Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial
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Acute kidney 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.
To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients.
Design, setting, and participants
Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days.
Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care.
Main outcomes and measures
Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function.
474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated 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 difference 0.21 AKI days per 10 patient ICU days, 95 % CI −0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m2 (95 % CI 1.0–14.5 mL/min/1.73 m2, P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145–455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21).
Conclusion and relevance
Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction.
anzctr.org.au Identifier: ACTRN12609001015235.
KeywordsClinical trial Protein Acute kidney injury Amino acids Nutrition
Dr. Doig reported receiving academic research grants from Fresenius Kabi Deutschland GmbH and Baxter Healthcare Pty Ltd and speakers’ honoraria from Fresenius Kabi Deutschland GmbH, Baxter Healthcare Australia, Pty Ltd and Nestle Healthcare, Vevy, Switzerland. Ms. Simpson reported receiving academic research grants from Fresenius Kabi Deutschland GmbH and Baxter Healthcare Australia Pty Ltd and speakers’ honoraria from Fresenius Kabi Pty Ltd and Baxter Healthcare Australia Pty Ltd. Dr. Harrigan has no potential conflicts to declare. No other authors reported disclosures.
This work was supported by a peer-reviewed academic grant from the Australian National Health and Medical Research Council (NH&MRC). Baxter Healthcare Pty Ltd supplied the study amino acids.
Role of the sponsors
As a peer review funding body, the NH&MRC provided constructive comments on the study design. Baxter Healthcare Pty Ltd played no role in the design or conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. Although participating sites were compensated for the costs of conducting the trial, site investigators did not receive financial compensation for their contributions.
- 15.Doig GS, Simpson F, Bellomo R, The ANZICSCTG (2009) Improved nutritional support is associated with reduced renal dysfunction in critical illness: a post hoc exploratory subgroup analysis. Am J Respir Crit Care Med 179:A1567Google Scholar
- 19.Bernard GR, Doig GS, Hudson LD, Lemeshow S, Marshall JC, Russel J et al (1995) Quantification of organ failure for clinical trials and clinical practice. Am J Respir Crit Care Med 151:A323Google Scholar
- 26.Doig GS, Simpson F, Sweetman EA, Heighes PT, on behalf of the Nephro-Protective Trial Management Committee (2013) Statistical analysis plan for a multi-centre randomised controlled trial: nephro-protective effects of L-amino acids in critically ill patients. EvidenceBased.net, SydneyGoogle Scholar
- 35.Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204–R212PubMedCentralPubMedCrossRefGoogle Scholar