Acute kidney injury in COVID-19 patients receiving remdesivir: A systematic review and meta-analysis of randomized clinical trials

Shams, Golnaz; Kazemi, Asma; Jafaryan, Khatereh; Morowvat, Mohammad Hossein; Peymani, Payam; Karimzadeh, Iman

doi:10.1016/j.clinsp.2023.100200

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Review articles • Clinics 78 • 2023 • https://doi.org/10.1016/j.clinsp.2023.100200 copy

Acute kidney injury in COVID-19 patients receiving remdesivir: A systematic review and meta-analysis of randomized clinical trials

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objectives:

Remdesivir is an antiviral agent with positive effects on the prognosis of Coronavirus Disease (COVID-19). However, there are concerns about the detrimental effects of remdesivir on kidney function which might consequently lead to Acute Kidney Injury (AKI). In this study, we aim to determine whether remdesivir use in COVID-19 patients increases the risk of AKI.

Methods:

PubMed, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, medRxiv, and bio-Rxiv were systematically searched until July 2022, to find Randomized Clinical Trials (RCT) that evaluated remdesivir for its effect on COVID-19 and provided information on AKI events. A random-effects model metaanalysis was conducted and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. The primary outcomes were AKI as a Serious Adverse Event (SAE) and combined serious and non-serious Adverse Events (AE) due to AKI.

Results:

This study included 5 RCTs involving 3095 patients. Remdesivir treatment was not associated with a significant change in the risk of AKI classified as SAE (Risk Ratio [RR]: 0.71, 95% Confidence Interval [95% CI] 0.43‒1.18, p = 0.19, low-certainty evidence) and AKI classified as any grade AEs (RR = 0.83, 95% CI 0.52‒1.33, p = 0.44, low-certainty evidence), compared to the control group.

Conclusion:

Our study suggested that remdesivir treatment probably has little or no effect on the risk of AKI in COVID-19 patients.

Keywords:
SARS-COV-2; COVID-19; Acute Kidney Injury; Remdesivir; Systematic review; Meta-analysis

Study	Study design and setting	Country	Male (%)	Age (median/mean) (years)	Comparator	Dose and duration of remdesivir	Severity at baseline (%)			Comorbidities (%)	Data source of outcome	Follow-up (days)
Study	Study design and setting	Country	Male (%)	Age (median/mean) (years)	Comparator	Dose and duration of remdesivir	No oxygen	Low flow	High flow/ventilated	Comorbidities (%)	Data source of outcome	Follow-up (days)
Ader 2022 DisCoVeRy NCT04315948	Open-label, adaptive, multicenter, inpatient	France, Belgium, Austria, Portugal, Luxembourg	69.5	64	Standard care (n = 428)	200 mg IV on Day 1, 100 mg on Days 2‒10 (n = 429)	1.8	57.2	41.0	Obesity (34.1), Chronic cardiac disease (27.9), Diabetes mellitus (26.8), Chronic pulmonary disease (18.0), Smoking (current or former) (17.6), Chronic kidney disease (6.6)	Publication, Preprint	90
Beigel 2020 ACTT-1 NCT04280705	Double-blind, multicenter, inpatient	United States, Denmark, United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore	64.4	58.9	Placebo (n = 521)	200 mg IV on Day 1, 100 mg on Days 2‒10 (n = 541)	13.0	41.0	45.0	Hypertension (51), Obesity (46), Diabetes (31), Asthma (12), coronary artery disease (13), Neoplasm malignant (8), Chronic kidney disease (7), Chronic respiratory disease (7)	Publication, Clinicaltrials.gov	28
Spinner 2020 SIMPLE-Moderate NCT04292730	Open-label, multicenter, inpatient	United States, China, France, Germany, Hong Kong, Italy, Japan, Korea, Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom	61.1	NR	Standard care (n = 200)	200 mg IV on Day 1, 100 mg on Days 2‒5 (n = 199) or 200 mg IV on Day 1, 100 mg on Days 2‒10 (n = 197)	84.1	15.0	0.9	Cardiovascular disease (56.3), Hypertension (42.5), Diabetes (39.7), Asthma (13.9)	Publication, Clinicaltrials.gov, Clinical Study Report	28
Wang 2020 NCT04257656	Double-blind, multicenter, inpatient	China	59.3	65	Placebo (n = 79)	200 mg IV on Day 1, 100 mg on Days 2‒10 (n = 158)	1.3	82.2	16.5	Hypertension (43.2), Diabetes (23.7), Coronary heart disease (7.2)	Publication	28
Goldman 2020 SIMPLE-Severe NCT04292899	Open-label, multicenter, inpatient	United States, Italy, Spain, Germany, Hong Kong, Singapore, South Korea, Taiwan	63.7	NR	–	200 mg IV on Day 1, 100 mg on Days 2‒5 (n = 200) or 200 mg IV on Day 1, 100 mg on Days 2‒10 (n = 197)	13.9	55.4	30.7	Hypertension (49.9), Diabetes (22.7), Hyperlipidemia (22.4), Asthma (12.3)	Publication, Clinicaltrials.gov	28

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[1] *Corresponding author. E-mail address:karimzadee@sums.ac.ir (I. Karimzadeh).