Remdesivir Use in the Setting of Severe Renal Impairment: A Theoretical Concern or Real Risk?

Abstract

Background Remdesivir (RDV) is US FDA approved for coronavirus disease 2019 (COVID-19) but not recommended in severe renal impairment (SRI, Creatinine clearance <30mL/min or requiring renal replacement therapy). Few studies have evaluated RDV in patients with SRI. Methods Hospitalized patients who received RDV between 1 May 2020 and 31 October 2020 were analyzed in a retrospective chart review. We compared incident adverse events (AEs) in patients with and without SRI, including hepatotoxicity, nephrotoxicity, any reported AE, mortality, and length of stay. Results Of a total of 135 patients, 20 had SRI. Patients with SRI were significantly older (70 vs 54 years, P = .0001). The incidence of possible AEs was 30% among those with SRI vs 11% without (P = .06). Liver function test (LFT) elevations occurred in 10% vs 4% (P = .28), and serum creatinine (SCr) elevations in 27% vs 6% (P = .02) of patients with SRI vs without, respectively. LFT and SCr elevations were not attributed to RDV in either group. Mortality and length of stay were consistent with historical controls. Conclusions RDV AEs occurred infrequently and overall were not significantly different between those with and without SRI. While more of patients with SRI experienced SCr elevations, 3 (75%) patients had acute kidney injury prior to RDV. The use of RDV in this small series of patients with SRI appeared to be relatively safe, and the potential benefit outweighed the theoretical risk of liver or renal toxicity. Additional studies are needed to confirm this finding.

Impact of Kidney Failure on the Severity of COVID-19

“…According to the summary of product characteristics, the application of RDV was significantly lower in CKD patients; however, five individuals with severe renal failure scored at baseline in category 5 on an ordinal scale and received off-label RDV, and one of them died; however, it should be pointed out that in the remaining four patients no deterioration in renal function was documented [ 37 ]. Similar observations in a small series of 20 patients with ESKD treated with RDV were published by Pettit et al, where therapy appeared to be relatively safe and the potential benefit outweighed the theoretical risk of renal toxicity [ 38 ].…”

Renal and Hepatic Toxicity Analysis of Remdesivir Formulations: Does What Is on the Inside Really Count?

“…6 Furthermore, an observational study has reported no significant difference in the risk of adverse effects when remdesivir injectable solution was administered in 20 patients with renal impairment compared to patients without renal impairment. 7 These findings were consistent with our previous experience which also failed to identify a significantly increased risk of AKI or abnormal liver function tests among 40 patients with a creatinine clearance (CrCl) of less than 30 ml/min who received remdesivir injectable solution. 8 However, in the absence of robust data, and continued concern for SBECD accumulation, the lyophilized formulation remains reserved for patients at risk for renal injury at some institutions.…”

“…However, while accumulation of SBECD in animals has been associated with liver necrosis and nephrotoxicity, these adverse effects have not been observed in humans ( 6 ). Furthermore, an observational study has reported no significant difference in the risk of adverse effects when remdesivir injectable solution was administered in 20 patients with renal impairment compared to that in patients without renal impairment ( 7 ). These findings were consistent with our previous experience, which also failed to identify a significantly increased risk of acute kidney injury (AKI) or abnormal liver function tests among 40 patients with a creatinine clearance (CrCl) of less than 30 ml/min who received remdesivir injectable solution ( 8 ).…”

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

“…We used our standard renal‐sparing immunosuppression protocol (basiliximab, corticosteroids, mycophenolate mofetil), except we held mycophenolate mofetil given her active SARS‐CoV‐2 infection and data suggesting increased mortality in LT recipients on mycophenolate mofetil 12 . We started remdesivir immediately after LT, despite the known risk of elevated liver tests with this medication as well as the patient's renal failure, as we thought the risk of COVID‐19 outweighed the risk of remdesivir side effects 18,19 . It is unknown whether remdesivir contributed to the patient's eventual recovery from COVID‐19 or if it contributed to the elevated aminotransferases after LT.…”