Following hospitalization with COVID-19, remdesivir improved kidney function in most patients with eGFRs of less than 30 mL/min/1.73 m2 and was generally well-tolerated, according to study findings.
“Remdesivir (GS-5734), a nucleotide prodrug that inhibits RNA-dependent RNA polymerase, accelerates recovery in patients with moderate to severe COVID-19 and was approved by emergency use authorization in May 2020,” Christopher Estiverne, MD, of Brigham and Women’s Hospital, Harvard Medical School, and colleagues wrote. “However, all studies of remdesivir have excluded patients with kidney impairment, using estimated glomerular filtration rate (eGFR) cutoffs of 30 [mL/min/1.73 m2] or 50 mL/min/1.73 m2, due to theoretical concerns about accumulation of remdesivir’s active metabolite or its sulfobutylether-b-cyclodextrin (SBECD) carrier.”
According to the researchers, it is crucial to study the impact of remdesivir in patients with lower eGFRs because “antiviral strategies are desperately needed in this population.”
To investigate, Estiverne and colleagues identified 18
patients hospitalized with COVID-19 between May and July 2020 who had an eGFR of less than 30 mL/min/1.73 m2 or who were receiving kidney replacement therapy at the time of remdesivir initiation. Investigators focused on changes in alanine aminotransferase (ALT) and serum creatinine during the therapy, considering reported adverse events attributed to the medication.
Two patients developed ALT greater than five times the upper limit of normal, which the researchers determined was due to shock liver and not remdesivir.
“Eight of 13 patients not requiring [renal replacement therapy] RRT at the time of remdesivir initiation experienced improved creatinine during remdesivir, while [five] worsened, including [four] who progressed to require RRT,” the researchers wrote. “In one case, study investigators determined the worsening creatinine was likely attributed to remdesivir.”
Regarding adverse events, Estiverne and colleagues found the treatment was well-tolerated overall, though there were cases of hyperglycemia, anemia and burning at the infusion site, with two patients discontinuing therapy due to burning at IV site during the final dose and worsening kidney function.
All patients who did not require intensive care at baseline survived to 28 days.
“The exclusion of patients with eGFR [less than] 30mL/min/1.73 m2 from clinical trials has created an important gap in knowledge of safety data for remdesivir, as up to one in three critically ill patients with COVID-19 may have eGFR [less than] 30mL/min/1.73 m2,” the researchers wrote. “Concerns about accumulation of the SBECD carrier should be allayed by the available safety data in patients with kidney failure treated with voriconazole, which uses the same carrier.”
According to Estiverne and colleagues, there continues to be an “urgent need for prospective studies in this common and high-risk population.”
