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

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.

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.

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.

Discontinuing PPIs within 90 days after initiation was associated with better kidney outcome.