Renal & Urology News - Nov-Dec 2020 issue

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Hospitals Turned to PD During Pandemic


Dialysis demand in New York hospitals led to rapid creation of peritoneal dialysis programs

A SURGE IN COVID-19-RELATED AKI forced hospitals to embrace peritoneal dialysis.

KTRs Hit Hard by COVID-19 BY JODY A. CHARNOW KIDNEY TRANSPLANT recipients (KTRs) hospitalized for COVID-19 have high rates of death and acute kidney injury (AKI), according to separate studies presented at the American Society of Nephrology’s Kidney Week 2020 Reimagined virtual conference. The studies provide details of the clinical presentation and disease course of COVID-19 among KTRs admitted to hospitals with COVID-19, as well as patients’ comorbidities and the treatments they received. An analysis of retrospective data from the TANGO International Transplant Consortium by Leonardo V. Riella, MD, of Massachusetts General Hospital in Boston, and colleagues found that

44 (30%) of 145 KTRs hospitalized with COVID-19 in March and April died after a median follow-up of 10 days following hospital admission for COVID-19. AKI developed in 46% of cases, and respiratory failure requiring intubation occurred in 29% of cases. Vinay Nair, DO, and colleagues at Northwell Health in Great Neck, New York, found that 10 (33%) of 30 KTRs admitted to hospitals in their system with COVID-19 from March 1 to April 30 died after a median follow-up of 19 days. AKI occurred in 39% of cases. The study by Dr Riella’s group included 9697 KTRs followed at 11 transplant centers, of whom 145 (1.5%) were hospitalized with COVID-19. Of continued on page 10

BY JODY A. CHARNOW UNUSUALLY HIGH demand for dialysis to treat acute kidney injury (AKI) in patients hospitalized with COVID-19 led to rapid adoption of acute peritoneal dialysis (PD) programs at institutions in New York, according to reports presented at the American Society of Nephrology’s Kidney Week 2020 Reimagined virtual conference. At Montefiore Medical Center, severe personnel shortages necessitated creation of an urgent PD service, Maryanne Y. Sourial, DO, and colleagues reported in a poster presentation. Transplant surgeons performed bedside laparoscopically assisted flexible PD catheter placement for intubated and intensive care unit (ICU) patients.

Voclosporin Use for LN Backed by a New Study POOLED ANALYSES of data from 2 clinical trials provide additional support for the safety and efficacy of voclosporin (VCS), a novel calcineurin inhibitor, in the treatment of lupus nephritis (LN), according to a presentation at the American Society of Nephrology’s Kidney Week 2020 Reimagined virtual conference. Adding voclosporin to background therapy with mycophenolate mofetil and corticosteroids increased the complete renal response rate early in the course of treatment, and this was increased further in 1 year, lead investigator Brad H. Rovin, MD, of Ohio State University Wexner Medical Center in Columbus, Ohio, said in a slide presentation. In addition, the study found no increase in safety concerns and demonstrated that voclosporin treatment was associated with a minimal decline in estimated glomerular filtration rate (eGFR) over time, “suggesting voclosporin may represent another tool in continued on page 10

Interventional radiologists performed fluoroscopy-guided flexible PD catheter placement for non-intubated non-ICU patients. Many residents, fellows, attending physicians, nurse practitioners, and nurses were trained in administering manual PD. Some attending physicians and nurse practitioners were trained in automated PD. Of 164 patients with severe AKI requiring renal replacement therapy (RRT), 30 were treated with PD. As of May 14, 14 (47%) of the 30 patients started on PD died during their hospitalization. Eight patients were discharged home or to a rehabilitation facility; of these, 3 were receiving PD and 5 no longer needed RRT due to continued on page 10


Novel IV drug eases pruritus in patients on hemodialysis


Neutrophil-to-lymphocyte ratio may be prognostic in AKI


Finerenone shown to slow CKD advancement in diabetics


Infection risk factors in patients with glomerular disease identifed


Venous thromboembolism linked to worse RCC surgical outcomes


Fruits and vegetables effective for metabolic acidosis in CKD


Alpha blockers may increase the risk for CKD progression

Prostate cancer care in rural areas differs from that in urban centers. PAGE 6  NOVEMBER/DECEMBER 2020

Renal & Urology News 1


Medical Director, Nephrology

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

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

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

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

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

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

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

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

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

Renal & Urology News Staff

Editor Jody A. Charnow

Web editor Natasha Persaud

Production editor Kim Daigneau Group creative director Jennifer Dvoretz Production manager Brian Wask

Vice president, sales operations and production Louise Morrin Boyle

Director of audience insights Paul Silver National accounts manager William Canning Editorial director, Haymarket Oncology Lauren Burke

Vice president, content, medical communications Kathleen Walsh Tulley

General manager, medical communications James Burke, RPh President, medical communications Michael Graziani Chairman & CEO, Haymarket Media Inc. Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 19, Number 6. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). For reprint/licensing requests, contact Customer Service at 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.

Dialysis Is Not Going Away Anytime Soon


s I was nearing graduation from medical school in Bonn, Germany, in May 1991 and preparing to start residency training in a large nephrology center in Nuremberg, Germany, one of my mentors said I should think twice before choosing nephrology as a career because dialysis would soon be obsolete and replaced by implantable or wearable artificial kidneys. Another mentor told me that with the rise of ACE inhibitors and new data showing that these agents can slow kidney disease, there would not be kidney failure in the future. I became a nephrologist anyway, first in Germany, then in the United States. Now, 30 years later, dialysis has expanded tremendously in the United States and Europe, and its use is expanding exponentially in such emerging economies as India, China, and Brazil. Some medical students and residents recently asked me whether there is any future in nephrology if dialysis would soon dissipate. My response is that dialysis is not likely to become obsolete — despite advances such as SGLT2 inhibitors that have been demonstrated to slow kidney disease progression — and nephrology goes way beyond renal replacement therapy. Recent trends to avoid or stop dialysis have been heightened by perverse financial incentives to reduce length of hospital stay and prevent 30-day readmissions of patients with kidney problems. Nephrologists may feel pressured to get their dialysis and kidney transplant patients out of needed intensive care unit (ICU) beds via discontinuation of immunosuppression medication or abrupt dialysis withdrawal to expedite hospice transition. Patients and family members may feel coerced by medical teams to choose the end-of-life route portrayed to them as the best option. Other options are available to ameliorate pressure to decrease hospital lengths of stay and prevent readmissions. These include conservative measures that can delay the need for dialysis among patients with chronic kidney disease, such as diet and lifestyle modifications.1 Under a presidential executive order issued in July 2019 (the Advancing American Kidney Health Initiative), the Department of Health and Human Services hopes to achieve a 25% decrease in the incidence of end-stage kidney disease by 2030. It would be against the choice and hope of many patients if this is to be achieved at least in part by steering patients toward palliative and supportive care rather than dialysis. Each time a patient under my care expresses thoughts to stop therapy to die, I spend extra time to discuss all options. I explain to patients and their families why it may still not be time to give up. I tell my patients that, as long as I am around, you will be, too, if you choose to be. Kam Kalantar-Zadeh, MD, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine, Orange, CA Twitter/Facebook: @KamKalantar 1. Kalantar-Zadeh K, Wightman A, Liao S. Ensuring choice for people with kidney failure – Dialysis, supportive care, and hope. N Engl J Med. 2020;383:99-101.

2 Renal & Urology News




Nephrology 4



this month at 5

Clinical Quiz Test your knowledge by taking our latest quiz at run-quiz


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

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

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

Drug May Prevent CV Events in High-Risk Diabetic CKD Apabetalone decreased the likelihood of major cardiovascular events among patients with diabetic nephropathy who recently suffered from acute coronary syndrome. Finerenone Slows CKD Advance in Diabetics Patients treated with the investigational mineralocorticoid receptor antagonist had an 18% decreased risk for deteriorating kidney function. Fruits, Vegetables Ease Metabolic Acidosis A healthy diet may be a cost-effective way for patients with chronic kidney disease to manage a potentially serious abnormality.


CALENDAR Editor’s note: With the cancellation of in-person medical conferences thus far in 2020 in response to the COVID-19 pandemic and the status of meetings unclear, we are providing listings of 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 6

NAC Offers Survival Edge in UTUC Neoadjuvant chemotherapy prior nephroureterectomy is associated with superior 5-year survival, a study found.


RT for Abdominal, Pelvic Cancers Ups Risk for Secondary Sarcomas Radiotherapy combined with chemotherapy is associated with the greatest risk.



Prostate Cancer Management Falls Short in Rural America The likelihood of undergoing certain procedures is diminished compared with urban centers, studies show.


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

Novel IV Drug Eases Pruritus in HD Patients In a phase 3 trial, difelikefalin decreased moderate to severe itching.

Earlier Surrogate for Survival After RP Relapse Possibly ID’d Castration-resistant prostate cancer-free survival after post-RP biochemical recurrence could serve as an intermediate endpoint in clinical trials.

Departments 1

From the Medical Director Will there always be a need for dialysis?


News in Brief Pulse pressure prior to hemodialysis may predict mortality risk


Ethical Issues in Medicine Physician virtues may help them navigate possible COVID-19 ethical dilemmas


Practice Management Experts suggest ways to deal with psychological stress during the pandemic

The understandable challenge is to get

patients to change their diets, something that we all recognize is very difficult to do. See our story on page 9  NOVEMBER/DECEMBER 2020

Renal & Urology News 3

News in Brief

Please visit us at for the latest news updates from the fields of urology and nephrology

Short Takes Subcutaneous Fat Affects mCRPC Therapy Response

patients who underwent abdomino-

Greater subcutaneous fat is associated

patients younger than 10 years and

with improved response to chemother-

older than 90 years, as well as patients

apy combined with maximal androgen

undergoing kidney, ureter, and bladder

ablation among men with metastatic

scans for urolithiasis-associated symp-

castration-resistant prostate cancer

toms and those with already known

(mCRPC), according to data presented

urolithiasis. Incidental stones were

at the European Society for Medical

found in 20 patients: 11 male and 9

Oncology Virtual Congress 2020.

female. Of the 20 stones, 18 were in

In a study of 58 men with mCRPC,

pelvic CT scans. The study excluded

the kidneys and 2 were in the ureters.

­Andrew E. Hahn, MD, of The University in Houston, and colleagues found

CKD Worsens Prognoses in Patients With VTE

that patients who had an objective re-

Patients with venous thromboembo-

sponse to chemotherapy plus maximal

lism (VTE) and concomitant moderate

androgen ablation had a significantly

to severe chronic kidney disease

higher subcutaneous adipose tissue

(CKD) have worse prognoses com-

index than those who had no response

pared with those who have VTE but no

(87.9 vs 62.7 cm2/m2).

or mild CKD, data suggest.

of Texas MD Anderson Cancer Center

In a cohort study of 8979 adult pa-

New Study Characterizes Incidental Urinary Stones

tients with VTE, patients with moderate

Computed tomography (CT) revealed

risk of all-cause mortality, major

incidental urinary stones in 2.8% of pa-

bleeding, and recurrent VTE within 12

tients in a Pakistani study, according to

months of VTE diagnosis compared

a report in Cureus (2020;12:e1037).

with patients with no or mild CKD, in ad-

Sajeel Saeed, MD, and colleagues

justed analyses, Shinya Goto MD, PhD,

to severe CKD had a 1.4-fold increased

at Rawalpindi Medical University in

of Tokai University School of Medicine

Rawalpindi, Pakistan, retrospectively

in Kanagawa, Japan, and colleagues

reviewed findings from 721 consecutive

reported in JAMA Network Open.

SBRT Outcomes Durable Stereotactic body radiation therapy (SBRT) for localized prostate cancer offers high rates of long-term oncologic control with mild toxicity, according to study results presented at the American Society for Radiation Oncology 2020 virtual annual meeting. Shown here are the 12-year rates of biochemical disease-free survival (bDFS) stratified by risk category.


