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Asymmetric and symmetric dimethylarginines: metabolism and role in severe sepsis


Asymmetric dimethylarginines (ADMA) and symmetric dimethylarginines (SDMA) are markers of protein breakdown; both compete with arginine for cellular transport and are excreted in urine. In addition, ADMA is a nonselective inhibitor of NO synthase, and is also metabolized by dimethylarginine-dimethylaminohydrolase (DDAH), a specific hydrolase whose activity in stress is controversial [1]. While the ADMA increase is associated with adverse events in many critical conditions, little attention has been focused on the role of SDMA [2].


In three Italian university ICUs we measured plasma ADMA, SDMA, their ratio (a marker of ADMA catabolism, a rough indicator of DDAH activity), arginine, IL-6, TNFα, and C-reactive protein (CRP) level at days 1, 3, 6, 9, 12 and at discharge in 72 consecutive patients with severe sepsis/septic shock.


Basal glycaemia, creatinine, IL-6, TNFα, CRP, ADMA and SDMA were higher than normal; arginine was normal. ADMA was related to total Sequential Organ Failure Assessment and arginine, inversely related to IL-6 and CRP; SDMA was related to Simplified Acute Physiology Score II score, daily, worst-day, total Sequential Organ Failure Assessment score, blood urea, creatinine, and arginine. The ADMA/SDMA ratio was inversely related to IL-6. In 58 patients discharged alive, creatinine, IL-6 and CRP decreased over time, ADMA increased, SDMA remained stable, and the ADMA/SDMA ratio increased. In 14 patients who died in the ICU, creatinine, IL-6, TNFα, CRP, and ADMA did not vary, SDMA significantly increased, and ADMA/SDMA ratio variation was not significant. In both groups the last ICU day confirms data trends. SDMA but not ADMA was associated with ICU mortality.


In severe sepsis SDMA is a more robust predictor of organ failure/mortality than ADMA. Stress reaction seems to activate ADMA catabolism, while in survivors, when inflammation subsides, the catabolism seems to be reduced.


  1. 1.

    Zoccali C, et al.: Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections. Nephrol Dial Transplant 2007, 22: 801-806. 10.1093/ndt/gfl719

  2. 2.

    O'Dwyer MJ, et al.: Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study. Crit Care 2006, 10: R139. 10.1186/cc5053

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Umbrello, M., Pavini, F.C., Bolgiaghi, L. et al. Asymmetric and symmetric dimethylarginines: metabolism and role in severe sepsis. Crit Care 13, P361 (2009).

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  • Arginine
  • Severe Sepsis
  • Sequential Organ Failure Assessment Score
  • Acute Physiology Score
  • Protein Breakdown