ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease

Atheroscler Suppl. 2003 Dec;4(4):23-8. doi: 10.1016/s1567-5688(03)00030-8.


Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase. By competitively displacing L-arginine from the substrate binding site of NO synthase, ADMA interferes with many of the physiological functions of NO, like endothelium-dependent vasodilation and leukocyte adhesion. ADMA, like its biologically inactive regioisomer, symmetric dimethylarginine (SDMA), can be found in human plasma and urine in low concentrations. The concentrations of both dimethylarginines are increased in patients with end-stage renal disease, which may explain at least in part endothelial dysfunction and cardiovascular complications in this patient population. In addition, the metabolism of ADMA, but not SDMA, occurs via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Data from experimental studies suggest that ADMA inhibits vascular NO elaboration at concentrations that can be measured in plasma of patients with renal disease. Interestingly, ADMA and SDMA are poorly eliminated during hemodialysis. This is probably due to a high level of binding of both molecules to plasma proteins. High ADMA concentrations in patients with end-stage renal disease may contribute to their excess cardiovascular event rate, as in clinical studies a relationship between ADMA and carotid artery intimal thickening was found. Moreover, in a prospective study we demonstrated recently that determination of ADMA plasma concentration is useful to predict future cardiovascular event rate and total mortality in this patient population. As other researchers reported observations that are in line with our findings, there is evidence that ADMA may be a novel cardiovascular risk factor.

Publication types

  • Review

MeSH terms

  • Arginine / analogs & derivatives*
  • Arginine / antagonists & inhibitors
  • Arginine / pharmacology*
  • Arginine / physiology*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / physiopathology
  • Nitric Oxide Synthase / drug effects
  • Risk Factors


  • Enzyme Inhibitors
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase