Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial

Doig, Gordon S, Simpson, Fiona, Bellomo, Rinaldo, Heighes, Philippa T, Sweetman, Elizabeth A, Chesher, Douglas, Pollock, Carol, Davies, Andrew, Botha, John, Harrigan, Peter and Reade, Michael C (2015) Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial. Intensive Care Medicine, 41 7: 1197-1208. doi:10.1007/s00134-015-3827-9


Author Doig, Gordon S
Simpson, Fiona
Bellomo, Rinaldo
Heighes, Philippa T
Sweetman, Elizabeth A
Chesher, Douglas
Pollock, Carol
Davies, Andrew
Botha, John
Harrigan, Peter
Reade, Michael C
Title Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial
Journal name Intensive Care Medicine   Check publisher's open access policy
ISSN 1432-1238
0342-4642
Publication date 2015-04-30
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s00134-015-3827-9
Open Access Status Not yet assessed
Volume 41
Issue 7
Start page 1197
End page 1208
Total pages 12
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Subject 2706 Critical Care and Intensive Care Medicine
Abstract Importance: 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. Objective: 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. Interventions: 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. Results: 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 m (95 % CI 1.0–14.5 mL/min/1.73 m, 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. Trial registration: anzctr.org.au Identifier: ACTRN12609001015235.
Formatted abstract
Importance
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.

Objective
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.

Interventions
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.

Results

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.
Keyword Clinical trial
Protein
Acute kidney injury
Amino acids
Nutrition
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
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