Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury ☆ Sean M. Bagshaw MD, MSc a,b, ⁎ , Shigehiko Uchino MD c , Rinaldo Bellomo MD a , Hiroshi Morimatsu MD d , Stanislao Morgera MD e , Miet Schetz MD f , Ian Tan MD g , Catherine Bouman MD h , Ettiene Macedo MD i , Noel Gibney MD b , Ashita Tolwani MD j , Heleen M. Oudemans-van Straaten MD k , Claudio Ronco MD l , John A. Kellum MD m , for the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators a Department of Intensive Care and Department of Medicine, Austin and Repatriation Medical Centre, Melbourne, Australia b Division of Critical Care Medicine, University of Alberta, Edmonton, Canada c Intensive Care Unit, Department of Anesthesiology, Jikei University School of Medicine, Tokyo, Japan d Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, Japan e Department of Nephrology, University Hospital Charité, Berlin, Germany f Dienst Intensieve Geneeskunde, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium g Intensive Care Unit, Department of Anaesthesia, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China h Adult Intensive Care Unit, Academic Medical Center, Amsterdam, Holland i Nephrology Division, University of São Paulo School of Medicine, São Paulo, Brazil j Department of Medicine, Division of Nephrology, The University of Alabama at Birmingham, AL, USA k Department of Intensive Care, Onze Lieve Vrouwe Gasthius, Amsterdam, The Netherlands l Nephrology - Intensive Care, St. Bortolo Hospital, Vicenza, Italy m Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA Keywords: Acute renal failure; Acute kidney injury; Critical illness; Renal replacement therapy; Hemofiltration; Dialysis; Timing; Delay; Mortality; Length of stay; Renal recovery Abstract Purpose: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. Methods: This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients. Results: Timing of RRT was stratified into “early” and “late” by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early (b2 days), delayed (2-5 days), and late (N5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea ≤24.2 mmol/L vs 61.4% for urea N24.2 mmol/L; odds ratio [OR], 0.92; 95% confidence interval [CI], 0.73-1.15; P = .48) or covariate-adjusted mortality (OR, 1.25; 95% CI, 0.91-1.70; P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine N309 μmol/L vs 71.4% for creatinine ≤309 μmol/L; OR, 0.46; 95% CI, 0.36-0.58; P b .0001) and covariate-adjusted mortality (OR, 0.51; 95% CI, 0.37-0.69; P b .001). ☆ All authors have seen and approved the final version of the manuscript. Authors have no conflicts of interest to declare. ⁎ Corresponding author. Division of Critical Care Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada T6G2B7. Tel.: +1 780 407 6755; fax: +1 780 407 1228. E-mail address: bagshaw@ualberta.ca (S.M. Bagshaw). 0883-9441/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2007.12.017 Journal of Critical Care (2008) xx, xxx–xxx ARTICLE IN PRESS