Renal Outcomes With Potassium-Competitive Acid Blockers Versus Proton Pump Inhibitors in CKD

Introduction: Potassium-competitive acid blockers (P-CABs) have emerged as a promising alternative to proton pump inhibitors (PPIs) because of their rapid and sustained acid suppression. However, their renal safety in patients with chronic kidney disease (CKD) has not been thoroughly evaluated. Given concerns about PPI-associated renal risks, we conducted a target trial-emulated cohort study to compare renal safety of P-CABs versus PPIs. Methods: Using Korean National Health Insurance data, we identified patients with CKD newly initiating P-CABs or PPIs for gastroesophageal reflux disease (GERD) between 2019 and 2022. Patients with previous renal replacement therapy (RRT) were excluded. The primary outcome was the first initiation of RRT. Propensity score (PS) matching (1:4) was applied, and hazard ratios (HRs) were estimated using Cox proportional hazards models. An intention-to-treat (ITT) analysis was also performed. Results: A total of 34,077 patients were included, and 4107 P-CAB and 16,428 PPI users remained after matching. Over 60% in both groups were aged ≥ 65 years, and males were slightly more prevalent. P-CAB use was significantly associated with a lower risk of composite RRT initiation than PPI use (HR: 0.63, 95% confidence interval [CI]: 0.45-0.88). Although HRs for individual RRT events favored P-CABs, statistical significance was not reached. The ITT analysis showed consistent results (HR: 0.90, 95% CI: 0.82-0.99). Conclusion: In this study, P-CABs were associated with a reduced risk of renal function deterioration compared with PPIs in patients with CKD with GERD. These findings suggest the potential clinical utility of P-CABs as a safer treatment option in this high-risk population.