M A R C H /A P R I L 2 0 2 1
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VOLUME 20, ISSUE NUMBER 2
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MRI Shows Promise for PCa Screening
© SIMON FRASER / SCIENCE SOURCE
Short noncontrast MRI may offer a better balance between the potential benefits and harms of screening
PROSTATE MRI COULD HAVE a role in community-based prostate cancer screening.
Post-RC Surveillance Crucial BY NATASHA PERSAUD NEW STUDY FINDINGS support the use of routine post-radical cystectomy (RC) surveillance for asymptomatic recurrence of muscle-invasive bladder cancer, which is associated with better cancer-specific and overall survival compared with symptomatic recurrence, according to data presented at the virtual 2021 Genitourinary Cancers Symposium. Of 3822 patients who underwent RC from 1980-2018, 1100 experienced bladder cancer recurrence over a median 2.4 years. Of these, 789 (71.7%) had symptomatic recurrence and presented with pain (70.2%), constitutional symptoms such as fever or weight loss (50.7%), gastrointestinal symptoms (23.3%), and/or
urinary symptoms (23.3%). Another 311 patients (28.3%) had no symptoms and cancer recurrence was detected only during surveillance. Recurrence was significantly delayed for patients with asymptomatic rather than symptomatic recurrence: median 13.2 vs 10.8 months, Abhinav Khanna, MD, MPH, and collaborators from the Mayo Clinic in Rochester, Minnesota, reported. During the median 2.4–year followup period, 997 patients died, including 840 from bladder cancer. According to the investigators, the group with asymptomatic recurrence had significantly longer cancer-specific survival (median 54.5 vs 27.3 months) and overall survival continued on page 11
BY JODY A. CHARNOW SHORT NONCONTRAST magnetic resonance imaging (MRI) may offer a better approach to community-based prostate cancer (PCa) screening compared with PSA testing alone or ultrasonography, recent study findings suggest. Using a validated 5-point scale of suspicion, with higher scores indicating a greater likelihood of clinically significant cancer, investigators found that prostate MRI using a score of 4-5 to define a positive test result compared with PSA levels of 3 ng/mL or higher alone was associated with more men diagnosed with clinically significant PCa without increasing the number of men advised to undergo prostate biopsy or who are overdiagnosed with clinically insignificant
CTC Count in mHSPC Linked to Death Risk BY JODY A. CHARNOW HIGH BASELINE circulating tumor cell (CTC) counts are strongly associated with inferior progression-free and overall survival in patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), according to real-world data presented at the virtual 2021 Genitourinary Cancers Symposium. Investigators believe their study is the first to demonstrate this association. “Identifying patients who have poor prognosis can help with counseling and enrollment in clinical trials to help improve outcomes,” lead author Umang Swami, MD, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City, told Renal & Urology News. The study included 99 patients with newly diagnosed mHSPC initiating androgen deprivation therapy (ADT). Patients had a mean age of 67 years. At ADT initiation, the 99 patients had continued on page 11
cancer. They found no evidence that ultrasonography (US) would have performed better than PSA testing alone. “The findings of this study indicated that an MRI score of 4 or 5 may provide a better balance between the potential benefits and harms of screening,” David Eldred-Evans, MBBS, of Imperial College London in London, UK, and colleagues wrote in JAMA Oncology. The study included 408 men who underwent screening with noncontrast biparametric MRI (with an acquisition time of approximately 15 minutes), US, and PSA testing. The investigators considered an MRI or US score of 3-5 and a PSA level of 3 ng/mL or higher to be positive test results. A systematic continued on page 11
IN THIS ISSUE 5
Salvage RP outcomes vary by primary PCa treatment
NLR increase found to predict mRCC therapy failure
BPH medications may increase likelihood of heart failure
Kidney stones are associated with increased stroke risk
Q&A: New algorithm addresses cisplatin underuse
AKI due to COVID-19 vs other causes has a worse prognosis
BMD screening for patients with kidney stones may be inadequate Socioeconomics may affect the care that men with prostate cancer receive. PAGE 32
2 Renal & Urology News
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New Model May Predict Post-AKI Pregnancy Issues BY JOHN SCHIESZER INVESTIGATORS HAVE developed a new model to explore alterations in kidney function following acute kidney injury (AKI) in women with the goal of predicting and preventing pregnancy complications, according to a recently published report.
“Studies in pregnant women to fully understand the early pathogenesis of pregnancy-related complications are difficult and severely lacking,” said corresponding author Ellen Gillis, PhD, a postdoctoral fellow at the Medical College of Georgia at Augusta University. “Identification of rodent models that
mirror what we see in pregnant women can serve as useful tools to better explore the changes in renal function early in pregnancy. Now that we have identified this rodent model of pregnancy after renal injury, we can start to study these early time points, which are difficult to capture in pregnant women.”
Many women of childbearing age experience AKI and recover based on usual measures of kidney function, but problems with the mother or baby or both still occur. During pregnancy, maternal circulation must support fetal circulation so cardiac output increases, total body volume increases, and plasma
www.renalandurologynews.com MARCH/APRIL 2021
volume increases, Dr Gillis explained. As a result, the kidneys have an increased load to filter. Plasma volume increases to ensure the high metabolic demands of both baby and mother are met, but the baby actually gets preferential protection, she said. The incidence of AKI has been on the increase, and the COVID-19 pandemic appears to have accelerated the trend. “We know that AKI is common among
hospitalized COVID patients, and we think the COVID-19 pandemic will increase the number of young women with AKI to make pregnancy after AKI a growing problem,” Dr Gillis said. Two previous clinical studies looked at women years out from their AKI episode, with multiple assessments indicating their kidneys had recovered. Yet, the researchers found significant increases in problems with both mother
and baby, including preeclampsia, low birthweight, and miscarriage.1,2 An animal model developed by Dr Gillis and her colleagues, which is described in the Journal of the American Society of Nephrology,3 showed that throughout pregnancy, uterine artery resistance increased, uterine blood flow decreased, and the offspring were born smaller because they were not getting adequate nutrition. “It’s still early in our s tudies
Renal & Urology News 3
to fully understand the magnitude of our findings, but we hope to fill an important gap in the literature with our focus on recovery mechanisms after ischemia reperfusion injury in females and subsequent changes in renal function early in pregnancy,” Dr Gillis said. In this model, pregnancy appeared to induce renal insufficiency, driving up levels of creatinine and urea in the blood. Plasma volume, which should
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AKI pregnancy issues continued from page 3
double, increased some but not sufficiently, Dr Gillis said. It is unknown what the exact mechanism is and why plasma volume increase is insufficient, but it is theorized the kidneys simply cannot handle the volume. The researchers report there is crosstalk between the kidneys, uterus, and placenta
that the previous insult to the kidney appears to change. Ziyad Al-Aly, MD, chief of research and development service at the VA Saint Louis Health Care System in Missouri, who was not involved in the current study, said there are more than 30 million people with COVID in the US and a great proportion are women of child bearing age. “Greater understanding of how COVID and its
attendant consequences will impact long-term health among women of child bearing age and other population groups will be important,” Dr Al-Aly said. “The US has the highest maternal mortality rate among developed countries. This is very disappointing, and we must change that. Upstream drivers of maternal mortality in the US must be identified, and this problem should be tackled.” ■
REFERENCES 1. Tangren JS, Wan MD, Adnan WAH, et al. Risk of preeclampsia and pregnancy complications in women with a history of acute kidney injury. Hypertension. 2018;72:451-459. doi:10.1161/ HYPERTENSIONAHA.118.11161 2. Tangren JS, Powe CE, Ankers E, et al. Pregnancy outcomes after clinical recovery from AKI. J Am Soc Nephrol. 2017;28:1566-1574. doi:10.1681/ ASN.2016070806 3. Gillis EE, Brands MW, Sullivan JC, et al. Adverse maternal and fetal outcomes in a novel experimental model of pregnancy after recovery from renal ischemia-reperfusion injury. J Am Soc Nephrol. 2021;32:375-384. doi:10.181/ASN.2020020127.
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Renal & Urology News 5
SRP Outcomes Vary by Primary PCa Treatment SALVAGE RADICAL prostatectomy (SRP) complication rates and functional outcomes are better after primary focal therapy (FT) than after primary radiation therapy (RT) for prostate cancer, investigators reported in The Journal of Urology. In the study, 95 men had primary FT and 90 men had primary RT (external
beam radiation therapy [EBRT] or brachytherapy) followed by SRP. The Clavien-Dindo I-IV complication rate within 30 days was significantly higher in the RT than FT group: 34% vs 5%, respectively, with 19% vs 1%, respectively, experiencing a Clavien-Dindo III a/b complication, Paul Cathcart,
MBBS, MD, of Guys and St Thomas NHS Foundation Trust in London, UK and colleagues reported. Continence rates at 12 months were significantly higher in the FT than RT group (83% vs 49% pad-free), whereas potency outcomes were similar (14% FT vs 11% RT).
With respect to oncologic outcomes, the RT group was significantly more likely to have a higher positive surgical margin rate than the FT group: 37% vs 13%. Biochemical recurrence rates at 3 years were 35% FT vs 32% RT. In multivariable analysis, the RT group had a significant 64% lower risk of biochemical recurrence than the FT group. The investigators said they believe all men considering SRP after FT should undergo cross-sectional imaging utilizing, for example, prostate-specific membrane antigen positron emission tomography, to exclude micrometastatic disease. “Traditionally SRP has been associated with signiﬁcant functional toxicity,” Dr Cathcart’s team wrote. “However, we demonstrate that the functional outcome of SRP is not universally poor and is dependent on primary prostate cancer treatment. Therefore, we would encourage urologists reviewing men with recurrent prostate cancer after FT to consider salvage surgery as an alternative to salvage radiotherapy or whole gland ablation.”
Salvage radical prostatectomy may be a better option after focal therapy. In an accompanying editorial, Thomas J. Polascik, MD, of Duke Cancer Institute in Durham, North Carolina, commented: “Overall, this is good news for SRP after FT with less salvage toxicity, but the reader should keep in mind that there are also other salvage options that may have a potentially lower toxicity profile, namely whole gland ablation or salvage RT after FT failure.” The median ages of the patients was 66 years in the RT group and 65 years in the FT group. Of the 95 patients in the FT group, 65 (68%) underwent high-intensity focused ultrasound and 17 (18%) had cryotherapy. The remaining patients underwent various other treatments (electroporation, vascular photodynamic therapy, and the investigational agent topsalysin PRX302). Of the 90 patients in the RT group, 56 (62%) received EBRT, 27 (30%) had low-dose brachytherapy, 4 (4%) had high-dose brachytherapy, 1 (1%) underwent Cyberknife, and 2 (2%) received EBRT and brachytherapy. ■
6 Renal & Urology News
MARCH/ APRIL 2021
this month at renalandurologynews.com
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HIPAA Compliance Read timely articles on various issues related to keeping protected health information secure.
Drug Information Search a comprehensive drug database for prescribing and other information on more than 4000 drugs.
Conservative Management Use for PCa Varies Widely Uptake of active surveillance and watchful waiting for low-risk prostate cancer differs across the United States, with socioeconomics and patient perceptions among the possible reasons. Prostate Cancer Treatment Delivered Safely During COVID-19 Peak in New York City At a large medical center, no severe SARSCoV-2 infections occurred among patients who underwent RP or RT for localized disease.
Nicotinamide May Improve Phosphate Control in HD In a phase 3 trial, nicotinamide combined with a phosphate binder improved hyperphosphatemia compared with a phosphate binder alone.
Low Zinc in Advanced CKD Ups Risk of Infection-Related Hospitalizations In a recent study, the hospitalizations were approximately twice as likely to occur among patients with low compared with high serum zinc levels.
Kidney Stones Tied to Higher Stroke Risk Kidney stones are significantly associated with an overall 24% increase risk of stroke, a meta-analysis shows.
News Coverage Visit our website for daily reports on the latest developments in clinical research.
Enzalutamide for mHSPC More Effective in Black Men Adding enzalutamide rather than bicalutamide to ADT improved outcomes in Black men, but not men of other races.
CALENDAR ERA-EDTA Annual Congress Berlin, Germany June 5–8 Canadian Urological Association Annual Meeting Niagara Falls, Ontario, Canada June 26–29 European Association of Urology Annual Congress Milan, Italy July 9–13 American Urological Association Annual Meeting Las Vegas, Nevada September 10–13 International Continence Society Annual Meeting Melbourne, Australia October 12–15 American Society of Nephrology Kidney Week San Diego, California November 2-7 Society of Urologic Oncology Annual Meeting Washington, DC December 1-3
Job Board Be sure to check our latest listings for professional openings across the United States.
BPH Drugs Tied to Heart Failure Risk Men taking alpha-blockers alone had a 22% increased risk for heart failure.
VOLUME 20, ISSUE NUMBER 2
Fewer Kidneys from HCV+ Donors Discarded Use of kidneys from aviremic seropositive and seronegative donors is now equivalent, according to investigators.
