Association Between Discontinuation of Proton-Pump Inhibitors and Kidney Outcome Among Patients with CKD: The OCKR Study

Background: Proton pump inhibitors (PPIs), one of the most widely used medications, are known to be 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 could reduce the risk of kidney failure in patients who initiated PPIs. Using a causal inference approach, we investigated the potential benefits of discontinuing PPI on kidney prognosis. Methods: The Osaka Consortium for Kidney Disease Research (OCKR) is a retrospective, multicenter cohort study that includes patients who attended the nephrology outpatient departments at five hospitals in Osaka, Japan, from January 2005 to December 2021. For this analysis, we included PPI-naïve patients with an estimated glomerular filtration rate (eGFR) of 10–60 mL/min/1.73 m2. The primary outcome was kidney failure with replacement therapy (KFRT). We examined the association of PPI use with KFRT using marginal structural models to account for potential time-dependent confounding factors. Furthermore, we compared the risk of KFRT between discontinuing PPIs within 90 days after initiation and continuing PPIs, using a clone-censor-weighting approach. Results: Among the 14,796 patients included in this analysis, the mean age and eGFR at baseline were 69 years and 35 mL/min/1.73 m2, respectively, and 60% were male. Over a median (IQR) follow-up of 2.7 (0.9–5.8) years, 4,187 patients (28.3%) initiated PPI therapy, and 1,593 patients (10.8%) developed KFRT. After adjusting for potential confounders, PPI use was significantly associated with a higher hazard of KFRT (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.03–1.55). Of those who initiated PPI therapy, 1,254 patients (30.0%) discontinued PPIs within 90 days. Discontinuing PPIs was significantly associated with a 22% lower risk of KFRT (95% CI, 8–33) compared to continuing PPIs. Conclusion: The increased risk of KFRT associated with PPI use may be reduced by discontinuing these drugs within 90 days.