Abstract Background: Use of proton pump inhibitor (PPI) has been associated with adverse health outcomes, including increased risk of all-cause mortality. Evidence suggests that individuals with kidney disease who use PPIs may experience higher mortality, though the nature of this association is not well established. Objective: To assess the relationship between PPI use and mortality among individuals with kidney disease through a systematic review and meta-analysis. Methods: A comprehensive search of Ovid-MEDLINE, Ovid-EMBASE, and Cochrane CENTRAL was conducted through April 2025 to identify randomized controlled trials and observational studies examining mortality among PPI users versus non-users with kidney disease. Both unadjusted mortality rates and adjusted hazard ratios (aHRs) were extracted. A random-effects meta-analysis was performed using the Hartung-Knapp-Sidik-Jonkman method, with the Sidik-Jonkman estimator used for between-study variance (τ²). Study heterogeneity was evaluated using the I² statistic and Cochran’s Q test. Subgroup analyses were carried out based on follow-up length, population characteristics, geographic region, and risk of bias level. Results: The review included 24 observational studies encompassing 216,032 individuals with kidney disease. Across 20 cohorts from 17 observational studies, mortality was 23.2% among PPI users and 22.1% among non-users. Pooled adjusted estimates from 18 studies (20 cohorts) indicated a significantly increased risk of death in PPI users (aHR 1.26; 95% CI, 1.11–1.42). Considerable heterogeneity was observed, but subgroup analyses revealed consistent trends. Conclusions: Our meta-analysis showed that PPI use was linked to elevated mortality risk in kidney disease populations. Careful consideration is advised when prescribing PPIs, and further research is needed.
Park et al. (Tue,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: