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Meta-Analysis
. 2023 Apr 22;24(1):107.
doi: 10.1186/s12882-023-03171-9.

Risk factors of immune checkpoint inhibitor-associated acute kidney injury: evidence from clinical studies and FDA pharmacovigilance database

Pengwei Chen #  1   2 , Jianhong Zhu #  2   3 , Yanchun Xu  1   2 , Qiuyan Huang  1   2 , Jianan Su  1   2 , Ziqing Gao  1   2 , Min Feng  4   5
Affiliations
Meta-Analysis

Risk factors of immune checkpoint inhibitor-associated acute kidney injury: evidence from clinical studies and FDA pharmacovigilance database

Pengwei Chen et al. BMC Nephrol. .

Abstract

Background: Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study.

Methods: We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR).

Results: A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78-2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24-1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01-1.65), diuretics (OR = 2.00, 95%CI 1.38-2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04-1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15-1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25-2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96-3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91-2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95-3.57), NSAIDs (ROR = 3.06, 95%CI 2.81-3.32) or diuretics (ROR = 2.82, 95%CI 2.50-3.19) were observed significant signals associated with AKI in ICIs-treated patients.

Conclusions: Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

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

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Flow chart of study selection for systemic review
Fig. 2
Fig. 2
Forest plot of associations between concurrent drugs exposures with risk AKI in patients with ICIs. PPI Proton pump inhibitors, ACEI Angiotensin-converting enzyme inhibitor, ARB Angiotensin receptor blocker, NSAID Nonsteroidal anti-inflammatory drug, AKI Acute kidney injury, ICIs Immune checkpoint inhibitors
Fig. 3
Fig. 3
Forest plot of association between DM and AKI in ICIs-treated patients. DM Diabetes mellitus, AKI Acute kidney injury, ICIs Immune checkpoint inhibitors
Fig. 4
Fig. 4
Forest plot of associations between genitourinary cancer and AKI in ICIs-treated patients. AKI Acute kidney injury, ICIs Immune checkpoint inhibitors
Fig. 5
Fig. 5
Forest plot of associations between combination therapy and AKI in ICIs-treated patients. AKI Acute kidney injury, ICIs Immune checkpoint inhibitors
Fig. 6
Fig. 6
Forest plot of associations between extra-renal irAEs and AKI in ICIs-treated patients. irAEs Immune checkpoint inhibitor related adverse events, AKI Acute kidney injury, ICIs Immune checkpoint inhibitors
See this image and copyright information in PMC

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