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Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD

2016/03/14 by Yan Xie, Benjamin Bowe, Tingting Li +3 · 4 citations
Medicine · #Gastroesophageal reflux and treatments #Nephrotoxicity and Medicinal Plants #Potassium and Related Disorders

paper · doi:10.1681/asn.2015121377

openalex publication_date 2016/03/14 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI ( n =173,321) and new users of histamine H 2 -receptor antagonists (H 2 blockers; n =20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H 2 blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m 2 and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31–90, 91–180, 181–360, and 361–720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H 2 blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.

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