title: Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.
abstract: BACKGROUND
  Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown.
  
  
  RESULTS
  We conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06-1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11-2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81-1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54-2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients.
  
  
  CONCLUSIONS
  PPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia. Please see later in the article for the Editors' Summary.
authors.affiliation: Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zipursky
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Macdonald
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Hollands
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tara
authors.initials: T
authors.lastname: Gomes
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Applied Health Research Centre, St. Michael's Hospital, Toronto, Ontario, Canada; King Saud University, Riyadh, Saudi Arabia.
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Mamdani
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada, Canada.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Paterson
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nina
authors.initials: N
authors.lastname: Lathia
authors.affiliation: Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006760:Hospitalization; D006801:Humans; D053565:Hypercalciuria / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D009397:Nephrocalcinosis / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D009864:Ontario / Q000453:epidemiology; D011159:Population Surveillance / Q000379:methods; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D015499:Renal Tubular Transport, Inborn Errors / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*
chemical_list: D054328:Proton Pump Inhibitors