title: Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality.
abstract: OBJECTIVE
  Accumulation of asymmetrical dimethylarginine (ADMA) has been linked to endothelial dysfunction, and is an important risk factor for cardiovascular disease. Its elimination from the body is dependent on urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase. This enzyme is highly expressed in the liver, and in rat studies a high net hepatic uptake of asymmetrical dimethylarginine was found. In critically ill patients, we investigated the relation between indicators of renal and hepatic dysfunction and plasma ADMA concentration, and tested the association between ADMA concentration and outcome.
  
  
  METHODS
  We prospectively collected blood samples from a cross-section of critically ill patients (n=52) with clinical evidence of dysfunction of more than two organs. We identified correlates of plasma ADMA concentration with laboratory values, organ failures score and outcome by univariate and multiple regression analyses.
  
  
  RESULTS
  In critically ill patients, plasma ADMA concentration was independently related to the presence of hepatic failure (b=0.334, 95% CI: 0.207-0.461; P<0.001), and to lactic acid (b=0.395, 95% CI: 0.230-0.560; P<0.001) and bilirubin (b=0.121, 95% CI: 0.031-0.212; P=0.009) concentration as markers of hepatic function. Twenty-one (40%) patients deceased during their ICU stay. In a logistic regression model, plasma ADMA ranked as the first and strongest predictor for outcome, with a 17-fold (95% CI: 3-100) increased risk for ICU death in patients who were in the highest quartile for ADMA.
  
  
  CONCLUSIONS
  In critically ill patients, plasma ADMA concentration is a strong and independent risk factor for ICU mortality, and hepatic dysfunction is the most prominent determinant of ADMA concentration in this population.
authors.affiliation: Department of Surgery, Institute for Cardiovascular Research-VU / VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Nijveldt
authors.forename: T
authors.initials: T
authors.lastname: Teerlink
authors.forename: B
authors.initials: B
authors.lastname: Van Der Hoven
authors.forename: M P C
authors.initials: MP
authors.lastname: Siroen
authors.forename: D J
authors.initials: DJ
authors.lastname: Kuik
authors.forename: J A
authors.initials: JA
authors.lastname: Rauwerda
authors.forename: P A M
authors.initials: PA
authors.lastname: van Leeuwen
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D016638:Critical Illness / Q000401:mortality*; D003430:Cross-Sectional Studies; D004791:Enzyme Inhibitors / Q000097:blood*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D017093:Liver Failure / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000401:mortality*; D010865:Pilot Projects; D051437:Renal Insufficiency / Q000097:blood*; D012307:Risk Factors
chemical_list: D004791:Enzyme Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine