Proton Pump Inhibitor Use and Worsening Kidney Function: A Retrospective Cohort Study Including 122,606 Acid-Suppressing Users.

Abstract

Background: The impact of proton pump inhibitors (PPIs) use on worsening renal function is controversial and lacks a solid pathophysiological explanation.

Objective: To assess the risk of worsening renal function and acute kidney injury (AKI) in PPI initiators as compared with H2-blockers initiators.

Design: Retrospective cohort study using longitudinal records from BIGAN, a population-based health database of Aragón (Spain).

Participants: PPIs (n = 119,520) and H2-blockers (n = 3,086) initiators between 2015 and 2020 with preserved renal function. They were followed until the occurrence of an adverse kidney event, death, lost to follow-up or June 2021.

Main measures: Primary endpoints were worsening kidney function (measured as sCr ≥ 2 times baseline, eGFR < 60 ml/min/1.73m², a decrease in eGFR 30-50% from baseline or end stage renal disease) and AKI (measured by Aberdeen algorithm or hospitalization due to AKI). Incidence rates (IRs) per 1,000 persons-years were reported and Cox regression was used to calculate Hazard ratios (HRs), adjusted for confounders.

Key results: Crude IRs for worsening kidney function were consistently lower for ranitidine than for PPIs (eGFR < 60 ml/min/1.73m²: IR 18.7 95%CI (12.0-27.8) for ranitidine, IR 31.2 95%CI (29.9-32.5) for omeprazole). However, the risk of incident worsening function did not significantly differ in the Cox regression analysis adjusting for confounders (HR 0.99 95%CI (0.66-1.48) for omeprazole, as compared to ranitidine). PPI initiators consistently showed lower IRs of AKI using Aberdeen algorithm (IR 33.8 95%CI (32.4-35.1) for omeprazole, IR 52.8 95%CI (40.9-67.1) for ranitidine) and lower risk of AKI (HR 0.54 95%CI (0.42-0.70) for omeprazole, as compared to ranitidine).

Conclusions: No clinically relevant differences were observed for worsening kidney function between PPIs and H2-blockers initiators. PPIs users presented a reduced risk of AKI compared to ranitidine initiators.