A Meta-Analysis of Proton Pump Inhibitor Use and the Risk of Acute Kidney Injury: Geographical Differences and Associated Factors

Proton pump inhibitors (PPIs) are widely prescribed in medical practice for the treatment of several gastrointestinal disorders. Previous epidemiology studies have reported the association between PPI use and the risk of AKI, although the magnitude of the association between PPIs and the risk of acute kidney injury (AKI) remains uncertain. Therefore, we conducted a meta-analysis to determine the relationship between PPI therapy and the risk of AKI. We systematically searched for relevant articles published before January 2023 on PubMed, Scopus, and Web of Science. In addition, we conducted a manual search of the bibliographies of potential articles. Two independent reviewers examined the appropriateness of all studies for inclusion. We pooled studies that compared the risk of AKI with PPI against their control using a random effect model. The search criteria based on PRISMA guidelines yielded 568 articles. Twelve observational studies included 2,492,125 individuals. The pooled adjusted RR demonstrated a significant positive association between PPI therapy and the risk of AKI (adjusted RR 1.75, 95% CI: 1.40–2.19, p < 0.001), and it was consistent across subgroups. A visual presentation of the funnel plot and Egger’s regression test showed no evidence of publication bias. Our meta-analysis indicated that persons using PPIs exhibited an increased risk of AKI. North American individuals had a higher risk of AKI compared to Asian and European individuals. However, the pooled effect from observational studies cannot clarify whether the observed association is a causal effect or the result of some unmeasured confounding factors. Hence, the biological mechanisms underlying this association are still unclear and require further research.