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

• Published in: BMC nephrology Vol. 24; no. 1; pp. 107 - 12
• Main Authors: Chen, Pengwei, Zhu, Jianhong, Xu, Yanchun, Huang, Qiuyan, Su, Jianan, Gao, Ziqing, Feng, Min
• Format: Journal Article
• Language: English
• Published: London BioMed Central 22.04.2023; BioMed Central Ltd; BMC
• Subjects: Acute kidney injury; Acute Kidney Injury - chemically induced; Acute Kidney Injury - epidemiology; Adverse events; Angiotensin; Angiotensin Receptor Antagonists - pharmacology; Angiotensin-converting enzyme inhibitors; Angiotensin-Converting Enzyme Inhibitors - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Brand names; Chronic kidney failure; Chronic obstructive pulmonary disease; Diabetes; Diabetes mellitus; Diuretics; Dosage and administration; Enzyme inhibitors; FDA Adverse Event Reporting System; Heart failure; Humans; Hypertension; Immune checkpoint inhibitor; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immunosuppressive agents; Immunotherapy; Inflammation; Internal Medicine; Investigations; Kidneys; Liver diseases; Lung cancer; Medicine; Medicine & Public Health; Melanoma; Meta-analysis; Monoclonal antibodies; Nephrology; Nonsteroidal anti-inflammatory drugs; Observational studies; Patient outcomes; Peptidyl-dipeptidase A; Pharmacovigilance; Prevention; Proton pump inhibitors; Real-world pharmacovigilance; Retrospective Studies; Risk Factors; Systematic review; Colombia; Canada; United States > US; North America; Japan; Systematic review; Real-world pharmacovigilance; Immune checkpoint inhibitor; Acute kidney injury; FDA Adverse Event Reporting System
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-023-03171-9

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.