title: Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial.
abstract: Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g·kg(-1)·day(-1); group A, n = 5) or no supplement (group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 ± 34 vs. 258 ± 19 μmol·kg(-1)·h(-1), citrulline: 5.7 ± 0.4 vs. 2.8 ± 0.4 μmol·kg(-1)·h(-1), and arginine: 50 ± 4 vs. 26 ± 2 μmol·kg(-1)·h(-1), P < 0.01), as was the synthesis of citrulline from glutamine (4.8 ± 0.7 vs. 1.6 ± 0.3 μmol·kg(-1)·h(-1)), citrulline from arginine (2.3 ± 0.3 vs. 0.96 ± 0.1 μmol·kg(-1)·h(-1)), and arginine from glutamine (7.7 ± 0.4 vs. 2.8 ± 0.2 μmol·kg(-1)·h(-1)), respectively (P < 0.001 for all). In conclusion, the production of citrulline and arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury.
authors.affiliation: Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands; sj.brinkmann@vumc.nl.
authors.forename: Saskia J H
authors.initials: SJ
authors.lastname: Brinkmann
authors.affiliation: Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Nikki
authors.initials: N
authors.lastname: Buijs
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Mechteld A R
authors.identifier: 0000-0002-5776-6117
authors.initials: MA
authors.lastname: Vermeulen
authors.affiliation: Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands; and.
authors.forename: Efraim
authors.initials: E
authors.lastname: Oosterink
authors.affiliation: Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands; and.
authors.forename: Henk
authors.initials: H
authors.lastname: Schierbeek
authors.affiliation: Department of Intensive Care, VU University Medical Center, Amsterdam, The Netherlands; Department of Surgery, Medical Centre Alkmaar, Trial Center Holland Health, Alkmaar, The Netherlands; Department of Intensive Care, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: Albertus
authors.initials: A
authors.lastname: Beishuizen
authors.affiliation: Department of Vascular Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands;
authors.forename: Jean-Paul P M
authors.initials: JP
authors.lastname: de Vries
authors.affiliation: Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Willem
authors.initials: W
authors.lastname: Wisselink
authors.affiliation: Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
mesh_terms: D000328:Adult; D000368:Aged; D001014:Aortic Aneurysm / Q000378:metabolism / Q000601:surgery*; D001120:Arginine / Q000096:biosynthesis*; D005260:Female; D005973:Glutamine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D058017:Vascular Grafting / Q000009:adverse effects* / Q000379:methods
chemical_list: D005973:Glutamine; D001120:Arginine
keywords: acute kidney injury; arginine; citrulline; glutamine; ischemia-reperfusion injury