Renal & Urology News - May-June 2020 issue by Haymarket Media

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COVID-19 Impacts Transplant Centers BY JODY A. CHARNOW RECIPIENTS of transplanted kidneys and other organs are at high risk for COVID-19 as a result of being on immunosuppressive medications, and those who contract the disease often experience a disease course that is more severe than in the general population. As a result, transplant centers have decreased the number of transplants they perform, according to the findings of a national survey of solid organ transplant (SOT) programs conducted by Dorry L. Segev, MD, PhD, of Johns Hopkins Medical Institutions in Baltimore, and colleagues.

Of 111 transplant centers surveyed, 79.3% responded, Dr Segev’s team reported in an article published online in the American Journal of Transplantation. Of the programs that perform live-donor kidney transplants, 71.8% reported complete suspension of these transplants. In addition, 80.2% of deceased-donor kidney transplant programs reported operating with at least some restrictions. Respondents reported a total of 148 SOT recipients with COVID-19 who were less than 1 year to more than 10 years post-transplant. Of these, 69.6% were kidney recipients. Survey results

Higher Uric Acid Ups HTN Risk ELEVATED SERUM uric acid (SUA) levels are associated with development of hypertension and vascular and renal target organ damage, according to a new long-term study. Investigators studied 961 parents and 570 children who were initially healthy at the time of recruitment into the STANISLAS cohort, a singlecenter familial longitudinal cohort that

Researchers found the association in a study of a familial longitudinal cohort.

began recruiting patients during 1993 to 1995. The primary objective of the cohort was to investigate gene-gene and gene-environment interactions as they relate to cardiovascular diseases. A team led by Patrick Rossingnol, MD, of Université de Lorraine, INSERM CIC-P, CHRU de Nancy, Nancy, France, analyzed the impact of SUA on hypertension risk and target organ damage using values obtained at visit (V) 1 (baseline), V2 and V3 (conducted approximately 5 and 10 years later, respectively), and V4 (conducted from 2011 to 2016). Among the parents, each 0.79 mg/ dL (70 µmol/L) increment in SUA level at V1 and V4 was significantly associated with 32% and 33% greater odds of continued on page 8

Most programs put live-donor transplants on hold

FEWER KIDNEY TRANSPLANTS are taking place during the COVID-19 pandemic.

showed that 78.1% of respondents used hydroxychloroquine, 46.9% used azithromycin, 31.3% used tocilizumab, and 25% used remdesivir to treat patients. “In conclusion,” the authors wrote, “this national survey of SOT programs suggests that COVID-19 is widely

COVID-19 Not Tied to RAAS Inhibitor Use INHIBITORS of the renin-angiotensinaldosterone system (RAAS) do not appear to increase the risk of COVID19 or its severity, according to the findings of 3 studies published in the New England Journal of Medicine. Physicians have been concerned about a potential increased risk of COVID-19 related to medications that act on the RAAS because the viral receptor is angiotensin-converting enzyme 2. One study, by Harmony R. Reynolds, MD, and collaborators at New York University Grossman School of Medicine, examined the relationship between previous treatment with ACE inhibitors, angiotensin-receptor blockers (ARBs), beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative COVID-19 test result. The study included 12,594 patients who were tested for COVID-19. Of the 5894 patients (46.8%) who tested positive, continued on page 8

recognized in the United States as a major threat to the field of SOT. However, there were no consistent policies, testing practices, or treatment mechanisms.” In an article published online in The Lancet on May 11, French researchers continued on page 8

IN THIS ISSUE 10

CKD predicts worse outcomes after radical prostatectomy

Medication found to alleviate CKD-associated pruritus

Voclosporin shows promise in lupus nephritis cases

Coffee drinkers are at lower risk for kidney disease

NSAIDs found safer than opioids in patients with CKD

Study reveals a new risk factor for calciphylaxis

COVID-19 pandemic forces doctors to adapt and improvise

Earlier use of radium-223 may improve quality of life among men with mCRPC by preventing skeletal events. PAGE 13

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American Urological Association 2020 Virtual Experience

Survival Predictors of Post-RP PSA Relapse Identified READILY AVAILABLE clinical variables can predict the long-term risk of death from prostate cancer (PCa) and other causes among men who experience biochemical recurrence of PCa

following radical prostatectomy (RP), according to new study data. Using a statistical method called recursive partitioning, investigators found that men at highest risk for PCa-

specific mortality (PCSM) are those with a PSA doubling time (PSADT) of less than 9 months and those who preoperatively had high-risk tumors according to D’Amico criteria. Men at highest

risk of other-cause mortality (OCM) are those aged 70 years and older with any major comorbidity, according to a team led by Timothy J. Daskivich, MD, of Cedars-Sinai Medical Center in Los

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Angeles. The study also demonstrated that the 10-year cumulative incidences of PCSM and OCM are low, even among men with high-risk tumors. “Potential applications of this data include individualizing prognosis for men with biochemical recurrence afterradical prostatectomy by readily available

clinical variables,” Dr Daskivich said during a virtual press conference. The study included 1225 men who had biochemical recurrence (BCR) following RP from 2000 to 2017 identified using the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Men had a median age of

65 years at BCR. Preoperative D’Amico tumor risk was low in 278 patients (23%), intermediate in 520 (42%), and high in 427 (35%). During a median follow-up time from BCR of 5.6 years, 68 patients (6%) died from PCa and 243 patients (20%) died from other causes, the researchers reported.

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Compared with men who had low-risk tumors by D’Amico criteria, those with high-risk tumors had 4.1-fold and 3.3fold increased risks for PCSM and metastasis, respectively. A PSADT less than 9 months was significantly associated with nearly 2.5-fold and 2.3-fold increased risks for PCSM and metastasis, respectively.

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American Urological Association 2020 Virtual Experience

Post-RP PSA relapse

continued from page 3

The 10-year cumulative incidence of PCSM was 4%, 6%, and 14% among men with D’Amico low-, intermediate-, and high-risk tumors, respectively. The 10-year cumulative incidence of

metastasis for these risk groups were 5%, 11%, and 16%, respectively. The 10-year cumulative incidence of PCSM was higher for men with a PSADT of shorter than 9 months than those with a longer PSADT (9% vs 4%). The 10-year cumulative incidence of metastasis for these PSADT groups was 16% and 8%,

respectively. Men aged 70 years or older had a 2-fold increased risk of OCM compared with men younger than 65 years. Compared with men who had a Charlson comorbidity score of 0 at BCR, those with a score of 1, 2, and 3 or more had significant 1.6-, 1.6-, and 2.4-fold increased risks for OCM, respectively. The 10-year

cumulative incidence of OCM for men older than 70 years with at least 1 major comorbidity was 40% or higher. “Integration of this information into clinical practice can help patients and physicians understand the disease better and hopefully lead to better management,” Dr Daskivich said. ■

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■ NKF 2020

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National Kidney Foundation 2020 Live-Virtual Spring Clinical Meetings

Rapid-Progressing ADPKD Most Common in South PATIENTS with autosomal dominant polycystic kidney disease (ADPKD) who live in the southern United States are the most likely to be at risk for rapid progression and chronic kidney disease (CKD)

stage 4 or 5. These differences may be related to a higher prevalence of risk factors for CKD progression in the southern United States, such as obesity and hypertension, as well as sociocultural and envi-

ronmental differences, such as disparities in access to healthcare, Cynthia Willey, PhD, of the University of Rhode Island in Kingston, and colleagues concluded in a poster presentation.

“Increased awareness of the social and environmental factors that contribute to CKD disparities could lead to a better understanding of how contextual risk factors modify ADPKD progression,” they wrote. Using IBM MarketScan administration claims in 2017, the investigators studied 4536 patients who had continuous health plan enrollment and 2 or more ADPKD diagnoses. The proportion of patients at risk of rapid progression was highest in the South (42.1%) and lowest in the West (31.6%). The proportion of patients with CKD stage 4/5 or who had a kidney transplant by age 55 ranged from 13.1% in the West and Northeast to 18.2% in the South. The proportion of patients on dialysis ranged from 7.1% in the West to 11.0% in the South. The proportion of obese patients ranged from 10.6% in the West to 15% in the South. ■

High IL-6 Ups Risk of CAC Progression DIALYSIS PATIENTS with high levels of interleukin 6 (IL-6) may have greater risks for progression of coronary artery calcification (CAC) and death. Neil Roy, MBBS, and Sylvia E. Rosas, MD, MSCE, of Joslin Diabetes Center, Harvard Medical School, Boston, studied CAC progression in 101 incident dialysis patients. At baseline, Agatston calcium scores for individuals with high vs low IL-6 (using a median 3.1 pg/mL as a cutoff) were 55.2 vs 4.75. Over 12 months, patients’ calcium scores increased to 120.9 and 22.1, respectively. Results showed that 28% of participants with IL-6 above the median died compared with 18% of those below the median. On multivariable linear regression, IL-6 was an independent risk factor for CAC progression. Each 1 log increase in IL-6 was associated with a 2.4-fold increase in death risk. Fibroblast growth factor 23, smoking, and diabetes were not found to be major contributors. ■

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Contents

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VOLUME 19, ISSUE NUMBER 3

Nephrology 11

ONLINE

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

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

Drug Relieves CKD-Associated Pruritus Difelikefalin, an investigational oral medication, shows promise in treating the condition regardless of chronic kidney disease stage. CKD Risk Lower Among Coffee Drinkers Meta-analysis reveals a significant 13% decreased risk among individuals who drink coffee compared with those who do not. Microwave Ablation Safe for SHPT Investigators report significant declines in parathyroid hormone over 6 months. SGLT2 Inhibitors Better for Kidney Health Sodium-glucose co-transporter 2 inhibitors are associated with a lower risk for serious renal events than dipeptidyl peptidase-4 in patients with type 2 diabetes.

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

Greater Muscle Mass Predicts Longer OS in Advanced PCa Each 1 mm2/m2 increase in muscle mass was significantly associated with a 1% decreased risk of death, a study found.

Cryoablation Efficacious for Small Renal Tumors In a study, estimated local tumor progressionfree survival rates at 3 and 5 years were 98.3% and 94.9%, respectively.

Job Board

Earlier Radium-223 Use May Improve mCRPC Outcomes Median overall survival time was 15 months for the entire cohort but 23 months among those who received the drug as first-line therapy.

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

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

Editor’s note: With the cancellation of medical conferences thus far in 2020 in response to the COVID-19 pandemic and the status of other meetings unclear, we are providing listings of medical conferences scheduled for 2021. Genitourinary Cancer Symposium San Francisco January 21 to 23, 2021 American Urological Association Annual Meeting Las Vegas May 13–14, 2021 ERA-EDTA Annual Congress Berlin, Germany June 5–8, 2021 Canadian Urological Association Annual Meeting Niagara Falls, Ontario, Canada June 26–29, 2021 International Continence Society Annual Meeting Melbourne, Australia October 12–15, 2021

Urology

Drug Information

CALENDAR

Ureteroscopy Prior to UTUC Surgery Ups IVR Risk Patients who underwent preoperative ureteroscopy had a 1.4-fold increased risk of intravesical recurrence compared with patients who did not.

We know that achieving remission status in lupus

kidney disease correlates with good long-term kidney survival and so the results of this study are very encouraging. See our story on page 11

Departments 7

From the Editor The COVID-19 pandemic shows how small the world really is

News in Brief Variant RCC subtypes increase the risk of cancerspecific mortality

Ethical Issues in Medicine Apologizing for a medical error has benefits

Practice Management Ensure good cybersecurity when using telemedicine

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Renal & Urology News 7

FROM THE EDITOR EDITORIAL ADVISORY BOARD

The World Is Small. A Pandemic Proves It

he rapid spread of coronavirus disease 2019 (COVID19) caught the world by surprise. Whatever becomes the new normal, the United States will be a different country from what it was on March 13, when President Donald J. Trump declared a national emergency. At this writing on May 28, more than 100,000 people in the United States have died from the disease. Much of the nation’s population has had to hunker down at home and nonessential businesses have had to close on orders from state governors, and the economy has shriveled. Americans now need no convincing that pandemics are a real and grave threat. The nation must treat them as such and make rigorous preparations for the next one. Physicians and other caregivers were severely hampered by shortages of personal protective equipment, ventilators, and other lifesaving devices. Stockpiling of these items for future use as well as development of protocols for handling massive influxes of critically ill patients into hospitals should be a priority for medical centers and government agencies so they are prepared for whatever infectious disease crisis comes next. And the world is ripe for pandemics. Cities around the globe continue to grow and increase in population density. Passenger jets crisscross oceans and continents, flying millions of people internationally each year. When it comes to opportunities to spread, contagions have never had it so good. Eliminating these opportunities, therefore, is key to stopping outbreaks, with social distancing, sanitizing surfaces, washing hands, and wearing face masks fundamental to the effort. COVID-19 has forced an unprecedented proportion of the American workforce to work from home, enabling people to avoid contracting the disease from coworkers and fellow commuters on buses and trains. Thanks to telemedicine, physicians replaced thousands of in-person medical visits nationwide with virtual encounters, thereby eliminating the risk of viral transmission between patients and caregivers. It took a novel coronavirus that surfaced half way around the world to demonstrate the interconnectedness of the nations of the world and show Americans the danger of complacency about infectious disease outbreaks in faraway lands. With contagions, international travel and trade have made the distance between places largely irrelevant. But so has the internet. Although China has been accused of withholding information early on about the true transmissibility of the coronavirus, physicians in Italy and elsewhere who eventually had to grapple with COVID-19 outbreaks were able to share their experiences quickly and widely via social media and online journals, giving doctors worldwide a speedy heads-up about what to expect. The world is small indeed. Jody A. Charnow Editor

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, medical communications Jennifer Dvoretz Production manager Brian Wask Vice president, sales operations and production Director of audience insights National accounts manager Editorial director, Haymarket Oncology

Louise Morrin Boyle Paul Silver William Canning Lauren Burke

Vice president, content, medical communications Kathleen Walsh Tulley General manager, medical communications President, medical communications Chairman & CEO, Haymarket Media Inc.

James Burke, RPh Michael Graziani Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 19, Number 3. 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 reprints/ licensing, email Kerry Niessing at kerry.niessing@haymarketmedia.com, or call (646) 638-6026. 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 © 2020.

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Transplant centers continued from page 1

reported that deceased-donor organ transplantations during the pandemic declined by 51.1% and 90.6% in the United States and France, respectively. The reduction in both countries was driven mostly by a decrease in kidney transplantation, according to Alexandre Loupy, MD, PhD, of the Paris Translational Research Centre for Organ Transplantation, and colleagues. “Transplant professionals will need to adapt to these rapidly changing circumstances, provide reassurance to their patients, and remain poised to reinvigorate the valuable transplant infrastructure when the COVID-19 crisis begins to abate,” they wrote.

Zero risk does not exist Richard N. Formica, MD, Director of Transplant Medicine the Yale School of Medicine in New Haven, Connecticut, and President-Elect of the American Society of Transplantation, said transplant programs should not allow the risk of infection with the SARS-CoV-2 coronavirus, the cause of COVID-19, to dissuade transplantation. Programs that do not want to perform transplants to protect patients “are not truly weighing the risks,” believing they are taking the safe option for patients, Dr Formica said. The notion of zero risk does not

RAAS inhibitor use continued from page 1

1002 (17%) had severe illness. A total of 4357 patients (34.6%) had a history of hypertension. Of the 2573 (59.1%) patients with a positive test, 634 (24.6%) had severe illness. Dr Reynolds’ team reported finding no association between any single medication class and an increased likelihood of a positive test. In a population-based case-control study in the Lombardy region of Italy, Giuseppe Mancia, MD, at the University of Milano-Bicocca, and colleagues

Uric acid and HTN risk continued from page 1

hypertension, respectively, after adjusting for age, gender, smoking status, and other possible confounding variables, Dr Rossingnol and his colleagues reported in the American Journal of Hypertension. Each increase of 0.57 mg/ dL in SUA between V1 and V4 was significantly associated with 25% greater odds of hypertension.

exist. The programs need to consider the risks that patients with organ failure face by not receiving a transplant. For example, dialysis patients who are candidates for a kidney transplant already are at risk of exposure to SARS-CoV-2 in dialysis units as well as traditional infections associated with dialysis, such as bacterial infections from vascular access. They also are at risk of other dialysis related complications. “This is the new environment we are in, and we need to figure out a way to do our jobs in these new conditions,” he said. Dr Formica’s program, which has about 40 kidney transplant recipients who have tested positive for COVID19, has instituted measures to protect patients. Staff members advise patients to follow recommendations from the Centers for Disease Control and Prevention and emphasize the need for social distancing, wearing face masks in public, and washing hands. They advise patients to monitor their temperature twice a day. In the outpatient setting, he said, immunosuppressive regimens remain the same for patients who do not have COVID-19. Physicians maintain immunosuppression for patients who test positive for COVID-19, but discontinue antimetabolites and decrease tacrolimus dosages. “For new transplant recipients, we’re still immunosuppressing based upon

Center in Bronx, New York, 10 (28%) died during a median follow-up of 21 days, Enver Akalin, MD, and colleagues reported online in the New England Journal of Medicine on April 24. Of 11 patients who were intubated, 7 (64%) died. Of the 36 patients, 28 (78%) were hospitalized and 8 (22%) were in stable condition without major respiratory symptoms and were monitored at home.

“Our results show a very high early mortality among kidney-transplant recipients with Covid-19—28% at 3 weeks as compared with the reported 1% to 5% mortality among patients with Covid-19 in the general population who have undergone testing in the United States and the reported 8 to 15% mortality among patients with Covid-19 who are older than 70 years of age,” the authors wrote. Writing in the American Journal of Transplantation, physicians at Columbia University Irving Medical Center and Weill Cornell Medicine in New York reported their initial experience with 90 solid organ transplant recipients— including 46 kidney recipients (51%)— with COVID-19. All had tested positive for SARS-CoV-2 in an inpatient or outpatient setting from March 13 to April 3, 2020. Of the 90 patients, 68 were hospitalized. Twenty-three patients (26% overall, 34% of inpatients) required ICU admission. Overall, 16 (18%) died from COVID-19 complications. The death rate was 24% of inpatients and 52% of ICU patients. In the same journal, Vinay Nair, DO, and colleagues reported on a case series of 10 KTRs who tested positive for COVID-19 at Northwell Health acute care hospitals in the New York area, 9 of whom were hospitalized. Three patients (30%) died, and AKI developed in 5 (50%). ■

c ompared 6272 confirmed COVID-19 cases to 30,759 controls matched by age, sex, and municipality of residence. Because of their greater prevalence of cardiovascular disease (CVD), the COVID19 patients were more likely to use ACE inhibitors and ARBs. The researchers found no evidence, however, that these drugs influenced COVID-19 risk. The third study evaluated the relationship of CVD and drug therapy with inhospital mortality among 8910 patients with COVID-19 at 169 hospitals in Asia, Europe, and North America. Of these, 515 (5.8%) died in the hospital and 8395

(94.2%) survived to discharge. The study, led by Mandeep R. Mehra, MD, of Brigham and Women’s Hospital in Boston, found no increased risk of inhospital death associated with the use of ACE inhibitors or ARBs. “We were not able to confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital mortality in this clinical context,” Dr Mehra’s team wrote. “Taken together, these three studies do not provide evidence to support the hypothesis that ACE inhibitor or ARB use is associated with the risk of

SARS-CoV-2 infection, the risk of severe Covid-19 among those infected, or the risk of in-hospital death among those with a positive test,” John A. Jarcho, MD, a deputy editor for the New England Journal of Medicine, and coauthors wrote in an accompanying editorial. “Each of these studies has weaknesses inherent in observational data, but we find it reassuring that three studies in different populations and with different designs arrive at the consistent message that the continued use of ACE inhibitors and ARBs is unlikely to be harmful in patients with Covid-19.” ■

An analysis of the whole study population (parents and children) found that each 0.79 mg/dL increment in SUA was significantly associated with 28% increased odds of hypertension at V1, but was not significantly associated with hypertension at V4. Each 0.57 mg/dL (50 µmol/L) increment in SUA between V1 and V4 was significantly associated with 25% increased odds of hypertension. Higher baseline SUA was marginally associated with an increased risk of

having high carotid-femoral pulse wave velocity, the investigators reported. The study found an association between SUA with blood pressure (BP) that was dependent on body mass index, with the increase in BP being greater in leaner participants. The association between SUA and decline in estimated glomerular filtration rate (eGFR) was age dependent, with older individuals experiencing greater eGFR declines. Dr Rossingnol’s team found

no significant association between SUA and diastolic dysfunction or left ventricular hypertrophy. A major strength and novelty of the study was that it looked at an initially generally healthy population with a large sample size that included children, and had long-term term follow-up, the investigators noted. Study limitations included its observational nature, which precluded establishing a cause link between hypertension and uric acid. ■

what we assume their risk profile was and how we would have done it before,” Dr Formica said. “We’re doing that because we don’t want to end up setting up a situation where we under immunosuppress somebody upfront, they have a rejection, and then you’ve got to dump immunosuppression on them.”

Transplant recipients hard hit Recently published medical papers reveal how severe COVID-19 can be in transplant recipients. In a case series of 36 consecutive adult kidney transplant recipients who tested positive for COVID-19 at Montefiore Medical

Transplant patients hospitalized with COVID-19 have a high death rate.

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Urologic cancer spike continued from page 1

a result of elective surgeries that had been postponed during the peak of COVID-19 restrictions. “These run the gamut from robotic prostatectomies to vasectomies; essentially anything that was not truly deemed ‘emergent’ was subject to a delay,” Dr Holton said. “In our state, the stay-at-home order was in place for about 7 weeks so, for some types of procedures, literally hundreds were deferred. Addressing this backlog is a priority for our practice, and we are working to optimize our resources with staffing, location, and coordinating with our hospitals to get these done expediently.” “I definitely think that many patients are choosing to defer visits for standard-of-care procedures such as PSA screening or evaluation of pain and blood in the urine,” said Sumanta

AYA testosterone levels continued from page 1

424.96, 431.76, and 451.22 ng/dL in 2003-2004, 2011-2012, 2013-2014, and 2015-2016, respectively, The declining trend was statistically significant.

Body mass index is a factor Elevated body mass index (BMI) was significantly and independently associated with decreased TT levels, with mean BMI rising from 25.83 kg/m2 in 19992000 to 27.21, 27.12, 27.81, 27.96 kg/m2 in 2003-2004, 2011-2012, 2013-2014 and 2015-2016, respectively. Even in men with normal BMI (18.5-24.9 kg/m2), TT levels declined from 664.79 to 529.24 ng/ dL between 1999-2000 and 2015-2016. The decline in testosterone in AYA men in the United States has many potential causes. “The biggest and most seemingly obvious may be the rise in obesity and BMI in young men,” Dr Lokeshwar told listeners. According to the Centers for Disease Control

Expanded PN use continued from page 1

nephrectomy even in high-risk cohorts,” Dr Abel told Renal & Urology News. The inclusion of only the highest-risk patients from 4 high-volume centers is a distinguishing feature of the study, said Dr Abel, Associate Professor of Urologic Surgery. Dr Abel and his collaborators identified recurrent disease in 256 patients

Pal, MD, a medical oncologist and Co-Director of the Kidney Cancer Program at City of Hope, a comprehensive cancer center in Duarte, California. “I anticipate that there will likely be a big spike in cases that we see in the clinics once quarantine measures are lifted, and my greatest fear is that many of these will be advanced cases that could have been prevented with earlier intervention.” “We may see patients presenting with more advanced cancers,” said urologist Brian Stone, MD, who is in private practice at Jasper Urology in Jasper, Alabama. In response to state-imposed restrictions, his practice had to decrease patient flow by limiting their workload to urgent cases. This affected patients with elevated PSA levels who had been referred for evaluation or were already scheduled to undergo biopsies, thereby possibly delaying prostate cancer diagnoses. He and his colleagues have been using magnetic resonance imaging

and Prevention, the US prevalence of obesity was 13.9% in 1999-2000, and this rose to 18.5% in 2015-2016, he pointed out. Other possible explanations include a decline in physical activity and changes in body composition over time. “Even in men with a normal BMI, body fat percentage may have increased on a national scale, which may be due to this decrease in physical activity,” he said.

(MRI)-ultrasound fusion technology for several years and addressed this delay by using that technique to screen patients who had high PSA levels and insurance coverage for the procedure “so at least we could stratify patients based on a PIRAD score and risk.” They typically would biopsy patients with high PIRAD scores (4 or 5).

Deferred patient visits could delay diagnostic work-ups that result in detection of cancer. Judd W. Moul, MD, Professor of Surgery in the Division of Urologic Surgery at Duke Cancer Institute in Durham, North Carolina, said “there is going to be pent up demand once primary care doctors start seeing patients again for check-ups and once patients

are not scared to go to the ER and to the doctor for various complaints.” The Duke Cancer Institute has a strong working relationship with the Duke Primary Care Network, which is a source of referrals. Although phy etwork have not been sicians in the n on the front lines of routine care since around March, and North Carolina has not been hit hard by COVID-19, the pandemic has affected the institute’s caseload. “Our referrals for elevated PSA have pretty much dried up temporarily,” Dr Moul related. “This is leading now to less prostate biopsies now in midMay, and fewer men coming in for newly diagnosed prostate cancer.” In addition, “bread-and-butter” urologic consultations, such as those for cases of hematuria and incidental renal masses, are down temporarily, Dr Moul said. “This will gradually change as healthcare opens back up, but it is not just like turning the spigot back on,” he said. ■

Low testosterone (less than 300 ng/ dL) was detected in 2201 men (29%). On multivariable analysis, men whose activity level exceeded the recommended activity level had significant 37% decreased odds of low testosterone compared with those who had lower than recommended activity levels (reference group). Meeting the recommended physical activity levels had no significant effect on the likelihood of low testosterone.

Effects of low testosterone Declining testosterone levels in AYA men with increased obesity could lead to the early development of cancer. “And testosterone levels in AYA men are utilized as the benchmark normal levels for testosterone,” Dr Lokeshwar said. “This is very scary because generally when we think of normal values of testosterone, we treat based upon this age group. This may ultimately lead to the undertreatment of testosterone deficiency, which can

have large ramifications and severe consequences.” For the study looking specifically at the effect of physical activity and serum testosterone levels, Richard Fantus, MD, of the University of Chicago, and collaborators used 2011-2016 NHANES data from 7597 men who met inclusion criteria. They converted all physical activity into metabolic equivalent of task (MET) minutes per week. Using recommendations from the US Physical Activity Guidelines Advisory Committee, Dr Fantus’ team divided the cohort into 3 groups based on activity level: less than recommended (below 500 MET minutes per week), recommended (from 500 to 1000 MET minutes per week), and greater than recommended (above 1000 MET minutes per week). Of the 7597 men, 4461 (58.7%) exceeded the recommended activity level, 703 (9.3%) met the recommended activity level, and 2433 (32%) did not meet the recommended activity level.

(26.4%) at a median of 8.3 months following attempted curative surgery. On multivariable analysis, tumor diameter, nuclear grade, tumor thrombus, and systemic symptoms were independently associated with RCC recurrence risk. Recurrence risk did not differ between PN and RN. In a study of 446 patients with clinical T2 renal masses—a group that consisted of 73 PN patients propensity score matched to 373 RN patients—

Matvey Tsivian, MD, and colleagues at Mayo Clinic in Rochester, Minnesota, reported finding that complication rates were similar for the PN and RN patients (19% vs 13%, respectively). Severe complications were more common in the PN group (4% vs 2%), but the difference was not statistically significant. The decline in estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) at 1 and 3 years was more pronounced

in the RN than PN group (16 vs 5 and 13 vs 2, respectively). A greater proportion of RN patients had new-onset eGFR below 60 at 1 and 3 years (55% vs 17% and 48% vs 17%, respectively). Clinical and radiographic features were well balanced between the groups, the investigators noted. In a subset of patients with RCC, overall, cancer-specific, and metastasisfree survival rates were similar, according to Dr Tsivian’s team. ■

Association limited to obesity When the investigators stratified the population according to BMI, they found that the association of higherthan-recommended activity with a reduced risk of low T was present only among obese men. When counseling men regarding low T and exercise, “it’s incredibly important to really counsel the obese population, as exercise independent of weight loss may show additional benefits,” Dr Fantus said. ■

www.renalandurologynews.com MAY/JUNE 2020

Renal & Urology News 9

News in Brief

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

Short Takes FDA Okays Lokelma Label Update for HD Patients

denosumab (60 mg) reduced serum

The FDA has approved a label update

no significant increases in mean CAC

for AstraZeneca’s oral potassium

volume score (-165 mm3) or Agatston

binder sodium zirconium cyclosilicate

score (-133) over 6 months. In con-

(Lokelma) to include a dosing regimen

trast, a control group of 21 age- and

to treat hyperkalemia in patients on

sex-matched patients receiving standard

hemodialysis (HD). According to the

therapy had significant increases in both

update, clinicians should use a starting

mean CAC volume score (188 mm3)

dose of 5 g once daily on non-dialysis

and Agatston score (387) from base-

days. In patients with serum potassium

line based on serial electrocardiography-

levels higher than 6.5 mmol/L, they

gated computed tomography.

calcium and phosphate and resulted in

should consider a starting dose of 10 g discontinue the medication if predialysis

Drug for Low-Grade UTUC Gets Expedited Approval

serum potassium after the long interdia-

UroGen Pharma has received FDA

lytic interval falls below target range or

expedited approval of mitomycin for

hypokalemia develops.

pyelocalyceal solution (Jelmyto) to

once daily on nondialysis days and

treat low-grade upper tract urothelial

Denosumab May Slow CAC Progression in Severe SHPT

carcinoma (UTUC) in adult patients.

Denosumab may slow progression

on data from the ongoing open-label,

of coronary artery calcification (CAC)

single-arm phase 3 OLYMPUS trial,

and potentially reverse osseous

which assessed the efficacy of the

calcification in patients with secondary

drug in 71 adults with treatment-naïve

hyperparathyroidism (SHPT) who have

or recurrent noninvasive low-grade

severe cases of high bone turnover,

UTUC. Of these patients, 41 (58%)

according to new research published

achieved a complete response (CR) at

in Osteoporosis International.

3 months after the start of treatment.

In a study of 21 dialysis patients with low bone mass, treatment with

The FDA granted the approval based

Investigators estimated the durability of CR at 12 months to be 84%.

Hypertension in the US During 2017-2018, the prevalence of age-adjusted hypertension among individuals aged 18 or older in the United States was 45.4%, and was higher among men than women (51% vs 39.7%), data from the National Health and Nutrition Examination Survey show. The prevalence increased with age, as shown below. 74.5%

54.5%

22.4% 20

18-39

40-59 Age Group (in years)

Source: CDC. National Center for Health Statistics.

60+

Multifocal Tumors in UTUC Patients Up Recurrence Risk P

atients who have upper tract urothelial carcinoma (UTUC) with multifocal tumors have a higher risk for the most common type of recurrence following surgery, data suggest. Of 550 patients with UTUC (median age 68 years; 57% female) from Taichung Veterans General Hospital in Taiwan, urinary bladder recurrence occurred in 164 patients (29.8%) at a median 8.4 months from radical nephroureterectomy. Another 5.5% of patients experienced contralateral recurrence. In a multivariate analysis of 15 clinicopathological factors, such as tumor grade and stage and lymphovascular invasion, UTUC tumor multifocality emerged as the sole significant prognostic factor for urinary bladder recurrence, Chuan-Shu Chen, MD, and collaborators from the hospital reported in Diagnostics. Patients with multifocal tumors had a 40% higher risk for urinary bladder recurrence than patients with single tumors.

Early RRT for Severe AKI Found Not to Up Survival T

he timing of renal replacement therapy (RRT) initiation does not appear to influence survival in critically ill patients with severe acute kidney injury (AKI) who have no life-threatening conditions, researchers reported in The Lancet. A team led by Didier Dreyfuss, MD, of the University of Paris Louis Mourier Hospital in France, conducted a systematic review and meta-analysis of 9 randomized trials with a low risk of bias published during 2008 to 2019. Of 1879 patients with AKI stage 2 or 3 based on Kidney Disease Improving Global Outcomes (KDIGO) guidelines or a renal Sequential Organ Failure Assessment score of 3 or higher, 946 were assigned to the delayed RRT group and 933 to the early RRT group. Similar proportions of the early and delayed RRT groups died within 28 days (44% vs 43%), 60 days (51% vs 51%), and 90 days (55% vs 56%), Dr Dreyfuss’ team reported. A subgroup analysis also found no significant differences in mortality between patients with and without pre-existing chronic kidney disease.

Study: Variant RCC Subtypes Linked to Increased CSM S

ome variant histological subtypes of renal cell carcinoma (RCC) are associated with an increased risk of cancer-specific mortality (CSM) compared with the clear-cell RCC subtype, investigators reported in The Journal of Urology. Of 69,785 RCC patients in the Surveillance, Epidemiology, and End Results registry, 2495 had variant histology. Among variant cases, 70.1% were sarcomatoid, 11.2% collecting duct, 7.6% mesenchymal, 3.8% neuroendocrine, 2.9% renal medullary, 2.5% mucinous tubular and spindle cell (MTSCC), and 2.0% rhabdoid tumors. Marina Deuker, MD, of University Hospital Frankfurt in Germany, and colleagues reported finding a significant 1.6- and 1.8-fold higher CSM risk for collecting duct and sarcomatoid subtypes, respectively, and 1.7- and 1.5-fold increased CSM risk for renal medullary and rhabdoid subtypes, respectively, compared with grade 4 clear cell RCC. The researchers found similar cancer death rates for mesenchymal, neuroendocrine, and MTSCC subtypes.

