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Augmented Renal Clearance in the ICU: Results of a Multicenter Observational Study of Renal Function in Critically Ill Patients With Normal Plasma Creatinine Concentrations*

Udy, Andrew A. BHB, MBChB, FCICM1,2; Baptista, João P. MD3; Lim, Noelle L. MBBS, MMed, FAMS4; Joynt, Gavin M. MBBCh, FFA, FHKCA, FHKCA (IC), FHKAM, FCICM1,5; Jarrett, Paul DipHE2; Wockner, Leesa PhD6; Boots, Robert J. MBBS, PhD, MMedSci, MHAIS, FRACP, FCICM1,2; Lipman, Jeffrey MBBCh, DA, FFA, FFA (Crit Care), FCICM, MD1,2

doi: 10.1097/CCM.0000000000000029
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Objective: To describe the prevalence and natural history of augmented renal clearance in a cohort of recently admitted critically ill patients with normal plasma creatinine concentrations.

Design: Multicenter, prospective, observational study.

Setting: Four, tertiary-level, university-affiliated, ICUs in Australia, Singapore, Hong Kong, and Portugal.

Patients: Study participants had to have an expected ICU length of stay more than 24 hours, no evidence of absolute renal impairment (admission plasma creatinine < 120 µmol/L), and no history of prior renal replacement therapy or chronic kidney disease. Convenience sampling was used at each participating site.

Interventions: Eight-hour urinary creatinine clearances were collected daily, as the primary method of measuring renal function. Augmented renal clearance was defined by a creatinine clearance more than or equal to 130 mL/min/1.73 m2. Additional demographic, physiological, therapeutic, and outcome data were recorded prospectively.

Measurements and Main Results: Nine hundred thirty-two patients were admitted to the participating ICUs over the study period, and 281 of which were recruited into the study, contributing 1,660 individual creatinine clearance measures. The mean age (95% CI) was 54.4 years (52.5–56.4 yr), Acute Physiology and Chronic Health Evaluation II score was 16 (15.2–16.7), and ICU mortality was 8.5%. Overall, 65.1% manifested augmented renal clearance on at least one occasion during the first seven study days; the majority (74%) of whom did so on more than or equal to 50% of their creatinine clearance measures. Using a mixed-effects model, the presence of augmented renal clearance on study day 1 strongly predicted (p = 0.019) sustained elevation of creatinine clearance in these patients over the first week in ICU.

Conclusions: Augmented renal clearance appears to be a common finding in this patient group, with sustained elevation of creatinine clearance throughout the first week in ICU. Future studies should focus on the implications for accurate dosing of renally eliminated pharmaceuticals in patients with augmented renal clearance, in addition to the potential impact on individual clinical outcomes.

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1Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia.

2Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia.

3Serviço de Medicina Intensiva, Hospitais da Universidade de Coimbra, EPE Praceta Prof. Mota Pinto, Coimbra, Portugal.

4Anaesthesia and Surgical Intensive Care, Changi General Hospital, Singapore.

5Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin NT, Hong Kong SAR.

6Statistics Unit, Level 3 Clive Berghofer Cancer Research Centre, Queensland Institute of Medical Research, Herston, QLD, Australia.

* See also p. 728.

This work was performed at Royal Brisbane and Women’s Hospital, Hospitais da Universidade de Coimbra, Changi General Hospital, and The Chinese University of Hong Kong, Prince of Wales Hospital.

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Dr. Udy is employed by Queensland Health. He and his institution received grant support from the Royal Brisbane and Women’s Hospital Research Foundation (research scholarship and project grants). Dr. Baptista received support for travel from Pfizer. Dr. Lim received support for article research from the Changi General Hospital Research Grant. Dr. Lipman consulted for Janssen-Cilag Pty, Merk Sharp Dohme (Aust) Pty Pfizer Australia, and AstraZeneca; received grant support from AstraZeneca; and lectured for Wyeth Australia Pty, AstraZeneca, and Pfizer Australia Pty. His institution is part of the Bayer European Society of Intensive Care Medicine Advisory Board. The remaining authors disclosed that they do not have any potential conflicts of interest.

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© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins