Authors’ Reply

In their letter, Gevers and colleagues¹ highlight concerns that remdesivir and its metabolite, GS-441524, may carry a risk of toxicity to the renal tubular epithelium, and that risks may be more considerable for patients with predialysis CKD. We agree that the potential risks of remdesivir and the concern for nephrotoxicity are likely greater in patients with predialysis CKD who have an eGFR of <30 ml/min per 1.73 m² compared with patients receiving dialysis.

There have been two important updates in the literature regarding coronavirus disease 2019 since we originally wrote our perspective. First, the Solidarity Trial—an unblinded, randomized trial that assigned 2750 patients to remdesivir—found that remdesivir did not reduce mortality, initiation of ventilation, or hospitalization duration compared with standard of care, which has led many to question the effectiveness of remdesivir.² Second, three retrospective studies now provide clinical experience of remdesivir use in patients with an eGFR of <30 ml/min per 1.73 m². Thakare et al.³ reported no cases of worsening kidney function attributed to remdesivir in 46 patients with an eGFR of <30 ml/min per 1.73 m²; 30 of these patients were not on dialysis at baseline. Estiverne et al.⁴ reported no severe liver-function abnormalities attributed to remdesivir among 18 patients with an eGFR of <30 ml/min per 1.73 m²; among 13 patients who were not on dialysis, multiple patients had improving kidney function on remdesivir, with only one case of worsening kidney function considered likely to be related to remdesivir by the study investigators. Ackley et al.⁵ found that, among 40 patients receiving remdesivir with an eGFR of <30 ml/min per 1.73 m², only two patients had a >50% increase in creatinine during treatment with remdesivir, and both patients had alternative explanations for AKI.

Although these new data are reassuring, we reiterate the statement we made in our perspective that “conclusive data on the safety of remdesivir among individuals with eGFR <30 ml/min per 1.73 m² are lacking.” We also enthusiastically agree, and reiterate, that only through well-designed, randomized, placebo-controlled trials that include patients with an eGFR of <30 ml/min per 1.73 m² can we truly understand the safety and efficacy of remdesivir in patients with advanced kidney disease. Currently, our hospital’s approach is to consider remdesivir (lyophilized powder formulation) in patients with an eGFR of <30 ml/min per 1.73 m² who are deemed most likely to benefit (hospitalized within 10 days of symptom onset, requiring supplemental oxygen for pneumonia associated with coronavirus disease 2019, and not yet mechanically ventilated). After discussing risks and benefits with the infectious-diseases and nephrology consult teams, we engage in shared decision making with patients and caregivers, highlighting the lack of trial data in patients with an eGFR of <30 ml/min per 1.73 m².

Disclosures

M.E. Sise has received research funding from Abbvie, Gilead, Merck, and EMD Serono; has served as a scientific advisory board member for Gilead in the area of viral hepatitis; has consultancy agreements with Bioporto; and has received honoraria from lecturing for the International Society of Hemodialysis–Hemodialysis University. All remaining authors have nothing to disclose.

Funding

None.