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Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure

Kamo et al., In Vivo, doi:10.21873/invivo.13637
Jun 2024  
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Retrospective 176,197 adverse event reports in Japan showing paxlovid and remdesivir associated with increased risk of acute kidney injury (AKI) in COVID-19 patients.
Gérard, Zhou, Wu, Kamo, Choi show significantly increased risk of acute kidney injury with remdesivir.
Study covers paxlovid and remdesivir.
Kamo et al., 27 Jun 2024, Japan, peer-reviewed, 3 authors. Contact:
This PaperRemdesivirAll
Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure
Masahiro Kamo, Ph.D Rintaro Sogawa, Chisato Shimanoe
In Vivo, doi:10.21873/invivo.13637
Background/Aim: Reports regarding the association of remdesivir use for the treatment of Coronavirus disease 2019 with the development of acute kidney injury (AKI) are inconsistent, and the associations between the use of other antivirals and AKI remain unclear. Therefore, this study investigated whether the use of antiviral drugs for the treatment of COVID-19 is a risk factor for the development of AKI. Patients and Methods: This study analyzed 176,197 reports submitted to the Japanese Adverse Event Reporting Database between 2020 and 2022. Reporting odds ratios (RORs) and 95% confidence intervals (95%CIs) for AKI that were associated with the use of antiviral drugs in patients with COVID-19 were calculated after adjusting for potential confounders. Results: Overall, 5,879 of the reports analyzed were associated with AKI. Signs of AKI were detected with the use of remdesivir [crude ROR (cROR)=2.45; and nirmatrelvir/ritonavir (cROR=6.07; 95%CI=4.06-9.06). These results were maintained even after adjusting for potential confounders [remdesivir: adjusted ROR (aROR) =2.18; nirmatrelvir/ritonavir: aROR=5.24;]. However, when analyzing data stratified by reporting year, the association between remdesivir and AKI appeared to diminish over time and was not sustained. Conclusion: Nirmatrelvir/ritonavir use may be associated with developing AKI. This knowledge may be useful in helping patients with COVID-19 avoid AKI complications. Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has become a global pandemic. However, on May 4, 2023, the World Health Organization announced the end of its declaration of a "public health emergency of international concern", though mutant strains of COVID-19 continue to emerge and infect individuals. SARS-CoV-2 often causes upper respiratory tract symptoms, including sore throat, nasal discharge, and nasal obstruction, and systemic symptoms, such as fatigue, fever, and myalgia (1). In addition, acute kidney injury (AKI) has been reported as a complication in patients with severe COVID-19 (2). A recent meta-analysis reported that 29% of patients with COVID-19 developed AKI (3). AKI due to COVID-19 is thought to be caused by tubulopenia (4, 5). In addition, antiviral drugs used as therapy against COVID-19 may also be associated with the development of AKI. Remdesivir, molnupiravir, nirmatrelvir/ritonavir, and ensitrelvir are antiviral drugs that are currently used to treat COVID-19. Remdesivir was the first approved treatment, and renal impairment due to accumulation of the additive sulfobutylether-β-cyclodextrin (SBECD) has been reported (6). In addition, an analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) has shown an association between remdesivir and AKI (7). In contrast, a meta-analysis reported that remdesivir does not affect the risk of AKI (8). Another previous study revealed that remdesivir can be safely used..
Conflicts of Interest The Authors have no conflicts of interest to declare in relation to this study. Authors' Contributions M.K. and R.S. designed the study and analyzed the data. M.K., R.S. and C.S. drafted the manuscript. All Authors have read and approved the final manuscript.
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