Asymmetric dimethylarginine (ADMA) as a cardiovascular risk factor in end-stage renal disease (ESRD)

Abstract

Evidence is emerging that a defect in vasculoprotection, triggered by accumulation of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA), plays a role of paramount importance in the high cardiovascular (CV) risk of patients with end-stage renal disease (ESRD). The idea that ADMA accumulation may be a CV risk factor in these patients was suggested by Vallance in 1992 and supported by a cross-sectional study by Kielstein in 1999. In the past 6 years we have thoroughly re-examined the problem by analysing the relationship between ADMA and several outcome measures in dialysis patients. We found that ADMA is strongly associated to intima-media thickness of the carotid artery and that this link is independent of other CV risk factors. Of note, ADMA is also directly related to left ventricular mass and to relative wall thickness, suggesting that it triggers concentric left ventricular hypertrophy. Furthermore in a cohort study in 225 dialysis patients, we observed a strong and independent link between ADMA, all-cause mortality and CV events. Finally, we have gathered circumstantial evidence that norepinephrine and ADMA may be in the same causal pathway leading to CV complications in ESRD.