Acute kidney injury associated with immune checkpoint inhibitors: A pharmacovigilance study

Abstract

Background: Acute kidney injury (AKI) is a rare but severe adverse event of immune checkpoint inhibitors (ICIs). With the increasing reports of ICIs, it's necessary to put new insights into ICIs-related AKI. We conducted a systematic review of randomized controlled trials(RCTs) and a real-world study by extracting data from the US FDA Adverse Event Reporting System (FAERS) database.

Methods: We explored ICIs-related AKI events in RCTs available in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to August 2021. Meta-analysis was performed by using risk ratios (RRs) with 95 %CIs. In a separate retrospective pharmacovigilance study of FAERs, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC).

Results: A total of 79 RCTs (500,09 patients) were included, and ICIs were associated with increased risk of all-grade (RR = 1.37, 95 %CI:1.14-1.65) and high-grade AKI (RR = 1.60, 95 %CI:1.16-2.20). Results of subgroup analysis indicated that RR of ICI-related AKI did not vary significantly by cancer type, treatment regimen (monotherapy or combination of ICIs), study design (double-blind or open-label), individual ICIs and publication status (published or unpublished). FAERS pharmacovigilance data identified 1918 cases of AKI related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of AKI (ROR = 2.38, 95 %CI:2.27-2.49; IC = 1.22, 95 %CI:1.16-1.27). The median onset time of AKI was 48 days, 77.5 % of patients discontinued the use of ICIs, and 15.9 % of patients resulted in death.

Conclusions: These data suggest that ICIs were significantly associated with increased risk of AKI in both trial settings and clinical practice.

Keywords: Acute kidney injury; FDA Adverse Event Reporting System; Immune checkpoint inhibitors; Real-world pharmacovigilance; Systemic review.