Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study

Background Proton pump inhibitors (PPIs) cause interstitial nephritis and are an underappreciated cause of acute kidney injury. We examined the risk of acute kidney injury and acute interstitial nephritis in a large population of older patients receiving PPIs.

Methods We conducted a population-based study involving Ontario residents aged 66 years and older who initiated PPI therapy between Apr. 1, 2002, and Nov. 30, 2011. We used propensity score matching to establish a highly comparable reference group of control patients. The primary outcome was hospital admission with acute kidney injury within 120 days, and a secondary analysis examined acute interstitial nephritis. We used Cox proportional hazards regression to adjust for differences between groups.

Results We studied 290 592 individuals who commenced PPI therapy and an equal number of matched controls. The rates of acute kidney injury (13.49 v. 5.46 per 1000 person-years, respectively; hazard ratio [HR] 2.52, 95% CI 2.27 to 2.79) and acute interstitial nephritis (0.32 vs. 0.11 per 1000 person-years; HR 3.00, 95% CI 1.47 to 6.14) were higher among patients given PPIs than among controls.

Interpretation In our study population of older adults, those who started PPI therapy had an increased risk of acute kidney injury and acute interstitial nephritis. These are potentially reversible conditions that may not be readily attributed to drug treatment. Clinicians should appreciate the risk of acute interstitial nephritis during treatment with PPIs, monitor patients appropriately and discourage the indiscriminate use of these drugs.