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Implications of augmented renal clearance in critically ill patients

Nature Reviews Nephrology volume 7, pages 539–543 (2011)Cite this article

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Abstract

Critically ill patients can display markedly abnormal physiological parameters compared with those in ward-based or ambulatory settings. As a function of both the underlying inflammatory state and the interventions provided, these patients manifest substantial changes in their cardiovascular and renal function that are not always immediately discernable using standard diagnostic tests. Impaired renal function is well documented among such individuals; however, even patients with normal serum creatinine concentrations might display elevated glomerular filtration rates, a phenomenon we have termed augmented renal clearance (ARC). This finding has important ramifications for the accurate dosing of renally eliminated drugs, given that most pharmaceutical dosing regimens were validated outside the critical care environment. Empirical approaches to dosing are unlikely to achieve therapeutic drug concentrations in patients with ARC, placing them at risk of suboptimal drug exposure and potential treatment failure. With an increasing appreciation of this phenomenon, alternative dosing strategies will need to be investigated.

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Figure 1: Mechanisms underlying augmented renal clearance.

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Acknowledgements

The authors' work is supported in part by a grant from the National Health and Medical Research Council, Australia (NHMRC Project grant number 519702). A. A. Udy is supported by a Royal Brisbane and Women's Hospital Research Scholarship. J. A. Roberts is supported in part by the National Health and Medical Research Council, Australia (Australian Based Health Professional Research Fellowship grant number 569917).

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Authors and Affiliations

  1. Burns, Trauma, and Critical Care Research Center, University of Queensland, Royal Brisbane and Women's Hospital, Herston, 4029, QLD, Australia

    Andrew A. Udy, Jason A. Roberts & Jeffrey Lipman

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Contributions

J. Lipman, J. A. Roberts and A. A. Udy contributed equally to discussion of the article content and reviewing/editing the manuscript before submission. A. A. Udy researched data for the article and wrote the initial draft.

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Correspondence to Andrew A. Udy.

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Competing interests

J. A. Roberts has acted as a consultant to AstraZeneca, and is a member of advisory boards with AstraZeneca, Janssen-Cilag and Johnson and Johnson. Dr. Roberts has also received unrestricted grant funding from Astra-Zeneca, Janssen-Cilag and Novartis, and is listed in the Speakers bureau with Astra-Zeneca. J. Lipman has acted as a consultant for AstraZeneca, Janssen-Cilag, and Wyeth Australia. He has received grant/research support from AstraZeneca. A. A. Udy declares no competing interests.

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Udy, A., Roberts, J. & Lipman, J. Implications of augmented renal clearance in critically ill patients. Nat Rev Nephrol 7, 539–543 (2011). https://doi.org/10.1038/nrneph.2011.92

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