Low risk: 92%

Intermediate risk: 79.1%

High risk: 64% 0






Source: Katz AJ, Kang J. Efficacy and toxicity of stereotactic body radiation therapy for localized prostate cancer: A twelve year study. Presented at: ASTRO 2020 virtual annual meeting, October 25 to 28. Poster 4026.

Shortened Course of PTNS Effective in OAB, Data Show A

shortened 6-week protocol of percutaneous tibial nerve stimulation (PTNS) can effectively treat refractory nonneurogenic overactive bladder (OAB), according to data presented at the European Association of Urology 2020 virtual congress. Ahmed M. Lashin, MD, and colleagues of Mansoura University in Mansoura, Egypt, randomly assigned 50 patients to receive 6 weekly PTNS treatments or sham therapy. Fifty-two percent of the PTNS group reported significant, moderately improved symptom scores after week 7 and months 3 and 6, compared with no patients in the sham therapy group. According to voiding diaries at 6 weeks, PTNS patients had significant improvements in frequency, voided volume, and urge incontinence episodes compared with sham therapy. No serious device-related adverse events or malfunctions were reported. “The duration of treatment with PTNS can be halved compared to the conventional 12 weeks, which would make it more acceptable and cost effective for patients,” Dr Lashin’s team concluded in a study abstract.

Pulse Pressure Prior to HD May Predict Mortality Risk P

atients’ pulse pressure (PP) prior to hemodialysis (HD) sessions may predict mortality, investigators reported at the American Society of Nephrology’s Kidney Week 2020 Reimagined virtual conference. The finding may aid in HD patient risk stratification. Consistently high PP values are associated with arterial stiffness, whereas low PP values may be associated with congestive heart failure, the investigators explained. The association between pre-HD PP with mortality among HD patients is not well understood. Based on an analysis of data from 152,625 patients receiving HD at Fresenius Medical Care facilities, Hanjie Zhang, PhD, and colleagues at the Renal Research Institute in New York, found that the association of pre-HD PP with mortality is nonlinear: pre-HD PP less than 49.2 mm Hg and higher than 74.7 mm Hg were associated with higher mortality compared with a PP range of 49.2 to 74.7 mm Hg.

Race Disparity in Survival Absent in Metastatic PCa N

o racial differences exist in survival outcomes of men with metastatic prostate cancer (PCa), but the mortality risk among men with nonmetastatic PCa is higher for Blacks than Whites, according to study findings presented at the American Society for Radiation Oncology 2020 virtual annual meeting. The study, by Toms Vengaloor Thomas, MD, and colleagues at the University of Mississippi Medical Center in Jackson, was a retrospective review of data from 26,639 patients with bone metastases, 952 with metastases at locations other than bone, such as the liver, lung, and brain, and 579,202 without metastases. The investigators found no significant difference in survival between Black and White PCa patients with bone metastases or with metastases at other sites. Among men with nonmetastatic PCa, however, Blacks had a significant 17% increased risk of death compared with Whites.

4 Renal & Urology News



American Society of Nephrology’s Kidney Week 2020 Reimagined

Novel IV Drug Eases Pruritus in HD Patients Difelikefalin significantly decreased moderate to severe itching, phase 3 trial data show TREATMENT WITH difelikefalin (DFK), an investigational medication, is associated with rapid and sustained itch reduction and improvement in itchrelated quality of life among patients on hemodialysis suffering from moderate to severe chronic kidney disease (CKD)-associated pruritus, according to phase 3 study results. The medication, a novel peripherally restricted and selective kappa opioid receptor agonist that is administered intravenously, was generally well tolerated, and safety was consistent with findings from prior studies, according to Thomas D. Wooldridge, MD, of Nephrology and Hypertension Associates, Ltd, in Tupelo, Mississippi, and colleagues. The latest results are from the KALM-2 trial, in which investigators randomly assigned 473 patients on hemodialysis (HD) in the United States,

NLR May Be Prognostic in AKI Cases THE NEUTROPHIL-to-lymphocyte ratio (NLR) may predict morbidity and mortality in patients with communityacquired acute kidney injury (AKI), data suggest. In a study of 308 patients with AKI (mean age 73 years; 58% male) attending a nephrology clinic in Spain, the mean NLR was 9.14. A total of 14.6%, 11.0%, and 74.4% of patients had Kidney Disease Improving Global Outcomes (KDIGO) AKI stage 1, 2, and 3, respectively. In addition, 68.8% had chronic kidney disease, and 17.2% required hemodialysis. The source of AKI was prerenal in 69.5% of cases, renal in 23.1%, and obstructive in 7.5%, the researchers reported. The NLR according to this etiology was 8.55 prerenal, 9.37 renal, and 13.99 obstructive. Patients with prerenal AKI complicated by acute tubular necrosis had a significantly higher NLR compared with their counterparts: 10.7 vs 7.8.

Europe, and Asia to receive DFK 0.5 mcg/kg (237 patients) or placebo (236 patients). The patients had moderate to severe CKD-associated pruritus. The primary endpoint was the proportion of patients who achieved a 3-point or greater improvement (that is, a decrease

Patients reported an improvement in their itch-related quality of life. in score) from baseline in the weekly mean of the daily Worst Itching Intensity Numerical Rating Scale (WI-NRS) score at week 12. The scale ranges from 0 (no itch) to 10 (worst itching imaginable). At baseline, the mean weekly WI-NRS scores were 7.3 and 7.1 in the DFK and

NLR significantly correlated with peak creatinine and serum albumin, José M. Peña Porta, MD, and colleagues from the Lozano Blesa University Clinical Hospital in Zaragoza, Spain, reported. NLR was independently associated with longer hospital stay and higher mortality. Of the 308 patients in the cohort, 12.3% died. The best cut-off point for NLR to predict mortality was 6.68, with a sensitivity of 60% and specificity of 58%, the investigators reported. Sex, age, Charlson comorbidity index, peak creatinine, serum albumin, chronic kidney disease, etiology of AKI, serum potassium, AKI stage, need for hemodialysis, and the plateletto-lymphocyte ratio did not independently predict outcomes after AKI. “The NLR has been identified as a marker of inflammation and endothelial dysfunction,” Dr Peña Porta told Renal & Urology News. “Although more research is needed, NLR can serve as a predictive tool for the prognosis of community-acquired AKI.” The ease of obtaining NLR coupled with its low cost make it a potentially useful marker in assessing the hazards of AKI, he explained. The team is currently working on a follow-up study to gauge NLR’s utility. ■

placebo arms, respectively. Results showed that 54% of patients who received DFK achieved at least a 3-point improvement in WI-NRS compared with 42% of the placebo group. The proportion of patients who achieved a 4-point or higher improvement also was significantly greater with DFK than placebo (41% vs 28%). Itch reduction was evident at week 1 and was sustained through week 12, according to the investigators. They also observed improvement in itch-related quality of life (QoL) among DFK recipients as measured using the 5-D Itch and Skindex-10 questionnaires. Treatment-emergent adverse events (AEs) that occurred in 5% or more of patients occurred more frequently in DFK-treated patients than placebo recipients: diarrhea (8.1% vs 5.5%), fall (6.8% vs 5.1%), dizziness (5.5% vs 5.1%), vomiting (6.4% vs 5.9%), and

nausea (6.4% vs 4.2%). The incidence of serious AEs was similar between the study arms. The new findings follow publication of the results from the phase 3 KALM-1 trial in the New England Journal of Medicine. In that trial, investigators randomly assigned 378 patients on HD who had moderate to severe pruritus to receive DFK 0.5 mcg/kg or placebo. The primary outcome was the proportion of patients with a 3-point or greater improvement in WI-NRS score from baseline to week 12. A significantly higher proportion of patients in the DFK-treated patients than placebo recipients achieved the primary endpoint (51.9% vs 30.9%) as well as a 4-point or greater improvement in WI-NRS score (40.5% vs 21.2%). DFK recipients also experienced a significant improvement in itch-related QoL as assessed by the 5-D itch scale and Skindex-10 scale. ■

Drug May Prevent CV Events in High-Risk Diabetic CKD APABETALONE substantially reduces

compared with placebo in the study

the risk for major cardiovascular events

population as a whole. In the new

(MACE) among patients with both

analysis looking at patients with CKD,

chronic kidney disease (CKD) and type

a­pabetalone-treated patients had a sig-

2 diabetes mellitus who recently suf-

nificant 50% decreased risk of MACE (car-

fered from acute coronary syndrome

diovascular death, nonfatal myocardial

(ACS), data show.

infarction, or stroke) compared with pla-

The findings are based on an analysis

cebo recipients in adjusted analyses, lead

of data gathered from the phase 3

investigator Kamyar Kalantar-Zadeh, MD,

BETonMACE clinical trial, in which investi-

PhD, MPH, of the University of California

gators randomly assigned 2425 patients

Irvine in Orange, California, reported. The

with type 2 diabetes mellitus and recent

apabetalone group also had a significant

ACS to receive apabetalone or placebo

74% decreased risk for hospitalization for

in addition to standard therapy. Of

congestive heart failure.

these patients, 288 (12%) had CKD stage

The patients with CKD were older

3 or 4 (defined as an estimated glo-

than those without CKD (71 vs 61 years)

merular filtration rate less than 60 mL/

and were more likely to be female (42%

min/1.73 m ).

vs 23%). They also had a significantly


The original report of findings from the

longer duration of diabetes (mean 11.3

BETonMACE trial, published in the Journal

vs 8.2 years) and higher serum alkaline

of the American Medical Association

phosphatase levels (mean 91 vs 81 U/L).

(2020; 323:1565-1573), found that

The proportion of patients who received

apabetalone added to standard therapy

metformin was significantly lower in the

did not significantly reduce MACE risk

CKD than no-CKD group (69% vs 84%). ■  NOVEMBER/DECEMBER 2020

Renal & Urology News 5

Finerenone Slows CKD Advance in Diabetics Investigational drug also decreased the risk of major cardiovascular events, a study found BY JODY A. CHARNOW FINERENONE, an investigational mineralocorticoid receptor antagonist (MRA), slows progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus compared with placebo, according to phase 3 trial results. “This is great news for people with type 2 diabetes and CKD,” said study investigator Rajiv Agarwal, MD, MS, professor of medicine at Indiana University in Indianapolis, who presented study findings at the conference. “They now have another option to protect their heart and their kidneys through finerenone.” Finerenone is a selective nonsteroidal MRA. In the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) trial, the drug, when added to the maximum tolerated dose of guideline-directed therapy, was associated with an 18% decreased risk of a composite endpoint

of time to kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) of 40% or more from baseline over a period of at least 4 weeks, or renal death compared with placebo over a median follow-up duration of 2.6 years. According to investigators, 29 patients would need to be treated to prevent a primary composite endpoint event at 36 weeks, which Dr Agarwal said “would be considered pretty good.” In addition, finerenone treatment was significantly associated with a 14% decreased risk of a key secondary endpoint — a composite of time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure — compared with placebo over a median follow-up of 2.6 years. The FIDELIO-DKD trial is the first large contemporary positive outcomes study in patients with both CKD and type 2 diabetes mellitus with a ­primary

composite endpoint exclusively ­consisting of kidney-specific outcomes, according to a press release from Bayer, the pharmaceutical company developing the drug. Investigators randomly assigned 5734 patients to receive finerenone or placebo. Enrollment criteria

Researchers report an 18% decreased risk of deteriorating kidney function. include an eGFR (in mL/min/1.73 m2) of 25 or higher but less than 75 and a urinary albumin-to-creatinine ratio of 30 to 5000 mg/g. Patients in both study arms received standard of care, including glucoselowering medications and maximum tolerated doses of drugs that block the renin-angiotensin system such as

Sodium Abnormalities Up Mortality HOSPITALIZED patients with serum sodium levels outside of the optimal range when they are discharged are at increased risk of dying within 1 year, investigators reported. Hypernatremia at hospital discharge more strongly influenced 1-year mortality than hyponatremia at discharge. In a single-center study of 59,901 hospitalized patients, a team led by Charat Thongprayoon, MD, of Mayo Clinic in Rochester, Minnesota, found that 1-year mortality rates were 26.1%, 15.5%, 11.6%, 17.2%, and 49.4% for

patients with serum sodium values of 132 or less, 133-137, 138-142, 143-147, and 148 mEq/L or higher, respectively. Compared with a reference value of 138-142 mEq/L, those with values of 132 or less, 133-137, 143-147, and 148 mEq/L or higher had significantly increased odds of 1-year mortality by a factor of 1.43, 1.10, 1.35, and 3.86 (all P values less than or equal to .001), respectively, after adjustment for age, sex, race, admission serum sodium values, Charlson comorbidity score, and other potential confounders, according to the investigators.

