All-cause and immune checkpoint inhibitor–associated acute kidney injury in immune checkpoint inhibitor users: a meta-analysis of occurrence rate, risk factors and mortality

Abstract

Background Immune checkpoint inhibitors (ICIs) have been associated with acute kidney injury (AKI). However, the occurrence rate of ICI-related AKI has not been systematically examined. Additionally, exposure to proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) were considered as risk factors for AKI, but with inconclusive results in ICI-related AKI. Our aim was to analyse the occurrence rate of all-cause AKI and ICI-related AKI and the occurrence rates of severe AKI and dialysis-requiring AKI, and to determine whether exposure to PPIs and NSAIDs poses a risk for all-cause and ICI-related AKI. Methods This study population was adult ICI recipients. A systematic review was conducted by searching MEDLINE, Embase and PubMed through October 2023. We included prospective trials and observational studies that reported any of the following outcomes: the occurrence rate of all-cause or ICI-related AKI, the relationship between PPI or NSAID exposure and AKI development or the mortality rate in the AKI or non-AKI group. Proportional meta-analysis and pairwise meta-analysis were performed. The evidence certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Results A total of 120 studies comprising 46 417 patients were included. The occurrence rates of all-cause AKI were 7.4% (14.6% from retrospective studies and 1.2% from prospective clinical trials). The occurrence rate of ICI-related AKI was 3.2%. The use of PPIs was associated with an odds ratio (OR) of 1.77 [95% confidence interval (CI) 1.43–2.18] for all-cause AKI and an OR of 2.42 (95% CI 1.96–2.97) for ICI-related AKI. The use of NSAIDs was associated with an OR of 1.77 (95% CI 1.10–2.83) for all-cause AKI and an OR of 2.57 (95% CI 1.68–3.93) for ICI-related AKI. Conclusions Our analysis revealed that approximately 1 in 13 adult ICI recipients may experience all-cause AKI, while 1 in 33 adult ICI recipients may experience ICI-related AKI. Exposure to PPIs and NSAIDs was associated with an increased OR risk for AKI in the current meta-analysis.

Association of Proton Pump Inhibitor Use and Immune Checkpoint Inhibitor-Mediated Acute Kidney Injury: A Meta-Analysis and a Review of Related Outcomes

“…After adjusting the OR for other medications including nonsteroidal anti-inflammatory agents, diuretics, and renin-angiotensin aldosterone system inhibitors, they observed an OR of 2.07 [95% CI 1.58-2.71], which is similar to our finding. Interestingly, a recent metaanalysis by Chen et al [22] reported that the occurrence rate of ICI-AKI was 3.2% and that exposure to non-steroidal anti-inflammatory agents was almost equally effective in contributing to the increased risk of ICI-AKI similar to PPIs with OR of 2.57 (95% CI 1.68-3.93) and 2.42 (95% CI 1.96-2.97), respectively. Notably, the reported median time of onset of ICI-AKI is also hugely variable with the onset as early as 5 weeks to more than a year in some cases [2,9,12,23].…”