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


METHODS
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.


METHODS
Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care.


METHODS
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(2) (95 % CI 1.0-14.5 mL/min/1.73 m(2), 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).


CONCLUSIONS
Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction.


BACKGROUND
anzctr.org.au Identifier: ACTRN12609001015235.
The Northern Clinical School Intensive Care Research Unit, University of Sydney, Sydney, Australia, gdoig@med.usyd.edu.au.
Gordon S
GS
Doig
Fiona
F
Simpson
Rinaldo
R
Bellomo
Philippa T
PT
Heighes
Elizabeth A
EA
Sweetman
Douglas
D
Chesher
Carol
C
Pollock
Andrew
A
Davies
John
J
Botha
Peter
P
Harrigan
Michael C
MC
Reade
D058186:Acute Kidney Injury / Q000517:prevention & control*; D000368:Aged; D000596:Amino Acids / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D016638:Critical Illness / Q000628:therapy*; D055316:Cystatin C / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged
D000596:Amino Acids; D055316:Cystatin C; D003404:Creatinine