A single measurement of potassium is like a
photograph, but the serial measurement of potassium after an episode of hyperkalemia is like a video… See our story on page 12
From the Medical Director The difference between caregivers and care-partners
News in Brief Donating a kidney may be safe despite kidney stones
Ethical Issues in Medicine Strategies to address patients’ COVID-19 vaccine hesitancy
Practice Management Optimizing digital tools to facilitate hospital discharge
8 Renal & Urology News
MARCH/APRIL 2021 www.renalandurologynews.com
FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD
Caregiver vs Care-Partner For Patients With CKD
rganizers of the 2021 World Kidney Day (WKD) on March 11, which had as its theme “Living Well with Kidney Disease,” describe the important role of “family members and other carepartners” in helping patients with kidney disease. But what is the difference between a caregiver and a care-partner? A caregiver provides care for someone who is unable to care for themselves, whereas a care-partner is often an informal caregiver who is also a family member or close friend of the patient. According to Huntington’s Outreach Project for Education at Stanford University, “The difference between caregiver and care-partners is that of a one- versus a two-way street.” A caregiver can be a paid helper to look after a sick or disabled person. When the caregiver is a family member or a friend, however, regardless of being compensated or not, the person is often more intensely involved than a hired caregiver with an otherwise independent life during non-caregiving hours. If a patient suffers from a chronic or debilitating disease state with multimorbid conditions such as advanced CKD, the day-to-day activities of the care-providing family member may be more profoundly affected. The resulting relationship between the patient and caregiver evolves into a natural partnership given joint responsibilities with implications on life participation for both. Caring for a partially incapacitated family member with progressive CKD can impose a substantial burden on a care-partner and may impact family dynamics. Care-partners of patients with CKD may take on a wide range of responsibilities, such as preparing for and transitioning to dialysis therapy, transporting patients to and from dialysis treatment and other appointments, administering oral medications and injections, assisting with home dialysis, and meal preparation. For care-partners, who are often spouses or children or parents of the patient, these activities may take a toll on their daily lives for an extended period. Not infrequently, this involvement in a patient’s care has a negative effect on care-partners’ career goals, leisure activities, and other aspects of their lives. Care-partners may experience depression, fatigue, and isolation, resulting in overload and burnout. As healthcare providers, it is imperative that we accurately understand and appreciate the status of care-partners for patients with CKD, especially now given the greater complexity of caring for patients during the COVID-19 pandemic. Therefore, our efforts to improve patient empowerment, health outcomes, and quality of life should apply to family members and friends. Let’s team up to support and empower both patients and their care-partners to live well with kidney disease. Kam Kalantar-Zadeh, MD, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine, Orange, CA Twitter/Facebook: @KamKalantar
Medical Director, Urology
Medical Director, Nephrology
Robert G. Uzzo, MD, MBA, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman Department of Surgery Fox Chase Cancer Center Temple University School of Medicine Philadelphia
Kamyar Kalantar-Zadeh, MD, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine Orange, CA
Nephrologists Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, NC
Urologists Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City
David S. Goldfarb, MD Professor, Department of Medicine Clinical Chief New York University Langone Medical Center Chief of Nephrology NY Harbor VA Medical Center
R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto
Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center Memphis
Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD Chief Executive Officer Inova Health System Falls Church, VA Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology (ret.) Cleveland Clinic Lerner College of Medicine Cleveland Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology UC Irvine School of Medicine Orange, CA James M. McKiernan, MD John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology Columbia University College of Physicians and Surgeons New York Kenneth Pace, MD, MSc Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Vancouver, Canada
Edgar V. Lerma, MD Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA Chief Medical Officer, DaVita Inc. Denver Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Associate Professor of Medicine Wayne State University School of Medicine Detroit Vice President of Medical Affairs, DaVita Healthcare Denver Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital Teaneck, NJ
Renal & Urology News Staff
Editor Jody A. Charnow
Web editor Natasha Persaud
Production editor Kim Daigneau Group creative director Jennifer Dvoretz Production manager Brian Wask
Vice president, sales operations and production Louise Morrin Boyle
Director of audience insights Paul Silver National accounts manager William Canning Editorial director, Haymarket Oncology Lauren Burke
Vice president, content, medical communications Kathleen Walsh Tulley
Chief commercial officer James Burke, RPh President, medical communications Michael Graziani Chairman & CEO, Haymarket Media Inc. Lee Maniscalco
Renal & Urology News (ISSN 1550-9478) Volume 20, Number 2. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). For reprint/licensing requests, contact Customer Service at email@example.com. Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2021.
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Renal & Urology News 9
Nicotinamide May Improve Phosphate Control in HD NICOTINAMIDE modified release (NAMR) combined with phosphate binders improves hyperphosphatemia and calcification propensity in patients on hemodialysis (HD) compared with phosphate binders alone, a study found. In a double-blind, randomized controlled trial, investigators assigned 539
patients with serum phosphate levels of 4.5 mg/dL or greater despite phosphate binder use to receive NAMR (250-1500 mg/d) and 183 patients to receive placebo, along with 1 to 2 phosphate binders. Some patients with secondary hyperparathyroidism also received active vitamin D analogues and calcimimetics. Patients
in the nicotinamide and placebo arm had a mean age of 61.8 and 62.0 years, respectively. Approximately 80% of patients in both groups were on HD. After 12 weeks, serum phosphate concentration was a significant 0.51 mg/dL lower in the nicotinamide than placebo group, Richard Ammer, MD,
of Universitätsklinikum Münster in Germany, and colleagues reported in Kidney International Reports. Further, more nicotinamide recipients achieved target range serum phosphate (31.5% vs 20.8%). They had a significant 78% and 28% higher likelihood of achieving serum phosphate levels of 4.5 mg/dL or less or 5.5 mg/dL or less, respectively, compared with patients receiving placebo. Concurrently, intact parathyroid hormone (iPTH) declined significantly by 21.9 pg/mL in the nicotinamide group to 292.4 pg/mL over 12 weeks, whereas it increased by 28.5 pg/mL to 337.0 pg/mL in the placebo group. The investigators found that nicotinamide treatment significantly prolonged T50 time, a measure of calcification propensity, compared with placebo: 23.8 vs 2.3 minutes, “indicating a relevant biological and potentially vasculoprotective effect of the intervention.”
Nicotinamide added to phosphate binders demonstrates benefit in a phase 3 trial. With respect to adverse events, more patients taking nicotinamide experienced diarrhea (30.7% vs 12.6%) and pruritus (9.8% vs 2.7%). Use of phosphate binders results in upregulation of the sodium-dependent phosphate cotransporter 2b, but it may be prevented by coadministration of nicotinamide, Dr Ammer’s team explained. The investigators concluded that “the results of this phase III study prove the phosphate-lowering potential of [nicotinamide modified release] as an add-on therapeutic approach to established, but insufficiently effective, [phosphate binder] therapy in hemodialysis patients. They also show that the additional phosphate reduction achieved may be associated with favorable changes of other CKD-MBD parameters.” With regard to study limitations, the authors noted that “patients started randomized treatment without passing through a run-in phase with repeated measurement of serum phosphate. Thus, we cannot exclude that some patients may have entered the study because of a single elevated serum phosphate concentration value and thus did not bona fide represent patients with therapy- refractory hyperphosphatemia.” ■
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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 ED Reported by More than 14% of Young Men
Methodist Hospital in Houston, Texas,
A cross-sectional study of 2660 sexu-
hypertension, proteinuria, and reduced
ally active men aged 18 to 31 years
estimated glomerular filtration rate were
found that 11.3% and 2.9% of them
similar between the groups. No end-
self-reported having mild and moder-
stage kidney disease occurred among
ate-to-severe erectile dysfunction (ED),
the donors with stones after 16.5 years
respectively, investigators reported in
from donation to study close.
and colleagues found that the risks for
The Journal of Urology. partner had significant 65% lower odds
Parkinson’s Risk Lower With Some BPH Drugs
of moderate-to-severe ED compared
Men who use terazosin, doxazosin, or
with single men in adjusted analyses,
alfuzosin are at lower risk for Parkin-
according to Jerel P. Calzo, MD, of
son’s disease (PD) than those who
the San Diego State University School
use tamsulosin, investigators reported
of Public Health, and colleagues.
online in JAMA Neurology.
Married men or those living with a
The researchers defined ED using
Using Danish nationwide health
the International Index of Erectile
registries and the Truven Health
Analytics MarketScan database, Jacob E. Simmering, PhD, of the University
Donating a Kidney Is Safe Despite Kidney Stones
of Iowa in Iowa City, and colleagues
Kidney stones may not necessarily
matched pairs of patients who used
disqualify individuals from being living
terazosin, doxazosin, or alfuzosin and
kidney donors, according to data
those who used tamsulosin. Analysis of
published in Clinical Transplantation.
data from the Danish registries and the
In a study comparing 227 living
studied 147,248 propensity score-
Truven database showed that use of
kidney donors with stones and 908 pro-
terazosin, doxazosin, or alfuzosin was
pensity score-matched donor controls
significantly associated with a 12% and
without kidney stones, investigators led
37% decreased risk of PD, respectively,
by Hassan N. Ibrahim, MD, of Houston
compared with use of tamsulosin.
COVID-19 and Kidney Transplantation After years of annual increases, the number of kidney transplants in the United States declined from 2019 to 2020, a decrease that data suggest is related to the COVID-19 pandemic. Early in the pandemic, most transplant centers temporarily suspended living-donor transplantation to avoid exposing donors and recipients to COVID-19 coronavirus.1,2 25,000 20,000
■ All donors ■ Deceased donors ■ Living donor
Boyarsky BJ et al. Early impact of COVID-19 on transplant center practices and policies in the United States. Am J Transplant. 2020;20:1809-1818. 2 Bordes SJ, et al. Trends in US kidney transplantation during the COVID-19 pandemic. Cureus. 2020;12:e12075. Source: Organ Procurement and Transplantation Network/United Network for Organ Sharing. 1
Comorbidity Burden in RCC Predicts Survival, Data Show I
ncreasing comorbidity burden is associated with diminishing survival among patients with renal cell carcinoma (RCC), investigators reported at the virtual 2021 Genitourinary Cancers Symposium. In a study of a nationwide registry-based cohort of 7894 patients aged 18 years or older diagnosed with RCC in Denmark, Lars Lund, MD, of Odense University Hospital in Odense, Denmark, and colleagues examined overall survival according to comorbidity status using the Charlson Comorbidity Index (CCI) among patients younger than 70 years and aged 70 years and older. The investigators followed patients’ vital status for up to 13 years. In age- and gender-stratified analyses, patients with a CCI score of 1-2 and 3 or more had significant 15% and 56% increased mortality risks, respectively, compared with patients who had no comorbidities, Dr Lund and colleagues noted. The investigators observed similar patterns among patients aged 70 years or older and younger than 70 years.
Thiazides Up Hyponatremia Hospital Admission Risk T
hiazide diuretics may be responsible for approximately 1 in 4 hospitalizations for hyponatremia, according to the findings of a Swedish study published online in the European Journal of Clinical Pharmacology. Buster Mannheimer, MD, of Karolinska Institutet in Stockholm, and colleagues conducted a population-based case-control study comparing with 11,213 patients hospitalized with a principal diagnosis of hyponatremia with 44,801 controls. Patients initiating thiazide diuretic therapy had an adjusted 48-fold increased odds of hospitalization for hyponatremia during the first week of treatment compared with controls. The risk gradually decreased to 4.1-fold by week 13 of treatment and 2.9-fold for patients treated for longer than 13 weeks. The attributable risk of hyponatremia-associated hospitalization due to thiazide diuretics of any treatment length was 27%, Dr Mannheimer’s team reported.
