(193) Proton pump Inhibitors are associated with an Increased risk of mortality among patients with kidney disease: A systematic review and meta-analysis

Background: : Proton pump inhibitor (PPI) use has been linked to various serious adverse outcomes, including an increased risk of death from all causes. Notably, higher mortality rates related to kidney disease have been reported among PPI users. However, the relationship between PPI use and mortality in patients with kidney disease remains uncertain.

Objective: : This systematic review and meta-analysis aimed to evaluate the association of PPI use on mortality among patients with kidney disease.

Methods: : We searched Ovid-MEDLINE, Ovid-EMBASE, and Cochrane CENTRAL through April 2025 to identify randomized controlled trials (RCTs) and observational studies examining the relationship between PPI use and mortality risk in patients with kidney disease. Study outcomes included mortality rates among PPI users and non-users, as well as adjusted hazard ratios (HRs) comparing the risk of death between groups, accounting for demographic and clinical variables. To calculate pooled HRs with 95% confidence intervals (CIs), a random-effects meta-analysis was conducted using the Hartung-Knapp method for confidence interval adjustment. Between-study variance (τ²) was estimated using the restricted maximum likelihood (REML) method. Statistical heterogeneity was assessed using the I² statistic and Cochran’s Q test. Subgroup analyses were performed based on follow-up duration, patient population, and study location.

Results: : This systematic review encompassed 216,032 patients with kidney diseases from 24 cohort studies and ad hoc analyses of randomized controlled trials. Included patients had dialysis, chronic kidney disease, renal cancer, or a kidney transplant. Among 20 cohorts from 17 observational studies, mortality was observed in 23.2% of PPI users (15,755 out of 67,853) and 22.1% of non-users (28,986 out of 131,009). After adjusting for confounding variables in 18 studies (20 cohorts), PPI use was significantly associated with a 26% increased risk of mortality in patients with kidney disease compared to those not using PPIs (HR 1.26; 95% CI, 1.11–1.42). Substantial heterogeneity was observed across the studies. The subgroup analyses further confirmed that this elevated mortality risk among PPI users remained consistent across different subgroups.

Conclusions: : Our meta-analysis found a potential risk of death associated with PPI use in patients with kidney disease. While additional studies are necessary to confirm this risk, the prescription of PPIs in this population should be approached with caution.

Sponsorship:: None