10 Renal & Urology News

■ AUA 2020

MAY/JUNE 2020 www.renalandurologynews.com

American Urological Association 2020 Virtual Experience

Data Support AS for Small Renal Masses Active surveillance offers long-term oncologic efficacy similar to that of partial or radical nephrectomy ACTIVE surveillance (AS) for small renal masses (SRMs) among older patients offers long-term oncologic efficacy equivalent to surgery, and it is not inferior to primary intervention for patients with SRMs suspicious for renal cell carcinoma, data from separate studies suggest. Mark Sullivan, MD, and colleagues at Oxford University Hospitals in the UK reviewed findings from 208 patients with 212 T1a SRMs. Of these, 76 were managed with AS, 93 with partial nephrectomy (PN), and 39 with radical nephrectomy (RN). Over a median follow-up of 9.4 years, the mean growth rate of SRMs managed by AS was 0.9 mm/year, with 55% of these SRMs showing zero or negative growth. Fourteen (18%) of AS patients underwent intervention due to tumor growth or patient choice. Metastatic disease developed in 7.8% of AS patients compared with 12.9% and 10.3% of PN and RN patients, respectively. A tumor growth rate greater than 5 mm per year

CKD Predicts Worse Post-RP Complications PATIENTS WITH chronic kidney disease (CKD) and end-stage renal disease (ESRD) are at higher risk for worse postoperative outcomes after radical prostatectomy (RP) compared with patients without CKD. In an analysis of 2009 to 2015 data from 23,014 RP patients New York State, Olamide Omidele, MD, and colleagues at the Icahn School of Medicine at Mount Sinai in New York found that CKD patients had significant 3.7-fold increased odds of a long hospital stay and 1.6- and 4.4-fold increased odds of 30-day and 90-day hospital readmission, respectively. Patients with ESRD had nearly 3.7fold increased odds of a long hospital stay and 4.4-fold increased odds of both 30-day and 90-day hospital readmission, the investigators reported in a poster presentation.

Active Surveillance vs Nephrectomy A study found no statistically significant difference in overall and cancer-specific survival among patients who underwent active surveillance and partial and radical nephrectomy for small renal masses. ■ Active surveillance

■ Partial nephrectomy

97.1%

100

90.3%

75.3%

80 60

■ Radical nephrectomy

52.9%

89.7%

41%

20 0

Overall survival

Cancer-specific survival

Source: Sullivan M, et al. Active surveillance of small renal masses in an older population offers long-term oncological efficacy equivalent to partial or radical nephrectomy. Presented at the American Urological Association 2020 Virtual Experience held in May. Abstract MP80-18.

on AS approached statistical significance for development of metastases. Dr Sullivan’s team observed no significant difference among the groups with regard to overall survival (OS) and cancerspecific survival (CSS): 52.9% and 97.1%, respectively, for the AS group,

CKD and ESRD were not significantly associated with mortality at 1 year, according to the researchers. Dr Omidele and his collaborators also documented an increase in the proportion of RP patients with CKD or ESRD, which rose from 1.6% in 2009 to 3.6% in 2015. “The results suggest that the number of patients undergoing radical prostatectomy with CKD or ESRD is increasing, and these patients are at significant risk for postoperative complications,” Dr Omidele said in a virtual presentation.

Largest study of its kind For the study, the investigators used data from the Statewide Planning and Research Cooperative System (SPARCS) database, which is an allpayer statewide reporting system maintained by the New York State Department of Health. The study involved the largest real-world cohort of patients with CKD and ESRD who have undergone RP, according to the investigators. With regard to study limitations, the authors pointed out that the SPARCS database lacked pathologic and staging data. ■

75.3% and 90.3% for the PN group, and 41% and 89.7% for the RN group. In another study, Joseph Cheaib, MD, MPH, of the Brady Urological Institute at Johns Hopkins University School of Medicine in Baltimore, along with principal investigator Phillip Pierorazio,

MD, and colleagues analyzed 10-year prospective data from the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) registry showing that AS appears to be as safe as, and not inferior to, primary intervention among carefully selected patients with SRMs suspicious for RCC. Of 785 enrolled patients, 348 (44.3%) opted for primary intervention and 437 (55.7%) chose AS. Out of the AS cohort, 67 (15.3%) underwent delayed intervention. The median follow-up time for the entire study population was 3.3 years, with 287 patients (36.6%) followed up for 5 years or more. The researchers observed no significant difference in CSS at 10 years between the primary intervention and AS groups (99.2% vs 99.7%, respectively). OS, however, was higher among the primary intervention patients than the AS group at 7 years (90.9% vs 64.2%) and 10 years (83.4% vs 58.5%). The AS cohort had a 10-year progressionfree survival rate of 63.8%. ■

Greater Muscle Mass Predicts Longer OS in Advanced PCa OBESITY AND SARCOPENIA are asso-

nonmetastatic castration-resistant,

ciated with worse overall survival (OS)

and metastatic castration-resistant

in men with metastatic or castration-

disease, respectively.

resistant prostate cancer, new study findings suggest. Greater muscle mass, however, independently predicts longer OS. “This study explores the complex

Sarcopenia (muscle mass less than 550 mm2/m2) was present in 64 patients (40.6%) and obesity (30 kg/m2 or higher) was present in 68 men (60.3%). Sarcopenia was associated with worse

interplay of body composition and

OS and obesity was associated with

metabolism with advanced prostate

better OS over a mean 3.18 years of

cancer outcomes, highlighting the

follow up, Dr Huelster and her colleagues

important role of nutritional and lifestyle

reported in a poster presentation.

counseling in comprehensive prostate

On multivariate analysis, higher muscle

cancer care,” lead investigator Heather

mass was a significant predictor of

Huelster, MD, of Vanderbilt University

longer OS survival, and increasing age

Medical Center in Nashville, Tennessee,

was a significant predictor of worse

told Renal & Urology News.

OS. Each 1 mm2/m2 increase in muscle

The findings are from a study of 182

mass was significantly associated with a

men with a mean age of 70.7 years.

1% decreased risk of death. Each 1-year

Of these men, 30.2%, 22%, and 47.8%

increase in age was significantly associ-

had metastatic castration-sensitive,

ated with a 3% increased risk of death. ■

12 Renal & Urology News

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CKD Risk Lower Among Coffee Drinkers Meta-analysis reveals a significant 13% decreased risk of incident chronic kidney disease

NSAIDs Safer Than Opioids in CKD Cases OPIOID USE IS more strongly associ ated with adverse events than nonste roidal anti-inflammatory drug (NSAID) use among patients with chronic kidney disease, new data suggest. In a study of 3939 participants in the Chronic Renal Insufficiency Cohort (CRIC) study, investigators found that time-updated cumulative opioid use, compared with nonuse, was sig nificantly associated with a 1.4-fold increased risk of a kidney disease com posite outcome of a 50% reduction in glomerular filtration rate (GFR) from baseline or kidney failure requiring kidney replacement therapy (KRT), after adjusting for time-dependent covariates. Opioid use also was signifi cantly associated with 1.4-, 1.5- and 1.7fold increased risks for kidney failure with KRT, pre-kidney failure death, and hospitalization, respectively, a team led by Jeffrey C. Fink, MD, MS, of the University of Maryland School of Medicine in Baltimore, reported in the American Journal of Kidney Diseases.

Drinking coffee is renoprotective, data show.

for comorbidity and other potential confounders, suggest that coffee itself was responsible for the lower risk,” the authors wrote. “However, the exact mechanisms that could lead to the reno-protective effect of coffee are not known with certainty and further investigations are required.”

Similar results emerged from an analysis restricted to a subcohort of participants who reported ever using other analge sics (non-opioid and non-NSAID) or tramadol. In that subcohort, opioid use, compared with nonuse, was significantly associated with a 1.6-, 1.5-, 1.6-, and 1.7fold increased risk for the kidney disease composite outcome, kidney failure with KRT, pre-kidney failure death, and hos pitalization, respectively. Time-updated cumulative NSAID use in the full cohort, compared with non use, was significantly associated with a 1.2-fold increased risk for the kidney disease composite outcome and 1.1-fold increased risk of hospitalization. Among black individuals, however, NSAID users had a significant 1.3-fold increased risk of the kidney disease composite out come compared with nonusers. In the subcohort, the investigators found no significant association between NSAID use and any of these outcomes. “In conclusion, our study findings sug gest that opioid use is associated with greater harm than NSAIDs, with a sub stantial increase in risk for death and poor kidney outcomes,” the authors wrote. The cohort had a median 6.84 years of follow-up. Of the 3939 participants, 391 (9.9%) and 612 (15.5%) reported baseline use of opioids and NSAIDs, respectively. ■

Anti-oxidative effects The most plausible explanation is related to anti-oxidative effects of coffee as atherosclerotic injury to the kidneys is among the most common underlying mechanisms in the patho genesis of CKD, according to the inves tigators. In vitro and clinical studies have demonstrated that caffeine has anti-oxidative and anti-inflammatory effects that can reduce oxidative stress, they noted. One of the studies included in the meta-analysis was an analysis of 14,209 participants in the Atherosclerosis Risk in Communities (ARIC) study. During a median follow-up duration of 24 years, 385 cases of incident CKD devel oped. Compared with individuals who never drank coffee, those who drank 3 or more cups per day had a signifi cant 16% decreased risk of CKD after adjusting for clinical, demographic, and dietary factors, Emily A. Hu, MHS, of

the Welch Center for Prevention, and Clinical Research at Johns Hopkins University in Baltimore, and colleagues reported in a paper published in 2018 in the American Journal of Kidney Diseases. Each additional cup of cof fee consumed per day was significantly associated with a 3% lower risk of inci dent CKD. Another study in the meta-analysis included 8717 individuals with nor mal renal function recruited from the Korean Genome and Epidemiology Study cohort. In adjusted analyses, consuming 1 cup of coffee and 2 or more cups per day was significantly associated with a 24% and 20% decreased risk of CKD , respectively, compared with nondrinkers, Jong Hyun Jhee, MD, of Inha University College of Medicine in Incheon, Korea, and colleagues reported in a 2018 article in the American Journal of Medicine. ■

Cryoablation for Small RCC Tumors Found Safe, Efficacious IMAGE-GUIDED percutaneous cryoabla-

researchers reported in the American

tion is a safe and efficacious treatment

Journal of Roentgenology. The investiga-

for selected small renal cell carcinoma

tors identified residual unablated tumor

(RRC) tumors, new findings suggest.

on the first follow-up scan in 4 (2.2%) of

Joint first authors Emma Lim, MBChB,

183 tumors. The estimated local tumor

and Shankar Kumar, MBBS, senior

progression-free survival at 3 and 5

author, and attending interventional radi-

years was 98.3% and 94.9%, respec-

ologist Miles Walkden, FRCR, and others

tively. No distant metastases or deaths

at University College London Hospitals

attributable to RCC occurred.

NHS Foundation Trust and University

The mean estimated glomerular

College London, studied 180 patients

filtration rate (in mL/min/1.73 m2 ) was

who underwent image-guided percutane-

69.7 after the procedure and 70.7 and

ous cryoablation for a total of 185 clinical

69.8 at 1 and 2 years post-procedure,

stage T1 biopsy-proven RCC lesions. “To

respectively. These values did not

our knowledge this series represents

differ significantly from the mean value

one of the largest cryoablation cohorts

before the procedure (72.4 ).

in the literature and is the first to shed

Major complications (Clavien-Dindo

some light on the effect of cryoablation

classification grade III or higher)

on renal function,” the authors noted.

occurred in 4 (2.2%) of 185 cases.