“The optimal range of serum sodium at hospital discharge was 138 to 142 mEq/L, but almost half of hospitalized patients were discharged with serum sodium outside of this optimal range,” Dr Thongprayoon told Renal & Urology News. “Targeting serum sodium to the optimal range before hospital discharge may potentially lead to more favorable long-term survival.” The study population was 54% male and 93%White. Discharge serum sodium values were the last measurements within 48 hours before discharge. ■

angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Dr Agarwal noted that nearly 90% of the patients in FIDELIO-DKD had macroalbuminuria and more than half had an eGFR less than 45. If results of the sister study FIGARO-DKD (Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease) — in which approximately half of the patients have microalbuminuria and a mean eGFR of 68 — are also positive “the impact of finerenone will be even more broadly felt. It may then be used by most patients with type 2 diabetes and CKD.” Results of FIGARODKD are expected in 2021, he said. He cautioned that finerenone use requires close monitoring of serum potassium levels, “much like we do currently with ACE inhibitors and ARBs.” Study findings were published concurrently in the New England Journal of Medicine. ■

AKI Worsens Outcomes in Flu Patients PATIENTS HOSPITALIZED with influenza who develop acute kidney injury (AKI) experience worse morbidity and mortality than their counterparts without AKI, investigators reported. Among 120,730 influenza hospitalizations in a National Inpatient Sample (2012 to 2014), 16,270 (13.5%) were complicated with AKI. In adjusted analyses, patients with AKI had 3.8-, 8.7-,

New-Onset Dyslipidemia Associated With CKD CHRONIC KIDNEY disease (CKD) is associated with new-onset dyslipidemia, according to investigators. Using the Japanese Specific Health Check and Guidance System, Takaaki Kosugi, MD, of Nara Medical University in Kashihara, Nara, Japan, and colleagues identified 51,009 patients with

CKD and 254,884 without CKD who at baseline were free of dyslipidemia, which is a significant risk factor for cardiovascular disease. Over a median 3.1 years, 14.8%, 17.0%, and 4.3% of individuals experienced high levels of triglycerides (150 mg/dL or greater) and low-density lipoprotein (LDL; 140 mg/dL or greater)

and low levels of high-density lipoprotein (HDL; less than 40 mg/dL), respectively. After adjusting for potential confounders, patients with CKD had significant 10% and 16% greater risks for high triglycerides and low HDL, respectively, but no elevated risk for high LDL, compared with patients who did not have CKD. ■

9.5-, 3.0-, and 5.6-fold increased odds for mortality, severe sepsis, septic shock, rhabdomyolysis, and intubation, respectively, compared with patients without AKI, Nasha Elavia, MD, of the Wright Center for Graduate Medical Education in Scranton, Pennsylvania, and colleagues reported. Patients with AKI also had a significant 1.8-day longer length of stay. ■

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Prostate Cancer Management Falls Short in Rural America Men with the malignancy are undertreated in sparsely populated areas of the US BY JODY A. CHARNOW

A shortage of urologists in rural areas may contribute to disparities in care.

Cancer Registry to identify all patients diagnosed with PCa in the state from 2009 to 2015. The study is among the first to examine rural and urban disparities in PCa among all payers within a state, the investigators noted. “Our most important finding is that rural patients are undertreated for prostate cancer, even when stratified by disease risk,” Dr Maganty told Renal & Urology News. “Meaning, even patients with intermediate- or high-risk cancers were less likely to be treated if they resided in rural areas, when controlling for age, race, insurance, stage, and other clinical factors. We included this risk stratification in our study because for some types of prostate cancer, such as low-risk cancers, active surveillance, as opposed to definitive treatment, is a reasonable course of action.” Mounting evidence suggests that the healthcare gap between urban and rural

populations is on the rise, Dr Maganty said. “Few studies have examined this gap as it relates to urologic malignancies. In this study, we have shown that the health disparity is also affecting urologic cancer care.” Reasons for the healthcare disparity remain unclear, Dr Maganty said. Current theories attribute the differences to determinants of health that include socioeconomics, environmental factors, health-related behaviors, access to care, and quality of care. The data gathered by his team did not directly allow the researchers to identify the etiology for this disparity, but they attempted to account for some of these health determinants. They added Area Deprivation Index (which takes into account education, income/employment, housing, and household characteristics) and urologist density as surrogates for socioeconomic status and access to care, respectively.

“After adding these variables to our model, we found that the reduced rates of treatment for rural patients previously identified was mitigated, although still less compared to their urban counterparts,” Dr Maganty said. “This suggests that some of the treatment differences we are seeing within the rural population [are] accounted for by socioeconomic status and proximity to a urologist. However, there are still additional factors that are intrinsic to a rural population that we could not account for with the available data.” He and his colleagues found that rural patients are more likely than their urban counterparts to have Medicare coverage, whereas urban resident are more likely to have private insurance. “Some theorize that this difference in insurance status can be attributed to several factors,” Dr Maganty explained. “Rural residents are thought to be older and of varying socioeconomic status, making them more likely to have Medicare. Additionally, rural residents may be more likely to be self-employed in small businesses or farming, which could make obtaining private insurance less economically feasible.”

Lower Definitive Treatment Rates In an earlier study, Laura-Mae Baldwin, MD, MPH, of the University of Wash­ ing­ton in Seattle, and colleagues found that rural patients had lower rates of definitive treatment for early-stage PCa and were less likely to undergo RP compared with urban patients.2 The study, which included 51,982 men with earlystage PCa identified using Surveillance, Epidemiology and End Results (SEER) cancer registry data, found that the adjusted rate of definitive treatment



atients with cancer who live in rural areas face challenges in receiving optimal medical treatment compared with their urban counterparts, with geographic barriers and limited availability of medical specialists cited as possible contributing factors.1,2 Urologists are among the specialists in short supply in sparsely populated areas. According to the American Urological Association’s 2019 annual urology workforce census, 62.4% of counties in the United States had no urologist.3 Further, it has been found that men with prostate cancer (PCa) in rural areas are less likely to receive treatment2,4 and make followup visits with urologists after undergoing radical prostatectomy (RP).5 These patients are also more likely to receive surgery rather than androgen deprivation therapy (ADT).6 The decreased likelihood of receiving PCa treatment in rural areas surfaced in a recent study of 51,024 men with either localized or metastatic prostate cancer in Pennsylvania.4 In this study, researchers found that patients living in rural areas had a 28% decreased odds overall of undergoing treatment compared with urban patients after adjusting for potential confounding factors. Avinash Maganty, MD, a 6th-year resident at the University of Pittsburgh, and colleagues documented similar findings when patients were stratified according to disease risk. Among men with low-, intermediate-, and high-risk cancer, rural residents had a 23%, 29%, and 32% decreased odds of undergoing treatment, respectively, compared with urban patients. For the study, which was published in The Journal of Urology, Dr Maganty and his collaborators used the Pennsylvania  NOVEMBER/DECEMBER 2020

was 83.7% for rural patients compared with 87.1% for urban patients. The investigators pointed out that they conducted their analyses with and without men who were candidates for active surveillance (AS), and in both analyses, rural patients were less likely to receive definitive therapy compared with urban patients. “This suggests that the lower rate of definitive treatment in our rural study population cannot be explained by the higher use of active surveillance,” Dr Baldwin’s team wrote. Moreover, rural patients had a lower adjusted rate of radical prostatectomy (RP) compared with urban patients (52.9% vs 55.9%), but a higher adjusted rate of receiving brachytherapy (20.7% vs 17.9%). Dr Baldwin’s team reported that 94.2% of urban patients had both a urologist and radiation oncologist in their county, whereas only 51.1% and 23.4% of rural patients had a urologist and radiation oncologist, respectively, in their county. Still, rural and urban patients had similar rates of receiving external beam radiation therapy (21.9% vs 21.4%), a finding that suggests rural patients in SEER registry areas were not making treatment decisions based on distance to care, according to the investigators. “It appears that rural patients were taking advantage of the multiple treatment options available for earlystage prostate cancer,” they wrote.

Follow-Up Visits Less Likely In addition, among men who undergo RP, those in rural places are less likely than those in urban areas to make followup visits with a urologist after surgery.5 In a study of 1158 men who underwent RP, a team led by Bettina F. Drake, PhD, MPH, of Washington University in St Louis School of Medicine in Missouri, demonstrated that patients living in rural areas had 39% and 28% decreased odds of follow-up visits with a urologist within the first and second year post-RP, respectively, compared with their urban counterparts.

Surgical vs Medical ADT Rural–urban differences also may extend to the type of ADT patients receive. A study of 10,675 men with metastatic PCa found that those who lived in rural areas had a 49% increased odds of undergoing surgical (bilateral orchiectomy) rather than medical ADT compared with urban patients.6 “Because individuals diagnosed in rural settings were more likely to receive surgical ADT, these results support the idea that travel burden may

affect cancer treatment plans, even in individuals with advanced disease,” the investigators, led by Hala T. Borno, MD, of the University of California, San Francisco, wrote.

Urologists Absent in Many Places Part of the access-to-care issue in rural areas could relate to the scarcity of specialists.1,2 According to the United States Census Bureau, 19.3% of the nation’s population lives in rural areas,7 yet data from the American Urological Association’s 2019 workforce census show that only 1358 (10.4%) of 13,044 practicing urologists in the United States practiced in nonmetropolitan areas.2 Specifically, only 57 urologists (0.4%) practiced in rural areas, 221 (1.7%) practiced in small towns, and 1080 (8.3%) practiced in micropolitan areas, which are defined by the US Office of Management and Budget as an urban cluster with a population of at least 10,000 but fewer than 50,000 people. Oncologists also are rare in rural America. According to 2018 practice census data from the American Society of Clinical Oncology, only 849 (7%) of the 12,423 oncologists in the United States practiced in rural areas.8

PCa Mortality Not Necessarily Worse Although rural residents apparently are less likely to receive treatment than urban residents, they may not have worse survival outcomes. Study data presented at the American Urological Association’s 2020 Virtual Experience suggest that state rurality does not increase the risk of PCa mortality.9 For each state, the study compared the percent of the population that is rural with both the PCa death rate and PSA screening rate among men older than 50 years and found no correlation between rurality and either rate. Lead investigator Katie S. Murray, DO, of the University of Missouri in Columbia, said she attributes the lack of a correlation between PCa mortality and rurality to PSA screening. “Prostate cancer screening has a low barrier to entry,” Dr Murray told Renal & Urology News. “It consists of a simple blood test that does not require a highly skilled and specialized operator. For this reason, we believe prostate cancer mortality is not negatively affected by living in a rural community.” As for why she and her colleagues conducted the study, Dr Murray observed, “In recent years, there has been a push in medicine to expand care to underserved areas throughout America. We wanted to investigate if the barriers associated with living in these communities negatively affected prostate cancer mortality.”

