Causal Effects of Early Discontinuation of Proton Pump Inhibitors on Kidney Failure

INTRODUCTION: Proton pump inhibitors (PPIs) are associated with adverse kidney outcomes. In clinical practice, however, long-term PPI use without a clear indication is common. It remains unclear whether discontinuing PPIs reduces the risk of kidney failure in patients who initiate PPIs. Using a target trial emulation approach, we estimated the causal effects of initiation and discontinuation of PPIs on the risk of kidney failure. METHODS: Using data from the Osaka Consortium for Kidney Disease Research, a retrospective multicenter cohort in Japan, we emulated 2 target trials in patients with nondialyzed chronic kidney disease (CKD). First, we compared the risk of kidney failure with replacement therapy (KFRT) between PPI use and histamine₂ receptor antagonist (H₂ blocker) use, using an active comparator new user design. Second, the estimated effect of PPI discontinuation within 90 days after initiation on KFRT was evaluated using a clone-censor-weighting approach. RESULTS: We identified 3512 PPI new users (76.1%) and 1102 H₂ blocker new users (23.9%). At treatment initiation, the mean age and estimated glomerular filtration rate (eGFR) were 71 years and 30 ml/min per 1.73 m², respectively. Over a median follow-up of 2.1 years, 654 (14.2%) progressed to KFRT. PPI initiation was significantly associated with a higher hazard of KFRT (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.13-1.72). Of 4187 patients who initiated PPIs, 1254 (30.0%) discontinued PPIs within 90 days. Discontinuation was significantly associated with a lower hazard of KFRT (HR: 0.85; 95% CI: 0.72-0.97) than continuation. CONCLUSION: Discontinuing PPIs within 90 days after initiation was associated with better kidney outcome.