case Western Reserve University in Cleveland, Ohio. “There are best practice guidelines for treatment, but treatment may or may not be effective and patients may or may not continue treatment. So, management of LUTS is not optimal.” “The association of even moderate symptoms with mortality is a little surprising,” said Yair Lotan, MD, professor and chair of urology at the University of Texas Southwestern Medical Center at Dallas, Texas, who was not part of the current study. “What is not clear is whether treating these symptoms will reduce mortality.” He pointed out, however, that the study was conducted in Finland so the findings are not necessarily a reflection of US practices. ■

avoidance or decrease in time under anesthesia and catheterization time.” Physician-driven incentives may include reimbursement practices, marketing of PUL technology to providers, and ease of use in office practice, such as diminished anesthesia costs without routine post-procedure hospital admission, Dr Thorogood said. These incentives may explain why the odds of performing PUL are higher among group private practice urologists compared with academic urologists. Dr Thorogood and colleagues identified 4131 urologists who p erformed

48,610 surgeries for BPH from 2015 to 2021. They also identified 786 urologists who performed 7895 PUL procedures, including 24 who performed only PUL procedures, and 3345 who did not use PUL. In adjusted analyses, andrology subspecialization was significantly associated with 4.0-fold increased odds of performing PUL procedures compared with general urology practice, Dr Thorogood reported. Compared with urologists in academic facilities, those in private practice groups had significant 2.7-fold increased odds of

using PUL. Each per-case increase in BPH surgical volume was significantly associated with 2% increased odds of performing PUL procedures. Urologists practicing in an area with a population higher than 1 million had significant 55% increased odds of performing PUL procedures compared with those practicing in areas with a population less than 100,000, according to the investigators. Endourology subspecialization was significantly associated with 60% lower odds of performing the procedures compared with general practice. ■

Albuminuria Is Associated With Increased Cancer Risk ALBUMINURIA MAY INCREASE the

eGFR, Ronald Gansevoort, MD, PhD,

risks for cancer, independent of kidney

of the University of Groningen in The

function, investigators reported at the

Netherlands, and colleagues reported. In

European Renal Association’s 59th

addition, each doubling of UAE was inde-

Congress held in Paris, France, and

pendently associated with a significant

virtually.

13% increased risk for both urothelial cell

Among 8490 Dutch adults in the

carcinoma and lung cancer, and a signifi-

Prevention of Renal and Vascular End-

cant 29% increased risk for head and

Stage Disease (PREVEND) study, de

neck cancer. The investigators found

novo cancer developed in 1789 over a

no relationship between UAE and mela-

median follow-up of 17.7 years. At base-

noma or breast, prostate, and colorectal

line, median urinary albumin excretion

cancers. They noted that patients with

(UAE) was 9.4 mg/24 h and estimated

higher UAE were more likely to be older

glomerular filtration rate (eGFR) was

and male and to have hypertension,

94.6 mL/min/1.73 m based on the 2012

diabetes, and lower eGFR.

CKD-EPI creatinine-cystatin C equation.

Although previous studies have found

In an age- and sex-adjusted model,

links between moderate to severe CKD

each doubling of UAE was significantly

and cancer risk, this study extends the

associated with a 7% increased risk for

association to patients with mild CKD

cancer overall that was unaffected by

defined by albuminuria only. ■

Male LUTS continued from page 1

surveys in 1999, 2004, 2009, and 2015. A subset of 1167 men were followed through 2018. Over the 24-year period, 591 (50.6%) of men in the subset died. Men with moderate or severe voiding LUTS had a 1.2-fold increased risk of death and those with storage LUTS had a 1.4-fold higher risk. Men with daytime frequency and those with nocturia had a 1.3- and 1.5-fold increased risk for death independent of symptom severity. “This suggests considering daytime voiding interval of 3 hours or less and any nighttime voiding as patient-important especially when appearing as persistent symptoms,” the authors wrote.

PUL use increasing continued from page 1

Urological Association] with its utility limited to prostates under 80 grams without significant median lobe hypertrophy in men who particularly desire ejaculation preservation, the rapid adoption of PUL demonstrated in this study is likely in part influenced by other incentives,” Dr Thorogood told Renal & Urology News. “Patientdriven incentives may include directto consumer marketing and increased visibility of PUL technology as well as

Higher-grade PCa rising continued from page 1

In this cohort, the median PSA at diagnosis significantly increased from 6.2 to 7.1 ng/mL. Use of magnetic resonance imaging (MRI) and biomarkers increased from 7.2% in 2012 to 17% in 2019 and 1.3% in 2012 to 13% in 2019, respectively. “Changes in screening practices are the best primary explanation for the grade shift observed, as there was

Changes in screening practices offered as an explanation for the observed trend.