Rural Urologists’ View Patrick E. Davol, MD, who practices in Medford, Oregon, is among the urologists who serve a largely rural population. In his area, the challenge is not patient access to technology, but rather ensuring patients can make appointments. “Many patients come from a couple of hours away,” Dr Davol explained. The logistics and cost of transportation are difficult for some patients, many of whom live on Social Security, he said. A major problem he sees among rural residents is limited access to primary care, with many patients not getting annual checkups. He has found that patients with PCa who reside in places far from medical facilities tend to opt for surgery (“a oneand-done treatment with an overnight hospital stay”) over radiation therapy, which requires frequent travel. Dr Davol also observed that “there is a cultural difference in the rural populations.” Patients from rural areas are more likely than urban patients to put their care in the doctor’s hands. Urban patients typically have researched their condition and treatments prior to consultation (“they’ve Googled everything”) and “have a pretty good idea of what they want.” Another urologist who treats rural patients, John S. Banerji, MD, who completed his fellowship training at Virginia Mason Medical Center in Seattle and now practices at Penn Highlands Urology in DuBois, Pennsylvania, (2018 population of 7415), has made the same observation. “In the urban environment, a lot of people come [to the doctor] with what they think they want,” Dr Banerji said. “The average person who walked into our clinic [in Seattle] had a college degree.” Patients tended to research their condition and treatments before a visit and often have formed a decision about what they want after getting input from their peers or perhaps doctors they know, he said. “They look at [the doctor] as a means of achieving that end.” In rural communities, however, patients rely to a greater extent on the doctor for information and advice. “They want you to be part of their decision-making process,” he explained. “That’s the biggest difference that I’ve noticed [between urban and rural patients].” Rurality may influence treatment selection, he said. For example, AS is more likely to be accepted by urban patients because they are apt to be aware that their cancer, at its current stage, is unlikely to kill them, Dr Banerji said.

Renal & Urology News 7

“They are happy to go through the multiple processes in an AS protocol, whereas in a rural area, the moment you tell patients that they’ve got a diagnosis of cancer, even though you say this cancer is not likely to kill them in their lifetime, they want something done. They’re not very comfortable in knowing they have a cancer and doing nothing about it.”

The Future of Rural Urology The underlying causes of PCa care disparities between rural and urban areas remain unclear, but if a shortage of rural urologists is a major factor, the outlook for narrowing the care gap is ominous in part because of an aging rural urologist workforce. An analysis of 2014 to 2016 AUA census data found that the proportion of rural urologists aged 65 years or older rose from 29% in 2014 to 48% in 2016, investigators reported in The Journal of Rural Health.10 “A high proportion of urologists in rural communities is approaching retirement age without signs of impending replacement with younger workers,” Andrew J. Cohen, MD, of the University of California, San Francisco, and colleagues concluded. “Simultaneously, dramatic increases in the number of older Americans seeking health care are forthcoming.” Possible solutions to the rural urologist shortage, according to the investigators, include realigning financial incentives for rural recruitment, incorporating telemedicine and advance care practitioners into practices, and increasing residency training opportunities. ■ REFERENCES 1. Charlton M, Schlichting J, Chioreso C, et al. Challenges of rural cancer care in the United States. Oncology (Williston Park). 2015;29(9):633-640. 2. Baldwin LM, Andrilla CHA, Porter MP, et al. Treatment of early-stage prostate cancer among rural and urban residents. Cancer. 2020;119(16):3067-3075. 3. 2019 The State of the Urology Workforce and Practice in the United States. American Urological Association. research-resources/aua-census/census-results. Accessed July 28, 2020. 4. Maganty A, Sabik LM, Sun Z, et al. Undertreatment of prostate cancer in rural residents. J Urol. 2020;203(1):108-114. 5. Khan S, Hicks V, Rancilio D, et al. Predictors of follow-up visits post radical prostatectomy. Am J Mens Health. 2018;12(40):760-765. 6. Borno HT, Lichtensztajn DY, Gomez SL, et al. Differential use of medical versus surgical androgen deprivation therapy for patients with metastatic prostate cancer. Cancer. 2019;125(33):453-462. 7. America Counts Staff. One in five Americans lives in rural areas. US Census Bureau. https://www.census. gov/library/stories/2017/08/rural-america.html. Published August 9, 2017. Accessed July 11, 2020. 8. Kirkwood MK, Hanley A, Bruinooge SS, et al. The state of oncology practice in America, 2018: Results of the ASCO Practice Census Survey. J Oncol Pract. 2018;14(7):e412-e420. 9. Anderson A, Woldu H, Mitchem J, Murray KS. State rurality does not increase the risk of prostate cancer death. Poster presented at: the American Urological Association’s 2020 Virtual Experience; June 27-28, 2020. Poster MP75-02. 10. Cohen AJ, Ndoye M, Fergus KB, et al. Forecasting limited access to urology in rural communities: Analysis of the American Urological Association census. J Rural Health. 2020;36(3):300-306.

8 Renal & Urology News


Infection Risk in Glomerular Disease Patients Characterized

VTE Worsens RCC Surgical Outcomes

Hospitalizations and emergency department visits common

BY JODY A. CHARNOW VENOUS thromboembolism (VTE) at the time of surgery for suspected renal cell carcinoma (RCC) is associated with significantly higher rates of minor and major complications and death, according to study findings presented at the 2020 virtual International Kidney Cancer Symposium. The findings are from a study of 122,342 patients undergoing elective surgical resection for renal masses from 2013 to 2017. Of these, 83,692 patients underwent radical nephrectomy (RN) and 38,650 underwent partial nephrectomy (PN), Hiren V. Patel, MD, PhD, of the Section of Urology at Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School in New Brunswick, and colleagues reported in a poster presentation.

BY JOHN SCHIESZER INFECTION-RELATED acute care events in children and adults with glomerular disease are common and associated with a number of risk factors, according to a new study. “We undertook this study to update our knowledge regarding the epidemiology of infections in patients with glomerular disease. This is especially important because our therapies and regimens have evolved since much of the literature in this area was published,” said lead investigator Dorey A. Glenn, MD, an assistant professor in the Division of Nephrology and Hypertension at the University of North Carolina Kidney Center in Chapel Hill, North Carolina. “Patients with glomerular disease suffer from more frequent, and sometimes severe infections. We also have data showing that these patients worry about infections and that infections affect quality of life.” Dr Glenn and his colleagues examined risk factors for time to first infection-related acute care events (hospitalization or emergency department [ED] visit) in a prospective, multicenter study of 1741 children and adults who within 5 years of enrollment were diagnosed with biopsy-proven minimal change disease, focal segmental glomerulosclerosis (FSGS), membranous nephropathy, or IgA nephropathy/vasculitis. The study enrolled patients at 72 participating clinical sites in the United States, Canada, Italy, and Poland. Of the 1741 patients, 163 (9%) experienced infection-related acute care events over a median follow-up period of 17 months. The unadjusted incidence rates of these events were 13.2 per 100 person-years among pediatric patients and 6.2 events per 100 person-years among adult patients, according to the investigators. “We found that infection-related ED visits and hospitalizations were associated with younger age, steroid exposure, and hypoalbuminemia with nephrotic range proteinuria,” Dr Glenn told Renal & Urology News. Infections were particularly frequent among those exposed to corticosteroids during the first year of study follow-up.

The unadjusted incidence rates of infection-related acute care events during the first year of follow-up were 50.6 per 100 person-years among patients with corticosteroid exposure at enrollment compared with only 28.6 per 100 person-years among those without corticosteroid exposure. Over a median follow-up time of 16 months, 537 all-cause acute care events occurred among pediatric participants. Of these, 134 (25%) were infection-related. The incidence rate of

Researchers identify younger age, steroid use, and low albumin as risk factors. all ­infection-related acute care events (including first and recurrent infections) among pediatric participants was 13.2 per 100 person-years. Over a median follow-up time of 17 months, 507 allcause acute care events occurred among 1027 adult participants, and 93 (18%) of the events were infection-related. Of the 1741 patients in the study, 372 (21%) subjects had minimal change disease, 411 (24%) had FSGS, 329 (19%) had membranous nephropathy, and 629 (36%) had IgA nephropathy/vasculitis. The cohort was 43% female, 68% white, and 41% were under age 18. The investigators excluded patients with kidney failure, a kidney transplant, diabetes mellitus, systemic lupus erythematosus, HIV infection, active malignancy, or hepatitis B or C at time of first kidney biopsy.

Limitations The study was limited by the lack of a control group and inability to estimate the risk of infection attributable to glomerular disease, Dr Glenn’s team noted. Additionally, the researchers were unable to account for infections managed at home or by a primary care physician. “Our findings generally reinforce what nephrologists have thought for some time about risk of infection in this patient population,” Dr Glenn

said. “Pediatric nephrologists need to ­counsel families regarding infection risk, especially during periods of steroid exposure and disease relapse. Apart from greater awareness, patient and family counseling strategies to reduce exposure to infectious agents and more diligent attention to recommended vaccination regimens are needed, ­especially for influenza and pneumococcal disease.” Nephrologist Panduranga Rao, MD, professor of internal medicine at the University Michigan in Ann Arbor, said the study findings are clinically relevant because they better define the magnitude of infection risk as well as the burden of hospitalization in this patient population. “It also helps us in quantifying the risk imposed by various features of glomerular disease such as low serum albumin as well as level of proteinuria,” Dr Rao said. “I was a little surprised to see that children … had a greater risk of infection than adults, as normally you would expect adults to do worse in view of the many comorbidities they accumulate over time.”

Importance of Tailored Therapy The current study, he said, highlights the importance of tailoring therapy to the type of kidney disease. Noting that steroids are commonly used for many glomerular diseases, he added: “These treatments come with a broad range of side effects. If we are able to direct therapy to specific disease pathways, it is possible we may be able to reduce the morbidity associated with treatment.” Rakesh Gulati, MD, a clinical associate professor and the director of the Nephrology/Transplant Fellowship Programs at Jefferson Health in Philadelphia, said low serum albumin, as shown in the current study, is a marker of malnutrition and more aggressive disease, so it is not surprising that the study cohort had a relatively high rate of infections. The study findings, he said, may be more relevant to pediatric glomerular disease cases. “Antibiotic prophylaxis as well as ageappropriate immunizations for respiratory illness in such subjects may prevent much morbidity and readmissions in such patients,” Dr Gulati said. ■

Study documents an increased risk of complications and mortality. The predicted probability for a nonfatal minor complication (Clavien 1-2) within 90 days was significantly higher among patients with VTE compared with those who did not have VTE (RN: 34.2% vs 21.1%; PN: 36.9% vs 22.5%), according to the researchers. The predicted probability for nonfatal major complications (Clavien 3-4) within 90 days was significantly higher among patients with vs without VTE (RN: 10.6% vs 5.2%; PN: 21.5% vs 5.0%). The predicted probability for death also was higher among patients with VTE (RN: 2.6% vs 1.0%; PN: 1.3% vs 0.3%).

Increased Costs The 90-day median costs, in 2019 dollars, were greater for the VTE vs no VTE patients (RN: $24,648 vs 13,951; PN: $19,338 vs $13,694), according to the investigators. “Given the increased risk of complications and mortality, patients with VTE at the time of nephrectomy should receive specific counseling and management to help mitigate complications and mortality,” the authors wrote. ■  NOVEMBER/DECEMBER 2020

Renal & Urology News 9

Fruits, Vegetables Ease Metabolic Acidosis A healthy diet may be a cost-effective way for CKD patients to manage a potentially serious abnormality


BY JOHN SCHIESZER DIETARY ACID REDUCTION with fruits and vegetables (F+V) or sodium bicarbonate supplements appear to produce comparable improvements in metabolic acidosis, but F+V may produce even greater improvements in several measured health outcomes in patients with chronic kidney disease (CKD) stage 3, according to a new post hoc analysis of data from a previously published clinical trial. The analysis also showed that F+V can produce improved health outcomes cost-effectively. Previous studies have shown that F+V can effectively treat metabolic acidosis and slow progression of CKD. In addition, adding F+V to diets of patients with CKD can improve their cardiovascular disease (CVD) risk profile similar to what has been shown in non-CKD populations. The new analysis included 108 macroalbuminuric patients with nondiabetic CKD stage 3 who had metabolic acidosis. Investigators randomly assigned patients to receive either F+V in amounts calculated to reduce dietary acid by half, oral sodium bicarbonate supplements, or usual care. They assessed patients annually for 5 years and calculated a mean overall health score based on plasma total CO2, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, change in medication dose, estimated glomerular filtration rate, and systolic blood pressure. The investigators, led by Donald E. Wesson, MD, professor of medicine at Texas A&M University College of Medicine in Dallas, also analyzed the number of cardiovascular disease (CVD) events, medication costs, and hospitalization costs. Same Effects on Plasma CO2 The study showed that the net plasma total CO2 increase at 5 years was the same for the sodium bicarbonate group and the F+V group. Average health scores at 5 years favored the F+V group. No CVD events occurred in the F+V group, 2 occurred in the sodium bicarbonate group, and 6 occurred in the usual care group, Dr Wesson and his colleagues reported in the Journal of Renal Nutrition. The investigators observed no differences in the total 5-year household costs per beneficial health outcome between the F+V group and sodium bicarbonate group. The usual care group

had the highest household costs per beneficial health outcome. “We were able to ascertain the costeffectiveness of the F+V intervention by looking at the overall population, not at individual participants,” Dr Wesson told Renal & Urology News. “The latter has implications that extend into policy as to what treatments we recommend for chronic diseases, in this case CKD.”

