Abstract
Plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide production, correlate with endothelial dysfunction and the development of cardiovascular events in patients with uremia. It is not known whether endothelial dysfunction contributes to the dysfunction of arteriovenous fistulas (AVFs) in hemodialysis patients. Here, we studied the predictive value of baseline plasma ADMA for symptomatic restenosis of an AVF after percutaneous transluminal angioplasty in dialysis patients. We obtained baseline plasma ADMA levels before percutaneous transluminal angioplasty in 100 consecutive patients with dysfunctional AVFs. Patients were followed up clinically for up to 6 mo after angioplasty for recurrent dysfunction. During the 6 mo after angioplasty, 46 patients experienced recurrent dysfunction of their AVF; of these, follow-up fistulography showed restenosis at the same location in 41, new stenosis at different locations in two, and no significant stenosis in three patients. Up to 60% of the patients with high levels of ADMA (>0.910 microM) had target lesion restenosis compared with 25% of those with low levels (<0.910 microM; P < 0.001). In multivariate analysis, plasma ADMA independently nearly tripled the risk for recurrent symptomatic stenosis of an AVF after percutaneous transluminal angioplasty (hazard ratio 2.65; 95% confidence interval 1.33 to 5.28). These results suggest a role for ADMA in the progression of symptomatic restenoses of AVFs after percutaneous transluminal angioplasty and call for preventive strategies that target ADMA and/or endothelial dysfunction to decrease the risk for AVF restenosis.