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Late Relapse Rare in Testicular Cancer Only 0.5% of men with clinical stage I disease experience relapse after 10 years, data show LATE RELAPSE (LR) of testicular cancer is rare, especially more than 5 years after treatment, according to the findings of a population-based study presented at the 2022 ASCO Annual Meeting. In addition, the study showed a decrease in LR rates and mortality over a nearly 3-decade period among patients with metastatic disease initially treated with chemotherapy. “We believe centralization of treatment, adherence to guidelines, and continuous evaluation of results are key to these improved outcomes,” lead investigator Torgrim Tandstad, MD, PhD, of St Olav’s University Hospital in Trondheim, Norway, said during the meeting. Using the Cancer Registry of Norway and Norwegian Cause of Death Registry, Dr Tandstad and colleagues identified 5712 patients diagnosed with testicular cancer from 1980 to 2009 (2978 seminoma and 2734 nonseminoma).

Recurrent MN Common After KT MEMBRANOUS nephropathy (MN) recurs after kidney transplantation in nearly a third of patients with a history of MN but it does not reduce graft survival, investigators reported at the 2022 American Transplant Congress meeting. Leonardo V. Riella, MD, PhD, of Harvard Medical School and Massachusetts General Hospital in Boston, Massachusetts, and colleagues identified 188 kidney transplant recipients (KTRs) with a history of MN from 16 transplant centers in The Post-Transplant Glomerular Disease (TANGO) Consortium. The median time from MN diagnosis in the native kidney to end-stage kidney disease was 86 months. Of the 188 KTRs, 40 experienced recurrent MN in the kidney graft based on biopsy findings. MN recurred in 30% of patients within 10 years of transplantation with a median time to recurrence of 4.9 years. The investigators found that the risk for graft loss did not differ significantly between KTRs with and without MN recurrence.

Men who had late relapse of clinical stage I disease had a 10-year OS rate of 76.8%.

The investigators divided patients into 2 cohorts based on when they were diagnosed: 1980-1994 (2207 patients) and 1995-2009 (3505 patients). The team defined LR as relapse occurring

“When effective therapy is administered, disease recurrence does not appear to correlate with worse kidney transplant survival,” Dr Riella explained. He recommends that transplant physicians perform a biopsy in cases of suspected MN recurrence. Treatment for recurrent MN involved additional renin-angiotensin-aldosterone system (RAAS) blockade in 73% of patients. Among a subset of patients who received B-cell depletion therapy, 60% achieved complete or partial remission. Only 38% of those who did not receive supplemental B-cell depletion therapy experienced remission. Dr Riella recommended that RAAS blockade be prescribed to all patients with posttransplant MN with careful monitoring of kidney function and potassium levels upon initiation. He also advocated rituximab prescription for all patients because in MN pathogenesis autoantibodies form against podocyte antigens. According to Dr Riella, rituximab leads to complete or partial remission in most patients with recurrent MN. “Early disease recognition is critical to prevent long-term damage to the kidney transplanted organ,” he said. PLA2R antibody titers correlate with MN disease activity, so Dr Riella and colleagues recommend routine testing for PLA2R antibody level titers before and after transplant. ■

more than 2 years after treatment. They also examined the rates of very late lapse (VLR) and extremely late relapse (XLR) — occurring more than 5 years and more than 10 years after treatment, respectively. Of 472 patients who had a relapse, 63% experienced it within 2 years after treatment. LR occurred at a median of 4.7 years after treatment. LR, VLR, and XLR occurred in 23%, 10.5%, and 3.5% of patients, the investigators reported.Among 3999 patients with clinical stage I disease, LR, VLR, and XLR occurred in 1.9%, 1.0%, and 0.5% of patients, respectively. Of the 61 patients with LR, 8 died, 4 from testicular cancer or its treatment. The 10-year overall survival (OS) and cancer-specific survival (CSS) rates were 76.8% and 81.4%, respectively. Dr Tandstad said the relatively low rate of relapse in clinical stage I disease