UTUC Preceding NMIBC May Predict Worse BCG Response A
history of upper tract urothelial carcinoma (UTUC) prior to the diagnosis of nonmuscle-invasive bladder cancer (NMIBC) is associated with increased recurrence and progression rates following adequate therapy with bacillus Calmette-Guérin (BGC) treatment, according to a recent study. Of 541 patients with NMIBC treated with adequate BCG, 59 (10.9%) were diagnosed with UTUC: 34 before and 25 after diagnosis of NMIBC, a team led by Ashish M. Kamat, MD, of the University of Texas MD Anderson Cancer Center in Houston reported online in BJU International. Compared with the no-UTUC group, those with UTUC preceding NMIBC had a significantly higher proportion of patients with recurrences (55.9% vs 34.0%), any stage/grade progression (23.5% vs 9.8%), and progression to muscle-invasive or metastatic disease (17.6% vs 6.4%), according to the investigators. In addition, patients with high-grade compared with low-grade UTUC prior to NMIBC were more likely to experience recurrence (68.2% vs 25.0%).
www.renalandurologynews.com MARCH/APRIL 2021
CTC count, death risk continued from page 1
a mean PSA level of 42.6 ng/mL, and 46 (46.5%), 26 (26.3%), and 27 (27.3%) patients had CTC counts of 0, 1-4, and 5 or more per 7.5 mL of blood. On multivariate analyses, CTC counts of 5 or more at ADT initiation were significantly associated with approximately 7.4-fold and 24.9-fold increased
High CTC counts were associated with a 24.9-fold increased risk for death. risks for progression and death, respectively, compared with a CTC count of 0, the investigators reported. High CTC counts were associated with poor progression-free survival (PFS) and overall survival (OS) even in
MRI for PCa screening continued from page 1
12-core prostate biopsy was performed on men with a positive result on any test. The investigators defined clinically significant PCa as Gleason score 3+4 or higher disease. The proportion of men with positive MRI results was higher than the proportion with positive PSA test results (17.7% vs 9.9%). The proportion with positive US results (23.7%) was also higher than proportion of those with positive PSA test results. Using a threshold score of 4-5, the proportion of men with positive MRI results (10.6%) was similar to the proportion with positive PSA test results (9.9%), as was the proportion with positive US results (12.8%). Positive PSA test results detected 7 clinically significant cancers, whereas a positive result on MRI and US (score 3 to 5) detected 14 and 9 clinically significant cancers, respectively. Using a score of 4-5 as the threshold for a positive
Post-RC surveillance continued from page 1
(median 43.0 vs 25.8 months) compared with the symptomatic recurrence group. In multivariable Cox proportional hazards models, symptomatic recurrence was associated with significant 66% and 48% increased risks of cancer-specific and all-cause mortality, respectively, in adjusted analyses.
a subgroup of patients receiving intensified ADT. After further validation, CTC counts may provide a simple way to risk stratify patients, Dr Swami said. Previous small studies conducted in the context of ADT without modern intensification with docetaxel or novel hormonal therapy have shown that baseline CTC counts in patients with mHSPC correlate with PSA responses and PFS, according to the investigators. Recently published results from the SWOG S1216 study — a phase 3 randomized trial comparing ADT plus the novel hormonal therapy orteronel and ADT plus bicalutamide in men with newly diagnosed mHSPC — demonstrated that baseline CTC count was highly prognostic of 7-month PSA (a surrogate for poor OS) and 2-year PFS, after adjusting for disease volume. None of these studies, however, correlated CTC counts with OS. The authors acknowledged that study’s retrospective nature was a limitation. ■
result, MRI and US detected 11 and 4 clinically significant cancers, respectively. Positive PSA test results detected 6 clinically insignificant cancers (Gleason score 3+3). Positive MRI and US results detected 7 and 13 clinically insignificant
Renal & Urology News 11
NLR Increase May Predict Worse mRCC Outcomes AN INCREASE in neutrophil-to- lymphocyte ratio (NLR) of 3 or more
Birmingham, and colleagues reported. In a model adjusted for NLR change,
at 2 months following initiation of
the value of baseline NLR for predict-
therapy for metastatic renal cell car-
ing OS of less than 1 year was not
cinoma (mRCC) predicts an increased
significant. Baseline NLR did not
risk for impending treatment failure
predict treatment failure in less than 6
and death, study findings presented at
months, whereas NLR failure predicted
the virtual 2021 Genitourinary Cancers
a significant 4.8-fold increased risk for
treatment failure in less than 6 months.
The study included 121 patients with
In addition, NLR failure at 2 months
mRCC (98 men, 23 women) who had
had a 78% positive predictive value
complete data on NLR at baseline and
(PPV) for survival of less than 1 year
after 2 months on therapy. An NLR of
and 86% PPV for treatment failure at 6
3 or more (NLR failure) at 2 months
months, according to the investigators.
was significantly associated with a
The cohort included 89 White patients,
6.8-fold increased risk for death in
15 Black patients, and 17 patients of
less than 1 year, Arnab Basu, MBBS,
other races. Of the 121 patients, 92
MPH, of the University of Alabama at
(76%) had clear cell RCC. ■
cancers, respectively, using a threshold score of 3-5, and 5 and 7 clinically insignificant cancers, respectively, using a threshold score of 4-5. “These findings suggest that a short noncontrast MRI may have favorable performance characteristics as a communitybased screening test,” the authors wrote. In an accompanying editorial, Susanna I. Lee, MD, PhD, and Aileen O’Shea, MBBCh, of Massachusetts General
Hospital and Harvard Medical School in Boston, observed that the new findings “clearly point to prostate MRI as a promising screening test.” Sanoj Punnen, MD, associate professor of urology in the Miller School of Medicine at the University of Miami in Miami, Florida, who was not involved in the current study, said the latest findings show that US would not improve PCa screening. When using a 3-5 score to define a positive US test, clinicians would perform more than twice the number of biopsies compared with basing biopsy decisions on PSA test results, with only a small increase in the number of clinically significant cancers detected and nearly a doubling of the number of indolent cancers detected. Even when using a score of 4-5 to be considered a positive US result, Dr Punnen said, clinicians would still do more biopsies but miss more clinically significant cancers compared with using positive PSA results, with a similar indolent cancer detection rate.
With respect to MRI, the current study showed that using a PIRADS 4-5 score as a positive finding would detect more clinically significant cancers without increasing the number of biopsies or patients with indolent cancer, he said. He pointed out, however, that there is variability in MRI reporting and discrepancy among providers as to what constitutes a positive test, and many clinicians would use PIRADS 3 as the threshold for possibly clinically significant cancer. This could result in almost twice the number of biopsies to diagnose more clinically significant cancers while detecting a similar or slightly higher number of indolent tumors. Because of variability in the interpretation of MRI findings and in how clinicians would manage patients with PIRADS 3 lesions, an MRI-based screening protocol may increase detection of clinically significant cancers at the expense of more biopsies. A better strategy would be to use MRI as a secondary screening tool following PSA testing, he said. ■
The authors noted that the American Urological Association, National Com prehensive Cancer Network, and European Association of Urology recommended routine surveillance for recurrence follow RC, but national data from the Surveillance, Epidemiology, and End Results (SEER) program suggest only a 9% rate of adherence to surveillance protocols in the first 2 years following surgery.
“The subject of whether to perform scheduled cancer surveillance in these patients has been considerably debated over time,” co-investigator Stephen A. Boorjian, MD, of FACS, told Renal & Urology News. “Reported rates of adherence to post-radical cystectomy surveillance guidelines in real-world practice have been as low as 9%, in part reflecting a nihilistic view held by many of the value of routine follow-up.
“We believe that these data support routine follow-up to detect disease recurrence prior to the onset of symptoms if possible,” he continued. “Symptomatic recurrence after RC is associated with worse oncologic outcomes than post-RC recurrence detected by routine surveillance.” Many factors should be considered for surveillance, including disease stage and patient factors, Dr Boorjian added. ■
Short noncontrast MRI may offer a better way to screen for prostate cancer.
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Researchers: Monitor K After Acute Hyperkalemia Episodes Post-event potassium trajectory predicts death risk, study finds BY JOHN SCHIESZER NEW STUDY FINDINGS highlight the importance of close monitoring of potassium levels after an episode of acute hyperkalemia, including among patients without chronic kidney disease (CKD), according to a recent study. “Surprisingly, the serum levels of potassium prior to a severe hyperkalemic event do not predict mortality,” said corresponding author Jose Luis Gorriz, MD, PhD, in the department of nephrology at Hospital Clínico Universitario Valencia in Valencia, Spain. “However, following an episode of severe hyperkalemia, serial kinetics of potassium trajectories predict the risk of death.” Dr Gorriz and his colleagues reported their findings in Nephrology Dialysis Transplantation, where they wrote, “To the best of our knowledge, this is the first study that evaluates the long-term prognostic implications of the kinetics of potassium after an episode of acute hyperkalemia.” His team conducted a retrospective observational study that included 160 patients (mean age 77 years) with acute severe hyperkalemia (potassium levels above 6 mEq/L). Of these, 25% did not have CKD. Potassium levels prior to an acute severe hyperkalemia episode did not predict mortality, but the effect of transitioning from hyperkalemia (potassium level higher than 5.5 mEq/L) to normokalemia (5.5 mEq/L or less) after the acute hyperkalemia episode was significantly and inversely associated with mortality risk, according to the investigators. Following their acute episode, patients who transitioned from normokalemia to hyperkalemia had a 7.7fold increased risk for death compared with patients who maintained normokalemia, Dr Gorriz and his colleagues reported. The higher excess risk occurred mostly in the first 6 months following hospital discharge. The study sample was predominately male (60.5%). The most frequent comorbidities were CKD (71.2%), heart failure (35%), and diabetes mellitus (56.9%). Of the 160 patients, 11.9% were on chronic dialysis.
Potassium Trajectory Analysis For their potassium trajectory analysis, the investigators evaluated 6 time points during the follow-up period, at each time point recording clinical data, treatments, serum creatinine, serum sodium, estimated glomerular filtration rate (eGFR), and serum potassium. The investigators analyzed 786 serum potassium measurements from the 160 patients. Patients had a mean potassium level of 6.6 mEq/L and eGFR of 23 mL/ min/1.73 m2 during the acute episode.
Mortality not linked to potassium levels prior to an acute hyperkalemia event. During a median follow-up of 17.3 months, 42.5% died and hyperkalemia recurred in 39.5% of patients who were monitored during follow-up. Causes of death included cardiovascular events (47.2%), infection (23.5%), malignancies (16.2%), liver gastrointestinal (11.8%), and other (1.5%). The mean survival rate was 73% at 3 weeks and 55% at 24 months. “A single measurement of potassium is like a photograph, but the serial measurement of potassium after an episode of hyperkalemia is like a video, which will provide much more information. That is what we have analyzed using the potassium trajectories” Dr Gorriz said. The new findings strengthen the importance of close clinical and potassium monitoring after an episode of acute hyperkalemia, Dr Gorriz said. Study limitations includes its retrospective design and the lack of relevant clinical information for analysis. Further, the authors noted that their findings may not be generalizable because it is a single-center study. “Acute hyperkalemia, if severe enough and especially if untreated, can lead to immediate morbidity or worse,” said Anushree Shirali, MD, a nephrologist at Yale Medicine and an associate professor of medicine at Yale School of Medicine in New Haven, Connecticut.
“What this study is saying, though, is that even with initial treatment of hyperkalemia, patients need to have regular monitoring of potassium levels and appropriate ongoing treatment if hyperkalemia persists,” Dr Shirali said.