Drugs Should Be Adjunctive to Diet Further, he stated that diet should be considered foundational to the ­management of patients with CKD

Sufficient data on the effectiveness of diets rich in fruits and vegetables in controlling metabolic acidosis are available to support widespread use of this approach, especially because such diets are healthier overall, he said. Dr Yee pointed out that patients in the usual care group fared worse than those receiving sodium bicarbonate supplements, even though the sodium bicarbonate prescription was somewhat less than what is normally administered by nephrologists who do not prescribe F+V diets for patients with CKD and metabolic acidosis.

Clinicians should try to educate patients with chronic kidney disease and their caregivers about the importance and benefits of dietary management, investigator says.

because of its potential to reduce mortality and morbidity. “Drugs should be considered adjunctive to diet,” Dr Wesson said. “Our current approach in the medical community is typically drugs first then diet added as adjunctive therapy if additional benefits are needed. The understandable challenge is to get patients to change their diets, something that we all recognize is very difficult to do.” Clinicians should attempt to educate patients with CKD and their caregivers about the importance and benefits of dietary management of CKD, he added. Jerry Yee, MD, chief of nephrology and hypertension at Henry Ford Hospital in Detroit, Michigan, called the findings of the new study highly relevant. “Many physicians would fear that the higher fresh fruits and vegetables diet would cause hyperkalemia. This did not occur,” Dr Yee said.

Nephrologist Leighton R. James, MD, of the Medical College of Georgia at Augusta University in Augusta, Georgia, said he has some concerns about the current study because of its design. The study did not clearly show that the amount of bicarbonate received from F+V was equivalent to that received from sodium bicarbonate tablets, Dr James said. “This is important as several fruits in the F+V group contain citrate, which is converted to bicarbonate,” he explained. “Each citrate molecule generates 3 molecules of bicarbonate. So, the study would have to show that the amount of bicarbonate supplied by each intervention was equivalent.” In response, Dr Wesson said his team did match the amount of alkali being given in the F+V and sodium bicarbonate participant groups. “Not only was that the study design, this is supported by the fact that the net serum total CO2 intake was nearly identical between the

F+V and sodium bicardonate groups, supporting that they received the same amount of alkali.” Because the study could not be blinded, Dr James said, participants would know what they are receiving, and this could change their behavior. For example, participants might increase their physical activity or consume fewer calories, possibly contributing to a lower body mass index in the F+V group.

Sodium from Sodium Bicarbonate In addition, he noted, the study did not control for the effect of sodium from sodium bicarbonate supplements, which can impact blood pressure. “The differences in blood pressure and need for blood pressure medications may be related to sodium intake rather the F+V, which typically has more potassium and less sodium,” Dr James said. In terms of overall health score, the reduction in medication was considered as an improvement. However, he said it is not clear that the observed reduction was directly related to F+V or not controlling for other factors such as fat intake and the quantity of bicarbonate ingested. Dr Wesson noted that the statistical analysis did not account for fat intake among the 3 groups. Nephrologist Christopher Passero, MD, clinical assistant professor of medicine in the Renal-Electrolyte Division at the University of Pittsburgh in Pittsburgh, Pennsylvania, said the findings from the new study are similar those from prior studies suggesting that an alkali-producing F+V diet can achieve the same effects as alkali therapy to correct the metabolic acidosis seen in patients with CKD. The meat-rich, high-protein diets common in the United States contribute to acid production, he said. Dietary modification involving increasing the proportion of fruits and vegetables could help individuals reduce daily protein intake. Generally, for patients with CKD, nephrologists recommend reducing protein intake to 0.6–0.8 g per kg body weight (which is about 2 portions of meat, 3 ounces each, per day for most people, or in the case of the current study, a vegetable equivalent), Dr Passero said. “It would be helpful if future studies described other considerations regarding diet, including sustainability, and avoidance of micronutrient and protein malnutrition.” ■

10 Renal & Urology News


Hospitals turned to PD continued from page 1

renal recovery by the time of d ­ ischarge. Eight patients remained hospitalized, and none remained on PD. Four patients were switched to either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD), and 4 patients had renal recovery and no longer needed RRT.

Advantages Dr Sourial’s team noted that PD use in the AKI setting has advantages, including no need for vascular access, reduced cost compared with CRRT and IHD, and no need for special plumbing to supply water for dialysate for IHD, “allowing for treatment in hospital rooms without adequate water supply.” In addition, staff can be educated to perform PD safely with few resources over a short period of time compared with other dialysis modalities. “Based on our experience, urgent PD is a feasible RRT option to treat patients with COVID-19 and AKI,” the authors concluded. A dramatic surge in ICU patients with COVID-19-related AKI also prompted Bellevue Hospital Center to institute an acute PD program. “Our ability to provide RRT with CVVH [continuous veno-venous hemofiltration] and IHD was severely limited by critical shortages of equipment and personnel,” Nina J. Caplin, MD, and colleagues concluded in a slide presentation.

KTRs and COVID-19 continued from page 1

the 145 patients, 55% were older than 60 years and 65% were male. The median time since receiving a transplant was 5 years; only 16% had received a transplant less than 1 year from presentation. Common symptoms at COVID-19 onset were fever and dyspnea (71%), myalgia (54%), and diarrhea (35%). During hospitalization, 83% of patients received hydroxychloroquine, 76% antibiotics, 13% tocilizumab, and 10% antivirals. Hypertension was the most common comorbidity (95%), followed by obesity, heart disease, and lung disease, which were present in 41%, 25%, and 19% of patients, respectively. The study by Northwell investigators examined data from 30 KTRs hospitalized with COVID-19. Death risk was higher if patients were admitted to a non-transplant hospital (80% vs 23%), lymphopenic at presentation (47%

In addition, patients with COVID-19 had increased clotting of membranes, circuits, and lines, at times rendering patients unable to tolerate and receive CVVH and/or IHD, they noted. “Acute PD more than adequately filled the gap in treatment options during this unprecedented crisis.” As of May 8, 39 patients received PD catheters and 36 of them PD. Of these, 20 died in less than 30 days; 15 survived for more than 30 days, and 8 of them recovered renal function. One patient had long-term end-stage kidney disease (ESKD) and lost all vascular access. That patient survived.

Rapid adoption of PD during the pandemic could encourage wider use of the modality. “Our experience provides a roadmap for responses to future crises with heavy burdens of AKI,” Dr Caplin and colleagues concluded. Also during the conference, Elly Varma, MBBS, and colleagues at Weill Cornell Medicine, reported their experience with the use of acute PD for 11 patients with COVID-19-related AKI that required RRT. The patients had undergone bedside PD catheter placement from April 1 to April 30. The median time from AKI to PD catheter insertion was 5 days. At 1 week,

vs 8%), and had an oxygen saturation less than 94% on admission (100% vs 57%), Dr Vinay and colleagues reported. During hospitalization, mortality also was higher among patients with elevated peak serum creatinine (3.2 vs 1.5 mg/dL), or if they required intubation (70% vs 14%). Increases in inflammatory markers, including peak D-dimer, peak C-reactive protein, ferritin, and procalcitonin, also predicted mortality. The study population was 61% male, 32% White, and 29% Black. The most common symptom was cough, followed by fever, shortness of breath, and fatigue. Ten patients required ventilation. Most patients were on triple immunosuppression (94% on tacrolimus, 90% on mycophenolate, and 74% on prednisone). With respect to treatment, 93% of patients received hydroxychloroquine, 50% received azithromycin, 14% received convalescent plasma, and 10% received an interleukin-6 inhibitor. One patient received the antiviral remdesivir. ■

10 catheters (91%) were functional with no leaks or bleeding detected. Only 1 patient was switched to CRRT due to primary PD catheter nonfunction. The median duration of follow-up from time of PD catheter insertion was 37 days. Of the 11 patients, 4 (36%) died, 5 (45%) had recovery of renal function, and 2 (18%) were alive and on HD. “We hypothesize that preservation of residual renal function utilizing PD may have contributed to the high rate of renal recovery observed,” the authors concluded. The rapid embrace of PD to address an explosive demand for dialysis brought on by the COVID-19 pandemic could contribute to increased uptake of the modality generally, according to Virginia Wang, PhD, MSPH, of Duke University School of Medicine in Durham, North Carolina, a coauthor of the study titled “Trends in Peritoneal Dialysis Use in the United States After Medicare Payment Reform,” which was published in 2019 in the Clinical Journal of the American Society of Nephrology. Noting that uptake of PD has risen only moderately in the last few decades, she said, “I’ve wondered whether and what kind of system shocks would propel faster growth in PD use. The COVID-19 pandemic may be one of them, as suggested by these case reports of hospitals’ experiences initiating acute PD programs for patients with COVID-related AKI.” Only a small minority of patients with ESKD in the United States receive PD

as their RRT. As of December 31, 2017, only 7.1% of prevalent ESKD patients in the United States were being treated with PD (compared with 62.7% HD), according to the US Renal Data System 2019 Annual Data Report. Many in the nephrology community say PD is underused.