The investigators identified 168 cT1a

The investigators concluded that

lesions (90.8%) and 17 cT1b lesions

“image-guided cryoablation offers a

(9.2%). The mean lesion size was

promising treatment option for cT1 RCC,

28.5 mm (range 11 to 58 mm).

offering long-term oncologic outcomes

The procedure was technically suc-

that rival more invasive methods with the

cessful in 183 (98.9%) of 185 cases, the

benefit of an improved safety profile.” ■

COFFEE CONSUMPTION is asso ciated with a reduced risk of incident chronic kidney disease (CKD), a recent systematic review and meta-analysis confirmed. The meta-analysis of pooled data from 4 cohort studies with a total of 25,849 participants found that cof fee drinkers had a significant 13% decreased risk of incident CKD com pared with nondrinkers, investiga tors Thatsaphan Srithongkul, MD, and Patompong Ungprasert, MD, MS, of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, reported in the European Journal of Internal Medicine. The current study is the first system atic review and meta-analysis to explore the risk of incident CKD among coffee drinkers compared with non-drinkers, Drs Srithongkul and Ungprasert noted. “All of the included studies compre hensively adjusted their effect estimates

www.renalandurologynews.com MAY/JUNE 2020

Earlier Radium-223 Use May Improve mCRPC Outcomes By avoiding skeletal events, a better quality of life is possible, researcher says eveloped halfway through treatment d in about 75% of men. “Our most considerable finding is the fact that anemia seems to be more the expression of advanced disease than an adverse effect of radium-223 therapy,” Dr Lodi Rizzini, a radiation oncologist, told Renal & Urology News. Patients treated

IMAGE COURTESY OF ALEXANDER KUTIKOV, MD, FOX CHASE CANCER CENTER

BY JOHN SCHIESZER RADIUM-223 treatment may be appropriate for first- or second-line therapy in men with metastatic castration-resistant prostate cancer (mCRPC). In a study of 63 men with mCRPC who underwent radium-223 treatment, the median overall survival (OS) time

First-line use of radium-223, a bone-seeking radioisotope, may improve outcomes in men with symptomatic bone metastases from advanced castration-resistant prostate cancer.

was 15 months for the entire cohort but 23 months for men who received the drug as first-line therapy, investigators reported in Scientific Reports. Radium-223 is an alpha-emitting bone-seeking radioisotope indicated for use in men with mCRPC and symptomatic bone metastases. In the study, which was conducted by Elisa Lodi Rizzini, MD, and colleagues at DIMES University of Bologna in Bologna, Italy, radium-223 was administered as first-line therapy to 11 patients, second-line therapy to 19 patients, third-line therapy to 16 patients, and in successive lines to 17 patients. Each man received radium-223 every 4 weeks for up to 6 cycles. Patients had a median age of 76.8 years, and more than 50% had comorbid heart disease. Of the 63 patients, 42 (67%) completed all 6 cycles. Within 1 month after the end of 6 cycles, 35.7% of men had achieved a partial response, 26.2% had stable disease, and 33.3% had progressive disease. Pain levels diminished with each successive cycle. The most frequent treatment-related toxicity was low-grade hematologic toxicity (predominantly G1-G2), which

early with supportive care (iron supplementation and/or blood transfusions) were able to complete radium-223 treatment with higher hemoglobin levels and less painful symptoms. “In our opinion, the best candidate for the therapy is the patient with higher hemoglobin levels, lower levels of osteoporosis, and with oligometastatic disease,” Dr Lodi Rizzini said. “Our take-home message, in contrast with the current guidelines, is that early treatment with radium-223 with an early supportive care (iron and anti-resorptive boneactive drugs) can significantly improve quality of life by avoiding skeletal events as well as prolong overall survival.” In the current study, 52 (82.5%) of the 63 men had received at least 1 line of systemic therapy and 33 (52.4%) had received 2 lines of systemic therapy, most commonly abiraterone and cabazitaxel before starting radium-223. Kelvin A. Moses, MD, PhD, Associate Professor of Urology at Vanderbilt University Medical Center in Nashville, Tennessee, said while radium 223 was approved for men with symptomatic bone metastases in the setting of CRPC based

on results from the ALSYMPCA trial, much is unknown about which patients may benefit the most. “Its role earlier in the disease process is unknown, as is the optimal sequence of therapy for men with mCRPC,” Dr Moses said. “This study in a small population of patients suggests that radium 223 as first-line or second-line treatment may be feasible.” “This study is not big enough to change clinical practice,” said Brent Hollenbeck, MD, Associate Professor of Urology at the University of Michigan in Ann Arbor, noting that although the findings are intriguing, the study is limited by its small sample size. “From a patient perspective, I think it may be a hard sell as first-line therapy over one of the oral agents since the majority of patients did not respond.” Judd W. Moul, MD, Professor of Surgery in the Division of Urologic Surgery at Duke Cancer Institute in Durham, North Carolina, said because the study is a small single-center its value is limited. Further, he said radium-223 had fallen out of favor due to the safety issues of using it with abiraterone. “The death rate was higher when patients received radium-223 plus abiraterone, and this put the use of this agent into a downward trend,” Dr Moul said. It might be better to sequence radium-223 earlier in the course of the disease so that patients are not so weakened from other therapies or their cancer when they get it, he said. “If a man is too advanced when he is prescribed radium 223, he will not be able to get the full course of 6 cycles,” Dr Moul said. “Without 5 to 6 cycles, there is felt to be minimal survival benefit. In this study, it is noteworthy and good that 67% of the study cohort were able to get all 6 cycles.” Phuoc T. Tran, MD, PhD, Professor of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins Medicine in Baltimore, said the new findings raise interesting issues involving the use of radium-223 earlier rather than later. “Sequencing of the life prolonging agents in the mCRPC space, of which radium-223 is one, has been and continues to be one of the most critical questions in the treatment of mCRPC.” ■

Renal & Urology News 13

Microwave Ablation Safe for SHPT MICROWAVE ablation (MWA) may be a safe and effective treatment for patients with secondary hyperparathyroidism (SHPT), according to investigators. Ming-An Yu, MD, PhD, of ChinaJapan Friendship Hospital in Beijing, and colleagues conducted a meta- analysis of 2 retrospective cohort studies and 6 self-control studies that included 233 patients with SHPT. Parathyroid hormone (PTH) levels significantly declined from baseline over 1 day, 1 week, 1 month, and 6 months of MWA, with weighted mean differences of 890, 860, 801, and 861 pg/mL, respectively. Serum calcium and phosphorus levels also significantly declined over 1 day and 1 week of MWA, but phosphorus fluctuated thereafter, according to results published in the International Journal of Hyperthermia. With respect to adverse events, hypocalcemia developed in 15.8% of patients treated with MWA, which is lower than the rate after parathyroidectomy. Another 1.2% of MWA patients experienced nerve injury. Temporary hoarseness occurred in 4.2%, which is higher than after parathyroidectomy, the investigators reported.

PTH levels declined during the 6 months after the procedure, meta-analysis finds. “This meta-analysis shows that MWA is a safe treatment for patients with SHPT,” Dr Yu’s team wrote. “The incidence of complications was below the threshold considered to indicate a lack of clinical safety.” MWA may translate into larger and more consistent ablation zones in less time compared with other thermal ablation procedures, they noted. “Compared to classical surgical treatment, MWA has many advantages, such as being minimally invasive, relieving pain, reducing costs, shortening the duration of hospitalization and decreasing recovery time,” the authors wrote. “Thus, MWA may become a valuable alternative treatment to treat SHPT in patients with enlarged parathyroid glands on ultrasonography.” ■

14 Renal & Urology News

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SGLT2 Inhibitors Better for Kidney Health Study supports use of this drug class in a broad range of patients with type 2 diabetes BY NATASHA PERSAUD SODIUM-GLUCOSE co-transporter 2 (SGLT2) inhibitors are associated with a lower risk for serious renal events than dipeptidyl peptidase-4 (DPP4) inhibitors in real-world patients with type 2 diabetes and various levels of renal function, according to new data from Sweden, Denmark, and Norway. Investigators used nationwide registry data to propensity-score match 29,887 new users of SLGT2 inhibitors (mostly dapagliflozin and empagliflozin) to 29,887 new users of DPP-4 inhibitors on 57 variables. Use of SGLT2 inhibitors was significantly associated with a 58% reduced relative risk of serious renal events (a composite of renal replacement therapy [RRT], death from renal causes, and hospitalization for renal events) and an absolute risk reduction of 3.6 events per 1000 person years (2.6 vs 6.2 events per 1000

Study: MetS Recovery Cuts CKD Risk INDIVIDUALS WITH metabolic syndrome (MetS) are at increased risk for chronic kidney disease (CKD), but those who recover from it have a reduced risk, according to a report in Kidney Research and Clinical Practice. In a population-based study in Korea, Sehoon Park, MD, of Seoul National University College of Medicine, and colleagues found that development of MetS was significantly associated with 26% increased odds of CKD in adjusted analyses, whereas recovery

person years, respectively), Peter Ueda, MD, PhD, of Karolinska Institutet in Stockholm, Sweden, and collaborators reported in BMJ. By individual component of the composite end point, use of SGLT2 inhibitors was significantly

Protective effects are independent of hyperglycemic control, data show. associated with a 68% and 59% lower risk for RRT and hospital admission for renal events, respectively, and a nonsignificant 23% lower risk for death from renal causes. The corresponding absolute risk reductions were −1.7 vs −2.9 vs −0.1 events per 1000 person-years, respectively.

In sensitivity analyses, the protective effect of SGLT2 inhibitors appeared independent from hyperglycemic control, reduced blood pressure, and weight loss, the researchers reported.

Effect greater in CKD patients In subgroup analyses, the decreased risk of the composite end point associated with SGLT2 inhibitors was significantly greater among patients with than without chronic kidney disease (70% vs 48%) and in those with than without cardiovascular disease (82% vs 48%), according to the investigators. “Although the absolute risk reduction associated with SGLT2 inhibitors was larger in patients with cardiovascular disease or chronic kidney disease, the protective association of SGLT2 inhibitors was also observed in patients without such history,” Dr Ueda’s team wrote. “The findings from this observational

study complement the data from clinical trials, as well as our previous observational study of cardiovascular outcomes, and provide further support for the use of SGLT2 inhibitors across a broad range of patients with type 2 diabetes with various levels of renal function.” In an accompanying editorial, Steven M. Smith, PharmD, of the University of Florida in Gainesville, praised the study while acknowledging that it is observational and subject to some confounding. Overall, the new findings “add to the impressive track record for SGLT2 inhibitors,” Dr Smith wrote. “Additional pragmatic comparative effectiveness trials in real world settings and more diverse populations could add further support for broader access to these drugs, not only in high income countries but also in lower income countries where the burden of kidney disease is disproportionately high.” ■

Epidural Risks in RC Cases Identified EPIDURAL USE AT time of radical cystectomy (RC) is associated with an increased risk for myocardial infarction (MI) and other adverse perioperative outcomes, but does not impact diseasespecific or overall survival, new study findings suggest. A comparison of perioperative outcomes among patients who underwent RC with and without epidural anesthesia found that the epidural group, compared with the no-epidural group, had a significantly higher rate of MI in the first 30 days after RC (2.6% vs 1.3%) and 30-day readmission (29.6% vs 26.2%) after propensity score adjustment, Brady L. Miller, MD, and colleagues at the University of Wisconsin in Madison

reported in the American Journal of Clinical and Experimental Urology. The epidural group also had a significantly longer median length of stay (9 vs 8 days) and had a decreased likelihood of being discharged directly to home without need for home health or skilled nursing care (21.6% vs. 29.1%). Perioperative 30-day mortality rates

Myocardial infarction is among the adverse perioperative outcomes, study finds.

did not differ s ignificantly between the groups. Epidural use was not associated with increased cancer-specific or overall survival, according to the investigators. The study included 7857 patients with non-metastatic bladder cancer identified using Surveillance, Epidemiology and End Results (SEER) and Medicare data. Of these patients, 1748 received an epidural and 6109 did not. Patients in both groups had a median age of 74 years. The authors said their results “may inform current clinical bladder cancer guidelines, which generally lack evidence for epidural use, especially in era of prioritizing readmission reduction, improved quality and cost- containment.” ■

from preexisting MetS was significantly associated with 16% decreased odds of CKD compared with those who had chronic MetS. Among the MetS components, change in hypertension was associated with the biggest difference in CKD risk. The study included 4,537,869 without MetS, 1,034,605 with chronic MetS, 438,287 who developed MetS, and 304,540 who recovered from preexisting MetS. ■

