title: A Retrospective Cohort Study of Acute Kidney Injury Risk Associated with Antipsychotics.
abstract: BACKGROUND
  A recent large database analysis raised concerns of potential acute kidney injury (AKI) risk associated with antipsychotics. However, whether individual atypical and typical antipsychotics are associated with differential AKI risks has not been investigated.
  
  
  OBJECTIVE
  The current study compared the risks of AKI and known causes of AKI associated with a broad range of atypical and typical antipsychotics.
  
  
  METHODS
  This retrospective cohort analysis used January 2007-June 2013 US nationwide Humana claims data to define episodes of antipsychotic drug therapy for patients with schizophrenia and bipolar disorder. Study drugs were aripiprazole, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Study outcomes were hospitalizations with AKI, and known causes of AKI, i.e., hypotension, acute urinary retention, neuroleptic malignant syndrome/rhabdomyolysis, and pneumonia. AKI was the primary outcome of the study. Cox regressions using haloperidol as the baseline comparator were used to estimate the impact of alternative antipsychotics on the risks of study adverse events following the initiation of treatment. The Cox models controlled for treatment history, comorbidities, and concomitant drug use in the prior 6 months. They also controlled for patient demographics and dose of current treatment.
  
  
  RESULTS
  The overall incidence of AKI was 25.0 per 1000 person-years. According to our multivariate regression results, the risk of AKI was significantly increased in patients taking olanzapine [hazard ratio (HR) 1.344, 95% confidence interval (CI) 1.057-1.708], quetiapine (HR 1.350, 95% CI 1.082-1.685), and ziprasidone (HR 1.338, 95% CI 1.035-1.729) relative to haloperidol. Aripiprazole (HR 1.152, 95% CI 0.908-1.462) and risperidone (HR 1.147, 95% CI 0.923-1.426) had insignificantly higher risks of AKI compared with haloperidol, whereas fluphenazine (HR 0.729, 95% CI 0.483-1.102) had an insignificantly lower risk of AKI. When compared between drug classes, atypical antipsychotics had a significantly higher risk of AKI (HR 1.313, 95% CI 1.083-1.591) than typical antipsychotics.
  
  
  CONCLUSIONS
  Antipsychotics are associated with differential AKI risks, with several atypical antipsychotics having higher risks than haloperidol. However, the overall incidence of AKI was moderate, and AKI risk should only raise concern for clinicians with elderly patients or patients who are vulnerable to kidney disease.
authors.affiliation: Department of Pharmaceutical and Health Economics, Leonard D. Schaeffer Center for Health Policy and Economics, School of Pharmacy, University of Southern California, USC Schaeffer Center, Verna and Peter Dauterive Hall (VPD), 635 Downey Way, Los Angeles, CA, 90089-3333, USA. yawenjia@usc.edu.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutical and Health Economics, Leonard D. Schaeffer Center for Health Policy and Economics, School of Pharmacy, University of Southern California, USC Schaeffer Center, Verna and Peter Dauterive Hall (VPD), 635 Downey Way, Los Angeles, CA, 90089-3333, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: McCombs
authors.affiliation: Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
authors.forename: Susie H
authors.initials: SH
authors.lastname: Park
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000188:drug therapy*; D015331:Cohort Studies; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents