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Peritoneal dialysis-associated peritonitis results in unacceptable outcomes, including hospitalisations, technique failure and even death. Proton pump inhibitors (PPIs) have been associated with an increased risk of peritonitis in some studies. (1) This relationship may result from alterations to the gut microbiome due to reduced gastric acidity, with subsequent translocation of bacteria into the peritoneal space. However, available data is conflicting, and no association was detected in a small Australian cohort. (2) We therefore evaluated whether PPIs were associated with an increased risk of peritonitis in our local population.
We retrospectively identified incident adult, peritoneal dialysis patients at a single centre in New South Wales, Australia, between 1 January 2012, and 31 December 2021. Patients were stratified by PPI exposure. Follow-up concluded at cessation of peritoneal dialysis or on 31 March 2023. Time to first peritonitis was compared between groups using multivariate Cox proportional hazard modelling. We adjusted for covariates previously associated with peritonitis risk, including age, sex, primary kidney disease, previous kidney replacement therapy, body mass index, diabetes mellitus, vascular disease, lung disease, smoking, baseline serum albumin concentration and exposure to histamine-2 receptor antagonists, activated vitamin D and immunosuppression. Unadjusted peritonitis rates were compared between groups as a sensitivity analysis using negative binomial regression.
219 peritoneal dialysis patients were included, of whom 95 (43%) were taking a PPI. Baseline characteristics were similar between the groups (Table 1). In patients taking PPIs, 40/95 (42%) developed peritonitis, compared to 56/124 (45%) in the unexposed group (Log-rank χ²(1)=1, p=0.3). PPI use was not associated with time to first peritonitis in the multivariate Cox model (Hazard Ratio (HR) 0.75, 95% Confidence Interval (CI) 0.49-1.17, p=0.2). Vascular disease, defined as the presence of coronary artery disease, cerebrovascular or peripheral vascular disease, was the only independent predictor of peritonitis in the multivariate model (HR 1.68, 95% CI 1.04-2.72, p=0.04). Peritonitis rates, expressed as episodes per patient year at risk, were similar in the PPI (0.32; 95% CI 0.25-0.41) and non-PPI groups (0.37; 95% CI 0.30-0.46, p=0.4).
Conclusions
PPI use did not increase the risk of peritoneal dialysis-associated peritonitis in this cohort. This is an important finding in the context of increasingly frequent PPI administration. Given that international studies have reported conflicting results, more work is required to clarify whether regional differences in gut flora and prescribing patterns modulate the relationship between PPI use and peritonitis.
References:
1. Zhang Y, Li J, Chen Z, et al. Proton pump inhibitor usage associates with higher risk of first episodes of pneumonia and peritonitis in peritoneal dialysis patients. Ren Fail. 2022 Dec;44(1):1623-31.
2. Walia N, Rao N, Garrett M, et al. Proton pump inhibitor use and the risk of peritoneal dialysis associated peritonitis. Intern Med J. 2023 Mar;53(3):397-403.