Monitoring by Non-Nephrologists Needed Nephrologists usually obtain regular laboratory tests for patients who are prone to hyperkalemia, but the new findings suggest that other clinicians need to consider closer monitoring of potassium levels following an episode of severe hyperkalemia, she said. “So in that sense, it doesn’t change my own personal practice, but it does suggest that we need to partner with emergency room and primary care providers to ensure that severe hyperkalemia is not treated as an isolated incident,” Dr Shirali said. “Patients presenting with such an episode need to have regular follow-up.” Although recurrent hyperkalemia is associated with increased mortality, it may not necessarily be the cause of it, she said. Not all patients in the study who initially presented with severe hyperkalemia had lab work in the follow-up period. “So, it may be that the ones who had follow-up labs had other reasons to have labs drawn, such as worsening of other co-morbidities, particularly cardiac or kidney disease, and these may explain the higher mortality,” Dr Shirali said. Nihar Desai, MD, associate chief of cardiovascular medicine at Yale Medicine and associate professor of medicine at Yale School of Medicine, said there are many underlying causes of hyperkalemia, but the condition can be caused by medications commonly used to treat congestive heart failure. In such cases, management options include discontinuing a medication or decreasing the dose, and using another medication to control potassium levels. ■ REFERENCE Gorriz JL, D’Marco L, Pastor-González A, et al. Long-term mortality and trajectory of potassium measurements following an episode of acute severe hyperkalemia. Published online January 28, 2021. Nephrol Dial Transplant. doi:10.1093/ndt/gfab003
BPH Drugs Tied to Heart Failure Risk HEART FAILURE RISK is increased among men taking an alpha-blocker (AB) or 5-alpha-reductase inhibitor (5-ARI) for benign prostatic hyperplasia (BPH), with greater risks among AB users, researchers reported in The Journal of Urology. Among 175,201 patients older than 66 years diagnosed with BPH and without a history of heart failure, 69,988 (39.9%), 8339 (4.8%), 55,383 (31.6%), and 41,491 (23.7%) men received no medication, a 5ARI alone (finasteride or dutasteride), an AB alone, or a combination of a 5-ARI and an AB, respectively. The risk for developing new heart failure was highest among users of ABs alone (22%), followed by combination therapy (16%), and 5-ARIs alone (9%), J. Curtis Nickel, MD, and colleagues from Queen’s University in Kingston, Ontario, Canada, reported. Nonselective ABs (terazosin, doxazosin, and alfuzosin) were significantly associated with an 8% higher risk for heart failure compared
Risk was highest among patients who used alpha blockers alone, study finds. with selective ABs (silodosin and tamsulosin), even after controlling for hypertension, diabetes, and previous myocardial infarction. Drug exposure longer than 420 days was significantly associated with a 16% and 14% increased risk for heart failure among users of ABs alone and selective ABs, respectively. The investigators noted that previous studies have suggested that men take BPH medications for several years, with primary care physicians prescribing a longer course of treatment than urologists. “It is important that urologists and primary care physicians be aware of this potential link,” Dr Nickel’s team stated. They advocated for more informed conversations with patients about the choices for contemporary management of BPH/ male lower urinary tract symptoms. Limitations of the study include its retrospective design and the accuracy of available diagnostic administrative codes, the authors noted. They also acknowledged that it is not possible to infer adherence to BPH drug therapy based on drugs dispensed. ■
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Low Zinc in Advanced CKD Ups Risk of Infection-Related Hospitalizations Serum zinc levels of 50 µg/dL or less predict a nearly 2-fold greater risk
Kidney Stones Tied to Higher Stroke Risk PATIENTS WITH kidney stones
PATIENTS WITH advanced chronic kidney disease (CKD) who have low serum zinc levels, particularly users of proton pump inhibitors (PPIs), are at higher risk for infection-related hospitalization compared with patients who have high levels, according to investigators. Among 223 patients with stage 5 CKD, including 46 (20.6%) receiving maintenance dialysis, the rate of infection-related hospitalization was significantly higher for patients with low zinc levels (50 µg/dL or less) compared with those who had high levels (above 50 µg/dL): 23.3% vs 12.6%, respectively. Further, patients with low zinc levels had a significantly higher rate of infection-related hospitalizations lasting more than 10 days: 23.3% vs 12.6%, investigators led by Yosuke Saka, MD, PhD, of Kasugai Municipal Hospital Takakicho in Aichi Prefecture, Japan, reported in the Journal of Renal Nutrition. During a median 36 months, 40 of the 232 patients were hospitalized for 60 infection events categorized as respiratory (17 events, 28.3%), soft t issue (11,
18.3%), abdominal (10, 16.7%), bacteremia (9, 15.0%), urinary tract (5, 8.3%), bone and joint (2, 3.3%), and other causes (6, 10%). In adjusted analyses, low zinc levels significantly and independently correlated with a 1.9-fold greater risk for infection-related hospitalization events
Users of proton pump inhibitors are at particularly increased risk. compared with high levels. For patients with low zinc currently taking PPIs, the risk was 2.7-fold greater. According to the investigators, previous research indicate that changes in gastric pH caused by long-term term use of PPIs interfere with the absorption of micronutrients, including zinc. “Patients with advanced CKD and low serum Zn concentration, especially when medicated with PPI, are at high risk of infection-related, and
subsequent long-term, hospitalization,” Dr Saka’s team stated. The researchers noted that, according to the International Zinc Nutrition Consultative Group, serum zinc concentrations are not reliable indicators of zinc status within an individual but are a useful indicator on a population level. “Consequently, the present findings cannot be applied to identifying individual patients with a Zn deficiency,” the authors wrote. “On the other hand, our findings indicated that most patients with advanced CKD are at risk of infectious diseases due to a Zn deficiency, as this study reflected Zn status at the population level among patients with advanced CKD.” The authors acknowledged some study limitations, including its having been conducted at a single center. In addition, they analyzed data only from patients with CKD whose serum zinc levels were measured to evaluate anemia. “Thus we did not measure Zn in all patients with CKD at our hospital. Nonetheless, we considered that Zn was measured in most patients, because anemia is a common complication of advanced CKD.” ■
Study: 5-ARIs Benefit Men on Prostate Cancer AS USE OF 5-alpha-reductase inhibitors (5-ARIs) by men on active surveillance (AS) for prostate cancer is associated with a lower likelihood of definitive treatment and pathologic progression, according to a new study. In a retrospective study of 361 men on AS for low- and intermediate-risk prostate cancer, the 5- and 10-year rates of
In a study, users of the drugs were less likely to cross over to treatment. treatment-free survival were 77% and 41% for the 5-ARI group, respectively, compared with 70% and 32% for the no 5-ARI group, respectively, investigators led by Andre Luis Abreu, MD, of the University of Southern California
in Los Angeles, reported in the World Journal of Urology. The 5- and 10-year rates of pathologic progression-free survival were 92% and 59% for 5-ARI users, respectively, compared with 80% and 51%, respectively, for nonusers. All of the between-group differences were statistically significant. On multivariable analysis, 5-ARI use, compared with nonuse, was significantly associated with a 50% and 42% decreased likelihood of definitive treatment and pathologic progression, respectively. “We believe our study, which is one of the largest series with the longest followup, is an important addition to the literature on 5-ARI use in active surveillance,” Dr Abreu and his colleagues wrote. Of the 361 men in the study, 119 used 5-ARIs and 242 did not. At baseline, users and nonusers of 5-ARIs had similar median ages (63 and 61 years, respectively) and median prostate volumes (35
and 41 mL). Both groups had the same median PSA level (4.8 ng/mL). The median follow-up duration was 5.7 years. Other predictors of definitive treatment and pathologic progression identified in the study included a baseline PSA level above 2.5 ng/mL and Gleason pattern 4 on initial prostate biopsy, according to the investigators. On multivariable analysis, Gleason pattern 4 on initial prostate biopsy, compared with Gleason pattern 3, was significant associated with a nearly 3.4fold increased likelihood of definitive treatment and pathologic progression. Maximum prostate biopsy percent core involvement and age at baseline were not associated with either outcome. The study’s retrospective design was its main limitation, the authors noted. In addition, the lack of prospective randomization and placebo control makes the study prone to confounding and selection bias. ■
have a modestly elevated risk for stroke, especially ischemic stroke, according to the findings of a recent meta-analysis. The meta-analysis, which examined data from 8 studies (7 cohort studies and 1 cross-sectional study), involved 3,526,808 participants, and found that the presence of kidney stones, compared with their absence, was significantly associated with a 24% increased risk of stroke, Min Yuan, MD, of Jiangxi Provincial People’s Hospital in Jiangxi, China, and colleagues reported online ahead of print in Neurologic Sciences. Kidney stones were significantly associated with a 14% increased risk of ischemic stroke and nonsignificant 7% increased risk of hemorrhagic stroke. When the investigators excluded studies with a high risk of bias from analysis, kidney stones were significantly associated with a 16% increased stroke risk. Kidney stones were significantly associated with an 18% increased stroke risk among individuals with a follow-up duration of 10 years or more. The investigators found no significant association between kidney stones and stroke risk among participants with a followup duration of less than 10 years. “Our meta-analysis found a moderate association between kidney stones and the risk of stroke incidence after adjustment of established cardiovascular risk factors, especially in ischemic stroke,” the authors concluded. Previous studies have shown that kidney stones are associated with hypertension, obesity, diabetes, hyperlipidemia, and smoking, all of which are known risk factors for stroke, they noted. “To our knowledge, this article provides a more systematic explanation of the relationship between kidney stones and stroke risk.” The authors acknowledged that the small number of studies included in their meta-analysis was a study limitation. ■
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BP Guidelines for CKD Patients Updated KDIGO recommends a systolic blood pressure target below 120 mm Hg for most patients THE KIDNEY DISEASE: Improving Global Outcomes (KDIGO) organization has released new 2021 clinical practice guidelines for blood pressure management in patients with chronic kidney disease (CKD) not receiving dialysis. The current guideline, updated from the 2012 version, recommends a systolic blood pressure (SBP) target of less than 120 mm Hg using standardized office readings for most patients with CKD (excluding kidney transplant recipients and children) largely based on evidence from SPRINT (Systolic Blood Pressure Intervention Trial). The KDIGO work group that developed the guidelines published its recommendations in Kidney International. “The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points,” they wrote. The guidelines recommend lifestyle interventions and provide management advice for patients who have CKD with or without diabetes, children with CKD, and kidney transplant recipients.
Potential Implications Kathryn E. Foti, PhD, MPH, of Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and
Increased Eligibility for BP Drugs Researchers estimated that the 2021 KDIGO systolic blood pressure (BP) target of less than 120 mm Hg would increase the proportion of patients with CKD eligible for BPlowering drugs compared with the 2012 KDIGO guidelines and the 2017 ACC/AHA* guidelines. 80
40 20 0
*American College of Cardiology/American Heart Association 1 3
SBP less than 120 mm Hg Less than 130/80 mm Hg
130/80 mm Hg with albuminuria, 140/90 mm Hg or less without albuminuria
Source: Foti KE, Wang D, Chang AR, et al. Potential implications of the 2021 KDIGO blood pressure guideline for adults with chronic kidney disease in the United States. Kidney Int. 99:686-695. doi:10.1016/j.kint.2020.12.019
colleagues separately examined how the new guidelines might change clinical practice using data from 9419 adults aged 20 years or older with CKD from the 2015-2018 National Health and Nutrition Examination Survey. The team estimated that the 2021 KDIGO SBP target of less than 120 mm Hg would increase the proportion of patients with CKD who are eligible for BP-lowering medications to 69.5%, compared with 55.6% and 49.8% based on the 2017 American College of Cardiology/
American Heart Association (ACC/ AHA) guideline (target BP less than 130/80 mm Hg) and the 2012 KDIGO criteria (target BP 130/80 mm Hg or less with albuminuria or 140/90 mm Hg or less without albuminuria), respectively. Among patients with albuminuria, 78.2% were eligible for an ACEi or ARB according to the 2021 KDIGO guidelines compared with 71.0% by the 2012 KDIGO guidelines. Yet only 39.1% were taking an ACEi/ARB, according to Dr Foti’s team.
The investigators published their findings in Kidney International, where they wrote that their findings “highlight opportunities to improve blood pressure management and reduce cardiovascular risk among adults in the United States with CKD.” George Bakris, MD, director of the American Heart Association Comprehensive Hypertension Center at the University of Chicago Medicine, has been involved in writing hypertension guidelines for more than 20 years and thinks the KDIGO target SBP of less than 120 mm Hg is unrealistic. Fewer than two-thirds of Americans have SBP controlled to a goal of less than 140 mm Hg, let alone to below 120 mm Hg, he told Renal & Urology News. In Dr Bakris’ view, the 2017 ACC/ AHA guidelines, while stretching some data from SPRINT, was reasonable in its approach and settled on 130/80 mm Hg as a goal. Overwhelming evidence shows that achieving this target slows CKD progression and reduces CV risk, he said. He added that he thinks future guidelines should focus on ways to get to a goal BP. Medication adherence declines when people take 2 or more BP medications, so he would like to see a major push to develop a single BP combination pill. ■
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Enzalutamide for mHSPC More Effective in Black Men ADDING ENZALUTAMIDE rather than bicalutamide to androgen deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC) is associated with improved outcomes in Black men, according to a new study distinguished by its relatively high enrollment of patients in this racial group. In a phase 2 trial that included 71 men with mHSPC randomly assigned to receive either enzalutamide or bicalutamide in addition to androgen deprivation therapy (ADT), the 7-month PSA response rate — the primary end point — among Black patients was significantly higher among enzalutamide-treated patients compared with bicalutamide recipients (93% vs 42%). Among non-Black patients, the response rate was 94% among enzalutamide recipients and 86% among those taking bicalutamide, a difference that was not statistically significant.
The investigators, led by Ulka N. Vaishampayan, MD, of the University of Michigan in Ann Arbor, defined PSA response as achieving and then sustaining a PSA level of 4.0 ng/mL or less within 7 months of starting therapy. At the time of the investigators’ report, 20 (28%) of the 71 patients had PSA progression. Enzalutamide treatment significantly prolonged time to PSA progression and overall survival (OS). Compared with bicalutamide, enzalutamide was significantly associated with an 85% decreased risk for PSA progression and 69% decreased risk for death. Time to pathologic progression and OS did not differ by race. “The incorporation of enzalutamide in mHSPC therapy overcame the disparity in biochemical response rate and OS outcomes between Black and nonBlack patients,” and colleagues reported in JAMA Network Open. “The regimen
was well tolerated, and the favorable risk benefit profile makes it crucial to strongly consider the addition of enzalutamide to ADT in Black patients with mHSPC.” For the overall cohort, the PSA response rates with enzalutamide and bicalutamide at 12 months were 84% and 34%, respectively.
