Background: Patients with renal insufficiency have an increased risk of cardiovascular disease that is not fully explained by the presence of known cardiovascular risk factors. In patients with end-stage renal disease, increased serum concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), has been linked to excess cardiovascular morbidity. We investigated, in patients with mild-to-moderate renal failure, the relationship between plasma ADMA and three surrogate markers of atherosclerosis that have been shown to have prognostic value, namely carotid intima-media thickness (IMT), plasma soluble vascular cell adhesion molecule-1 (sVCAM-1), and plasma C-reactive protein (CRP).
Methods: We used baseline data of an ongoing randomized trial in which the effects of oxidative stress-lowering treatment on vascular function and structure are studied in patients with chronic nondiabetic renal failure without clinical evidence of atherosclerosis (GFR 15 to 70 mL/min/per 1.73 m(2) according to the Cockcroft-Gault equation; ATIC study).
Results: Data from 93 patients were used. Creatinine clearance was inversely related to plasma ADMA concentration (standardized beta after adjustment = -0.342, P = 0.023). Plasma ADMA was strongly related to carotid IMT in univariate (beta = 0.459, P < 0.0001) and multivariate analysis (beta= 0.444, P < 0.0001). Plasma ADMA was also significantly related with plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) in univariate (beta = 0.260, P = 0.010) and multivariate (beta = 0.242, P = 0.022) analysis. Plasma ADMA was not significantly related to C-reactive protein (beta = -0.134, P = 0.204).
Conclusion: In patients with mild-to-moderate renal failure, renal function is inversely associated with plasma ADMA, which, in turn, is positively associated with carotid IMT and plasma sVCAM-1 concentration. Increased plasma ADMA may be a link between renal function and cardiovascular disease in patients with mild-to-moderate renal failure.