#3958 PROTON PUMP INHIBITORS AND THE RISK OF ACUTE KIDNEY INJURY IN PATIENTS RECEIVING IMMUNE CHECKPOINT INHIBITORS: A POPULATION-BASED COHORT STUDY

Abstract

Abstract Background and Aims Proton pump inhibitors (PPI) are commonly used in cancer patients. Multiple studies have found that PPI use is associated with a more than 2-fold increased risk of acute kidney injury (AKI) in patients treated with immune checkpoint inhibitors (ICI). However, this association could possibly be explained by confounding by indication for PPI use. Method In a population-based cohort study, we compared the risk of AKI in users and non-users of PPI among cancer patients treated with ICI in Denmark during 2011-2021. We assessed exposure to PPI by filled prescriptions for PPI within 90 days before ICI initiation and identified AKI events within the first year after ICI initiation using plasma creatinine measurements from laboratory databases. We included information on potential confounders including important comorbidities and comedication. We estimated the propensity score for PPI use using logistic regression and calculated unweighted and standardized mortality ratio (SMR)-weighted absolute risks and hazard ratios (HRs) of AKI. To address any switch in PPI exposure during follow-up, we did an additional per-protocol analysis censoring patients upon switch in PPI exposure. We furthermore applied inverse probability of censoring (IPC) weights to mitigate informative censoring. Results We included 9,955 cancer patients treated with ICI. Among these, 2,668 (26.8%) were users of PPI. During the first year of follow-up, AKI occurred in 1,932 of the included patients, yielding an overall unweighted incidence rate of 30.1 per 100 person-years and a 1-year AKI risk of 21.3%. PPI users had an increased risk of AKI compared with non-users (1-year risk, 24.4% versus 20.2%; HR, 1.37 [95% CI, 1.24-1.51]); however, this association attenuated when accounting for confounders by SMR weighting (SMR-weighted 1-year risk, 24.0% versus 23.3%; SMR-weighted HR, 1.05 [95% CI, 0.93-1.18]). In the per-protocol analysis, the unweighted HR was 1.82 (95% CI, 1.60-2.07), while the SMR- and IPC-weighted HR was 1.22 (95% CI, 1.03-1.45). Conclusion PPI use at the time of ICI initiation was not associated with an increased risk of AKI after SMR weighting. When considering switching of PPI exposure during follow-up, we observed that PPI use was associated with an increased risk of AKI; however, the association was much weaker than previously reported.