Enzalutamide added to ADT overcame racial disparities in survival outcomes. The men in the study had a median age of 65 years. Black men made up 41% of the overall cohort. The median baseline PSA level was 56.3 ng/mL in the enzalutamide group and 60 ng/ mL in the bicalutamide arm. Of the 71
patients, 59 (83%) had bone metastases only, the researchers reported. Also as part of the trial, the investigators collected biopsy specimens to look for genetic biomarkers associated with PSA progression and OS. Black patients with high levels of ERG, CXCR4, or AKR1C3 had a numerically lower likelihood of having a PSA response compared with non-Black patients. Patients treated with bicalutamide who had a low copy number of these genes had a higher PSA response rate compared with those who had a high copy number. The authors noted that black men are “grossly underrepresented” in prospective trials that enroll men with advanced prostate cancer. “Given the potential for racial disparity in prostate cancer outcomes and the underrepresentation of Black men in mHSPC clinical trials, the current study design required at least 30% enrollment of Black patients.” ■
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Conservative Management Use for PCa Varies Widely Socioeconomics may have a role in the uptake of active surveillance and watchful waiting
nitial conservative management for men with low-risk prostate cancer (PCa), a strategy recommended in guidelines from major urology and oncology organizations, is increasing in the United States, but the extent to which this approach is used varies widely among urologists, practices, and facilities.1-4 Investigators cite multiple factors to explain the unequal uptake of such monitoring approaches as active surveillance (AS) and the less intensive watchful waiting (WW). “Ethnicity, race, socioeconomic status, geography, educational background, and personal patient experiences all, in my opinion, have a significant impact on selection of primary treatment for prostate cancer,” said Udit Singhal, MD, of the University of Michigan in Ann Arbor, Michigan. “There are substantial provider-dependent factors as well, including physician background and level of training, payer/reimbursement status in a given region, availability of resources, or even ambiguity of clinical guidelines.” In a recent study, Dr Singhal and colleagues documented wide variation in the use of WW for men with lowrisk PCa in Michigan. The investigators examined data from the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. MUSIC is a physician-led partnership of community and academic urology practices in Michigan. The study included 2393 men with PCa who had a life expectancy of less than 10 years at the time of their cancer diagnosis. Among the 358 men with low-risk PCa as defined by National Comprehensive Cancer Network (NCCN) criteria, 69.3% and 15.1% underwent AS and WW, respectively, and 15.6% received definitive
AS, WW Rates Vary Regionally A study found that active surveillance and watchful waiting rates for low-risk prostate cancer in the United States in 2010-2015 varied among Surveillance, Epidemiology, and End Results (SEER) registry regions. The proportion of men receiving these conservative management approaches in selected regions are shown here.
New Mexico Source: Washington SL 3rd, Jeong CW, Lonergan PE, et al. Regional variation in active surveillance for low-risk prostate cancer in the US. JAMA Netw Open. 2020;3(12):e2031349.
treatment, according to study findings published in Urology.1 Rates varied widely among practices: 44% to 81% for AS, 6% to 35% for WW, and 0% to 30% for definitive treatment.
Uniformity Difficult in AS “Integration of AS into practice requires navigation of numerous different criteria, and these are often institution- or practice-dependent,” Dr Singhal said. “In this sense I think it is difficult to achieve uniformity in AS for patients across practices. At the same time, urologists like to say that ‘no two prostate cancers are the same’ due to the clinical heterogeneity inherent in the disease, and therefore shared decision-making guides individual decisions.” He said he believes a drive toward more uniform AS protocols would benefit both providers and patients. Current protocols have varying inclusion criteria and disparate outcomes, and this can lead to difficulties in c omparing groups.
“Developing a uniform AS protocol would standardize this approach for treating prostate cancer, similar to standard dosing of radiation or standard techniques for prostatectomy,” Dr Singhal said.
Variation Across SEER Registry Regions Regional variation in the use of conservative management strategies for low-risk PCa emerged from a study of 79,825 men diagnosed with clinically localized, low-risk PCa from January 1, 2010 to December 31, 2015 in 17 SEER (Surveillance, Epidemiology, and End Results) registry regions who were eligible for AS or WW. The overall use of AS or WW in the study population was 22.1%, but varied by region, with the lowest rates in rural Georgia (4.1%) and New Mexico (9.3%) and the highest rates in San Jose-Monterey (33.9%) and San Francisco-Oakland (42.4%), investigators led by Matthew R. Cooperberg,
MD, MPH, of the University of California, San Francisco, reported in JAMA Network Open.2 The mean annualized percent increase in AS or WW rates from 2010 to 2015 ranged from 6.3% in New Mexico to 81% in New Jersey, according to the investigators. “Use of AS or WW varied substantially both across and within SEER regions, almost independent of patientand county-level characteristics, such as socioeconomic factors or medical resources, reflecting local disparities in the awareness or acceptance of AS,” the authors wrote. Differences in uptake of AS also were documented in a study of 2250 men diagnosed with PCa from January 2015 to November 2017 and who received care at facilities belonging to the Pennsylvania Urologic Regional Collaborative (PURC), a cooperative effort of urology practices in southeastern Pennsylvania and New Jersey.3 Overall, 57.4% of patients with very lowor low-risk PCa according to NCCN criteria received AS for initial management of their cancer. The AS rate, however, for these men varied widely among practitioners, ranging from 10% to 100%, investigators led by Adam C. Reese, MD, of Temple University School of Medicine in Philadelphia, Pennsylvania, reported in The Journal of Urology.3 In addition, a study of 20,597 men with low-risk PCa receiving care in the Veterans Affairs healthcare system found that although overall use of conservative management — either AS or WW — for low-risk PCa rose from 51% in 2010 to 76% in 2016, the proportion among facilities varied from 35% to 100%. The study also revealed geographical differences. Men receiving care at facilities in
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BY JODY A. CHARNOW
the Midwest and West had 23% and 36% increased odds, respectively, of undergoing conservative management compared with those receiving care at Northeast facilities. The authors, led by Stacy Loeb, MD, of New York University in New York City, published their findings in European Urology, where they concluded that “even within an integrated health care system, there remains significant heterogeneity in the uptake of conservative management for low-risk prostate cancer.”4
Socioeconomics Socioeconomic status (SES) might be among the reasons for heterogeneity in the uptake of AS or WW. A study led by Brandon A. Mahal, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, demonstrated that although use of these conservative approaches for low-risk PCa increased from 2010 to 2015 in the United States, their use varied by SES.5 AS or WW use for patients in the lowest, middle, and highest SES tertiles increased from 11.2% to 37.3%, 14.1% to 45.8%, and 17.6% to 46.4%, respectively, the investigators reported in Prostate Cancer and Prostatic Diseases. By 2015, patients in the lowest tertile had 27% decreased odds of being managed with AS or WW compared with those in the highest tertile. Further, a recently published study by Vishesh Agrawal, MD, and colleagues at Weill Cornell Medicine in New York, found that socioeconomic and demographic factors were associated with the use of AS for men with intermediate-risk PCa.6 For example, the proportion of men managed with AS varied by median annual income: from 14.4% of patients with an income less than $38,000 to 42.7% of those with an income of $63,000 or higher, according to findings published in The Journal of Urology. Patients living in a rural area had 28% increased odds of AS compared with those living in a metropolitan area. Compared with patients who had private insurance, those with no insurance or government insurance had significant 14% and 72% increased odds of AS. The likelihood of undergoing AS also varied from place to place depending on the proportion of the population who completed high
school. Men in regions where less than 7% of the population did not have a high school diploma had 24% lower odds of undergoing AS compared with places where 21% or more of the population did not complete high school.
Variability in Eligibility Criteria Dr Reese, who led the PURC study, said the disparity in the use of AS among institutions could stem in part from significant variability in criteria used to identify patients who are eligible for AS. “Furthermore, the fact that some criteria are much more strict than others has significant implications on the percentage of men eligible for AS,” said Dr Reese, chief of urologic oncology and director of the urology resident program at Temple University. “Very stringent AS eligibility criteria will result in relatively few men eligible for AS and many men potentially undergoing unnecessary treatment. In contrast, lenient eligibility criteria will allow more men to pursue AS, but potentially with an increased risk of developing progressive or metastatic disease.” Dr Reese said he believes providerrelated factors play a large role in the use of AS in contemporary practice. “When providers believe in the efficacy of AS and provide patients with honest and objective data regarding the pros and cons of AS, I think that a large percentage of patients will be willing to accept AS as an initial management strategy.” Another factor potentially contributing to the variation in AS use is patients’ anxiety over their cancer diagnosis, he said. Differences in the way physicians frame AS when counseling patients are probably the single biggest cause of variation in AS use, said Michael S. Leapman, MD, assistant professor of urology at the Yale School of Medicine in New Haven, Connecticut.
Patients’ Perceptions Patients’ perceptions about PCa, which might be influenced by personal experiences such as knowing somebody who suffered or died from PCa, can be an important factor in the care they choose, he said. A common first instinct for patients is to be treated right away rather than undergo monitoring, and
physicians may also feel reluctant to encourage them to be monitored due to their own perceptions about the risk. Although there has been significant uptake of AS, many patients who are candidates for this approach still are treated for low-grade PCa. “One of many approaches needed to bridge the gap is to keep physicians updated about clinical guidelines, and also to understand values, preferences, and biases that the patient may enter the discussion with,” Dr Leapman said. Clinical guidelines that recommend AS for low-risk PCa, such as those from the NCCN and American Urological Association, “do a very good job representing the current state of evidence” in support of AS and present clear recommendations, Dr Leapman said. Still, it is unclear whether physicians consult the guidelines or how much weight they place on the recommendations. A potential way to address variation in AS use is to identify parts of the country with relatively high levels of definitive treatment for low-risk PCa and then ferret out the barriers to wider AS use, he said.
Transitioning from AS to WW In addition, physicians may want to consider changing their approach to conservative management for low-risk PCa, Dr Leapman said. For example, a subset of patients with relatively short life expectancies because of their age and comorbidities might not need the intense monitoring of AS and can instead be managed with WW. “There are certainly some patients for whom doing close monitoring and biopsies and PSA testing is probably unlikely to make a difference in what we do [as physicians],” said Dr Leapman, who coauthored a 2020 paper in European Urology Focus titled “When and How Should Active Surveillance for Prostate Cancer be De-Escalated?”7 Physicians err on the side of being overly cautious, “which is probably a good thing, but may expose patients who are older or who have other medical problems to needless invasive diagnostic testing to find small changes in their prostate,” he said. A major challenge in identifying these patients is making accurate assessments of life expectancy, and then bringing
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that into discussions with patients, he said. “It’s always difficult when we have a patient in front us, to tell them, ‘We don’t think you’re going to be alive in 3 years, so we’re not going to follow [the cancer]. That’s a hard message to give, and one that we probably underperform in doing.” Some patients start on AS but then reach an age at which findings from PSA tests, imaging studies, and biopsies would not affect their clinical management, Dr Leapman said. In such cases, it makes sense to consider transitioning patients to less intensive monitoring, he said. Dr Reese agrees. “I certainly think it is appropriate to de-escalate the intensity of surveillance and transition towards a more watchful waiting approach as men age, or in those men with significant comorbidities.” he said. Prostate biopsies can result in complications, and therefore should be used judiciously in men with limited life expectancies. Individual treatment decisions should be based on shared decision-making, “but as urologists, we must do a better job of offering WW as a reasonable alternative for the appropriately selected patient,” Dr Singhal said. AS is not without potential harm, and this can be avoided in men who may not necessarily benefit from this approach. For men with low-risk PCa and a life expectancy less than 10 years, he said, WW should be the preferred management strategy. ■ REFERENCES 1. Singhal U, Tosoian JJ, Qi J, et al. Overtreatment and underutilization of watchful waiting in men with limited life expectancy: An analysis of the Michigan Urological Surgery Improvement Collaborative registry. Urology. 2020;145:190-196. 2. Washington SL 3rd, Jeong CW, Lonergan PE, et al. Regional variation in active surveillance for low-risk prostate cancer in the US. JAMA Netw Open. 2020; 3(12):e2031349. 3. Botejue M, Abbott D, Danella J, et al. Active surveillance as initial management of newly diagnosed prostate cancer: Data from the PURC. J Urol. 2019;201:929-936. 4. Loeb S, Byrne NK, Wang B, et al. Exploring variation in the use of conservative management for low-risk prostate cancer in the Veterans Affairs healthcare system. Eur Urol. 2020;77:683-686. 5. Butler SS, Loeb S, Cole AP, et al. United States trends in active surveillance or watchful waiting across patient socioeconomic status from 2010 to 2015. Prostate Cancer Prostatic Dis. 2020;23: 179-183. 6. Agrawal V, Ma X, Hu JC, et al. Active surveillance for men with intermediate risk prostate cancer. J Urol. 2021;205:115-121. 7. Rajwa P, Sprenkle PC, Leapman MS. When and how should active surveillance for prostate cancer be de-escalated? Published online February 1, 2020. Eur Urol Focus.
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24 Renal & Urology News
Algorithm Addresses Cisplatin Underuse Cisplatin-based neoadjuvant chemotherapy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). It yields a 30% to 40% pathologic complete response rate and correlates with improved overall survival. However, many patients are deemed ineligible for cisplatin due to their less-than-optimal kidney function. Renal & Urology News interviewed Srikala S. Sridhar, MD, MSc, of the Princess Margaret Cancer Centre, University of Toronto in Toronto, Ontario, Canada, about her team’s new algorithm to reduce underuse of cisplatin in MIBC, which was recently published in Nature Reviews Urology.
Your team has proposed a new algorithm for determining cisplatin eligibility among patients with MIBC. Why?
