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J Am Soc Nephrol. 2016 Oct;27(10):3153-3163. Epub 2016 Apr 14.

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

Author information

1
Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System.
2
Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri.
3
Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System, Department of Biostatistics, College for Public Health and Social Justice, Saint Louis University.
4
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.

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 (H2 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 H2 blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m2 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 H2 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.

KEYWORDS:

ESRD; Epidemiology and outcomes; chronic kidney disease; clinical epidemiology; progression of chronic renal failure; renal progression

PMID:
27080976
PMCID:
PMC5042677
DOI:
10.1681/ASN.2015121377
[Indexed for MEDLINE]
Free PMC Article

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