title: The Effects of Parenteral Amino Acid Therapy on Protein Carbamylation in Maintenance Hemodialysis Patients.
abstract: OBJECTIVE
  Protein carbamylation is a urea-driven post-translational protein modification associated with mortality in dialysis patients. Free amino acids (AAs) are competitive inhibitors of protein carbamylation and animal studies suggest increasing AA concentrations reduces carbamylation burden. We hypothesized that AA therapy in maintenance hemodialysis patients would reduce carbamylation, carrying the potential to improve clinical outcomes.
  
  
  METHODS
  Prospective pilot clinical trial (NCT1612429).
  
  
  METHODS
  The study was conducted from March 2013 to March 2014 in outpatient dialysis facilities in the Boston metropolitan area.
  
  
  METHODS
  We enrolled 23 consecutively consenting hemodialysis subjects, infusing the first 12 individuals with 250 cc of AAs 3 times per week postdialysis over 8 weeks. The remaining 11 subjects served as controls.
  
  
  METHODS
  Change in carbamylated albumin (C-Alb), a measure of total body carbamylation burden, between baseline and 8 weeks was the primary outcome.
  
  
  RESULTS
  The treated and control groups had similar clinical characteristics and similar baseline C-Alb levels (mean ± SE 9.5 ± 2.4 and 9.3 ± 1.3 mmol/mol, respectively; P = .61). The treated arm showed a significant reduction in C-Alb compared with controls at 4 weeks (8.4% reduction in the treated arm vs. 4.3% increase in controls; P = .03) and the effect was greater by 8 weeks (15% reduction in the treated vs. 1% decrease in controls; P = .01).
  
  
  CONCLUSIONS
  In this pilot study, AA therapy appeared safe and effective at reducing C-Alb levels in hemodialysis patients compared with no treatment. The impact of reduced protein carbamylation on clinical outcomes should be further investigated.
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: skalim@partners.org.
authors.forename: Sahir
authors.initials: S
authors.lastname: Kalim
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ortiz
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Trottier
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Deferio
authors.affiliation: Division of Nephrology and Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ravi I
authors.initials: RI
authors.lastname: Thadhani
authors.affiliation: Division of Clinical Chemistry, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Berg
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D002219:Carbamates / Q000097:blood*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010288:Parenteral Nutrition / Q000379:methods*; D010865:Pilot Projects; D011446:Prospective Studies; D006435:Renal Dialysis; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D002219:Carbamates; D012709:Serum Albumin