title: Identifying High-Risk Medications Associated with Acute Kidney Injury in Critically Ill Patients: A Pharmacoepidemiologic Evaluation.
abstract: BACKGROUND
  Nephrotoxic medications are a common cause of acute kidney injury (AKI). Critically ill children receive more medication than other inpatients; however, the risk of nephrotoxic medication-induced AKI in these children is not well understood.
  
  
  OBJECTIVE
  The aim of this study was to determine the association between exposure to nephrotoxic medications in the intensive care unit (ICU) and the development of AKI amongst critically ill children, adjusting for differences in underlying risk.
  
  
  METHODS
  We conducted a nested case-control study among a cohort of patients admitted to a paediatric intensive care unit between January 2006 and June 2009. Cases were identified according to the RIFLE criteria. Using incidence density sampling, controls were matched 1:1 according to pre-ICU nephrotoxic drug exposure. Administration of nephrotoxic medications and other known risk factors of AKI were evaluated during the ICU stay prior to the diagnosis of AKI.
  
  
  RESULTS
  A total of 914 patients in the cohort developed AKI and had an identifiable matched control. Eighty-seven percent of cases and 74% of controls were exposed to one or more nephrotoxic medications in the ICU during the study period. Furosemide (administered to 67.8% of patients), vancomycin (28.7%), and gentamicin (21.4%) were the most frequently administered nephrotoxic drugs. Patients who developed AKI were more likely to be exposed to at least one nephrotoxic medication and risk increased with increasing number of nephrotoxic medications. Ganciclovir (adjusted odds ratio [AOR] 4.7; 95% CI 1.7-13.0), furosemide (AOR 1.9; 95% CI 1.4-2.4), and gentamicin (AOR 1.8; 95% CI 1.4-2.4) significantly increased the odds of developing AKI after adjusting for underlying differences in risk factors of AKI.
  
  
  CONCLUSIONS
  This is the first study to assess the association between risk-adjusted nephrotoxic medication exposure and the development of AKI in critically ill children. Nephrotoxic medication exposure was common amongst children in the ICU and we found AKI was associated with the administration of specific drugs after adjustment for important risk factors.
authors.affiliation: Department of Critical Care Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.|Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Morgan B
authors.initials: MB
authors.lastname: Slater
authors.affiliation: Department of Family Medicine, University of Alberta, Edmonton, AB, Canada.|Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.|Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.|Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gruneir
authors.affiliation: Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.|Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.|Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.|Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Rochon
authors.affiliation: Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada.|Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.|Division of Orthopaedic Surgery, The Hospital for Sick Children, Toronto, ON, Canada.|Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Howard
authors.affiliation: Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.affiliation: Department of Critical Care Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. chris@sickkids.ca.|Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada. chris@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. chris@sickkids.ca.|Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON, Canada. chris@sickkids.ca.|Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. chris@sickkids.ca.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Parshuram
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005665:Furosemide / Q000009:adverse effects; D005839:Gentamicins / Q000009:adverse effects; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D014640:Vancomycin / Q000009:adverse effects
chemical_list: D005839:Gentamicins; D014640:Vancomycin; D005665:Furosemide