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Atypical Antipsychotic Drugs and the Risk for Acute Kidney Injury and Other Adverse Outcomes in Older Adults: A Population-Based Cohort StudyAtypical Antipsychotic Drugs and the Risk for Acute Kidney Injury

Y. Joseph Hwang, MSc; Stephanie N. Dixon, PhD; Jeffrey P. Reiss, MD, MSc; Ron Wald, MD, MPH; Chirag R. Parikh, MD, PhD; Sonja Gandhi, BSc; Salimah Z. Shariff, PhD; Neesh Pannu, MD, SM; Danielle M. Nash, MSc; Faisal Rehman, MD; and Amit X. Garg, MD, PhD
[+] Article and Author Information

From Case Western Reserve University School of Medicine, Cleveland, Ohio; Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St Michael's Hospital, and University of Toronto, Toronto, Ontario, Canada; Yale University School of Medicine, New Haven, Connecticut; and University of Alberta, Edmonton, Alberta, Canada.

Grant Support: This study was supported by the Institute for Clinical Evaluative Sciences (ICES) Western site and conducted by members of the provincial ICES Kidney, Dialysis and Transplantation Program. ICES is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care, and ICES Western is funded by an operating grant from the Academic Medical Organization of Southwestern Ontario, the Schulich School of Medicine & Dentistry at Western University, and the Lawson Health Research Institute.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2796.

Reproducible Research Statement:Study protocol and statistical code: Portions are available to approved individuals through written agreements with Dr. Garg (e-mail, amit.garg@lhsc.on.ca). Data set: Not available.

Requests for Single Reprints: Amit X. Garg, MD, PhD, London Kidney Clinical Research Unit, Room ELL-101, Westminster, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada; e-mail, amit.garg@lhsc.on.ca.

Current Author Addresses: Mr. Hwang; Drs. Dixon, Shariff, and Garg; Ms. Gandhi; and Ms. Nash: London Kidney Clinical Research Unit, Room ELL-101, Westminster, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada.

Dr. Reiss: London Health Sciences Centre, Room B8-142, 800 Commissioners Road East, London, Ontario N6A 5W9, Canada.

Dr. Wald: Division of Nephrology, St. Michael's Hospital, 61 Queen Street East, Room 9-140, Toronto, Ontario M5C 2T2, Canada.

Dr. Parikh: Yale University and Veterans Affairs Medical Center, 60 Temple Street, Suite 6C, New Haven, CT 06510.

Dr. Pannu: Division of Nephrology and Critical Care, University of Alberta, 11-107 CSB, 8440 112 Street, Edmonton, Alberta T6G 2G3, Canada.

Dr. Rehman: University Hospital, Room ALL-139, 339 Windermere Road, London, Ontario N6A 5A5, Canada.

Author Contributions: Conception and design: Y.J. Hwang, S.N. Dixon, J.P. Reiss, C.R. Parikh, S. Gandhi, S.Z. Shariff, A.X. Garg.

Analysis and interpretation of the data: Y.J. Hwang, S.N. Dixon, J.P. Reiss, C.R. Parikh, S. Gandhi, S.Z. Shariff, N. Pannu, F. Rehman, A.X. Garg.

Drafting of the article: Y.J. Hwang, J.P. Reiss, C.R. Parikh, F. Rehman, A.X. Garg.

Critical revision of the article for important intellectual content: Y.J. Hwang, S.N. Dixon, J.P. Reiss, R. Wald, C.R. Parikh, S. Gandhi, S.Z. Shariff, N. Pannu, D.M. Nash, F. Rehman, A.X. Garg.

Final approval of the article: Y.J. Hwang, S.N. Dixon, J.P. Reiss, R. Wald, C.R. Parikh, S. Gandhi, S.Z. Shariff, N. Pannu, D.M. Nash, F. Rehman, A.X. Garg.

Provision of study materials or patients: A.X. Garg.

Statistical expertise: Y.J. Hwang, S.N. Dixon, S.Z. Shariff, A.X. Garg.

Obtaining of funding: A.X. Garg.

Administrative, technical, or logistic support: Y.J. Hwang, J.P. Reiss, A.X. Garg.

Collection and assembly of data: S.N. Dixon, S.Z. Shariff, A.X. Garg.


Ann Intern Med. 2014;161(4):242-248. doi:10.7326/M13-2796
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Background: Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis.

Objective: To investigate the risk for AKI and other adverse outcomes associated with use of atypical antipsychotic drugs versus nonuse.

Design: Population-based cohort study.

Setting: Ontario, Canada, from 2003 to 2012.

Patients: Adults aged 65 years or older who received a new outpatient prescription for an oral atypical antipsychotic drug (n = 97 777) matched 1:1 with those who did not receive such a prescription.

Measurements: The primary outcome was hospitalization with AKI (assessed by using a hospital diagnosis code and, in a subpopulation, serum creatinine levels) within 90 days of prescription for atypical antipsychotic drugs.

Results: Atypical antipsychotic drug use versus nonuse was associated with a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]). This association was consistent when AKI was assessed in a subpopulation for which information on serum creatinine levels was available (5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI, 0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all-cause mortality (RR, 2.39 [CI, 2.28 to 2.50]).

Limitation: Only older adults were included in the study.

Conclusion: Atypical antipsychotic drug use is associated with an increased risk for AKI and other adverse outcomes that may explain the observed association with AKI. The findings support current safety concerns about the use of these drugs in older adults.

Primary Funding Source: Academic Medical Organization of Southwestern Ontario.

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