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Identifying High-Risk Medications Associated with Acute Kidney Injury in Critically Ill Patients: A Pharmacoepidemiologic Evaluation

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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.

Conclusion

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.

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Acknowledgements

The authors would like to thank Dr. Valeria Rac, Dr. Joseph Amuah, Helena Frndova, Winnie Seto, Tony Pyle, Traci Peggie, Sarah Ashley, and Christina Stevancec for their advice and assistance. Morgan Slater was supported through a Canadian Institutes of Health Research Frederick Banting and Charles Best Canada Graduate Scholarship, the Ontario Student Opportunity Trust Fund—Hospital for Sick Children Foundation Student Scholarship Program, and an Ontario Graduate Scholarship.

Author information

Authors and Affiliations

  1. Department of Critical Care Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Morgan B. Slater & Christopher S. Parshuram

  2. Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada

    Morgan B. Slater, Andrew W. Howard & Christopher S. Parshuram

  3. Department of Family Medicine, University of Alberta, Edmonton, AB, Canada

    Andrea Gruneir

  4. Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada

    Andrea Gruneir & Paula A. Rochon

  5. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada

    Andrea Gruneir, Paula A. Rochon, Andrew W. Howard & Christopher S. Parshuram

  6. Institute for Clinical Evaluative Sciences, Toronto, ON, Canada

    Andrea Gruneir & Paula A. Rochon

  7. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Paula A. Rochon

  8. Division of Orthopaedic Surgery, The Hospital for Sick Children, Toronto, ON, Canada

    Andrew W. Howard

  9. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Andrew W. Howard

  10. Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    Gideon Koren

  11. Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON, Canada

    Christopher S. Parshuram

  12. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada

    Christopher S. Parshuram

Authors
  1. Morgan B. Slater
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  2. Andrea Gruneir
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  3. Paula A. Rochon
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  4. Andrew W. Howard
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  5. Gideon Koren
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  6. Christopher S. Parshuram
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Corresponding author

Correspondence to Christopher S. Parshuram.

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Disclosure of potential conflicts of interest

All authors (M. Slater, A. Gruneir, P. Rochon, A. Howard, G. Koren, C. Parshuram) declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Funding sources

This work was supported by the following scholarships awarded to Morgan Slater: a Canadian Institutes of Health Research Frederick Banting and Charles Best Canada Graduate Scholarship, the Ontario Student Opportunity Trust Fund—The Hospital for Sick Children Foundation Student Scholarship Program, and an Ontario Graduate Scholarship. Dr. C Parshuram received operational funding from the Canadian Institutes of Health Research that supported completion of the study and was administered by the SickKids Research Institute.

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Slater, M.B., Gruneir, A., Rochon, P.A. et al. Identifying High-Risk Medications Associated with Acute Kidney Injury in Critically Ill Patients: A Pharmacoepidemiologic Evaluation. Pediatr Drugs 19, 59–67 (2017). https://doi.org/10.1007/s40272-016-0205-1

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  • DOI: https://doi.org/10.1007/s40272-016-0205-1

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