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Critical Care

Open Access

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

  • RJ Nijveldt1,
  • T Teerlink1,
  • B van der Hoven1,
  • MPC Siroen1,
  • DJ Kuik1,
  • JA Rauwerda1 and
  • PAM van Leeuwen1
Critical Care20037(Suppl 2):P026

Published: 3 March 2003


Lactic AcidIndependent Risk FactorHepatic FailureHepatic DysfunctionHigh Quartile

Background and aims

Accumulation of 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.


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.


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.


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’ Affiliations

Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands


© BioMed Central Ltd 2003