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

Peritonitis is a critical complication in patients undergoing peritoneal dialysis (PD). The association between gastric acid suppressants (GAS), specifically proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H₂RAs), and peritonitis risk remains controversial, with conflicting evidence regarding their safety.

We conducted a target trial emulation using Hong Kong electronic health records (2006-2019), applying a 168-month sequential design to minimize immortal time bias. Using inverse probability of treatment weighting and discrete hazards regression, we estimated hazard ratios (HRs) for peritonitis, all-cause mortality, and peritonitis-related mortality among PPI initiators, H₂RA initiators, and non-initiators (95% confidence interval [CI] calculated using 500-resample bootstrapping). We also performed a PPI versus H₂RA head-to-head comparison and predictive approaches to treatment effect heterogeneity analysis.

Among 11,693 individuals (240,431 person-trials), PPI initiation (vs. 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). H₂RA use was also associated with 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 H₂RAs, 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). Predictive approaches to treatment effect heterogeneity analysis indicated that risk elevations were more pronounced in individuals with higher baseline risk.

In patients on PD, GAS initiation is associated with increased peritonitis and mortality compared with non-initiation. Furthermore, PPIs were associated with higher mortality risks than H₂RAs. These findings highlight the need for cautious use of acid-suppressive therapy.