in Norway corresponds to extensive use of adjuvant treatment for seminal and nonseminal cancers. Among 1713 patients with metastatic disease, LR, VLR, and XLR occurred in 3.6%, 1.6%, and 0.8% of patients, respectively. Of the 48 patients with LR, 24 died, 17 from testicular cancer or its treatment. For patients with metastatic disease initially treated with chemotherapy, the 10-year OS rate following LR was 49.7% for those diagnosed in 19802009, according to the investigators. The 10-year OS rate increased over time, from 34.6% for those diagnosed in 1980-1994 to 60.9% for those diagnosed in 1995-2009. The investigators observed a similar pattern for CSS. The 10-year CSS rate increased from 38.6% for those diagnosed in 1980-2009 to 64.6% for those diagnosed in 1995-2009. ■

Allopurinol May Prevent Contrast Nephropathy in CKD Patients ADMINISTERING the uric-acid lower-

60 mL/min/1.73 m2 and were sched-

ing drug allopurinol before contrast

uled to undergo coronary intervention.

medium exposure may reduce the

Contrast nephropathy, a serum

risk for contrast nephropathy in

creatinine rise of more than 25% (or

patients with chronic kidney dis-

more than 0.05 mg/dL) from baseline

ease. Investigators presented early

at 48 hours after contrast exposure,

trial results at the European Renal

occurred in a significantly lower propor-

Association’s 59th Congress held in

tion of the allopurinol than no allopurinol

Paris, France, and virtually.

group (5.3% vs 21.1%). In a subgroup

“Allopurinol may be a potential agent

analysis of patients who had elevated

for nephrologists treating patients with

serum uric acid levels at baseline,

CKD stage 3 and higher who need to

allopurinol recipients had a significantly

undergo contrast studies,” first author

lower rate of contrast nephropathy than

Muhammad Sajid Rafiq Abbasi, MBBS,

nonrecipients (11.1% vs 71.4%), accord-

of PAF Hospital in Islamabad, Pakistan,

ing to the investigators. The addition of

said in an interview. “Allopurinol was

allopurinol, a xanthine oxidase inhibitor,

more effective in the group with high

was significantly better at reducing

uric levels.”

contrast nephropathy risk than saline

Dr Abbasi and colleagues randomly

hydration alone among patients with

assigned 76 adults to saline hydration

elevated serum uric acid, Dr Abbasi’s

(0.5 mL/kg/h for 12 hours before and

team reported.

after contrast) with or without a single

The contrast nephropathy rate did

oral dose of 300 mg allopurinol at

not differ significantly for patients with

12 hours before contrast exposure.

normal serum uric acid levels. Contrast

All patients had an estimated glomeru-

dose and contrast volume were compa-

lar filtration rate (eGFR) less than

rable between groups. ■

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Digital Divide May Impede Telehealth Many individuals lack access to internet-connected devices and skill in using digital platforms BY JOHN SCHIESZER FOR PATIENTS TO participate in telehealth encounters, they have to use a number of proprietary health system specific portals and platforms. That can be challenging for many older adults and minority groups. Effective virtual care depends on digital fluency, meaning they need to be able to engage in all aspects of digital technologies, from accessing the internet to navigating telehealth applications and performing basic troubleshooting. Many people cannot do this, creating significant barriers to care for a large segment of the population. Researchers say the technology has the potential to reduce health disparities, but it also is exacerbating structural inequities. “Telehealth is here to stay, and has the potential to actually improve care outcomes, enhance the patient experience, reduce costs, and address health care inequities,” said Rebecca G. Mishuris, MD, MPH, an assistant professor of medicine at Boston University School of Medicine and Chief Medical Information Officer of the Boston Medical Center Health System in Massachusetts. “This, of course, will only be realized if we can address equity in engagement with telehealth, and fully

Unfamiliarity with digital technology often prevents people from using telehealth.

incorporate it into a holistic care delivery model that employs both virtual and in-person care.” Prior to the COVID-19 pandemic, telehealth was hampered by a lack of reimbursement and liability concerns. Those barriers, however, have largely come down. Dr Mishuris and colleagues conducted a study in which all patients scheduling appointments were asked: Do you have a smartphone or computer with a camera and microphone? Is that device connected to the internet? The answers to these

