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

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.

Graphical Abstract

AKI: acute kidney injury. eGFR: estimated glomerular filtrate rate. H2-blocker: Histamine 2 receptor antagonist. PPI: proton pump inhibitor. sCr: serum creatinine.