Background & Aims Proton pump inhibitors (PPI) have been associated with acute kidney injury and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD). Methods We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n = 105,305) and new users of H2 blockers (H2B; n = 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury. Complete collection of repeated PPI and H2B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated with cumulative PPI exposure. Results Users of PPIs, compared with users of H2Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05–1.51) and decrease in estimated glomerular filtration rate of 30% or more (11,045 events; 1.26; 95% CI, 1.16–1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 95% CI, 0.76–7.58) and acute kidney injury (HR, 1.30; 95% CI, 1.00–1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H2B use. Conclusions Initiation of PPI therapy and cumulative PPI exposure is associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.
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