Peritonitis and Mortality Risks of Gastric Acid Suppressants in Patients Undergoing Peritoneal Dialysis

Background Peritonitis is a critical complication in peritoneal dialysis (PD) patients. The association between gastric acid suppressants (GAS), specifically proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H 2 RAs), and peritonitis risk remains controversial, with conflicting evidence regarding their safety. Methods We conducted a target trial emulation using Hong Kong electronic health records (2006–2019), applying a 168-month sequential design to minimise immortal time bias. Using inverse probability of treatment weighting and discrete hazards regression, we estimated hazard ratios (HRs) for peritonitis, all-cause, and peritonitis-related mortality among PPI-initiators, H 2 RA-initiators, and non-initiators (95% CIs calculated via 500-resample bootstrapping). We also performed a PPI versus H 2 RA head-to-head comparison and Predictive Approaches to Treatment effect Heterogeneity (PATH) analysis. Results Among 11,693 individuals (240,431 person-trials), PPI initiation (versus non-initiation) was associated with higher risks of peritonitis (HR 1.53, 95% CI 1.31–1.80), all-cause mortality (HR 1.55, 95% CI 1.43–1.67), and peritonitis-related mortality (HR 1.39, 95% CI 1.05–1.58). H 2 RAs use was also associated with an increased risk of peritonitis (HR 1.21, 95% CI 1.08–1.35) and all-cause mortality risks (HR 1.13, 95% CI 1.06–1.20). Head-to-head analysis showed no significant increase in peritonitis risk with PPIs versus H 2 RAs, but revealed an association between PPI use and higher all-cause mortality (HR 1.38, 95% CI 1.23–1.54) and peritonitis-related mortality (HR 1.85, 95% CI 1.07–3.19). PATH analysis indicated risk elevations were more pronounced in individuals with higher baseline risk. Conclusions In PD patients, GAS initiation is associated with increased peritonitis and mortality compared to non-initiation. Furthermore, PPIs were associated with a higher mortality risks than H 2 RAs. These findings highlight the need for cautious acid-suppressive therapy use.