Renal and liver injury following the treatment of covid-19 by remdesivir

Remdesivir initially was intravenously administrated to treat the Ebola disease however right now it has been administered to treat COVID-19 in some countries. However it is necessary to find the exact effect of remdesivir in patients with COVID-19. Remdesivir solution is administered with a cyclodextrin carrier that filters solely by the glomeruli; thereby patients with abnormal renal function cannot eliminate it quickly; therefore, remdesivir can lead to renal failure or liver dysfunction during therapeutic process of COVID-19. Assessment of renal function in patients with COVID-19 who have acute kidney injury (AKI) or end-stage renal disease is fundamental. [1]

Since SBECD has a renal excretion root, patients with moderate or severe renal impairment have exposure to SBECD. Hence a close look on eGFR (estimated glomerular filtration rate) is needed in the time of administration of remdesivir, especially in patients with renal impairment. The discontinuation of remdesivir is required if eGFR levels drop to half level from baseline. Remdesivir has contraindication in patients with severe renal impairment (eGFR less than 30 mL/min) [2]

Based on a case study of COVID-19 in a single double-lung transplant patient admitted to the intensive care units (ICU) [3] there was a debate in the literature wether remdesivir, its metabolites or the carrier sulfobutyl ether beta-cyclodextrin (SBECD, Captisol) are responsible for the nephrotoxcity (4,5). It was concluded that AKI is of multifactorial origin: direct nephrotoxicity of SARS-CoV-2, hemodynamic alterations during sepsis, cytokine release, rhabdomyolysis, angiotensin II pathway activation, defects due to coagulation disorders and toxicity of both the drug metabolites and the carrier can contribute. No clear evidence of nephrotoxicity due to remdesivir was obtained in clinical trials and compassionate-use cohort, but as acute kidney injury (AKI) is more common in patients with severe COVID-19, particularly those in ICUs, and is considered as a negative prognostic factor for survival, the renal effects of remdesivir treatment should be considered.

Currently, there is very low-evidence regarding the potential hepatotoxicity of remdesivir. Considering its effective results in patients developed COVID-19 infection and the high frequency of liver involvement following COVID-19, the attribution of liver dysfunction to the administration of remdesivir is challenging and further studies are needed in this regard.