Duration and dosing of Proton Pump Inhibitors associated with high incidence of chronic kidney disease in population-based cohort

BACKGROUND: Proton Pump Inhibitors (PPIs) have been associated with chronic kidney disease (CKD). Our objective was to quantify the association between PPI use and incident CKD in a population-based cohort. METHODS AND FINDINGS: We used a population-based retrospective cohort, including people aged 15 years or over, between January 1, 2005 and December 31, 2012. PPI use was measured in a follow-up session by recording prescriptions. Incident CKD was defined as an estimated glomerular filtration rate < 60 ml/ min/1.73 m(2) and/or urinary albumin level to creatinine level ≥ 30 mg/g, in two or more determinations over a period of at least 3 months of the follow-up. Proton Pump Inhibitor use was associated with incident CKD in analysis adjusted for different clinical variables (Hazard Ratio (HR) 1.18; 95% CI 1.04–1.51) in individuals who used PPI in the basal visit (HR 1.37; 95% CI 1.25–1.50) and in those who started to use PPI during the follow-up. High doses of PPI increased the risk of incident CKD (HR 1.92; 95%CI 1.00–6.19) for any type of exposure to PPIs (HR 2.40; 95%CI 1.65–3.46) and for individuals who used high doses throughout the follow-up. This risk of incident CKD increased after three months’ exposure to PPIs, (HR1.78; 95% CI 1.39–2.25) between the third and sixth months and (HR 1.30; 95%CI 1.07–1.72) after the sixth month. CONCLUSIONS: PPI use is associated with a higher risk of incident CKD. This association is greater for high doses and becomes apparent after three months’ exposure.