Long-term use of proton pump inhibitors was associated with rapid progression to end stage kidney disease in a Korean nationwide study

Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. However, their influence on the progression of end-stage kidney disease (ESKD) in established chronic kidney disease (CKD) cases is unclear. Using the Korean Health Insurance Review and Assessment database encoded by the Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM), patients with stage 3 or 4 CKD initiating PPIs or histamine-2 receptor antagonists (H2RAs) for over 90 days were enrolled from 2012 through 2021. Incidence of ESKD events between the groups were compared using a cox proportional hazard model. A total of 34,656 eligible patients were included. Of the patients, 65.1% had CKD stage 3, 44.5% aged > 75 years, 59.8% were male individuals, and 68.3% had diabetes. After 1:1 propensity score matching, ESKD progression was observed in 2327 out of 19,438 patients and it was more frequent in PPI users (incidence rate, 10.5/100PYs) than that in H2RA users (incidence rate, 9.2/100PYs; IRR, 1.14 [1.07-1.12]). Using the subgroup analysis, IRR was significantly higher in patients with CKD stage 3 (IRR 1.40 [1.21-1.60]), whereas it was not in those with CKD stage 4 (IRR 1.04 [0.94-1.15]). A similar trend was observed in patients with CKD 3 or 4 with and without diabetes. In general, PPI use is associated with a 14% higher risk of ESKD progression in patients with CKD stage 3 or 4. However, the influence of PPIs differed according to the comorbidities and risks of adverse kidney outcomes.