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e GFR was the outpatient e GFR value within and most proximate to the end of the assessment period.

Number of outpatient serum creatinine measurements and number of hospitalisations were accumulated during the assessment period.

The VA Vital Status and Beneficiary Identification Records Locator Subsystem files provided demographic characteristics and death. Once cohort participants received PPI prescription, they were considered with the effect of PPI until the end of follow-up.

Risk of death associated with PPI use was increased among participants without gastrointestinal conditions: PPI versus H2 blockers (HR 1.24, CI 1.21 to 1.27), PPI use versus no PPI (HR 1.19, CI 1.18 to 1.20) and PPI use versus no PPI and no H2 blockers (HR 1.22, CI 1.21 to 1.23).To account for patients’ kidney function, only patients with at least one outpatient serum creatinine value before the first acid suppression therapy prescription were selected in the cohort, yielding an analytic cohort of 349 312 patients.Patients whose first acid suppression therapy was PPI (n=275 977) were considered to be in the PPI group during follow-up.Patients in both primary and secondary cohorts were followed until 30 September 2013 or death.The study was approved by the Institutional Review Board of the VA Saint Louis Health Care System, Saint Louis, Missouri.




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