uestions and follow-up interviews sugq gested some worrying trends. At her institution, which is a safety net hospital, 21% of Black/African American patients, 20% of Hispanic/ Latino patients, and 22% of White patients reported lacking access to a connected device with a camera or microphone. The study, published in the Journal of General Internal Medicine, also showed that 67% of White patients opted to schedule their telehealth visits by video compared with only 60% of Black and Latino patients. To overcome the barriers of device and broadband access, digital fluency, and health advocacy, she and her colleagues propose a multi-pronged approach of creating federal and state policies to democratize access to telehealth. Important first steps include establishing platform standards for accessing telehealth as well as supporting societal and health system investments to increase health literacy, advocacy and technology fluency. “We found that our patients in the safety net engage with telehealth, but there is inequity in the channels through which they engage by race and language,” Dr Mishuris said. “More

must be done to address digital access, digital literacy, and health advocacy through telehealth. As clinicians in the safety net, none of this was surprising to us, but we suspect it may surprise those who do not work in the safety net.” Telehealth equity cannot be the sole responsibility of health care institutions, Dr Mishuris said. Public policy, regulations, and other sectors of the economy may need to come together to ensure equitable digital engagement. “For the individual physician or practice, it is crucial to ensure that telehealth is offered equitably, on a platform that perpetuates equity, such as interpreter services and bandwidth variability,” she said. Yalini Senathirajah, PhD, of the Department of Biomedical Informatics at the University of Pittsburgh in Pennsylvania, said broadband access is a major determinant of telehealth use and only 43% of households have it. Patient experience may vary greatly for different patients, and patients themselves can have preferences around what technologies they want to use. Some patients may not want to have video calls because they are shy about the doctor seeing their living conditions, not because of a lack of access, Dr Senathirajah said. ■

RECENT REPORTS describing the transplantation of pig kidneys into humans suggest the potential feasibility of this approach. In the New England Journal of Medicine, a team from the NYU Langone Transplant Institute published results from 2 cases of transplanted kidneys from genetically modified pigs into brain-dead human recipients. The xenografts produced urine immediately after reperfusion, Robert A. Montgomery, MD, DPhil, and colleagues reported.

No Hyperacute Rejection Over 54 hours, estimated glomerular filtration rate (in mL/min/1.73 m2) increased from 23 to 62 in recipient 1 and from 55 to 109 in recipient 2. Serum creatinine level decreased from 1.97 to 0.82 mg/dL in recipient 1 and from 1.10 to 0.57 mg/dL in recipient 2. The transplanted kidneys were

ell-perfused with no signs of hyperw acute or antibody-mediated rejection in samples from biopsies performed at 6, 24, 48, and 54 hours, Dr Montgomery’s team reported. They did, however, observe early, focal C4d deposition. The pigs were bred with deletion of the alpha-1,3-galactosyltransferase gene (GGTA1) and with subcapsular autologous thymic tissue. “Our study of two successful renal xenotransplantations is reassuring in that, with the use of organs from alpha1,3-galactosyltransferase–knockout pigs with a negative or low positive cytotoxic xeno-crossmatch, the risk of hyperacute rejection was low and immediate catastrophic failure was unlikely,” Dr Montgomery’s team wrote.

The UAB Experience The new report follows publication earlier this year in the American Journal of Transplantation in which a team from the

University of Alabama at Birmingham (UAB) described their experience with transplanting 2 kidneys from a genetically modified pig into a brain-dead recipient. The kidneys remained viable until they were removed at 74 hours, but they did not achieve normal function, lead investigator Jayme E. Locke,

Investigators report encouraging results with the use of brain-dead recipients. MD, MPH, and colleagues reported. The kidneys produced variable amounts of urine, but creatinine clearance did not recover, the authors reported. The investigators observed no hyperacute rejection, but biopsies revealed thrombotic microangiopathy without

cellular rejection or deposition of antibody or complement proteins. Vascular integrity of the graft was maintained, despite the higher mean arterial pressure of humans compared with pigs. In all cases, recipients were treated with immunosuppression. The pig they used was genetically modified with deletion of 3 pig carbohydrate antigens (GGTA1, β4GALNT2, CMAH) and the pig growth hormone receptor gene. Human genes were inserted, including 2 human complement inhibitor genes, 2 human anticoagulant genes, and 2 immunomodulatory genes. The pig did not express red blood cell antigens and was considered a universal blood donor. “Our results add significantly to the prior knowledge generated in nonhuman primate models and suggest that many barriers to xenotransplantation in humans have indeed been surmounted,” the investigators wrote. ■

Pig-to-Human Kidney Transplantation Advances

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Ethical Issues in Medicine H

alfway through a hectic clinic afternoon, a patient well-known to you reports as an aside that she has been occasionally using cocaine when she goes out on the weekends to relieve stress from busy work and family life. After the visit, the medical student shadowing you wonders if you were obligated to notify the police about her illicit drug use or alert child protective services because she parents 3 school-aged children. Conflicts over protecting confidentiality and complying with legal obligations are common in clinical care. Protecting patients’ right to confidential care by keeping their medical information private is a central obligation of health care professionals. Physicians can take better care of patients when patients feel comfortable divulging information knowing that it won’t be shared or released without their consent. If patients are not comfortable sharing relevant medical information, the quality of health information that is shared with physicians will decline along with the quality of care patients’ receive.

