Disproportionate reporting of acute renal events and chronic kidney disease with proton pump inhibitors and the potassium-competitive acid blocker vonoprazan: A time-to-onset and signal-detection analysis of the FAERS and JADER databases

OBJECTIVE: To characterize renal injury reporting, separately for acute kidney injury (AKI) and chronic kidney disease (CKD), for proton pump inhibitors (PPIs) and the potassium-competitive acid blocker (P-CAB) vonoprazan. Reporting was analyzed in the U.S. FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) database. MATERIALS AND RESULTS: PPIs showed disproportionate reporting of AKI and CKD in both databases (FAERS overall ROR 5.21 and 13.21; JADER 1.25 and 1.76), concordant across measures and after excluding pre-existing renal disease. Signals for vonoprazan were weaker and database-dependent (no FAERS CKD signal, ROR 0.92; weak JADER signal, 1.95). Time-to-onset was short in JADER (median 35 days); FAERS onset estimates were unreliable (median 1,520 days). The PPI signals persisted after excluding vonoprazan or dexlansoprazole. CONCLUSION: Disproportionate reporting of AKI and CKD was observed for PPIs across two databases. These hypothesis-generating findings support renal monitoring and periodic reassessment of long-term acid suppression. The renal safety profile of vonoprazan remains inconclusive, and exposure-based studies are warranted.