title: Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.
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 H2-receptor antagonists (H2blockers; 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 H2blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m2and 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 H2blockers 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.
authors.affiliation: Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bowe
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System, Department of Biostatistics, College for Public Health and Social Justice, Saint Louis University.
authors.forename: Hong
authors.initials: H
authors.lastname: Xian
authors.affiliation: Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri; Division of Nephrology, Department of Medicine, Veterans Affairs Saint Louis Health Care System, Saint Louis, Missouri zalaly@gmail.com ziyad.alaly@va.gov.
authors.forename: Ziyad
authors.initials: Z
authors.lastname: Al-Aly
mesh_terms: D018450:Disease Progression; D005260:Female; D006635:Histamine H2 Antagonists / Q000009:adverse effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D012189:Retrospective Studies; D018570:Risk Assessment
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors
keywords: ESRD; Epidemiology and outcomes; chronic kidney disease; clinical epidemiology; progression of chronic renal failure; renal progression