Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase that has been linked to endothelial dysfunction and atherosclerosis in the general population. ADMA is also elevated in end-stage renal disease and may contribute to the high cardiovascular risk in patients with chronic renal failure. A prospective cohort study was performed to investigate the relationship between plasma ADMA, C-reactive protein (CRP), and intima-media thickness (IMT) in 90 patients undergoing hemodialysis. In the baseline study, plasma ADMA was directly related to IMT both on univariate analysis (r = 0.32, P = 0.002) and on multiple regression analysis (beta = 0.23, P = 0.01). In the follow-up study (15 mo) IMT changes were significantly related to ADMA (r = 0.51, P = 0.02) and serum CRP (r = 0.53, P = 0.01) in patients with initially normal IMT. In these patients, ADMA and CRP were strongly interrelated (r = 0.64, P = 0.002), and on multiple regression analysis the interaction between ADMA and CRP emerged as the sole independent predictor of the progression of intimal lesions. Independently of other risk factors, plasma ADMA in patients on hemodialysis is significantly related to IMT. Furthermore, in patients with initially normal IMT, ADMA and CRP are interacting factors in the progression of carotid intimal lesions. These data support the hypothesis that accumulation of this endogenous inhibitor of NO synthase is an important risk factor for cardiovascular disease in chronic renal failure and suggest a possible link between ADMA and inflammation.