Dr Sridhar: The main reason we proposed a new algorithm for this patient population is because the current consensus criteria were developed for patients with metastatic disease, and not for patients with potentially curable MIBC where cisplatin-based chemotherapy plays a key role in the curative approach. Instead of relying on an absolute renal function threshold of 60 mL/min, which excludes a significant proportion of patients with MIBC from receiving cisplatin, the new algorithm is less stringent and would allow more patients with MIBC to receive and potentially benefit from perioperative cisplatin-based chemotherapy. Please describe the new algorithm. How can it be incorporated into decision-making?
Dr Sridhar: The first step in the algorithm is to determine if a patient is fit to receive cisplatin based on 4 key aspects of the Galsky criteria, which
On The Web
include performance status, peripheral neuropathy, hearing loss, and heart failure. The next step is to determine the patient’s baseline renal function, using a 24-hour urine collection if feasible or the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) for estimated glomerular fi ltration rate (eGFR), until a better formula is developed. Patients with an eGFR of more than 60 mL/min/1.73 m2 are cisplatin eligible. Novelly, patients with an eGFR of 40 to 60 mL/min/1.73 m2 are potentially cisplatin-eligible but require additional strategies to minimize their risk of nephrotoxicity. Patients with an eGFR of less than 40 mL/min/1.73 m2 should not be offered cisplatin-based chemotherapy owing to the limited evidence of its safety in this setting. What would you advise a patient with an eGFR of greater than 50 mL/ min/1.73 m2 to do?
Dr Sridhar: For a patient with an eGFR of greater than 50 mL/min/1.73 m2,
who is otherwise fit for cisplatinbased chemotherapy according to the Galsky criteria, we would recommend a cisplatin-based combination chemotherapy regimen. We would also strongly encourage the use of mitigation strategies as outlined in the algorithm to minimize the risk of nephrotoxicity. And a patient with an eGFR of 40 to 50 mL/min/1.73 m2?
Dr Sridhar: We would discuss the risks and benefits of cisplatin-based chemotherapy and whether it is best administered in the neoadjuvant or adjuvant setting. For chemotherapy, we would offer a split-dose cisplatin-based regimen, consider extra hydration, and refer to nephrology. It’s important to monitor renal function closely during chemotherapy and offer dose adjustments if needed. What mitigation strategies do you suggest to minimize the risk of cisplatininduced nephrotoxicity in selected patients with impaired renal function?
Impaired renal function does not necessarily rule out cisplatin use. —Srikala S. Sridhar, MD, MSc
Dr Sridhar: Our team uses the following nephrotoxicity mitigation strategies: • Decompression if acute obstructive uropathy is present • Nephrology consultation before cisplatin administration • Aggressive hydration before, during, and after treatment • Minimization of concomitant nephrotoxic medications, such as non-steroidal anti-inflammatory drugs, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. We also suggest avoiding contrast use. • Dose reduction of conventional cisplatin regimens by 25% to 50% • Cisplatin dose fractionation using the split-dose gemcitabine and cisplatin regimen (cisplatin 35 mg/m² on day 1 and day 8) What has been your institution’s experience using the new algorithm for determining cisplatin eligibility?
Dr Sridhar: The staff at the Princess Margaret Cancer Centre frequently use the new algorithm. It allows us to treat more patients with cisplatinbased chemotherapy in the neoadjuvant setting. We hope this translates into more pathologic responses and improved overall outcomes. We’re fortunate to have dedicated onco-nephrology clinics to advise us when a patient’s cisplatin eligibility is unclear, renal function needs to be optimized, or renal function deteriorates during chemotherapy. For institutions without onco-nephrology clinics, we recommend creating a multidisciplinary team to address both cancer-related and kidney-related issues to optimize outcomes. Nephrologists knowledgeable in the complex aspects of cancer treatments are a valuable part of that team. Treating patients with MIBC and chronic kidney disease is particularly challenging because many of our current treatment strategies, including cisplatin-based chemotherapy, are potentially nephrotoxic. In addition, some of the novel therapies currently under investigation, such as immune checkpoint inhibitors, also have the potential to be nephrotoxic. ■
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AKI Prognosis Worse in COVID-19 Cases New findings suggest recovering patients need kidney function monitoring after hospital discharge AMONG PATIENTS who experience in-hospital acute kidney injury (AKI), those with AKI associated with COVID-19 have a greater rate of renal function decline after hospital discharge compared with those who did not have COVID-19, according to a new study. In addition, patients with COVID19-associated AKI whose AKI did not resolve by the time of discharge have a slower recovery of kidney function compared with their counterparts with AKI not related to COVID-19. “The new findings suggest that patients recovering from COVID-19associated acute kidney injury require monitoring of kidney function following hospital discharge,” investigators led by F. Perry Wilson, MD, MSCE, of the Yale University School of Medicine in New Haven, Connecticut, reported in JAMA Network Open.
Dr Wilson and colleagues studied 1612 patients who experienced AKI in the hospital: 182 patients with COVID-19 and 1430 patients without COVID-19. The study population had a median age
Renal recovery is slower when AKI is due to COVID-19 vs other causes. of 69.7 years and included 813 women (50.4%). The group with COVID-19associated AKI compared with those who had AKI not related to COVID19 had a higher proportion of Black patients (40.1% vs 15.7%) and Hispanic patients (22% vs 8.8%) and had fewer comorbidities than patients with AKI not associated with COVID-19.
“Our study’s inclusion of a comparison group of patients with AKI not associated with COVID-19 followed up longitudinally allows for testing of the hypothesis that COVID-19-associated AKI displays not only unique clinical and pathologic features, but also distinct sequelae from other causes of AKI,” the authors wrote. In a fully adjusted model, the mean estimated glomerular filtration rate (eGFR) declined by 16.7 min/1.73 m2 per year in the COVID-19 group and by 2.7 min/1.73 m2 per year in the group without COVID-19, a significant difference in mean eGFR slope of 14.0 min/1.73 m2 per year, Dr Wilson’s team reported in JAMA Network Open. The difference in eGFR slope was independent of patient demographic characteristics, AKI severity, and comorbidities, according to the investigators. In a subgroup of patients who had not yet recovered baseline kidney function
Osteoporosis, Fracture Common Ibuprofen in Patients With Kidney Stones Ups AKI Risk In Children
MANY PATIENTS with kidney stones
significant 20% lower odds of these
concurrently have or later experience
diagnoses compared with White
osteoporosis or fracture, a new study
of veterans suggests, but not enough receive bone mineral density screening. In the US Veterans Health
In addition, the investigators found that type 2 diabetes, metastatic cancer, inflammatory bowel disease,
Administration database, 531,431
hypogonadism, or primary hyperpara-
patients had a kidney stone diagnosis
thyroidism significantly increased the
during 2007 to 2015. Nearly 1 in 4
odds of an osteoporosis or fracture
of these patients (23.6%) also had a
diagnosis. Higher levels of 24-hour
coincident diagnosis of osteoporosis
urinary citrate excretion decreased the
or fracture, Calyani Ganesan, MD,
odds of these bone-related diagno-
of Stanford University in Palo Alto,
ses. No correlation was observed for
California, and colleagues reported
24-hour urinary calcium excretion.
in the Journal of Bone and Mineral
Dr Ganesan’s team found subpar use
Research. The mean age of these
of bone mineral density (BMD) screen-
patients was 64.2 years; 91.2% were
ing with dual-energy X-ray absorptiom-
men, and 8.8% were women. Non-hip
etry (DXA) in veterans with kidney stone
fracture, osteoporosis, and hip fracture
disease. Among those with no history
occurred in 19.0%, 6.1%, and 2.1%
of osteoporosis or BMD assessment,
of these patients, respectively, they
only 9.1% were screened with DXA
reported. According to a sex-stratified
within 5 years of their kidney stone
analysis, 23% of male and 34% of
diagnosis. Of these, 20% were subse-
female veterans with kidney stones had
quently diagnosed with osteoporosis,
concurrent osteoporosis or fracture.
19% with non-hip fracture, and 2.4%
Black veterans (13.9% of cohort) had
with hip fracture. ■
IBUPROFEN MAY increase the risk for acute kidney injury (AKI) in hospitalized children, particularly those with chronic kidney disease (CKD), a new study finds. In a cohort of 50,420 hospitalized children aged 1 month to 18 years (60.8% male) in China, 5526 (11.0%) received ibuprofen and 3476 (6.9%) experienced hospital-acquired AKI. Ibuprofen use was significantly associated with an adjusted 23% increased risk of AKI, defined as an increase in serum creatinine of 26.5 μmol/L or more within 48 hours or by 50% or more over baseline, corresponding author Xin Xu, MD, PhD, of the National Clinical Research Center for Kidney Disease at Southern Medical University in Guangzhou, China, and colleagues reported in JAMA Network Open. The risk for ibuprofen-associated AKI increased with age. Ibuprofen use was significantly associated with a 64% increased risk among adolescents older than 10 years compared with a 36% increased risk among children aged 1
at the time of hospital discharge, the COVID-19 group had a significantly lower rate of kidney recovery than those without COVID-19: 0.95 vs 1.73 per 100 patient-days. In adjusted analyses, patients in the COVID-19 group were 43% less likely to recover kidney function during outpatient follow-up compared with patients without COVID-19. Dr Wilson’s team noted that the pathologic mechanism by which SARS-CoV-2 causes AKI is multifactorial, with acute tubular injury the most common histologic diagnosis found on kidney biopsy in patients with COVID-19-associated AKI. Study findings could have implications for future research. “A better understanding of COVID-19-associated AKI should provide opportunities for clinical trials to improve outcomes and inform the guidelines of post-COVID19-associated AKI management,” the authors concluded. ■
to 10 years. Babies up to 1 year old had no increased risks. Children with CKD who used ibuprofen had a 2.3-fold increased risk of AKI, whereas children without CKD who used the pain reliever had a 1.2-fold increased risk. In addition, young patients taking ibuprofen who required intensive care had an increased risk for AKI compared with those who did not (47% vs 18%). Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), is a nonselective blocker of cyclooxygenase. It inhibits the synthesis of prostaglandin, which leads to vasoconstriction, increased preglomerular resistance, decreased renal perfusion, and increased risk of prerenal AKI, according to the study authors. Ibuprofen is frequently prescribed in children for diverse therapeutic indications, including fever, postoperative pain, tumors, and inflammatory disorders. In the study, as cumulative doses of ibuprofen increased so did AKI risk. Children with AKI tended to have a higher cumulative dose of ibuprofen than children without AKI: median 13.45 vs 12.02 mg/kg. The investigators found no interactions between ibuprofen and use of angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, diuretics, proton pump inhibitors, other NSAIDs, or contrast media. ■
www.renalandurologynews.com MARCH/APRIL 2021
VTE Risk Is Not Limited to Class 5 LN
Renal & Urology News 27
Prostate Cancer Treatment Delivered Safely During COVID-19 Peak in NYC Surgeries and radiotherapy resumed after a state-mandated 7-week pause
VENOUS THROMBOEMBOLISM (VTE) among patients with lupus nephritis (LN) is not limited to those with class 5 disease, but extends to those with class 3 or 4 disease, according to recent study findings. In a cohort of 534 patients with LN, 310 (58%) had class 3 or 4 disease and 224 (42%) had class 5 with or without class 3 or 4 (including 106 with pure class 5 disease). VTE occurred in 62 patients (11.6%) and included deep vein thrombosis (DVT), pulmonary embolism (PE), and superficial VTE (eg, fistula or graft thromboses). The odds of VTE did not differ significantly between patients with class 3 or 4 LN and patients with any class 5 disease, corresponding author Saira Z. Sheikh, MD, of the Thurston Arthritis Research Center at the University of North Carolina in Chapel Hill, and colleagues reported in Kidney International Reports. The investigators obtained similar results in sensitivity analyses using only pure class 5 as the comparator. In addition, the investigators observed an age effect: 2.75-fold increased odds of VTE at younger ages (estimated at age 16 years) for patients with class 3 or 4 LN compared with class 5. Older patients (estimated at age 46 years) with class 3 or 4 vs class 5 LN had 77% decreased odds of VTE. According to Dr Sheikh’s team, knowing the class-specific effects of LN on VTE risk could help riskstratify the need for VTE prophylaxis, anticoagulation duration, and diagnostic testing among patients with systemic lupus erythematosus. They suggested that the effects of LN on VTE risk may be mediated by different mechanisms in class 3 or 4 than in class 5. Alternately, increased VTE risk may be associated with disease duration, immunosuppression, infection, hospitalization, or kidney disease progression. ■
BY NATASHA PERSAUD RADICAL PROSTATECTOMY (RP) and radiation treatment (RT) for localized prostate cancer was performed with reasonable safety at a New York City cancer center during the first wave of the COVID-19 pandemic in the United States, investigators reported during the virtual 2021 Genitourinary Cancers Symposium. New York City was the epicenter of the largest initial COVID-19 spike in the United States. “At the onset of the pandemic in March 2020, our cancer center underwent a coordinated 7-week pause in both prostate cancer surgery and new radiation treatments in accordance with the executive order in New York state,” lead investigators Ariel Schulman, MD, and Andrew Wood, MD, of Maimonides Medical Center in Brooklyn, New York, explained in a joint statement to Renal & Urology News. Virtual Meetings Their multi-disciplinary team quickly converted to virtual meetings and continued to discuss patients prospectively.
