Gordon S. Doig Fiona Simpson Rinaldo Bellomo Philippa T. Heighes Elizabeth A. Sweetman Douglas Chesher Carol Pollock Andrew Davies John Botha Peter Harrigan Michael C. Reade Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial Received: 23 February 2015 Accepted: 15 April 2015 Published online: 30 April 2015 Ó Springer-Verlag Berlin Heidelberg and ESICM 2015 Take-home message: This multicenter clinical trial investigated whether an infusion of amino acids could preserve renal function during critical illness. Although the study intervention did not reduce the duration of renal dysfunction, estimated glomerular filtration rate and urine output were improved. Electronic supplementary material The online version of this article (doi:10.1007/s00134-015-3827-9) contains supplementary material, which is available to authorized users. G. S. Doig Á F. Simpson Á P. T. Heighes Á E. A. Sweetman The Northern Clinical School Intensive Care Research Unit, University of Sydney, Sydney, Australia R. Bellomo Á A. Davies School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia D. Chesher Á C. Pollock The Northern Clinical School, University of Sydney, Sydney, Australia J. Botha Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia P. Harrigan John Hunter Hospital, Newcastle, Australia M. C. Reade Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia D. Chesher New South Wales Health, Pathology, Newcastle, Australia G. S. Doig ( ) ) Intensive Care Unit, Royal North Shore Hospital, Pacific Hwy, St Leonards, NSW 2065, Australia e-mail: gdoig@med.usyd.edu.au Tel.: 612 9463-2633 Abstract Importance: Acute kid- ney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness. Objective: To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementa- tion with standard amino acids, preserves kidney function in critically ill patients. Design, setting, and par- ticipants: Multicenter, phase II, randomized clinical trial conducted between December 2010 and Febru- ary 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Par- ticipants were adult critically ill patients expected to remain in the study ICU for longer than 2 days. Interventions: Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care. Main outcomes and mea- sures: Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; uri- nary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function. Results: 474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allo- cated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre- existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean differ- ence 0.21 AKI days per 10 patient ICU days, 95 % CI -0.27 to 1.04, P = 0.45). Amino acid therapy sig- nificantly improved eGFR (treatment group 9 time interaction, P = 0.004), with an early peak dif- ference of 7.7 mL/min/1.73 m 2 Intensive Care Med (2015) 41:1197–1208 DOI 10.1007/s00134-015-3827-9 SEVEN-DAY PROFILE PUBLICATION