Proton Pump Inhibitors and Risk of Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Proton pump inhibitors (PPIs) are widely prescribed for acid-related disorders, yet growing evidence suggests a potential association between long-term PPI use and chronic kidney disease (CKD). This systematic review and meta-analysis aimed to evaluate the risk of CKD, disease progression, and end-stage renal disease (ESRD) among PPI users compared with nonusers or histamine-2 receptor antagonist users. A comprehensive search identified observational studies assessing renal outcomes among adult PPI users. Fifteen studies met the inclusion criteria, representing diverse populations across Asia, Europe, and the United States. Data on CKD incidence, progression, ESRD, and additional adverse effects were extracted. Pooled effect estimates were calculated using random-effects models. Heterogeneity, sensitivity analyses, and publication bias were evaluated using I², leave-one-out testing, and funnel plots. Our review included 15 studies, with sample sizes ranging from 3,023 to 462,421 participants. Meta-analysis of six studies (n = 594,680) demonstrated a significantly increased risk of incident CKD among PPI users (RR = 1.68, 95% CI: 1.20-2.34; p = 0.002; I² = 99%). Two studies (n = 171,583) assessing CKD progression showed a higher, but statistically nonsignificant, risk with PPI use (RR = 1.49, 95% CI: 0.84-2.65; p = 0.17; I² = 99.3%). Four studies (n = 149,702) examining ESRD found a modest yet significant increase in risk among PPI users (RR = 1.15, 95% CI: 1.00-1.32; p = 0.04; I² = 69%). Additional adverse events, including hypomagnesemia and acute kidney injury, were more frequent in PPI users. Asymmetry in the funnel plot suggested publication bias. PPI use is associated with an increased risk of CKD occurrence and ESRD, with a possible but uncertain link to CKD progression. Clinicians should carefully consider long-term PPI therapy, ensure appropriate indications, and monitor renal function in chronic users.