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Observational Study
. 2021 Dec 3;3(2):269-278.
doi: 10.34067/KID.0006152021. eCollection 2022 Feb 24.

A Propensity Score-Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney Disease

Rituvanthikaa Seethapathy  1 , Sophia Zhao, Joshua D Long, Ian A Strohbehn, Meghan E Sise
Affiliations
Observational Study

A Propensity Score-Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney Disease

Rituvanthikaa Seethapathy et al. Kidney360. .

Abstract

Background: Remdesivir is not currently approved for patients with eGFR <30 ml/min per 1.73 m2. We aimed to determine the safety of remdesivir in patients with kidney failure.

Methods: This study was a retrospective cohort study of patients with COVID-19 hospitalized between May 2020 and January 2021 with eGFR <30 ml/min per 1.73 m2 who received remdesivir and historical controls with COVID-19 hospitalized between March 1, 2020 and April 30, 2020 prior to the emergency use authorization of remdesivir within a large health care system. Patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. Adverse events and hospital outcomes were recorded by manual chart review.

Results: The overall cohort included 34 hospitalized patients who initiated remdesivir within 72 hours of hospital admission with eGFR<30 ml/min per 1.73 m2 and 217 COVID-19 controls with eGFR <30 ml/min per 1.73 m2. The propensity score-matched cohort included 31 remdesivir-treated patients and 31 nonremdesivir-treated controls. The mean age was 74.0 (SD=13.8) years, 57% were women, and 68% were white participants. A total of 26% had ESKD. Among patients who were not on dialysis prior to initiating remdesivir, one developed worsening kidney function (defined as ≥50% increase in creatinine or initiation of KRT) compared with three in the historical control group. There was no increased risk of cardiac arrythmia, cardiac arrest, altered mental status, or clinically significant anemia or liver function test abnormalities. There was a significantly increased risk of hyperglycemia, which may be partly explained by the increased use of dexamethasone in the remdesivir-treated population.

Conclusions: In this propensity score-matched study, remdesivir was well tolerated in patients with eGFR <30 ml/min per 1.73 m2.

Keywords: COVID-19; SARS-CoV-2; acute kidney injury; antiviral; chronic kidney disease; dialysis; propensity score; remdesivir.

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Conflict of interest statement

M.E. Sise reports consultancy agreements with Bioporto; research funding from Abbvie, EMD-Serono, Gilead Sciences, and Merck; honoraria from the International Society of Hemodialysis for the Hemodialysis University Lecture; and scientific advisor or membership with Gilead Sciences as a scientific advisory board member and Travere Therapeutics as an scientific advisory board member. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Patient flow and exclusions. COVID-19, coronavirus disease 2019; EUA, emergency use authorization; O2, oxygen.
Figure 2.
Figure 2.
Percentage of patients experiencing clinical events of interest. Clinical outcomes were adjudicated by two physicians who reviewed each physician and clinical nursing note for the 5-day remdesivir course +48 hours after remdesivir treatment (black bars) and the first 7 days of admission for historical comparators (gray bars). The only clinical event that was significantly increased in patients treated with remdesivir was the incidence of hyperglycemia (defined by glucose >200), which occurred in 81% of patients treated with remdesivir compared to 55% of controls. A total of 25 of 31 (81%) remdesivir-treated patients also received dexamethasone concurrently compared with three of 31 (10%) controls. Among the six remdesivir-treated patients who did not receive dexamethasone, three (50%) also had hyperglycemia >200 mg/dl. There were no significant differences in any of the other adverse events. ALT, alanine aminotransferase; AST, aspartate aminotransferase; HGB, hemoglobin; ULN, Upper limit of normal.
Figure 3.
Figure 3.
Box plots showing laboratory results in remdesivir-treated patients and controls. Box plots for the highest ALT, AST, and glucose and lowest hemoglobin for remdesivir-treated patients show interquartile range (box), median (line), and whiskers with 5th and 95th percentiles. Outliers are shown with solid circles. Only peak glucose significantly differed between matched remdesivir-treated patients and historical controls.
Figure 4.
Figure 4.
Creatinine trends among patients who were not on KRT at baseline. Serum creatinine values for each patient throughout the study period are shown on a log2 scale. Patients shown in red had ≥50% rise in serum creatinine or initiation of KRT. Initiation of KRT in one remdesivir-treated patient is demarcated by a dialysis machine icon.
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