Ureteroscopy Prior to UTUC Surgery Ups IVR Risk PREOPERATIVE diagnostic ureteroscopy (URS) before radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) predicts an elevated risk for intravesical recurrence, according to investigators. In a study of 453 patients with UTUC undergoing radical nephroureterectomy, a significantly higher proportion

of patients who underwent preoperative URS experienced intravesical recurrence (IVR) than those who did not (43.8% vs 26.9%), Younsoo Chung, MD, of Seoul National University Bundang Hospital in Seongnam, and colleagues reported in Investigative and Clinical Urology. Patients who underwent preoperative URS had a

significant 1.4-fold increased risk of IVR compared with patients who did not, after adjusting for tumor stage, location, and other factors, according to investigators. The median time to recurrence was 107 months. The 5-year IVR-free survival rates were significantly lower in the ureteroscopy group (56.2% vs 73.1%). ■

www.renalandurologynews.com MAY/JUNE 2020

Renal & Urology News 15

New Calciphylaxis Risk Factor Revealed Potential life-threatening condition in hemodialysis patients associated with unintentional weight loss BY NATASHA PERSAUD RESEARCHERS FOR THE first time have identified unintentional weight loss as a risk factor for calciphylaxis in patients on hemodialysis (HD), according to a report in BMC Nephrology. In a case-control study, Raphaël Gaisne, MD, of Nantes University Hospital Center in France, and colleagues examined the records of 89 patients with calciphylaxis, also called calcific uremic arteriolopathy (CUA). The group included 19 patients with chronic kidney disease not on dialysis and 70 patients on HD. “We were surprised to identify so many non-dialyzed patients with calciphylaxis,” the investigators wrote. “The frontier between uremic calciphylaxis and non-uremic calciphylaxis is difficult to define.” Dr Gaisne’s team matched each HD patient with calciphylaxis to 2 control HD patients by age, sex, time period,

and region of treatment. Two-thirds of patients with calciphylaxis had a triggering event such as local trauma or hypovolemia. Each patient displayed a median 5 lesions mostly on the lower limbs or trunk.

Odds of calciphylaxis increased by 66% with each 1 kg of weight loss, researchers found. More than half of patients were obese and 71.9% were taking vitamin K antagonists (VKAs). Inflammation and bone mineral disease abnormalities (especially hyperphosphatemia and hyperparathyroidism), and malnutrition (eg, weight loss and serum albumin decrease) preceded calciphylaxis onset by 6 months.

In the HD patients with calciphylaxis, each 5 kg/m2 increase in body mass index was significantly associated with 56% increased odds of calciphylaxis compared with the HD control group. Each 1 kg of weight loss within 6 months of calciphylaxis diagnosis was significantly associated with 66% increased odds of calciphylaxis. HD patients with calciphylaxis were 5 times more likely than the control group to be using VKAs. Malnutrition and inflammation preceded onset of skin lesions and could be warning signs among dialysis patients at risk, the authors noted. Multimodal treatment commonly involved wound care (98.9%), antibiotherapy (77.5%), discontinuation of VKA (70.8%), discontinuation of active vitamin D (70.0%), and intravenous sodium thiosulfate (STS, 65.2%). The study found that 40% of patients died within a year of developing

Greater Temperature Differences More IV Iron Found to Worsen BPH Symptoms Does Not Up Infection Risk

GREATER DAILY temperature differ-

For the study, Dr Yu and colleagues

ences are associated with worsening

analyzed patient data obtained from

lower urinary tract symptoms (LUTS) in

South Korea’s National Health Insurance

men with benign prostatic hyperplasia

Service database. They retrieved

(BPH), new study data show.

temperature information from the Korea

The link emerged from a retrospec-

Meteorological Administration data-

tive study analyzing the effect of

base, from which they collected daily

changes in temperature on LUTS

maximum, minimum, and day tempera-

among 1,446,465 men with BPH in 6

ture differences for 10 years.

metropolitan areas in South Korea. “The results of our study show that

Dr Yu and colleagues found that a daily average of 28.5 patients visited

daily temperature differences are

an emergency department (ED) when

associated with the deterioration of

daily temperature differences were

symptoms in BPH patients,” a team

less than 39.2° F (4° C), whereas a daily

led by Ji Hyeong Yu, MD, PhD, of Inje

average of 42.2 patients visited an ED

University Sanggye Paik Hospital in

when daily temperature differences

Seoul, reported in a paper published

were greater than 57.2° F (14° C), an

in Urology. “Specifically, as the daily

increase of about 48%. After visiting

temperature difference increased,

an ED, a daily average of 11.9 patients

the urination symptoms of BPH

with AUR had a urethral catheter

patients worsened, while the number

inserted at a daily temperature differ-

of patients who visited the emergency

ence less than 39.2° F. When the daily

room increased, as did the number

temperature difference was greater

of patients who underwent urethral

than 57.2° F, the daily average number

catheterization due to acute urinary

of urethral catheter insertion cases was

retention (AUR).”

17.8, a 49% increase. ■

INTRAVENOUS (IV) high-dose iron does not increase the risk of infection among patients on hemodialysis (HD) compared with IV low-dose iron, new study findings suggest. In a prespecified secondary analysis of data from the PIVOTAL (Proactive IV Iron Therapy in Haemodialysis Patients) trial, investigators found no significant differences between IV high-dose and low-dose iron therapy in event rates for all infections (46.5% vs 45.5%, respectively), rates of hospitalization for infection (29.6% vs 29.3%), and death from infection (46% vs 41%), according to study findings published in the Journal of the American Society of Nephrology. “Given the potential cardiovascular beneﬁts seen in the PIVOTAL trial, this analysis provides further support for administering higher doses of intravenous iron than are currently given in many units worldwide,” a team led by Iain C. Macdougall, MBChB, MD, of Kings College Hospital in London, concluded.

lesions, typically while receiving palliative care. Surgical debridement, distal CUA, localization to the lower limbs, and noncalcium-based phosphate binders were associated with better survival. “Our study confirms the data reported by others on CUA but showed for the first time the contribution of significant unintentional weight loss,” Dr Gaisne’s team wrote. “Few therapeutic measures seem efficient. Among them, STS is commonly used, but its benefit has still to be proved.” The researchers noted that the non- dialyzed CUA patients were more obese and had more severe inflammation prior to CUA onset than the HD patients with CUA. “A link between arteriolar calcification and adipocytes could explain the preferential localization of calciphylaxis in adipose tissue areas and the increased risk of calciphylaxis associated with obesity,” they wrote. ■

Dr Macdougall and his collaborators found a significant association between the risk of a first cardiovascular event and any infection in the previous 30 days. In addition, patients who dialyzed with a catheter had a significantly higher incidence of any infection, hospitalization for infection, or fatal infection compared with patients who had an arteriovenous fistula for vascular access, but IV iron dosing had no effect on these outcomes, the investigators found. Regarding study limitations, the authors noted that their study was an anlaysis of secondary outcomes. Although the PIVOTAL trial is the largest randomized trial of iron in any patient population, it was conducted using a cohort of patients receiving HD, Dr Macdougall and his colleagues explained. “This is a very specific group of patients, with different infection risks and profiles from other patient groups,” they wrote. “Given the high incidence of infection in this group of patients, it was a good way to test the hypothesis of iron treatment on the risk of infection, but extrapolating the findings to other patient populations may not be justified.” The authors also pointed out that iron sucrose was the IV iron preparation used in the PIVOTAL trial, and it is unknown whether their findings from the secondary analysis can be extrapolated to other IV iron preparations. ■

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n FEATURE

Practicing in a Pandemic: Doctors Adapt, Improvise Experiences during the COVID-19 crisis could speed changes in healthcare delivery BY JODY A. CHARNOW

ealthcare systems and governments in the United States and much of the world have had to take unprecedented emergency measures to contain the coronavirus disease 2019 (COVID-19) pandemic. Social distancing has been a key component in the effort to prevent person-to-person transmission of SARS-CoV-2, the novel coronavirus that causes the disease. Medical practices have had to postpone elective procedures and cancel non-urgent face-to-face patient encounters. Patients have avoided going to emergency departments out of fear they might contract COVID-19, perhaps delaying diagnoses of serious diseases. Lessons learned from the pandemic may trigger an evolution in American healthcare delivery. The crisis has compelled the use of telemedicine across medical specialties, which could lead to entrenchment of this modality in clinical practice if healthcare providers and patients find that they like this type of interaction. COVID-19 prompted healthcare providers to think about ways to protect vulnerable populations, such as patients on dialysis or those with compromised immune systems. Physicians could discover how much delays matter in the diagnosis and treatment of certain diseases. The pandemic may accelerate adoption of tests that make invasive procedures unnecessary and change how clinical trials are conducted.

Telemedicine “Telemedicine is assuming tsunami-like growth and has reached the critical mass where patients will expect that their provider will be able to conduct a virtual visit,” said Neil Baum, MD, Professor of Clinical Urology at Tulane Medical

Doctors have turned to telemedicine as way to provide care to patients while protecting them.

School in New Orleans, a proponent of virtual medicine. “Practices that don’t offer telemedicine will find that patients will seek out a provider who does offer this service.” Telemedicine can enable urologists to improve access to their practices, reduce costs, enhance productivity, improve patient satisfaction, and perhaps reduce the high rate of physician burnout, Dr Baum said. “I would like to think that this COVID-19 crisis has opened up a new way for the urologist to implement telemedicine into their practices,” he told Renal & Urology News. Only a few years ago, the use of telemedicine was relegated to treating patients in rural areas or patients who were far from “bricks and mortar practices,” Dr Baum said. The COVID19 crisis and relaxation of Centers for Medicare and Medicaid Services (CMS) requirements for conducting telemedicine have made this modality attractive

to urologists. “Now urologists can treat patients 24/7 from their homes using laptops and even mobile devices to communicate with patients,” Dr Baum said. “What was once done using a telephone is now accomplished using synchronous audiovisual communication.” “It has greatly accelerated our telemedicine efforts,” said urologic oncologist John L. Gore, MD, MS, Professor in Urology and Adjunct Professor in Surgery at the University of Washington in Seattle, referring to the pandemic. “We’ve converted the overwhelming bulk of our practice to telemedicine.” Nephrologists also have greatly expanded their use of telemedicine, which provides a safer way to care for patients with end-stage renal disease (ESRD). This patient population is at high risk of contracting infections and suffering severe complications from them as a result of underlying health problems.

“Health professionals across the US are witnessing a radical transformation from in-person face-to-face care to virtual [care] as we strive to decrease the transmission of COVID-19 to healthcare professionals and ESRD patients,” nephrologist Martin J. Schreiber, MD, Chief Medical Officer for DaVita Home Modalities, said in an April 9 webinar that was part of a COVID-19 webinar series sponsored by the American Society of Nephrology (ASN). “We are seeing great telehealth adoption that would previously take years to advance, now occurring in literally weeks.” Despite “myths” that virtual health is too difficult or not effective or that patients prefer in-person encounters, “we now see that COVID has proved to be the ultimate virtual health myth buster,” Dr Schreiber added.

Virtual visits skyrocket At DaVita Inc., one of the two major providers of dialysis care in the United States, total telemedicine appointments rose by 950% from before the COVID19 pandemic to April 3, Dr Schreiber reported. Between the time before the pandemic and March, the percentage of physician visits completed via telemedicine rose by 659%. Fresenius Medical Care North America (FMCNA), the other major dialysis provider, reported that its telemedicine workflow grew by more than 150,000 virtual visits from late March to the end of April. At Integrated Medical Professionals, a Farmingdale, New York-based independent urology group of more than 100 providers and a clinical affiliate of The Mount Sinai Health System in New York City, 73% of medical encounters in the week ending April 17 were

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via telemedicine and 27% were office visits, according to data provided by the group’s chairman and CEO Deepak A. Kapoor, MD. By comparison, for the week beginning March 9, all medical encounters were office visits. “Certainly, we can anticipate that for some patients there will be a great appetite to continue the [telemedicine] services,” Dr Kapoor said. “Whether we can and will do so depends largely on behavioral changes in the patient population and guidance from regulatory bodies.” “Telemedicine has become huge,” said nephrologist Rajiv Agarwal, MD, MS, Professor of Medicine at Indiana University School of Medicine in Indianapolis. “It is the primary way we are seeing our patients.” He estimates that 90% of medical encounters are now telemedicine visits. Dr Agarwal authored an editorial in Nephrology Dialysis Transplantation in which he observed that most routine medical services were suspended in response to the pandemic, leaving patients with chronic illnesses exposed to potential harm because of a lack of access to routine medical care. “COVID-19 was pushing all other diseases by the wayside, and telemedicine rapidly emerged,” Dr Agarwal wrote. “Many of the rules [regarding telemedicine use] that would have taken years to be approved were passed almost overnight.” Jeffrey Giullian, MD, Chief Medical Officer at DaVita, said the pandemic has been “a catalyst for telehealth adoption” by physicians and home dialysis patients. “This is especially pertinent at this time when limiting exposure to others will increase safety measures for all our patients, teammates and physicians.” “We expedited the rollout of telemedicine technology in our centers to enable more virtual visits for our home and in-center patients,” said Jeffrey Hymes, MD, Chief Medical Officer for Fresenius Kidney Care, which is part of FMCNA. “This included creating updated policies, trainings, and support lines as quickly as possible.” Telemedicine use at FMCNA increased sharply due to increased demand for it, helped along by waivers from CMS that allow for reimbursement. “We hope that as patients and caregivers become more comfortable and familiar with the technology, there will be further adoption of telemedicine when we return to regular operations.”

Home dialysis Patients on dialysis are at particularly high risk for infection and a severe disease course from infection because of underlying health problems. Dialyzing

at home rather than in a dialysis center has the potential to reduce the likelihood of patients becoming infected. “The pandemic and the requirement for social distancing, and at times, isolation, have highlighted the advantages of dialysis at home,” Dr Hymes said. “We expect that the increased interest in home dialysis will continue even after the acute crisis passes and help expand the strong growth in home dialysis we have experienced over the past year.” During the first quarter of 2020, he said, the number of home dialysis trainings FMCNA conducted grew by 25% compared with the same period in 2019.

Unique opportunity “COVID-19 provides a unique opportunity to further interest and choice in home dialysis options,” said Shaminder Gupta, MD, a nephrologist in private practice in Houma, Louisiana, and Corporate Medical Director at Monogram Health, a renal disease care management company. Approximately 40% of Dr Gupta’s patients with ESRD dialyze at home. “Patients are rightfully worried about being in environments where there are chances of exposure to COVID-19 and other communicable diseases,” Dr Gupta said. “Home dialysis eliminates this possibility, and the current COVID-19 crisis is making patients realize this. I have found that patients are much more open to listening to these options now, and I have had some patients commit to conversion to peritoneal dialysis or home hemodialysis over the past few weeks.” Even before the pandemic, the National Kidney Foundation (NKF) had been working to increase the use of home dialysis through education, a home dialysis initiative, participation in the Home Dialysis Alliance, and advocacy, especially in support of the Advancing American Kidney Health Initiative launched by the Trump Administration on July 10, 2019. In response to the pandemic, NKF has ramped up efforts to expand home dialysis use. “NKF has been working to increase access to home dialysis in a number of ways in the context of the COVID-19 pandemic that gives home dialysis that is not only a patient-centric kidney replacement therapy, but also should reduce the risk of exposure to SARS-CoV-2,” said nephrologist Joseph A. Vassalotti, MD, NKF’s Chief Medical Officer. Jeffrey Perl, MD, a member of American Society of Nephrology (ASN) COVID-19 Response Team and chair of ASN’s Home Dialysis Subcommittee, said that in the short term, compelling

reasons exist to consider transitioning patients from facility-based dialysis to a home modality during the pandemic. He noted, however, that he believes the bigger consideration is the lessons that will be learned from the pandemic regarding the long-term distribution of dialysis modalities. “I would like to think that as horrible as the COVID-19 pandemic is, it’s a wake-up call that if patients can receive home-based care, they possibly should receive home-based care for a myriad of reasons,” Dr Perl said. “COVID has really been a true catalyst in transforming the care model for home patients,” Dr Schreiber said in the ASN webinar. “It’s not just reimagining what might take place, it really is re-creating how dialysis care will look today and look going forward.”

Transplant population Transplant recipients are another group highly susceptible to infection because they require suppression of their immune systems to prevent rejection of their transplanted organ. An estimated 356,000 solid organ transplant recipients were alive in 2017 in the United States, a ccording to a study published in

Renal & Urology News 17

Transplantation Proceedings by Mark D. Brigham, MD, of Trinity Partners, LLC, in Waltham, Massachusetts, and colleagues. Members of the nephrology community must not let the pandemic dissuade them from performing kidney transplants, said Richard N. Formica, MD, President-Elect of the American Society of Transplantation. “This is our new normal, and we cannot fool ourselves,” said Dr Formica, Professor of Medicine (Nephrology) and Director of Transplant Medicine at the Yale School of Medicine in New Haven, Connecticut. “Patients who have organ failure are in a bad spot no matter what. And we cannot hide from the responsibility that we need to take, which is to help navigate these patients through the environment that we’re in. We have no control over that environment. We have to be smart about it.” Dr Formica said he does not foresee an end to the pandemic until development of an effective vaccine that has been given to enough of the population to create herd immunity. “In my mind, my timeline is looking out 18 to 24 months in terms of making plans for my program.” Meanwhile, the pandemic has caused a backload of cases. As of May 1, Dr Formica said, his program had 214

Twice-Weekly Hemodialysis Proposed to Reduce COVID-19 Infection Risk Hemodialysis (HD) delivered twice weekly rather than the standard regimen of thrice weekly should be considered as an option to protect patients with kidney failure from COVID-19, according to recent editorial in the Journal of the American Society of Nephrology. Timothy W. Meyer, MD, of Stanford University School of Medicine and Palo Alto Veterans Affairs Administration Medical Center, and coauthors contend that this approach could result in less exposure to COVID-19, reduction in dialysis staff work, greater spacing of patients, decreased transportation requirements, and conservation of personal protective equipment. “A shift of patients to less frequent hemodialysis schedules will not relieve all of the pressures that dialysis units face during this pandemic, but it should be considered as one option and would likely provide adequate control of uremia, at least over a matter of weeks.” Collectively, the data from studies looking at outcomes of twice-weekly versus thrice-weekly hemodialysis “suggest that twice-weekly treatment is less dangerous than commonly supposed,” they wrote. In an accompanying counterpoint editorial, Rajnish Mehrotra, MD, of the Kidney Research Institute at the University of Washington at Seattle, argued that the data comparing outcomes with twice- and thrice-weekly HD “are extremely limited and simply insufficient” to conclude that the regimens are equivalent. “I respectfully submit that this approach could be counterproductive and could result in increasing risk to the health and welfare of patients with resultant increasing—rather than decreasing—health care utilization,” Dr Mehrotra wrote. “As such, I think it would be prudent for us to exhaust other alternatives before considering twice-weekly hemodialysis.”

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Pandemic continued from page 17

patients waiting to be evaluated for kidney transplantation. The pandemic prompted Dr Formica’s team to rethink how they manage patients in the first year post-transplant. For example, instead of twice-weekly, inperson follow-up visits, they are considering substituting one of the visits with a telemedicine encounter. They also have looked at replacing some surveillance biopsies with a new blood test that has been shown to be a reliable substitute for those procedures. Marcus R. Pereira, MD, a transplant infectious disease specialist at Columbia University College of Physicians and Surgeons in New York City, said he predicts the pandemic will result in a long-term focus on, and investment in, infection prevention and control at transplant centers, with an emphasis on vaccinations, not just against the SARSCoV-2, but against viruses in general.

Ramped up vaccination efforts At Columbia, he and his colleagues are preparing for a surge of respiratory illness among transplant recipients that may result when influenza adds to the COVID19 caseload. “Come the end of fall, we’re going to have a whole different approach to respiratory infections that come along with fall and winter. I think that there will be a much greater concentration of effort for vaccinating these patients.” He added, “We had already been in the process of revising our vaccine protocols since last year, recognizing that not 100% of patients were getting the fully recommended schedule. So that’s actually well underway, and I think that will definitely be highlighted once we have a vaccine for this particular [SARS-CoV-2] virus. I think people will definitely pay a lot of attention [to vaccinations] and set up resources to make sure our patients, both pre- and post-transplant, get all the required vaccines.” Transplant recipients are not the only patients at risk of infection because of immunosuppression. Patients with glomerular diseases, such as lupus nephritis and glomerulonephritis (GN), can be at risk as well. In an article published online April 24 in the Clinical Journal of the American Society of Nephrology, Andrew S. Bomback, MD, and colleagues at the Center for Glomerular Diseases at Columbia University College of Physicians and Surgeons described how they adapted their care of g lomerular diseases to decrease complications from COVID-19 infections. For example,

nephrologists at the center still advise patients at high risk of progression to ESRD without immediate therapy to begin standard of care immunosuppressive regimens. For many patients who have a less ominous disease course but who otherwise would be treated with immunosuppression, they advise postponing treatment until the patients’ local COVID-19 transmission rates are low enough that social distancing measures are no longer recommended. Dr Bomback and his coauthors also speculated about the impact of COVID19 on their future practice. “We anticipate that our management of glomerular disease patients will be altered by our current COVID-19influenced practices even when the current pandemic has resolved,” they wrote. “We have seen significantly lower rates of rapidly progressive GN in our hospitalized patients and disease relapses in our clinic patients since widespread adoption of social distancing…This seemingly quiescent disease state supports the hypothesis that environmental exposures, including but not limited to infections, may be a major trigger of glomerular disease onset and relapse.”

Undiagnosed cancers Another possible effect of the pandemic is delayed diagnosis of cancer and other diseases because people have avoided emergency departments and other healthcare encounters out of concern about contracting COVID-19. “The number of new cancer cases has gone down quite a bit,” said Dr Gore, who is on the Fellowship Committee of the Society of Urologic Oncology. Men have not been receiving PSAbased prostate cancer screenings, leading to a drop in referrals for prostate biopsies and, consequently, new prostate cancer diagnoses, Dr Gore said. Cases of kidney cancer, an incidentally detected malignancy, are down because people are not going to emergency departments with symptoms such as abdominal pain, which would trigger radiographic studies. Dr Gore related that his institution is preparing for a surge of patients this summer and fall, a group that will include individuals with lower-risk cancers whose care had been deferred and those with urologic cancers that had not been diagnosed because they avoided doctors. Treatment deferrals have had a negative impact on patients, he said. “Even if we reassure them that [they have] a low-risk cancer and it’s perfectly safe to wait, it’s a huge source of anxiety for patients,” Dr Gore said.

Insights into care In response to the pandemic, Dr Gore and his colleagues have stepped up use of surveillance for cases of lower-risk bladder cancers, small renal masses, and intermediate-risk prostate cancer. “We’re making decisions about who needs care and who doesn’t,” Dr Gore said. Physicians in his department may come to realize it is perfectly safe to surveil cases currently thought of as requiring intervention and certain disease states usually considered urgent, such as high-risk prostate cancer, may not require immediate treatment, he said. Doctors also may gain insight into the impact of deferred diagnoses on such clinical factors as cancer stage at presentation and eventual cancer-specific outcomes, he said.

Clinical trials The impact of the COVID-19 pandemic on clinical trials could lead to changes in how these trials are conducted even after the crisis ends, according to the findings of a survey of clinical trial programs in the United States by the American Society of Clinical Oncology. “Numerous challenges with conducting clinical trials were reported, including enrollment and protocol adherence difficulties with decreased patient visits, staffing constraints, and limited availability of ancillary services,” David M. Waterhouse, MD, MPH, of Oncology Hematology Care in Cincinnati, Ohio, and collaborators wrote in JCO Oncology Practice. The investigators based their findings on 32 survey respondents representing 14 academic and 18 community-based clinical trial programs. “Although the survey reflects a small sample of research programs in the United States during a rapidly changing situation, the results provide insight into the state of clinical trials across a range of types of research programs in the early weeks of the COVID19 pandemic,” the investigators wrote. More than half of respondents said they observed a decrease in patient ability or willingness to come to their site, and cited the staff time needed to organize, implement, and conduct telehealth visits as a significant challenge. Results showed that 90% of respondents identified telehealth visits for participants as a potential improvement in conducting a clinical trial, and 77.4% indicated that remote patient review of symptoms held similar potential, according to the authors. “One of the early lessons has been that it is possible to conduct more streamlined or pragmatic trials,” Dr Waterhouse

and his coauthors wrote. “Many trials currently include tests, procedures, and strict data collection requirements and windows for assessment that are intended to maximize knowledge gained but may prove burdensome to both patients and trial programs.” Another lesson, they noted, is that trials could routinely leverage technology to limit in-person visits for trial programs and patients. Many visits by industry sponsors and contract research organizations are being conducted remotely, or in some cases, eliminated altogether, according to the report. “Given that trial activity is able to continue, many of these in-person visits should not be required postCOVID-19,” according to the report. Other opportunities to improve clinical trials, according to survey respondents, include shipping oral drugs directly to patients, remote adverse event assessments, and patient review of symptoms as well as streamlined data collection, including decreased collection of “unnecessary data.” “Increased remote work by research staff was noted as an opportunity to improve job productivity, satisfaction, and staff retention, as well as mitigate space issues at sites.”

Rough road ahead Infectious disease specialists and public health officials agree that the pandemic will persist for the foreseeable future. Medical practices are adapting to the new environment and gearing up for the backlogs of cases that have built up as a result of elective procedures being postponed. Such is the case at UroPartners, LLC, a large urology group practice that serves the Chicago area. Urologists are planning for a “tsunami” of cases in the next 2 or 3 months, said Richard Harris, MD, the group’s President and CEO, who is also President of the Large Urology Group Practice Association. “We have been putting policies in place for both patient and staff protection in order to do all of these cases safely,” he said. The process will be slow. “Nobody’s going to be able to ramp up their preCOVID levels [of cases] for a long time, maybe even a year,” he said. He added, “This COVID pandemic is just not going to go away with the flip of a switch. What’s going to happen is, it may taper down over the summer months, but of course, there is concern that it’s going to resurface in the fall and winter. Until we can get massive testing and a vaccine, it’s going to continue to be somewhat perilous.” n

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Renal & Urology News 19

Ethical Issues in Medicine A

cknowledgment of medical errors and the disclosure of the adverse events to patients has changed significantly over time. Over the past 40 years, such admissions have evolved from a topic that was rarely acknowledged in healthcare to one where identification and management are central to the ongoing safe provision of care. The expectation among patients today is that their physicians will be honest with them about information relevant to their care. This is related to a change in the culture of medicine, spurred by the publication of an influential 1999 Institute of Medicine report, To Err is Human, which helped to usher in greater attention and commitment to patient safety. This report also helped to put medical errors into a broader context, by replacing the outdated and oversimplified model of the “bad apple” healthcare professional, with one of a complex health care system with multiple factors that can contribute to bad outcomes. From an ethics perspective, disclosing adverse events to patients is predicated on the idea that physicians have obligations to tell the truth. Patients cannot be a partner in their care and physicians cannot engage in shared decisionmaking if patients do not have enough of their health information to make

For good reasons, physicians have generally been squeamish about issuing an apology to a patient after an adverse event. Physicians may worry that providing an apology will lead to greater responsibility for liability or that admitting fault is humiliating. Numerous states have passed “inadmissibility laws” that encourage physicians to apologize to patients after a medical error and allow such admissions of fault to be inadmissible in malpractice suits. The effect of these laws on malpractice suits is still unclear, but the moral basis for these laws is that the apology has value in and of itself, beyond simply the disclosure of the error.2 The value and use of apologies can extend broadly beyond medical errors. In fact, apologies can be most effective in the challenges of daily practice. Apologies can be offered, for example, when a patient has had to wait to see a physician or when a misunderstanding leads to a delay in diagnosis. When physicians take the lead on these discussions, it can help to prevent more complicated and lengthy disagreements in the future. Aaron Lazare, MD, the foremost scholar on the role of apology in medical practice who helped to establish an enduring conceptual framework for describing, understanding, and

From an ethics perspective, disclosing adverse events to patients is predicated on the idea that physicians have obligations to tell the truth. informed decisions. One of the roles of the disclosure process is to support the relationship in which it occurs. When medical errors affect patients, the disclosure process will proceed more smoothly when there is an accompanying apology. An apology can help patients feel heard, feel better, or maintain or even strengthen the relationship with their physician. This is because apologies can help patients feel cared for, validated, and respected.1

a nalyzing apologies, defined an apology as “an acknowledgement of responsibility for an offense coupled with an expression of remorse.”3 Beyond simply saying, “I’m sorry,” there are 3 critical components of an effective apology, and the lack of any one of these can lead to a “failed” apology, exacerbating the offense. The first element is a genuine acknowledgment and responsibility for the offense. The second is an expression of remorse, humility, or regret for the offense. The

Apologizing for medical errors, when done properly, can go a long way to maintaining doctor-patient relationships BY DAVID J. ALFANDRE, MD, MSPH

An apology can help patients feel cared for, validated, and respected.

third is an attempt to provide reparations to help heal the relationship. Some common pitfalls illustrate how apologies can go awry. Saying “I’m sorry for whatever I did,” or “mistakes were made” fails to address the first element, taking responsibility for the offense. Saying “I’m surprised this happened because I’m one of the most experienced and capable physicians in the hospital,” is not likely to address the second element: Failing to express remorse or humility can lead to an unsuccessful apology that exacerbates the original offense. Finally, saying “our hospital works very well, this was clearly an aberration,” doesn’t provide the needed plan for reparations that many patients expect after an adverse event. A better approach designed to strengthen relationships will address all of the critical elements of apology directly and empathically. Here’s an example that can be used in everyday practice. “I see that you had to wait 80 minutes to see me this afternoon. I know having to wait is unpleasant. I’m sorry about the delay; for that I take full responsibility. There was a problem with our scheduling system that resulted in some patients waiting longer than they should have. I’ve already asked our office manager to look into

the problem and identify a solution before the end of the week. Will you let me know if you have any feedback about this so I can pass it along to him? Now tell me how you are doing and how I can be helpful today.” If you read that aloud, you see the entire apology took less than 15 seconds. Simply saying, “I’m sorry,” and leaving it at that may exacerbate tensions with patients, which can lead to more time-consuming problems in the future. The apology process takes just a short amount of time, and can have a potentially large payoff. Consider it an investment in the future. ■ 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. Lazare A. Apology in medical practice: An emerging clinical skill. JAMA. 2006;296:1401–1404. 2. Dresser R. The limits of apology laws. Hastings Cent Rep. 2008;38:6-7. 3. Lazare A. On apology. Oxford University Press. 2004.

20 Renal & Urology News

MAY/JUNE 2020 www.renalandurologynews.com

Practice Management I

n response to increased need for expedient and distant health treatments during the COVID-19 pandemic, the US Department of Health and Human Services (HHS) is temporarily giving HIPAA-covered entities greater leeway in the delivery of virtual care. HHS recently announced that healthcare providers can offer telehealth services via previously noncompliant technologies. The department now allows doctors to provide health services through audio or video on sites like Skype and FaceTime so they can see a greater number of patients and reach out to those sheltering in their homes. The organization has said it will not impose penalties on providers using these alternative technologies. With these temporary rules and an increasing number of providers and staff working remotely, healthcare organizations need to understand how to provide telemedicine and allow staff to work off-site while ensuring good cyber control and reducing risk. “We are definitely living in an unprecedented time, and it is a time when providers are going to be providing care in different ways,” said Julie A. Pursley, Director of HIM Practice Excellence at American Health Information Management Association. “But this is not suspending HIPAA. They are relaxing the rules so providers can take care of patients in good faith during this public health emergency.”

Telemedicine updates The first thing to note is HHS is not waiving HIPAA requirements. They are just saying the health crisis has allowed them to be “judicious” when it comes to enforcements and penalties, said George Jackson, a senior principal consultant with Nashville, Tennesseebased Clearwater Compliance. Providers and staff dealing with patients can take time now to look over the guidelines and ensure everyone understands how technology can and cannot be used. Pursley said in cases in which the provider uses an allowed video messaging application

like Facebook Messenger, it is best for staff to use a company account rather a personal account in order to prevent sharing a provider’s personal information. Finally, she said, all virtual care provided should be documented like any other clinical visit. Now is a good time for doctors to work with patients so they understand the risks of communicating on systems that are not HIPAA compliant. All patients should have an updated privacy and consent notification, especially if they are using telemedicine services. Jackson recommends even having talking points or handouts prepared to make sure security is good on the patient’s end. Providers should also prepare for the possibility that some of the telemedicine changes may last beyond the pandemic, making the security changes permanent. “Will the genie go back in the bottle?” Pursley asked. “There is a lot of discussion out there that the pandemic is potentially going to be a catalyst for healthcare transformation, so we’ll see when all of this is over.”

Remote working Another consideration for providers during the pandemic is the increased number of people who may be working outside of the office. Whether clinical or administrative staff, Jackson said,

Providers need to be mindful of cybersecurity as they expand use of telemedicine during the COVID-19 pandemic BY TAMMY WORTH

Cybersecurity is an important telemedicine consideration for providers working remotely.

networks. For people who are not tech savvy, their internet service provider (ISP) can provide a security check up, Jackson said. The ISP can update an older system and implement patches to bring it up to date and thereby reduce risk.

Phishing Among the ploys criminals use to take advantage of people when creating malware is emotions. People may be surfing the web for any information about

Noncompliant technologies can now be used to provide virtual care, according to the US Department of Health and Human Services. there are some simple things to be aware of when working remotely. One consideration is cyber safety at home. Practices can set up virtual private networks (VPNs) so staff can log in to and work in a secured space. It is also important to ensure staffs’ home internet is as secure as possible. Most people use the default password, or none at all, on their home

pandemic, so staff members need to be quite vigilant about inadvertently clicking on phishing-related links. Now is the time to check with an ISP to make sure emails are being monitored for phishing attacks. Individuals should be advised not to click on a link that comes in an email with a subject line that induces panic, Jackson said. Pursley recommends not opening any

emails with COVID-19 in the title unless a user knows exactly who sent the message. “Healthcare organizations should have been receiving regular training to make sure staff is aware of potential phishing attacks,” Jackson said. Under the best of circumstances, humans are the weakest link in the security chain. When they are nervous, stressed and fatigued, it only makes them more prone to mistakes. Even though there has been some loosening of HIPAA guidelines, the major rules still apply. Pursley said she has already begun hearing about people posting personal information on social media or telling others they have seen someone in a clinic. Circumstances may stir temptation to snoop on people as well, Jackson said. Tools that track movement in a system can alert a provider if someone is looking in records they should not be accessing. As human error is not uncommon, Clearwater outlines how organizations can mitigate the vulnerabilities associated with careless users in its CyberIntelligence Institute Bulletin. ■ Tammy Worth is a freelance medical journalist based in Blue Springs, MO.