They also developed collaborative protocols to prioritize treatments for the highest-risk patients when it was safe to restart treatments. Strict hand washing, mask wearing, and social distancing policies were instituted.
No severe COVID-19 infections occurred among patients who underwent treatment. Of 75 patients at their cancer center, 20% had low-risk, 34.7 had favorable intermediate-risk, 18.7% had unfavorable intermediate-risk, and 26.7% had high-risk prostate cancer based on National Comprehensive Cancer Center criteria. Eleven patients continued previous RT once services resumed, including 1 who developed a symptomatic COVID-19 infection and required a 2-week pause in treatment. Once the operating room reopened, 11 patients underwent RP, including 8 with unfavorable intermediate-risk or
high-risk disease. A negative COVID19 PCR test was required within 72 hours of the procedure. When feasible, the team used same-day discharge to reduce patients’ postoperative exposures. The change did not increase complications or hospital readmissions. “There were no severe COVID-19 infections among patients finishing RT or among the first cohort of men having surgery during the restart of treatments, suggesting that localized prostate cancer treatments can be safely delivered in the event of a second wave,” Dr Schulman and Dr Wood said.
COVID vs Pre-COVID Cohort The researchers compared the 75-patient COVID cohort with a pre-COVID cohort (July 2019 to December 2019) of group of 100 patients with localized prostate cancer. The only significant differences in management between the groups was that the COVID-19 cohort had a longer time from initial visit to treatment (92.1 vs 71.0 days) and a greater proportion of patients who were seen but did not return for management (25.3% vs 14%). ■
Fewer Kidneys From HCV+ Donors Discarded DISCARDING OF KIDNEYS from donors exposed to hepatitis C virus (HCV) has decreased markedly from 2014 to 2019. “There is now equivalent use of kidneys from aviremic seropositive donors and kidneys from aviremic seronegative donors,” investigators led by Tarek Alhamad, MD, of Washington University School of Medicine in St. Louis, Missouri, concluded in the Clinical Journal of the American Society of Nephrology. Still, kidneys from viremic donors had 48% increased odds of discard in 2019, they noted. “There are opportunities for more transplant centers to utilize these organs to expand access to transplant, Dr Alhamad and colleagues wrote. “Broader utilization would benefit from financial coverage for post-transplant DAAs [direct-acting antivirals], which would result in wider adoption of protocols to transplant kidneys from viremic donors to uninfected recipients.”
Since 2014, use of DAAs for HCV treatment has results in a cure rate of greater than 90%, “which has revolutionized the practice for managing HCV infection,” the investigators pointed out. Using data from the Organ Procure ment and Transplantation Network (OPTN), Dr Alhamad and colleagues identified 225,479 deceased-donor kidneys recovered from 2005 to 2019 and performed 2 analyses. The first analysis looked only at donor HCV antibody status (HCV seropositive vs HCV seronegative). The second included 82,090 kidneys recovered after March, 31, 2015, when nucleic acid amplification testing (NAT) results were available to determine the presence or absence of viremia. This analysis considered both donor HCV antibody and viremia status. Investigators categorized patients as NAT positive, regardless of HCV antibody status, aviremic seropositive, and aviremic seronegative.
The first analysis showed that, compared with HCV-seronegative kidneys, the odds of HCV-seropositive kidney discard decreased from 7.43-fold in 2013 (prior to the DAA era) to 1.20fold in 2019, on multivariable analysis. In the second analysis, compared with HCV-aviremic seronegative kidneys, the odds of HCV-viremic kidney discard decreased from 7.09-fold in 2017 to 1.48fold in 2019, the researchers reported. By 2018 and 2019, aviremic seropositive status was not associated with higher odds of discard. Regarding study limitations, the authors noted that their investigation was retrospective, so their analyses relied on the accuracy of recorded data. In addition, NAT results were only available in OPTN data since March 31, 2015. “Therefore, we were unable to describe an earlier trend for viremic or aviremic seropositive kidney discards before and at the beginning of the DAA era.” ■
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Low SES Presents Prostate Cancer Treatment Barriers Transportation, poor health knowledge, and lack of insurance are among obstacles BY JODY A. CHARNOW
© EDDTORO / GETTY IMAGES
en of low socioeconomic status (SES) are more likely to present with metastases when they are diagnosed with prostate cancer (PCa) and are at higher risk for having advanced or aggressive PCa discovered at the time of radical prostatectomy (RP), according to recent studies.1,2 In addition, men of lower SES are less likely to undergo RP or external beam radiation therapy (EBRT) for localized PCa, and they have decreased cancer-specific survival after these treatments compared with men of higher SES.3 The reasons are unclear, but urologists in American cities with large poverty-stricken populations say impoverished men with PCa frequently encounter barriers to optimal care, such as poor fundamental health knowledge, no or inadequate health insurance, lack of social support, difficulties with arranging transportation to and from medical appointments, and unstable living situations. The consequences of these impediments include low rates of PCa screening and frequently missed medical visits that make patient follow-up and continuity of care problematic or impossible. “When you are treating patients of a lower socioeconomic status, you have to consider that there are lots of obstacles for them being able to come to the doctor regularly and get routine care,” said Alexander Sankin, MD, of the Montefiore Medical Center in the Bronx, New York, a facility that serves a population of which 85% of individuals are on Medicaid or Medicare. Depending on where patients live, transportation can be a significant issue, explained Dr Sankin, who is also associate professor of urology at Albert Einstein College of Medicine.
In addition, personal circumstances can prevent patients of low SES from keeping appointments. For example, with schools closed as a result of the COVID-19 pandemic, some men with PCa from impoverished neighborhoods have had to stay home with their children, making it difficult “to just head out and come to their routine doctor visits because they had to take care of their kids,” Dr Sankin said. Since the pandemic hit, however, “we really ramped up on telemedicine services here so that we are at least able to continue to provide some level of service to patients if they are not able to physically come in.”
Low Health Literacy Another challenge with low SES patients is that sometimes they have a lower level of health literacy compared
with other patients. In these cases, Dr Sankin said, he spends more time explaining the risks and benefits of the various treatments. Patients can “sometimes be a bit overwhelmed by the options available to them,” he said. Adam Reese, MD, chief of urologic oncology at Temple University Hospital in Philadelphia, Pennsylvania, which serves a largely poverty-stricken population, faces the same issue. “Some patients have low health literacy and have difficulty assimilating all the information and making an educated decision,” explained Dr Reese. “Even then, it sometimes is unclear to me that they truly grasp all the pros and cons of the various treatment options.” Patients’ inability to fully comprehend what different treatments entail could impair their engagement in shared decision making with their physician, he said.
Failure to Keep Appointments Failure to keep follow-up appointments is another commonly encountered problem with impoverished men with PCa. This could present problems if patients opt for active surveillance (AS), which requires a patient’s commitment to PSA testing at regular intervals, possible follow-up imaging studies, and prostate biopsies. For all patients considering AS, Dr Reese explained, he carefully explains the follow-up protocol and emphasizes the importance of keeping medical appointments. When patients have clearly shown they are unable to adhere to the follow-up requirements, Dr Reese said, he will reemphasize that adherence to follow-up is essential to make sure their cancer is well controlled. “But if they’ve missed multiple appointments despite my best attempts to contact them and reach out to them, then I will recommend that perhaps surveillance is no longer the best option and recommend a transition to definitive treatment.” In a small percentage of cases, patients “just disappear,” he said.
Third-Party Difficulties Insurance status also can present issues in PCa management. For example, getting third-party payer approval for magnetic resonance imaging (MRI) scans of the prostate prior to prostate biopsy, which has been shown to improve diagnostic precision, “can be a little more challenging in the underinsured or poorly insured patient.” Moreover, poverty-stricken patients who have undergone RP could face obstacles in obtaining treatments for postoperative complications, such as Transportation to medical visits can be a problem for men of low SES.
continued on page 34
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Bicalutamide Added to ADT for mCSPC Not Beneficial ADDING A FIRST-generation antiandrogen such as bicalutamide to androgen deprivation therapy (ADT) for metastatic castration-sensitive prostate cancer (mCSPC) does not improve outcomes compared with ADT alone, according to an analysis of real-world evidence presented at the virtual 2021 Genitourinary Cancers Symposium. In a retrospective study of data from the Veterans Health Administration database, a team led by Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and the Durham VA Medical Center in Durham, North Carolina, found that ADT plus a firstgeneration anti-androgen and ADT alone were associated with a similar time to
development of castration-resistant disease (21.4 vs 22.5 months). Both treatments also were associated with a similar death risk, with median overall survival not reached in either study arm. In an interview with Renal & Urology News, Dr Freedland noted that older data suggested that adding an antiandrogen to ADT improved survival, albeit modestly. It remains unclear, however, whether there is a true lack of benefit from this combination or whether the new results reflect more common use of anti-androgens to treat men with aggressive disease, he said. Their team was not able to adjust for all confounders. Still, the study suggests no benefit from adding a first-generation to ADT.
PCa treatment barriers
Another dilemma Dr Nabhami faces when treating indigent men with PCa is an inability to contact them to schedule and remind them of appointments, as these individuals may not have stable addresses and phone numbers. Courtney M.P. Hollowell, MD, chairman of urology at Cook County Health in Chicago, Illinois, which provides health care to a large underserved population, said he has found that patients of low SES with PCa are more likely than their high SES counterparts to present with locally advanced or metastasis disease. Dr Hollowell said he attributes this disparity in large measure to lower rates of PSA screening among
continued from page 32
pads for urinary incontinence and oral medications to treat erectile dysfunction, he said. Dr Reese led a study titled “Association of low socioeconomic status with adverse prostate cancer pathology among African American men who underwent radical prostatectomy” that was published in 2019 in Clinical Genitourinary Cancer.1 The research ultimately found that low SES was associated with more advanced pathologic stage and higher rates of seminal vesicle invasion and positive surgical margins and adverse features compared with high SES. “Low education levels are common among men with socioeconomically disadvantaged neighborhoods and this lack of education likely works in concert with SES in predisposing patients to adverse prostate cancer outcomes,” the authors wrote.1 Jamal Nabhami, MD, chief of urology at Los Angeles County + USC Medical Center (LAC + USC) in Los Angeles, California, which serves a predominantly low SES population, said patients’ lack of health insurance is his biggest impediment to treating and monitoring patients of low SES at his institution. In addition, these patients may have problems keeping medical appointments, such as transportation issues and loss of pay from having to take off work to make those visits. “Circumstances in life sometimes make follow-up more difficult,” he said. “In our healthcare system, we try to meet those needs as much as possible.” For example, staff will try to work with patients to schedule appointments that are convenient for them.
In a study, low SES increased the risk for adverse prostate cancer pathology. impoverished men caused in part by lack of access to regular preventative healthcare services, such as those provided by primary care doctors. “Patients of low socioeconomic status are much more likely to be uninsured and not be plugged into a healthcare system and see a doctor on a regular basis,” Dr Hollowell said, adding that many men consulting with him for the first time have never been screened for PCa, have a higher PSA at diagnosis, and a shorter survival rate than those of a higher SES.” Other reasons for the low rate of PSA screening among low-income men include a controversial 2012 recommendation against the practice from the US
Importantly, Dr Freedland said, the novel hormonal therapies (enzalutamide, apalutamide, and abiraterone) and docetaxel do offer a significant survival advantage and should be the drugs of choice to add to ADT.
The newer hormonal therapies or docetaxel should be the drugs of choice to add to ADT. The study included 1395 patients with mCSPC who initiated treatment from 2014 to 2018: 874 treated with ADT
Preventive Services Task Force and a general mistrust of the healthcare system. Moreover, some men of low SES “have the attitude of, ‘What you don’t know won’t hurt you,’” Dr Hollowell said. He noted that smoking, being overweight, physical inactivity, and other unhealthy lifestyle factors can be more prevalent in a low SES population and could also contribute to worse PCa outcomes.
