Elsevier

Clinical Nutrition

Volume 22, Issue 1, February 2003, Pages 23-30
Clinical Nutrition

Original Article
Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality

https://doi.org/10.1054/clnu.2002.0613Get rights and content

Abstract

Background and Aims: 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 bili-rubin (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.

References (31)

  • P Vallance et al.

    Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis

    J Cardiovasc Pharmacol

    (1992)
  • H Matsuoka et al.

    Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension

    Hypertension

    (1997)
  • J Leiper et al.

    Biological significance of endogenous methylarginines that inhibit nitric oxide synthases

    Cardiovasc Res

    (1999)
  • P Vallance et al.

    Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure

    Lancet

    (1992)
  • M Kimoto et al.

    Detection of NG,NG-dimethylarginine dimethylaminohydrolase in human tissues using a monoclonal antibody

    J Biochem (Tokyo)

    (1995)
  • Cited by (226)

    • ADMA and homoarginine independently predict mortality in critically ill patients

      2022, Nitric Oxide - Biology and Chemistry
      Citation Excerpt :

      Arginine, methylated arginines and homoarginine are important modulators of the nitric oxide pathway. Most interest has focused on asymmetric dimethyl-l-arginine (ADMA), which is a potent inhibitor of nitric oxide synthase, and its plasma concentration has been positively associated with mortality in healthy adults [5] and many patient groups including those with acute coronary syndrome [6], acute infection [7–10] and end-stage renal failure [11]. Monomethyl-l-arginine (MMA) also inhibits nitric oxide synthase, and was previously shown to increase mortality when used therapeutically in acute myocardial infarction [12], cardiogenic shock [12] and septic shock [13].

    • New Developments in Hepatorenal Syndrome

      2018, Clinical Gastroenterology and Hepatology
    • The Vascular Endothelium

      2018, Endothelium and Cardiovascular Diseases: Vascular Biology and Clinical Syndromes
    View all citing articles on Scopus

    Grant/fellowship: R.J. Nijveldt, MD, is a recipient of a fellowship from the Council for Medical Research of the Netherlands Organisation for Scientific Research

    f1

    (Correspondence to: PAML, Department of Surgery, VU Medical Center, Institute for Cardiovascular Research-VU, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands)

    View full text