Voclosporin use for LN

a slide presentation. VCS treatment was significantly associated with approximately 2.8-fold increased odds of renal response compared with controls. The 1-year renal response for Hispanic patients — a high-risk LN patient population — was 37.9% for VCS recipients compared with 19.4% for controls. The largest change in eGFR from baseline for VCS recipients compared with controls occurred early, declining by 5.6 mL/min/1.73 m2 by week 4. By week 52, the change in eGFR improved, declining by 3.7 mL/min/1.73 m2 compared with controls. The mean change from baseline of eGFR in the VCS arm at week 52 was –1.0 mL/min/1.73 m2, which was not statistically significant. The proportion of patients who experienced serious adverse events was similar between the VCS and controls groups (22.8% vs 18.8%). ■

continued from page 1

the management of patients with lupus nephritis.” Dr Rovin and colleagues analyzed combined data from the phase 2 AURA-LV and phase 3 AURORA clinical trials. Both trials demonstrated that VCS increased renal response significantly compared with mycophenolate mofetil. They defined renal response as a urine protein-to-creatinine ratio of 0.5 mg/mg or less, an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 or higher or no decline more than 20% from baseline, need for 10 mg prednisone or less 8 weeks prior to endpoint measurements, and no need for rescue medications. The integrated dataset included an intent-to-treat population of 268 patients treated with VCS at a dosage of 23.7 mg twice daily and 266 control patients. The renal response at 1 year was 43.7% for the VCS arm compared with 23.3% for controls, Dr Rovin’s team reported in

Why PD Is Underused Many factors in the healthcare delivery system are associated with underuse of PD, including lack of earlier CKD identification and timely preparation for kidney failure, inadequate patient education about all treatment options, and lack of PD availability at dialysis facilities, said Dr Wang, who is an associate professor in the Department of Population Health Sciences and Division of General Internal Medicine. Clinician lack of awareness of, and experience with, PD are commonly cited barriers to wider adoption and use of the modality and may be challenging to address, Dr Wang said. Healthcare providers are unable to get hands-on experience with PD because relatively few patients receive this form of dialysis. With few alternative solutions, the pandemic forced hospitals to train clinicians, including physicians, nurses, and surgeons, in all facets of PD care and in ways that were probably not well established before COVID-19, Dr Wang said. “In this way, the pandemic could inadvertently represent an opportunity for PD growth in the US.” ■

Disclosure: Aurinia Pharmaceuticals Inc., which is developing voclosporin, sponsored the study.  NOVEMBER/DECEMBER 2020

NAC Offers Survival Edge in UTUC BY NATASHA PERSAUD NEOADJUVANT chemotherapy (NAC) may improve overall survival in patients with upper tract urothelial carcinoma (UTUC), according to investigators. In a retrospective study of 10,315 patients with high-grade UTUC who underwent nephroureterectomy identified using 2004-2015 data the National Cancer Database, 296 patients (2.9%) received pre­ operative NAC. Use of NAC was significantly associated with superior 5-year survival (47% NAC vs 42% no NAC), Douglas S. Scherr MD, of New York Presbyterian Hospital, Weill Cornell Medicine in New York, and colleagues reported in Urology. When the team analyzed data by clinical stage, only patients with non-­organconfined tumors receiving NAC had significantly improved overall survival. Of these patients, 27.1% had organ-­confined disease at the time of surgery. In contrast, among patients without NAC, 1.4% had organ-confined disease at surgery. Significantly more patients who

Renal & Urology News 11

RT for Abdominal, Pelvic Cancers Ups Risk for Secondary Sarcomas Radiotherapy combined with chemotherapy is associated with the greatest risk BY JODY A. CHARNOW PATIENTS WHO receive radiation treatment (RT) or chemotherapy for nonmetastatic cancers of the prostate, bladder, and other abdominal or pelvic malignancies are at increased risk for secondary sarcomas compared with those treated with surgery alone. A combination of radiation and chemotherapy was associated with the greatest risk for sarcoma compared with surgery alone. “This study provides further evidence to support the association of radiotherapy with secondary sarcoma; the finding of an increase in risk with combination radiotherapy and chemotherapy, in particular, merits further study,” a team led by Robert K. Nam, MD, of Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada, wrote in a paper published in JAMA Network Open. The study included a populationbased cohort of 173,580 patients in Ontario, Canada, who had nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Of these, 125,080 (72.1%) were

Radiotherapy for pelvic or abdominal can­cers doubles the risk for secondary sarcomas compared with surgery alone.

men. Most patients had genitourinary cancers (86,235, 49.7%) and colorectal cancer (69,241, 39.9%). The cohort included 64,301 patients (37.1%) who had surgery alone, 51,220 (29.5%) radiation alone, 15,624 (9.0%) both radiation and chemotherapy, 15,252 (8.8%) radiation and surgery, and 11,822 (6.8%) all 3 treatments. During a median follow-up time of 5.7 years, sarcomas developed in 332 patients

(0.2%). The incidence of sarcomas was 0.3% among patients who had radiation therapy alone and radiation in addition to chemotherapy, 0.2% among those who had radiation and surgery as well as those who had all 3 modalities, and 0.1% among patients who received both surgery and chemotherapy. Compared with the surgery-only patients, patients who had a combination of radiotherapy and chemotherapy had a 4-fold increased risk of sarcoma, whereas those who received radiation alone, radiation with surgery, or all 3 modalities each had an approximately 2.3-fold increased risk, the researchers reported. Among patients with PCa, those who received radiation plus surgery had a relative rate of sarcoma double that of patients who had surgery alone. The relative rate was not significantly elevated among patients who had radiation plus chemotherapy. Compared with Ontario’s general population, patients treated with radiation had a 2.4-fold increased sarcoma rate compared with the general population (41.3 vs 17.2 events per 100,000 personyears), according to the investigators. ■

underwent NAC experienced pathologic downstaging: 10.8% NAC vs 1.4% no NAC), according to Dr Scherr’s team. On multivariate analysis, overall survival was significantly better for patients who received NAC. Survival was significantly worse for older patients and those with higher pT stages, increasing Charlson-Deyo score, and treatment at a comprehensive community cancer program, according to the researchers. “In a national contemporary cohort of patients who underwent [nephroureterectomy], administration of NAC was associated with improved survival across the entire cohort,” Dr Scherr and colleagues wrote. © MARK KOSTICH / GETTY IMAGES

“However, the bulk of the survival advantage due to NAC administration appears to be a result of significant pathologic downstaging only in patients with significant disease burden at time of biopsy.” ■

Conservative PCa Care Less Likely for Black Men BY NATASHA PERSAUD BLACK MEN ARE less likely than White men to receive conservative management for prostate cancer (PCa), but when they do, they are more likely to switch to definitive treatment, according to a new study. In a study of 51,543 Black and White veterans with low- to intermediate-risk PCa who had consistent care from the Veterans Administration’s health care system, 40.0% overall received conservative management, either active surveillance (AS) or watchful waiting (WW). But Black veterans (28.8% of cohort) with low- and intermediate-risk disease were 5% and 8% less likely to receive conservative management than White veterans, respectively, Ravi B. Parikh, MD, MPP, of the University of Pennsylvania in Philadelphia, and colleagues reported in JAMA Network Open. More importantly, Black men receiving conservative management had a

shorter median time from PCa diagnosis to definitive therapy: 719 vs 787 days. Black patients with low- and intermediate-risk disease receiving conservative management had a 71% and 46% greater likelihood of switching to definitive therapy within 5 years of diagnosis, respectively, compared with White veterans. Among the AS recipients, the likelihood of switching to definitive therapy was 53% and 56% higher for low- and intermediate-risk Black patients, respectively, compared with White patients. In the WW cohort, the likelihood was 80% and 48% greater for low- and intermediate-risk Black patients, respectively. In contrast, factors associated with a lower likelihood of definitive therapy within 5 years included lower absolute PSA level, being married, and living in a rural area. “The findings of this study suggest that conservative management for lowrisk and intermediate-risk prostate

cancer may be less durable for African American veterans compared with White veterans,” the authors wrote. Black patients also had lower restricted mean survival time at 5 years: 1679 vs 1740 days, respectively, Dr Parikh’s team reported. At baseline, Black veterans were more likely than their White counterparts to have intermediate-risk disease (57.5% vs 51.7%), 3 or more comorbidities (51.3% vs 42.1%), and high disability-related or income-related needs (31.1% vs 24.7%) compared with White veterans. The investigators controlled for several socioeconomic confounders, including driving distance to providers, area-level deprivation, and income and disability status. Among the study’s limitations, the team was unable to assess PSA levels, biopsy results, or prostate volume prior to definitive therapy, or distinguish between favorable and unfavorable intermediate-risk PCa. ■

12 Renal & Urology News


Fluciclovine PET May Improve PCa Salvage Radiotherapy Outcomes USE OF FLUCICLOVINE (18F) positron emission tomography/computed tomography in addition to conventional imaging to guide radiation therapy for men with recurrent prostate cancer (PCa) following radical prostatectomy (RP) is associated with improved outcomes compared with conventional imaging alone, investigators reported during the American Society for Radiation Oncology (ASTRO) virtual annual meeting. The finding is from the EMPIRE-1 (Emory Molecular Prostate Imaging

for Radiotherapy Enhancement) trial. Investigators randomly assigned 165 patients to receive external beam radiation therapy (EBRT) based on conventional imaging (bone scan plus CT or magnetic resonance imaging [MRI] of the abdomen and pelvis) or conventional imaging plus fluciclovine PET/CT. “What this research has found is that integrating advanced molecular imaging into the treatment planning process allows us to do a better job of selecting patients for radiation therapy, guiding radiation treatment decisions

Fluciclovine PET/CT vs Conventional Imaging Fluciclovine PET/CT added to conventional imaging decreases the likelihood of radiotherapy failure in men who have recurrent prostate cancer following radical prostatectomy, a study found. Shown here are the rates of failure-free survival at 3 and 4 years.






n PET/CT nC onventional imaging


40 20 0

3 years

Failure-free survival rate

4 years

Source: Jani A, Schreibmann E, Goyal S, et al. Initial report of a randomized trial comparing conventional- vs conventional plus fluciclovine (18F) PET/CT imaging-guided post-prostatectomy radiotherapy for prostate cancer. Presented at: ASTRO 2020 virtual annual meeting, October 23-29, 2020. Abstract LBA 1.

and p ­ lanning and ultimately, keeping patients’ cancer under control,” Dr Jani said in an ASTRO press release. To be enrolled in the study, patients needed to have detectable PSA following RP, negative bone scans, and no extra-pelvic metastases found on CT or MRI scans of the abdomen or pelvis. The treatment arms were balanced with respect to age, race, PSA level, androgen deprivation therapy use, and pathologic characteristics. The median follow-up duration was about 2.5 years overall and 3.0 years for the failure-free patients. The 3-year failure-free survival rate, the study’s primary endpoint, was significantly greater in the PET/CT group than the control group (75.5% vs 63.0%), co-principal investigator Ashesh B. Jani, MD, of the Winship Cancer Institute at Emory University School of Medicine in Atlanta, Georgia, reported in a late-breaking abstract session. The 4-year failure-free survival rate also was significantly greater in the PET/CT group (75.5% vs 51.2%). On multivariable analysis, patients in the PET/CT arm were twice as likely to be free of treatment failure compared with controls. ■

Radium-223 Response Is Tied to CTCs CIRCULATING TUMOR cells (CTCs) may be useful as biomarkers of response to radium-223 treatment for metastatic castration-resistant prostate cancer (mCRPC), according to study findings presented at the American Society for Radiation Oncology (ASTRO) 2020 virtual annual meeting. The study enrolled 22 patients with mCRPC. Of these, 8 patients (36%) had fewer than 6 metastases, 7 (32%) had 6-20 metastases, and 7 (32%) had more than 20 metastases. All progressed to mCRPC on androgen deprivation therapy, and 5 patients (23%) previously received docetaxel. The median overall survival was 18.4 months, according to Keisuke Otani, MD, PhD, of Massachusetts General Hospital in Boston, who presented study findings. Investigators measured CTCs using 2 methods: CellSearch to enumerate CTCs and a PCR-based prostate CTC expression assay to perform RNA expression analyses. They used the assay to arrive at a CTC RNA score. Pretreatment CTC counts of 5 or more CTCs per 7.5 mL of blood cor-

AKI Predictors in Cerebral Bleed Cases ID’d

related with worse survival compared

HIGHER BASELINE serum creatinine levels and treatment with higher doses of the antihypertensive drug nicardipine increase the risk for acute kidney injury (AKI) in patients with intracerebral hemorrhage (ICH), according to a new study. In addition, development of AKI is associated with higher rates of death and death or disability combined at 90 days. “New strategies aimed at reducing the risk of AKI in patients with ICH may reduce the rates of death or disability associated with ICH,” Adnan I. Qureshi, MD, of the University of MissouriColumbia, and colleagues concluded in a paper published in Stroke. The study included 1000 patients with intracerebral hemorrhage in the ATACH 1 (Antihypertensive Treatment of Cerebral Hemorrhage) clinical trial who had initial systolic blood pressure (SBP) values of 180 mm Hg or higher and were randomly assigned to intensive (goal 110139 mm Hg) or standard (goal 140-179

elevated pretreatment digital CTC

mm Hg) SBP reduction within 4.5 hours of symptom onset. Investigators identified AKI by serial assessment of daily serum creatinine for 3 days after randomization. AKI and renal adverse events (AEs), such as acute renal failure and abnormal renal function tests, developed in 149 patients (14.9%) and 65 patients (6.5%), respectively. On multivariate analysis, higher baseline serum creatinine (110 µmol/L or higher) was associated with significant 2.4-fold and 3.1-fold increased odds of AKI and renal AEs, respectively, compared with levels less than 60 µmol/L, the researchers reported. A higher area under the curve for intravenous nicardipine was associated with greater risk for AKI and renal AEs. “Higher doses of nicardipine may be a marker of more difficult to treat elevated SBP or may have a direct effect by decreasing renal vascular resistances and increasing transmission of SBP to the glomeruli,” the authors explained.

The proportion of patients who died within 90 days was significantly higher in the AKI than no-AKI group (14.1% vs 5.4%). The proportion of patients who died or experienced disability also was higher in the AKI group (53.0% vs 33.8%). In adjusted analyses, the presence of AKI, compared with its absence, was associated with a 2.9-fold greater risk for death at 90 days and a 2.7-fold greater risk for death or disability at 90 days, according to the investigators. Renal AEs were not associated with either of those outcomes. In a discussion of study limitations, the authors said ATACH 2 excluded patients with high anticipated mortality, “and thus our analysis may not have included the group of patients with perhaps a higher risk of AKI.” They also noted that the results of their post hoc analysis “may also be contaminated by chance, differences in patients’ clinical characteristics, and other concurrent interventions.” ■

with less than 5 CTCs per 7.5 mL (median 10.0 vs 29.2 months). An RNA score of 20 or higher calculated using the CTC RNA expression assay also was associated with worse survival compared with a score less than 20 (median 11.6 vs 29.2 months). The pretreatment digital CTC RNA score was significantly higher among patients who had demonstrated disease progression on bone scans at 6 months compared with those with stable or decreased disease burden. A previous study of 45 men with mCRPC treated with radium-223 found that median overall survival was 16 months, but it was significantly decreased (7 months) among patients with more than 5 CTCs per 7.5 mL at baseline, Joan Carles, MD, and colleagues reported in a 2018 paper in Clinical Genitourinary Cancer. ■  NOVEMBER/DECEMBER 2020

Renal & Urology News 13

Avelumab Ups Survival in Advanced UC Study shows benefit of adding the drug to best supportive care as part of first-line maintenance therapy BY JODY A. CHARNOW FIRST-LINE maintenance therapy with avelumab plus best supportive care (BSC) significantly prolongs overall survival (OS) compared with BSC alone among patients with unresectable locally advanced or metastatic urothelial carcinoma (UC) who had disease that did not progress while on first-line chemotherapy, according to study findings presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 and published concurrently in the New England Journal of Medicine. In the phase 3 JAVELIN Bladder 100 trial in which investigators randomly assigned 700 patients to receive avelumab, an immunotherapeutic drug, plus BSC or BSC alone, OS at 1 year was 71.3% in the avelumab group compared with 58.4% in the BSC-only arm, study investigator Petros Grivas, MD, PhD, of the University of Washington (UW) in Seattle, reported in a video

SU vs NU for Ureteral Tumors BY JODY A. CHARNOW SEGMENTAL ureterectomy (SU) may be an appropriate alternative to radical nephroureterectomy (NU) for the treatment of high-risk ureteral tumors. A retrospective analysis using data from 2006 to 2013 from the National Cancer Database (NCDB) revealed no significant difference in overall survival (OS) between patients treated with SU or NU after adjusting for multiple variables, Patrick M. Lec, MD, of the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues reported in Urologic Oncology. The study included 1962 patients with clinically localized high-risk ureteral tumors. Selection criteria aimed to approximate the European Association of Urology (EAU) definition of highrisk upper tract urothelial carcinoma (UTUC) within the limits of the NCDB, the researchers explained. Of the 1962 patients included, 1421 (72.4%) underwent radical NU and 541 (27.6%) underwent SU. Lymph­ a­de­nec­tomy was performed in only

Survival Rates at 1 Year First-line maintenance therapy with avelumab plus best supportive care (BSC) vs BSC alone significantly increased 1-year overall survival (OS) rates among patients with unresectable locally advanced or metastatic urothelial carcinoma whose disease had not progressed while on first-line chemotherapy, including a subset of patients with PD-L1-positive disease. 80




n Entire cohort


nP D-L1-positive patients


40 20 0

BSC alone Avelumab + BSC 1-Year Survival Rates

Source: Grivas P, Park SH, Voog E, et al. Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy (CTx) for advanced urothelial carcinoma (UC): Subgroup analyses from JAVELIN Bladder 100. Presented at: ESMO Virtual Congress 2020. Abstract 704MO

presentation. Median OS was 21.4 months in the avelumab group compared with 14.3 months in the control group. Avelumab treatment was significantly associated with a 31% decreased risk of death, according to Dr Grivas,

446 patients (22.7%). Among the 1092 patients with advanced pathology, 271 (24.8%) received adjuvant chemotherapy. The median follow-up time was 33.2 months for the radical NU group and 31.6 months for the SU group. In the NU group, lymphadenectomy was associated with a 42% decreased risk of death when more than 3 nodes were removed, the authors reported. Receipt of adjuvant chemotherapy for advanced pathology had no effect on OS in either treatment group. “This retrospective cohort study supports the performance of lymphadenectomy and SU in patients with high-risk ureteral tumors,” the authors concluded. Dr Lec and colleagues stated that their study had limitations that derive from shortcomings of data extraction methods in the NCDB. Although they were able to restrict their analysis to ureteral tumors, they were not able to discriminate between tumor locations along the ureter or other factors such as multifocality and hydronephrosis “that fall within the EAU definition of highrisk UTUC,” the investigators wrote. “This invites some degree of selection bias, as some of these features technically dictate NU (i.e., proximal location) and others reflect more aggressive disease biology that favor performance of radical extirpative surgery.” ■

associate professor of oncology at UW and director of UW Medicine’s Genitourinary Cancers Program. In addition, avelumab significantly prolonged OS among PD-L1–positive patients. OS at 1 year was 79.1% in the

avelumab group and 60.4% in the control group. Avelumab was significantly associated with a 44% decreased risk of death. The median progression-free survival (PFS) was 3.7 months in the avelumab group and 2.0 months in the control group in the study population as a whole and 5.7 months and 2.1 months, respectively, in the PD-L1-positive population. Avelumab was significantly associated with a 38% and 44% decreased risk for disease progression or death in the study population as a whole and the PD-L1-positive population, respectively, according to the investigators. The incidence of adverse events (AEs) from any cause was 98.0% in the avelumab group and 77.7% in the control arm, the study found. The incidence of grade 3 or higher AEs was 47.4% and 25.2%, respectively. The study was sponsored by Pfizer, and is part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany. ■

Earlier Surrogate for Survival After RP Relapse Possibly ID’d CASTRATION-RESISTANT prostate

Drs Freedland and Klaassen and their

cancer (CRPC)-free survival among men

colleagues conducted a retrospective

with biochemical failure following radical

cohort study that included 210 men who

prostatectomy (RP) is closely correlated

had biochemically recurrent PCa after

with metastasis-free survival (MFS), sug-

RP, a PSA doubling time of less than 9

gesting the former could be an interme-

months, and no evidence of metastasis

diate endpoint in clinical trials, research-

at the time of starting androgen depriva-

ers concluded in a poster presentation

tion therapy (ADT). The primary outcome

during the European Society for Medical

was the correlation between CRPC-free

Oncology Virtual Congress 2020.

survival (CRPC-FS) and MFS.

MFS is a surrogate for overall survival

During a median follow-up of 79.4

in men with localized prostate cancer,

months after initiation of ADT, CRPC

but this endpoint may take years to

or death occurred in 131 patients

develop in patients with nonmetastatic

and metastasis developed in 132

castration-sensitive disease, a team

patients. The median CRPC-FS and

co-led by Stephen J. Freedland, MD,

MFS was 100 months and 104 months,

of Cedars-Sinai Medical Center in Los

respectively. When limited to men with

Angeles, and Durham VA Medical Center

a PSA at ADT initiation greater than

in Durham, North Carolina, and Zachary

1 ng/mL and those with a Charlson

Klaassen, MD, of Augusta University

Comorbidity Index of 2 or less, there

in Augusta, Georgia, explained. “Other

was an approximately 85% and 88%

evidence-based intermediates that occur

correlation between CRPC-FS and MFS,

earlier in the disease course are needed

respectively, and 76% and 74% correla-

for clinical trial design to expedite

tion between time to CRPC and time to

evaluating new therapies,” they noted.

metastasis, respectively. ■

14 Renal & Urology News


Alpha Blockers Up CKD Progression Risk Use of these agents increases the likelihood of a 30% or greater eGFR decline, recent study shows BY JOHN SCHIESZER ALPHA BLOCKER USE to control hypertension may be associated with a higher risk for kidney disease progression but a lower risk for cardiac events and mortality compared with use of alternative antihypertensive medications in patients with chronic kidney disease (CKD), according to a recent populationbased retrospective study published in the American Journal of Kidney Diseases. Nuanced Discussions With Patients The findings could allow clinicians to have more nuanced discussions with patients who have CKD regarding the long-term risks associated with alpha blocker use, lead investigator Gregory L. Hundemer, MD, of the Ottawa Hospital Research Institute and The Ottawa Hospital, Riverside Campus, Ontario, Canada, told Renal & Urology News. “Nephrologists need to balance the pros and cons of prescribing alpha

blockers to their patients on a case-bycase basis,” Dr Hundemer said. Out of 381,120 patients aged 66 years or older living in Ontario who received treatment for hypertension from 2007 to 2015, the investigators identified 16,088 patients who were newly prescribed alpha blockers (doxazosin, terazosin, and prazosin) and matched them with 16,088 patients who were newly prescribed antihypertensive medications other than alpha blockers (ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and thiazide diuretics). Patients had a mean age of 76 years and mean estimated glomerular filtration rate (eGFR) of 62 mL/min/1.73m2. The investigators looked at the following outcomes: a 30% or larger decline in estimated glomerular filtration rate (eGFR), dialysis initiation or kidney transplantation, composite of acute myocardial infarction, coronary

Allopurinol Dosage Reduction Increases Risk of Gout Flares ALLOPURINOL DOSAGE reductions

similar between the groups, but the

in patients hospitalized with acute

allopurinol-reduced group had a

gout are associated with an increased

greater proportion of patients with

risk for gout flares within 3 months

acute kidney injury vs the comparator

of discharge compared with no

group (60% vs 36%). The allopurinol-

changes in dosage, according to study

reduced group had a significantly

findings published in the Journal of

higher rate of gout flares within 3


months of discharge vs the compara-

Irvin J. Huang, DO, of the University of

tor group (53% vs 22%).

Washington in Seattle, Washington and

The authors noted that dose reduc-

colleagues studied 59 patients who had

tion in their study was driven primarily

a diagnosis of gout and active prescrip-

by concerns that allopurinol use in

tions for allopurinol who were hospital-

patients with gout flares and renal insuf-

ized for acute gout flares. The study

ficiency can worsen renal function and

population had a median age of 58

increase the risk of allopurinol hyper-

years, and 92% of patients were male.

sensitivity syndrome. They pointed out,

The 59 patients had a total of 73

however, that current studies support

hospitalizations. Allopurinol was either

the safety of allopurinol use for gout

reduced or discontinued in 15 admis-

patients with concurrent renal insuf-

sions (allopurinol-reduced group),

ficiency. “Improved awareness of the

whereas the drug was increased or

current gout recommendations, as well

unchanged during the other 58 admis-

as the risks and benefits of allopurinol

sions (comparator group).

in the setting of concomitant renal dis-

The proportion of patients with chronic kidney disease (CKD) was

ease, is necessary to improve patient outcomes,” they wrote. ■

r­evascularization, congestive heart failure, or atrial fibrillation, safety (hypotension, syncope, falls, fractures) events, and mortality. The study excluded patients with prior cardiac events. Dr Hundemer and colleagues

Study finds a 28% greater likelihood of requiring renal replacement therapy. examined outcomes according to category of eGFR (in mL/min/1.73 m2): 90 or higher, 60-89, 30-59, and less than 30. Alpha blocker use was significantly associated with a 14% higher risk of a 30% or greater eGFR decline and 28% increased likelihood of dialysis initiation or kidney transplantation compared with use of medications other

RCC Surgery Delay Safe, Study Finds DELAYING SURGERY for clinically localized renal cell carcinoma (RCC) of up to 6 months does not increase the risk of tumor progression, a finding that has implications for RCC treatment during the COVID-19 pandemic, according to findings presented at the 2020 International Kidney Cancer Symposium and published in Urologic Oncology. In a study of 29,746 patients who underwent partial or radical nephrectomy for cT1b, cT2a, or cT2b RCC tumors, who were identified using the National Cancer Database, a team led by Eric A. Singer, MD, of the Rutgers Cancer Institute of New Jersey in New Brunswick, found that delaying surgery for more than 3 months after RCC diagnosis did not significantly increase the risk of upstaging to pT3a cancer. “During the current COVID-19 pandemic and subsequent recovery, urologists and their patients can expect delays in radical and partial nephrectomy for clinically localized RCC,” the researchers wrote in their journal paper.

than alpha blockers. The findings held regardless of eGFR category.

