Proton Pump Inhibitor Use and Risk of Chronic Kidney Disease
Abstract
Context
Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide, and have been linked to acute interstitial nephritis. Less is known about the relationship between PPI use and chronic kidney disease (CKD).
Objective
To quantify the association between PPI use and incident CKD in a population-based cohort.
Design, Setting and Participants
10,482 participants in the Atherosclerosis Risk in Communities (ARIC) study with an estimated glomerular filtration rate (eGFR) of ≥60mL/min/1.73m2 were followed from a baseline visit (1996–1999) to December 31, 2011. Findings were replicated in an administrative cohort of 248,751 patients with eGFR ≥60mL/min/1.73m2 from Geisinger Health System.
Exposure
Self-reported PPI use in ARIC, or an outpatient PPI prescription in the replication cohort. Histamine-2 receptor (H2) antagonist use was considered a negative control and active comparator.
Main Outcome Measure
Incident CKD, using diagnostic codes indicating CKD at hospital discharge or death. In the replication cohort, incident CKD was defined by outpatient eGFR <60 mL/min/1.73 m2.
Results
Compared to non-users, PPI-users were more often white, obese, and taking antihypertensive medication. In ARIC, PPI use was associated with incident CKD in unadjusted analysis (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.11–1.90), analysis adjusted for demographic, socioeconomic, and clinical parameters (HR, 1.50; 95% CI, 1.14–1.96), and in analysis with PPI ever-use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17–1.55). The association persisted when baseline PPI users were compared directly to H2-antagonist users (adjusted HR, 1.39; 95% CI, 1.01–1.91), and to propensity-score matched non-users (HR, 1.76; 95% CI, 1.13–2.74). In the replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new user design (adjusted HR 1.24; 95% CI, 1.20–1.28). Twice-daily PPI dosing was associated with a higher risk (adjusted HR, 1.46; 95% CI, 1.28–1.67) than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09–1.21).
Conclusions
PPI use is associated with a 20%–50% higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.
RPR Commentary
PPIs appear to be associated with both acute (interstitial nephritis) and chronic kidney problems. While this is an epidemiological study, proving association not causation, it may be the best evidence we will be able to get.