Skyrocketing Cancer Drug Costs Making anticancer medications available to patients presents a challenge to providing optimal care, he said. The cost of these drugs are rising at an alarming rate “while the poor [patients] I see every day struggle with out-of-pocket costs and sticker shock for these lifesaving cancer treatments,” Dr Hollowell said. “It’s difficult to make a decision between lifesaving treatment and food on the table.” Despite financial hardships faced by many patients with PCa, Dr Hollowell has found that these men generally take their disease management seriously. Socioeconomic status has not been a major barrier for patient follow-up, he said. “When patients know that they have a serious cancer, and they understand the importance of its treatment and follow-up, my patients not only show up, they show up on time, and they show up for every visit.” Mohummad Minhaj Siddiqui, MD, associate professor of surgery at the University of Maryland School of Medicine and director of urologic oncology and robotic surgery at the University of Maryland Greenebaum
alone; 338 treated with ADT plus an anti-androgen; 75 who received ADT plus abiraterone; and 108 who received ADT plus docetaxel. Dr Freedland and his colleagues pointed out in their poster presentation that the median time to castration-resistant disease and risk of death observed in their study for both ADT plus an anti-androgen and ADT alone were similar to published data from corresponding placebo arms in clinical trials of novel hormonal therapies, such as STAMPEDE and LATITUDE, but inferior to outcomes in the treated arms of these trials, “indicating significant room for survival improvement in the mCSPC population.” n
Comprehensive Cancer Center in Baltimore, sees many patients from impoverished parts of the city and outlying areas of the state. It is not uncommon for him to consult with patients who present with advanced or aggressive PCa, and he attributes this in part to a lack of health insurance. Without a way to pay for regular PCa screening, men may wait until they experience symptoms of later-stage disease such as pain to seek medical care, he explained, adding that some of his patients, prior to meeting with him, had not been to a doctor in many years. In addition, Dr Siddiqui related that some poverty-stricken patients struggle with the rigors of living on the streets, so routine medical care may rank low on their list of concerns. “If they’re dealing with homelessness, then prostate cancer screening is not a high priority in their lives,” Dr Siddiqui said. Still, although patients of low SES often face obstacles to adhering to follow-up appointments, they do take their PCa care seriously, Dr Siddiqui said, adding: “When patients are diagnosed with cancer, it’s surprising how motivated they can be no matter how crazy their lives may be.” n REFERENCES 1. Weprin SA, Parker DC, Jones JD, et al. Association of low socioeconomic status with adverse prostate cancer pathology among African American men who underwent radical prostatectomy. Clin Genitourin Cancer. 2019;17:e1054-e1059. doi:10.1016/j. clgc.2019.06.006 2. Weiner AB, Matulewicz RS, Tosoian JJ, et al. The effect of socioeconomic status, race, and insurance type on newly diagnoses metastatic prostate cancer in the United States (2004-2013). Urol Oncol. 2018;36:91.e1-91.e6. doi:10.1016/j. urolonc.2017.10.023 3. Hellenthal N, Parikh-Patel A, Bauer K, et al. Men of higher socioeconomic status have improved outcomes after radical prostatectomy for localized prostate cancer. Urology. 2010;76:1409-1413. doi:10.1016/j.urology.2010.03.024
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Renal & Urology News 35
Ethical Issues in Medicine Patients’ hesitancy to receive a COVID-19 vaccination may stem from their underlying moral values BY DAVID J. ALFANDRE, MD, MSPH
Concern About Safety Issues Vaccine hesitancy is not unique to the SARS-CoV-2 vaccine as evidenced by the extensive literature on the phenomenon particularly with pediatric vaccines. There are some unique elements to the current pandemic that are relevant for consideration, however. Although vaccine hesitancy for COVID-19 has been declining since September 2020, so called “nonintent” to receive the SARSCoV-2 vaccine is currently at 32%, which is high enough to potentially impair an effective public health response to hasten the end of the pandemic.1 Those who do not intend to receive the vaccine among those surveyed included
from a patient’s healthcare professional, and ensuring broad and equitable vaccine distribution across all populations.
Moral Foundations Theory Another possible approach is to persuade individuals with interactions guided by moral foundations theory. The theory describes the natural inclination to embed moral judgments within decision making.2 It suggests that human beings have innate intuitions that lead them to emotional responses for approval or disapproval. According to the theory, people make decisions based on these (often unconscious) intuitive processes and then after the fact generate reasons and justifications for their decision.3 Six moral foundations have been proposed, including care/harm, authority/ subversion, loyalty/betrayal, liberty/ oppression, purity/degradation, and fair ness/cheating. People either uphold these virtues or are vigilant against violations of them. A wide variety of research has tested the application of the moral foundations theory to predicting attitudes about climate change, suicide, philanthropy, and for our purposes, vaccines. Using validated measures of individuals’ morality, one of which is a 30-item questionnaire available at www. moralfoundations.org, investigators can
Whatever the strategy used to encourage patients to get vaccinated, it is important to be respectful and empathize with their concerns and perspectives. younger adults, women, non-Hispanic Black adults, adults living in nonmetropolitan areas, adults with less education and income, and those without health insurance. The most commonly cited reasons for nonintent were concerns about vaccine side effects and safety, lack of trust in the government, and concern that the vaccines were developed too quickly. Initial strategies to address this hesitancy include public health educational campaigns, trusted counseling
identify the moral valence of the subjects and then associate them with certain attitudes. For example, compared with research subjects who were not vaccine hesitant, subjects who were vaccine hesitant were significantly more likely to have moral foundations that rest on purity and liberty.4 These subjects were more likely to believe that vaccines were impure and should not be allowed to defile the body. The messages healthcare p rofessionals are using to persuade patients to accept
© FRANK HARMS / ALAMY STOCK PHOTO
he recent arrival of effective vaccines against SARS-CoV-2 was a major scientific and public health triumph over a devastating pandemic that has already resulted in more than 543,000 deaths in the United States as of March 22. But as we’re seeing, the scientific advances that made this vaccine possible are just the first step. We will not succeed unless we figure out how to get the vaccine into enough people’s arms. Even with flawless vaccine distribution, though, public health experts expect that a significant portion of the US population will be hesitant to accept the vaccine.
Persuading patients to get vaccinated may require ferreting out how they make decisions.
the vaccine may be falling on deaf ears. If vaccine-hesitant people are influenced by morality related to purity or liberty, then haranguing them about how the vaccine protects themselves or others in their community (ie, appealing to the moral foundation of care) is not likely to change their mind.
Whatever strategy clinicians use to encourage vaccinations, it is important to be respectful and empathize with patients’ concerns and perspectives. Get patients talking to assess how they make decisions. That is good for patient care and hopefully a more effective way to get more patients vaccinated. ■
Tap Into Decision-Making Processes Healthcare providers are not likely to have patients in their office fill out a 30-item moral foundation questionnaire, possibly making it difficult to know how they have made personal decisions in the past. Healthcare providers might want to engage patients in conversations to ferret out what sort of language they use to describe making such decisions. For example, do patients talk about loyalty or fairness or liberty in how they make decisions? Tapping into that decision-making process may help to break a logjam when struggling to provide medical advice. Patients who have previously talked about not wanting to take medication because they prefer natural products may have a moral valence towards purity. Rather than trying to convince them of vaccine efficacy, it may be more effective to say that vaccination boosts the body’s natural defenses against disease and that vaccination keeps the body free (and thus pure) of other dangerous infections.
David J. Alfandre MD, MSPH, is a healthcare ethicist for the National Center for Ethics in Health Care (NCEHC) at the Department of Veterans Affairs (VA) and an Associate Professor in the Department of Medicine and 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 NCEHC or the VA. REFERENCES 1. Nguyen KH, Srivastav A, Razzaghi H, et al. COVID-19 vaccination intent, perceptions, and reasons for not vaccinating among groups prioritized for early vaccination — United States, September and December 2020. MMWR Morb Mortal Wkly Rep. 2021;70:217–222. doi:10.15585/mmwr.mm7006e3 2. Graham J, Nosek BA, Haidt J, Iyer R, Koleva S, Ditto PH. Mapping the moral domain. J Pers Soc Psychol. 2011;101:366-385. doi:10.1037/a0021847 3. Hauser M, Cushman F, Young L, Kang-Xing Jin R, Mikhail J. A dissociation between moral judgments and justifications. Mind Lang. 2007;22,1–21. doi:10.1111/j.1468-0017.20066.00297.x 4. Amin AB, Bednarczyk RA, Ray CE, Melchiori KJ, et al. Association of moral values with vaccine hesitancy. Nat Hum Behav. 2017;1:873-880. doi:10.1038/ s41562-017-0256-5
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Practice Management I
nsights from a study published recently in the Journal of the American Medical Informatics Association may point the way to a new approach for better preparing patients for discharge from the hospital.1 The goal of the study was to see if it was possible to facilitate more proactive discharge preparations for patients or their designated caregivers by using digital health apps integrated with the electronic health record (EHR). The investigators administered a structured checklist and a video via mobile device through a patient portal. Participants were also given a webbased survey at least 24 hours prior to their anticipated discharge. The checklist responses were instantly available to clinicians to review via a safety dashboard accessible from the EHR.
Discharge ‘A Chaotic Time’ “We did this study because discharge can be a chaotic time for patients and their caregivers with lots of information, lots of new changes, medications, and follow-up instructions,” said lead investigator Anuj K Dalal, MD, an associate physician at Brigham and Women’s Hospital and an associate professor of medicine at Harvard Medical
significantly longer after implementation of the program compared with before implementation (10.13 vs 6.21 days). While it was not what the research team predicted or hoped, as a non-randomized study there were likely other factors at play that could have confounded the results, according to the investigators. “For example, patients who completed the checklist had many comorbidities, were sicker, and were less activated or engaged in their care overall,” Dr Dalal said. “I think the results are likely to be positively received in the medical community in terms of examining more closely what we as clinicians can do to better the process of discharging patients.” In theory, if clinicians proactively identify patients’ concerns a day or so before their anticipated discharge date, they can decrease the amount of time spent reacting to these concerns on the day of discharge. Dr Dalal said many of the instructions clinicians provide on the day of discharge can be overwhelming and difficult to remember. In the current study, the checklist results were sent to the EHR, but it still required clinicians to look at the results. The investigators avoided actively notifying clinicians to minimize the risk of “alert fatigue.”
Patient discharge can be hectic for hospital-based clinicians, who often are under a lot of pressure to ensure this process occurs efficiently and safely. School, Boston, Massachusetts. “It can also be hectic for hospital-based clinicians, who are often pulled in a multitude of directions, and under considerable pressure to get patients discharged efficiently and safely.” The current study included 673 general medicine patients older than 18 years who were hospitalized for at least 24 hours at Brigham and Women’s Hospital. Patients who completed the checklist had a longer length of stay. However, the mean length of stay was
Now is the time to consider how best to use new technology to optimize healthcare delivery systems and workflows in a way that centers on the patients’ concerns, especially around the time of discharge, Dr Dalal said. “That is truly the only way to deliver high quality and safe healthcare,” he said. “If this can be efficiently and effectively done, then ultimately this information can streamline the care process and help clinicians identify what is most important to patients and respond to it quickly.”
© PEOPLEIMAGES / GETTY IMAGES
Leveraging of digital tools is needed to improve hospital discharge preparedness and optimize healthcare delivery BY JOHN SCHIESZER
Identifying patients’ concerns a day or so before hospital discharge can facilitate the process.
UVA Health System Experience The University of Virginia (UVA) Health System in Charlottesville is among the institutions that has employed digital technology to improve healthcare delivery. Bethany M. Sarosiek, RN, MSN, who is with the UVA’s Enhanced Recovery After Surgery (ERAS) Program, said her health system uses the EPIC MyChart patient portal to communicate directly with patients. It has helped to streamline information delivery and ensure fast communication, particularly during the COVID-19 pandemic when clinical situations change day-to-day. “It has allowed us to send information about changing COVID policies, visitation restrictions, and modification of schedules in almost real time,” Sarosiek said. This portal requires active engagement by the patient to sign up for participation. Sarosiek said the best routes to assure sign-up or ease user burden are still being explored. “I believe ‘alert fatigue’ is always a potential issue with any electronic system we use. It’s a constant challenge to find the right balance between providing enough information to allow for full understanding at the risk of information overload,” Sarosiek said.
As part of the colorectal ERAS program, UVA Health worked with a local digital technology company, Willowtree®, to create a user-friendly app to assist with patient education delivery by issuing notifications, reminders, and direct provider communication. The app provides information “bites” around the time of the surgery, including medication instructions, information on preparation for surgery, parking instructions, and daily goal reminders. After discharge, patients receive reminders about appointments, and they are asked about their pain and wound healing. The patients have a direct way to communicate with their care team if issues arise. “With the support of this app, our ERAS program has continued to improve post-surgical outcomes and minimize postoperative complications, all while keeping patients engaged with their care teams and improving overall satisfaction with the ERAS program,” Sarosiek said. ■ John Schieszer is a freelance medical writer based in Seattle, Washington. REFERENCE 1. Dalal AK, Pniella N, Fuller TE, et al. Evaluation of electronic health record-integrated digital health tools to engage hospitalized patients in discharge preparation. Published online January 19, 2021. J Am Med Inform Assoc. doi:10.1093/jamia/ocaa321
Renal & Urology News publishes timely news coverage of scientific developments of interest to nephrologists and urologists, including in-dep...
Published on Mar 30, 2021
Renal & Urology News publishes timely news coverage of scientific developments of interest to nephrologists and urologists, including in-dep...