Gastric Acid Suppression Therapy and Its Association with Peritoneal Dialysis-Associated Peritonitis in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS)

Abstract

Key Points:

1. In a large multinational cohort of PD patients, any GAS use was not associated with an increased risk of all-organism peritonitis.

2. For peritonitis, risks were particularly high among certain classes of organisms particularly for Gram-negative, enteric, and streptococcal peritonitis episodes.

3. The association with enteric peritonitis appeared to be stronger among H2RA users.

Background: Peritonitis is a major peritoneal dialysis–related complication. We determined whether gastric acid suppression (GAS) (proton pump inhibitor [PPI] or histamine-2 receptor antagonists [H2RAs]) use was associated with all-cause and organism-specific peritonitis in peritoneal dialysis patients.

Methods: In the Peritoneal Dialysis Outcomes and Practice Patterns Study (595 facilities, eight countries, years 2014–2022), associations between GAS use and time to first episode of all-cause peritonitis were examined using Cox proportional hazards models. The primary exposure of interest was GAS and secondarily PPI or H2RA use. Secondary outcomes were organism-specific peritonitis, peritonitis cure rates, and death.

Results: Among patients (N=23,797) at study baseline, 6020 (25.3%) used PPIs, and 1382 (5.8%) used H2RAs. Overall risks of GAS use and peritonitis risk (adjusted hazard ratio [AHR]=1.05, 95% confidence interval [CI], 0.98 to 1.13]) and use of PPI (AHR 1.06 [95% CI, 0.99 to 1.14]) or H2RA (AHR 1.02 [95% CI, 0.88 to 1.18]) did not reach statistical significance. In organism-specific analyses, GAS users displayed higher peritonitis risks for Gram-negative (AHR 1.29, 95% CI, 1.05 to 1.57), Gram-positive (AHR 1.15, 95% CI, 1.01 to 1.31), culture-negative (AHR 1.20, 95% CI, 1.01 to 1.42), enteric (AHR 1.23, 95% CI, 1.03 to 1.48), and particularly Streptococcal (AHR 1.47, 95% CI, 1.15 to 1.89) peritonitis episodes. GAS was also associated with higher overall mortality (AHR 1.13 [95% CI, 1.05 to 1.22]).

Conclusion: The association between GAS use and peritonitis risk was weaker (hazard ratio [HR] 1.05 [0.98 to 1.13]) than for streptococcal (HR 1.57 [1.15 to 1.89]) and Gram-negative (HR 1.29 [1.05 to 1.57]) peritonitis. A better understanding of mechanisms surrounding the differential effects of GAS subtype on peritonitis risks is needed. Clinicians should be cautious when prescribing GAS. The impact of GAS deprescribing on peritonitis risk requires further evaluation.

Graphical abstract

Figure 1

Assembly of the study cohort. H2RA, histamine 2 receptor antagonist; PDOPPS, Peritoneal Dialysis Outcomes and Practice Patterns Study; PPI, proton pump inhibitor.

Figure 2

Cross-sectional distribution of gastric acid suppression medication use, by country at baseline. H2RA, histamine 2 receptor antagonist; PPI, proton pump inhibitor.

Figure 3

Clinical outcomes by GAS prescription—results of progressive adjustment. Outcomes shown are (A) peritonitis [n=22,287 patients, n=4063 events], (B) mortality [n=23,487 patients: n=3482 events], or (C) the composite of peritonitis or mortality. In all models, 6% of patients were prescribed H2RA, 25% PPI, 69% neither. Model 1 adjusted for patient age, sex, Black race, PD vintage, PD modality; model 2 adjusted for model 1+12 comorbidities; model 3 adjusted for model 2+serum albumin, 24-hour urine volume, potassium, and magnesium; model 4 adjusted for model 3+GI comorbidities. The estimate for GAS overall was estimated from a separate model. CI, confidence interval; GAS, gastric acid suppressants; GI, gastrointestinal; PD, peritoneal dialysis.