Association of Pneumonia, Fracture, Metabolic, and Renal Events With Long‐Term Proton Pump Inhibitor Use in Patients With Chronic Kidney Disease

ABSTRACT Background Proton pump inhibitors (PPIs) have been commonly used for gastroesophageal reflux disease (GERD) and peptic ulcers (PU), which are even more prevalent in patients with chronic kidney disease (CKD). Although PPI‐related adverse outcomes are well documented in the general population, evidence in patients with CKD remains limited. This study investigated the associations of PPI use and adverse outcomes in patients with CKD who had GERD or PU. Methods In this nationwide, retrospective cohort study, patients with CKD and also PU or GERD from 2006 to 2015 were enrolled and sorted into no‐, short‐term, and long‐term PPI groups. Incidence and risks of outcome events between these three groups were analyzed with the Cochran‐Armitage test and Cox proportional hazard analyses. Events‐free probability was estimated with the Kaplan–Meier method during follow‐up. Results In the study, 384,411 patients with CKD with PU or GERD were enrolled. The numbers of no‐, short‐term, and long‐term PPI treatments were 147,976, 14,153, and 3459, respectively. Relative to the no‐PPI group, the adjusted hazard ratios (aHRs) of admission for pneumonia and fracture, new diagnosis of type 2 diabetes mellitus (DM), and progression to end‐stage kidney disease (ESKD) in the short‐term (1.089, 1.083, 1.175, 1.22) and long‐term PPI groups (1.882, 2.601, 1.951, 1.714) remained statistically significant, respectively, even after adjustment for significant baseline variables; the aHR of dialysis was significant only in the long‐term PPI group. Kaplan–Meier analysis revealed significant outcome events in the long‐term PPI group during follow‐up. Conclusion PPI use is associated with an increased risk of pneumonia, fracture, incidence of type 2 DM, and progression to ESKD in patients with CKD, and the risk increases substantially with increased duration of PPI use.