Legitimate needs of the public Although patient confidentiality is central to high-quality medical practice, it is not without some ethically acceptable, well-defined limits. For example, when

significant public health considerations exist, patient primacy may be subsumed by physicians’ obligation to address the legitimate needs of the public. If failing to divulge a patient’s otherwise confidential information could result in a significant risk for serious imminent harm to a third party, and that harm can be mitigated by releasing that information, then violating confidentiality may be an ethically justifiable course. For example, when a patient with infectious tuberculosis (TB) refuses both antibiotic medication and isolation while infectious, a physician is often able to violate the patient’s confidentiality by notifying the local health department (often in concert with their institutions’ legal counsel and privacy experts). In this case, the health department is empowered by the state to use that patient information to mitigate the risk to the public from an actively infectious individual with the potential to spread a serious illness. The key ethical features of this scenario are that the patient posed a serious, imminent risk to the public and that violating confidentiality by notifying a specific entity (in this case the health department) was expected to mitigate the risk. In other words, violating confidentiality is justifiable when failing to do so will result in harm and doing

Under some circumstances, physicians are legally required to share relevant patient information with health departments and law enforcement. there is a clear public health interest that conflicts with keeping patient information confidential, physicians may have competing obligations to their patient and the public. In general, the practice of medicine defaults to patient primacy, that is, keeping the patient’s interest at the center of medical decision-making. Patients expect that physicians will be making decisions that represent their best interest, and not necessarily that of society of a third party. When

so provides a clear proportional benefit. This is in stark contrast to a patient with latent TB who would benefit from treatment but is not a public health risk currently. Violating this patient’s confidentiality would not be justified as there is not serious imminent risk to the public.

Divulge the minimum A related principle is that the even while violating a patient’s confidentiality may be justifiable under certain

Patient confidentiality is a bedrock principle in the practice of medicine but breaches are sometimes justified and required BY DAVID J. ALFANDRE, MD, MSPH

Public health concerns sometimes warrant breaches of patient confidentiality.

conditions, only the minimum amount of information necessary to mitigate the threat should be divulged. So the patient with infectious TB does not necessarily need her HIV status or other unrelated medical or psychiatric information revealed to mitigate the threat to the public.

The importance of patient trust Regarding the case described at the outset, how should the physician respond to the medical student’s question? First, the student should be reminded that health care professionals are privileged to be entrusted with protecting patient’s health information. Only special circumstances would provide an ethically justifiable exception to that default position. The patient has trusted the physician with information about her drug use because she expects that it will be kept private, but also because she understands and expects that the role of the physician is to help her, not police her behavior. Were the physician to report the patient’s drug use to the police or anyone else without her consent, the patient may lose trust not just in that physician, but in future health care providers and even the health care system in general. The physician would then ask the medical student if the patient’s reported

drug use is posing a serious imminent risk to the health or safety of the public for which the police or other authority should be alerted. Is there evidence that her drug use is posing a significant risk to her children that might constitute neglect or endangerment? Answering these questions may require the physician to ask the patient more about her drug use and whether it indeed poses risks to her children. But barring such a risk, the physician would not be obligated (and indeed is likely prohibited) from sharing that information outside of the treatment relationship without the patient’s consent. Rather, the physician should ask the patient about her willingness for drug treatment and how her health care team can be of service. Protecting patient’s confidentiality comes first, which often allows the other elements of her care to fall into place. ■ 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.

