Asymmetric Dimethylarginine (ADMA) as a Novel Risk Factor for Progression of Coronary Artery Calcification in Patients with Chronic Kidney Disease

<b>Background:</b> Vascular calcification (VC) is a characteristic feature of atherosclerosis in patients with chronic kidney disease (CKD), and coronary artery calcification (CAC) significantly impacts future cardiovascular events and mortality. Although factors associated with CAC are well reported, only a few studies have evaluated the factors associated with the progression of CAC in pre-dialysis patients with CKD. <b>Methods:</b> We quantitatively evaluated CAC progression using the CAC score (CACS) measured using 16-row multi-detector computed tomography and assessed associated factors in 74 patients with CKD. <b>Results:</b> The median annual increase in CACS was 23.7 (IQR 2.0-73.0). CAC progression was associated with serum phosphate and plasma asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric-oxide synthase and a marker of endothelial dysfunction and atherosclerosis, in univariate analysis. Multivariate analysis revealed that ADMA is an independent risk factor for CAC progression in patients with CKD. The annual change in CACS was significantly different between patients with ADMA values <0.51 and those with ADMA values >0.51 (<i>p</i> < 0.05). Elevated ADMA levels were also significantly associated with estimated glomerular filtration rate (eGFR) decline in the univariate analysis. <b>Conclusions:</b> ADMA is a novel risk factor for CAC progression in patients with CKD. Vascular endothelial cell dysfunction, represented by elevated ADMA levels, may contribute to the progression of vascular calcification in patients with pre-dialysis CKD.