Decreased Risk of Cardiac Events In addition, use of alpha blockers, compared with the use of other antihypertensive agents, was significantly associated with an 8% lower risk of cardiac events. Alpha blocker use was significantly associated with a 15% and 29% reduced risk of death among patients with an eGFR of 30-59 and less than 30, respectively. The authors note that the study is limited by its observational design and a lack of detailed blood pressure (BP) measurement data. “I think the current trial will sensitize physicians to the possibility that alpha blockers may have positive and negative effects beyond strict BP control,” commented Samuel N. Saltzberg, MD, associate professor of medicine at Rush Medical College in Chicago. ■ “In most patients with clinically localized cT1b tumors, surgery may be safely delayed for up to 6 months without significant sacrifices in overall survival.” For patients with cT2 tumors, they added, “we must carefully weigh tumor characteristics and patient comorbidities when discussing surgical delay. However, our data suggests that most patients experiencing a delay of 3 months due to the COVID-19 pandemic will not experience worse oncological outcomes.” Among patients with cT1b lesions, a surgical delay of 1-3 months and more than 3 months was significantly associated with a 13% and 55% increased risk of death, respectively, compared with undergoing surgery within 1 month of diagnosis, in adjusted analyses, the researchers reported. They pointed out, however, that these patients still have favorable overall survival. Patients with surgical delays of 1-3 and more than 3 months have 5-year overall survival rates of 80.1% and 70.9%, respectively. As surgical delay does not seem to predict upstaging, they noted, unmeasured confounding rather than tumor progression likely explains the adverse effect of delayed surgery on survival rates in patients with cT1b cancers. Surgical delay was not associated with worse survival among patients with cT2a or cT2b cancers. ■  NOVEMBER/DECEMBER 2020

Renal & Urology News 15

Ethical Issues in Medicine Physician virtues can help them navigate potential ethical dilemmas posed by the COVID-19 pandemic BY DAVID J. ALFANDRE, MD, MSPH

The Common Good Such extreme conditions (which have thus far been avoided in the United States) necessitate a shift in the standard of care so that treatment decisions are based not on what is best for an individual patient, but on what is best for the community. Such a fundamental shift in usual clinical decision-making must rest on strong moral foundations, which in this case is on the principle of utility: achieving the greatest good for the

good characteristics that will enable them to behave well.”1 It focuses on the actor — in this case, the physician — and is less about how one acts than the character traits one possesses and cultivates to enable the preferred behavior. Virtues are “a disposition that enables us to perceive, feel, want, and act in certain ways”2 — ways that physicians recognize, see in their colleagues, and commit to during their graduation oaths. Virtues include courage, prudence, justice, honesty, integrity, generosity, and empathy, among others, and serve as a center point between its natural extremes. For example, neither lying nor “truth dumping” are acceptable ways of promoting the virtue of honesty with patients.

Reflection and Reasoning In cultivating these virtues, one rationally and voluntarily chooses to exercise them, and creates space for the virtues to grow within oneself. Practicing this process is expected to lead to a desire (not necessarily a sense of duty) to meet one’s obligations, leading to a life that “flourishes.” Virtue ethics also demands that the individual recognize the importance of reflection and reasoning in applying these virtues thoughtfully and in context, with an appreciation for how emotion influences these virtues. In short, when

Virtue ethics can enable physicians to manage such dilemmas as patients refusing to wear face masks despite rules requiring them to do so. greatest number. Principlism is another form of moral reasoning familiar to most medical school graduates. The principles of autonomy, beneficence, nonmaleficence, and justice are simple, straightforward, and accessible, but they are often unhelpful to the practicing clinician. But there is another method of moral reasoning that could have practical value today: virtue ethics. Virtue ethics “explores how individuals can learn by habitual practice how to develop

confronted with an ethical challenge, this method of moral reasoning asks, “What would a virtuous doctor do?”3 Using virtue ethics can assist us in managing a modern-day ethical dilemma, such as encounters with patients who decline to wear a face mask during the current COVID pandemic. If you practice in a state or a health care system that requires masking, then from a rulesbased perspective the “right” answer is for the patient to simply follow the rules.



pproximately 2000 years ago, the ancient Greek rhetorician and grammarian Athenaeus observed that “goodness does not consist in greatness but greatness in goodness.” This has new relevance today during the COVID-19 pandemic. This public health crisis has sparked much talk of ethics, with the most intense discussions related to the prospect of demand for healthcare resources outstripping the supply. What would physicians and other healthcare providers do, for example, if the number of COVID-19 infections and hospitalizations rose so fast and so high that there were insufficient intensive care unit beds or mechanical ventilators to care for patients, forcing them to ration those life-saving resources to those most likely to survive?

The COVID-19 pandemic may put physicians in a position of deciding who gets an ICU bed.

This concern grows more complicated if the patient is severely short of breath and needs urgent medical care. From a principle-based perspective, framing the problem as one of autonomy vs justice does not necessarily help us decide which principle to prioritize in a given situation. However, from a virtue ethics perspective, we can ask ourselves, “What would a good doctor do in this situation?”3

Consider Patients’ Viewpoint A virtuous physician would show character traits like equanimity, compassion, integrity, and resolve. While the physician would expect and demand patients abide by the state laws that are designed to protect others from infection, they would also demonstrate compassion by appreciating what might lead someone to make a choice that violates the law. Such empathy allows for brainstorming to open one’s mind up to unconventional solutions. A virtuous physician might also recognize how their emotional responses and those of the patient provide important clinical data that can illuminate how to address the conflict. The patient might be feeling unheard, marginalized, and frightened, while the physician might be feeling frustrated, angry, and worried

about viral transmission. Finally, even when there is a supposedly “right” answer based on a rule or law, the virtuous physician may conclude that a rulesbased approach may be oversimplifying. An appreciation of the virtues one wishes to embody can help to navigate the complexity. In responding in this way, and doing so over time with reflection and thoughtfulness, the physician can develop the virtues needed to flourish and provide good medical care. ■ 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. Gardiner P. A virtue ethics approach to moral dilemmas in medicine. J Med Ethics. 2003;29:297-302. doi:10.1136/jme.29.5.297 2. Bellazzi F, Boyneburgk KV. COVID-19 calls for virtue ethics. J Law Biosci. 2020;7:lsaa056. doi:10.1093/ jlb/lsaa056 3. Pellegrino ED. Professionalism, profession and the virtues of the good physician. Mt Sinai J Med. 2002 Nov;69(6):378-384.

16 Renal & Urology News


Practice Management Doctors should focus on things under their control to cope with psychological distress during the COVID-19 pandemic BY TAMMY WORTH

Burnout or Depression? Burnout is a common malady among physicians as a result of working long hours and dissatisfaction stemming from having less time to spend with individual patients. But with many physicians working fewer hours now, mental health challenges they are dealing with may look more like depression. How can one tell the difference? Burnout, Dr Bernstein explained, tends to be more transient and is related to work situations. Symptoms can be emotional exhaustion, depersonalization and lack of effectiveness on the job. “If someone is saying they feel down and disconnected and angry and irritable, but when they get away from work those symptoms go away, that is more indicative of burnout than depression,” she said. It can be a bit more difficult to detangle those kinds of emotions during a pandemic when there are so many more stressors. But burnout is typically related to system issues in the workplace. Classic symptoms of depression, however, are feelings of sadness, hopelessness, and loss of sleep or too much sleep.

Symptoms tend to come on over a period of time and can stick around longer. If more serious symptoms arise, like dramatic changes in sleep or appetite, suicidal ideation, and not enjoying things that usually are pleasurable, it is important to seek help from a mental health professional, Dr Bernstein said. This can also be true if symptoms are milder but persist for weeks or months at a time.

Debriefings Held A few weeks after the pandemic hit, SBH Health System in the Bronx, New York, began providing debriefings — therapy-like sessions for all departments of the hospital — by psychiatrists and psychologists in its department of psychiatry. The fact that everyone was going through the same kinds of struggles made it easier for people to talk in those early days, said Lizica Troneci, MD, chair and residency program director in the department. “It was more acceptable to have debriefings and to talk about the feelings and experiences we have had, which, looking back, is different than discussing burnout we had experienced before,” Dr Troneci said. “The COVID-19 experience brought us together because everyone had fears and anxiety, and there was less stigma and more open-



ormer First Lady Michelle Obama broke the internet when she recently announced she had been suffering low-grade depression because of the pandemic and national upheaval. Her declaration appeared to resonate with people across the country suffering from physical illness, isolation, and income and job losses. A recent study published in JAMA Network Open found that 3 times more Americans are suffering from depression during the COVID-19 pandemic compared with before. Front-line workers have not been sheltered from this challenge, as borne out by high-profile physician suicides in COVID-19 hotspots. “We are all adapting to a situation where we don’t know what’s coming down the line,” said Carol Bernstein, MD, vice chair for faculty development at Montefiore Medical Center in New York City.

Exercising and getting healthy amounts of sleep may help ease distress, an expert says.

“It’s taboo to say we are struggling, and it’s a particular problem in medicine,” she said. “A lot of what people are feeling right now is normal in these circumstances and normalizing it will help people feel better.”

Get Together With Staff When talking about work issues, Dr Bernstein recommends trying not to focus too much on how awful things

‘Isolation only contributes to feelings of loss and depression, so acknowledging and talking about stressors can help people get through tough times.’ ness associated with talking about this.” This kind of assistance for physicians is extremely important, according to Dr Bernstein. Isolation only contributes to feelings of loss and depression, so acknowledging and talking about stressors can help people get through tough times, she said. The more prominent the people are who talk about feeling burned out or depressed, the easier it is for everyone to acknowledge and discuss their feelings, Dr Bernstein said.

are because that can be disheartening. Instead, she suggests having what she calls an appreciative inquiry. Staff members get together and focus on what is working well and how they can do more of that. “If you spend all of your time saying, ‘It’s awful and I can’t do this or that,’ it can perpetuate,” she said. “There is a delicate balance between sharing misery and looking at how you can proactively address things together.”

Whether struggling with burnout or depression, it is important to focus on the things that are under one’s control, Dr Bernstein said. Physicians should try to do things they enjoy. Dr Troneci recommends such routine activities as eating well, exercising, and getting healthy amounts of sleep.

Take One Day at a Time It is also important to remember to take one day at a time. “People don’t do that well, and doctors especially don’t,” Dr Bernstein said. “We are always focused on the future. We have to take one day at a time because we don’t know what’s coming, and eventually this will get under control.” Dr Bernstein equates moving forward now with the airline changes after the events of 9/11. At first, she said, it was a hassle to abide with the new encumbrances that went along with flying, but eventually people got used to them. “It’s important to maintain in your head that this is a time-limited thing and maintaining hope for the future is important,” she said. ■ Tammy Worth is a freelance medical journalist based in Blue Springs, MO.

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