Tony Antoniou1, Erin M Macdonald2, Simon Hollands2, Tara Gomes3, Muhammad M Mamdani3, Amit X Garg4, J Michael Paterson5, David N Juurlink6. 1. Department of Family and Community Medicine, St. Michael's Hospital, Toronto, Ont. ; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ont. ; Institute for Clinical Evaluative Sciences, Toronto, Ont. 2. Institute for Clinical Evaluative Sciences, Toronto, Ont. 3. Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ont. ; Institute for Clinical Evaluative Sciences, Toronto, Ont. ; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ont. 4. Institute for Clinical Evaluative Sciences, Toronto, Ont. ; Division of Nephrology, Department of Medicine, Western University, London, Ont. ; Department of Epidemiology and Biostatistics, Western University, London, Ont. 5. Institute for Clinical Evaluative Sciences, Toronto, Ont. ; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ont. ; Department of Family Medicine, McMaster University, Hamilton, Ont. 6. Institute for Clinical Evaluative Sciences, Toronto, Ont. ; Departments of Medicine and Pediatrics, University of Toronto, Toronto, Ont. ; Sunnybrook Research Institute, Toronto, Ont.
Abstract
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.
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.
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