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Practice Management I

t may be time for physicians to conduct yearly medication reviews with their patients aged 65 years or older to collaboratively assess whether the benefits of each of their medications outweighs the harms, according to Michelle S. Keller, PhD, MPH, assistant professor of medicine at Cedars-Sinai Medical Center in Los Angeles, California. Research shows that the prevalence of inappropriate polypharmacy is increasing, with the pandemic possibly adding to the problem. Inappropriate polypharmacy is at the root of a high percentage of emergency room visits by older adults due to adverse drug events. Inappropriate polypharmacy is the use of more medications than medically necessary or the use of multiple drugs that can cause harmful interactions. Patients aged 65 years or older commonly have multiple comorbidities and are under the care of a variety of clinicians. A clinician may prescribe a new drug without being aware of other drugs a patient is taking. Older adults can be especially prone to harm from inappropriate polypharmacy because of changes in how they metabolize and excrete drugs. Physicians need to engage patients in thorough discussions about the prescription medications

can have important clinical benefit, it is really critical that physicians assess regularly which medications are still helpful depending on an individual’s life expectancy, comorbid conditions, and overall medication regimen.” Geriatrician John Morley, MD, of Saint Louis University in Missouri, said it appears the pandemic has only added to the problem. “The reality is that people with COVID pain have a whole series of side effects. They are given drugs and doctors forget to stop the drugs,” Dr Morley said. Currently, the biggest concern is with anticholinergic drugs. Anticholinergics, which have been linked to dementia, are prescribed for many conditions common in older adults, such as depression, urinary incontinence, irritable bowel syndrome, and Parkinson’s disease. Further, many OTC sleep aids and allergy medicines contain anticholinergic agents. Belinda Vicioso, MD, a professor of geriatric medicine at UT Southwestern Medical Center in Dallas, Texas, said inappropriate polypharmacy continues to increase unabated for several reasons. “With the advent of direct-to-consumer advertising, shortened face-toface visits, and disjointed subspecialty care that is often not patient centered,

Older adults are particularly vulnerable because they often have multiple medical problems and see a variety of specialists. and over-the-counter (OTC) products, including dietary supplements and minerals, they are taking.

Psychotropic drugs Various factors are contributing to a rising incidence of inappropriate polypharmacy. “It is due to increased use of psychotropic medications such as benzodiazepines, antidepressants, and opioids, and the increased use of preventive medications such as statins,” Dr Keller said. “While all of these medications

polypharmacy is more common than ever,” Dr Vicioso said. Caroline Harada, MD, an associate professor in the Division of Gerontology, Geriatrics, and Palliative Care in the University of Alabama at Birmingham Marnix E. Heersink School of Medicine, said it is crucial to involve the patient in all conversations about polypharmacy, something that has traditionally not been done. “As a geriatrician, by far the most helpful thing I do for patients is review their medication lists

Doctors and other health care professionals need to address a growing problem with inappropriate polypharmacy BY JOHN SCHIESZER

Clinicians might prescribe a new drug without knowing about other drugs a patient is taking.

and start a conversation with my patient about which medications may be doing more harm than good,” Dr Harada said. “There are times when we have ‘cured’ a patient’s cognitive impairment or tendency to fall simply by stopping harmful medications such as benzodiazepines, anticholinergics, and opioids.”

Movement toward deprescribing There is a growing movement toward deprescribing to combat inappropriate polypharmacy. Deprescribing is a thoughtful and collaborative process of stopping or reducing the dose of a medication, Dr Keller said. The goal is to make sure that all of a patient’s drugs are medically appropriate and the patient is not taking one medication to combat the effects of another. “We use this term intentionally because in recent years we’ve seen physicians abruptly stop medications such as opioids, which has led to severe withdrawal effects and adverse outcomes such as increased suicides,” Dr Keller said. “Deprescribing should always include a conversation between the patient and the clinician to discuss the reasons for deprescribing and the process of slowly stopping or reducing the medication.”

Deprescribing takes work, thought, and collaboration with patients and families, but it is a worthwhile undertaking, Dr Vicioso said. Dementia symptoms often improve and patients become more mobile, he added. At Dr Keller’s institution, staff are working on various research projects in the inpatient and outpatient settings to help clinicians identify patients at highest risk for polypharmacy-related events to implement new deprescribing programs. One project involves sending educational materials about benzodiazepines to patients at elevated risk of benzodiazepine-related adverse events and letters from patients’ primary care provider urging patients to make an appointment to discuss these medications. “Through this simple intervention, we found that 35% of patients were eventually able to stop taking their benzodiazepines completely,” Dr Keller said. “We’re working on publishing these results and are also expanding the project. We recently mailed these education pamphlets and letters to more than 300 patients.” ■ John Schieszer is a freelance medical writer based in Seattle, Washington.

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