Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: Relationship to treatment method and atherosclerotic disease

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelia l nitric oxide (NO) synthase. Its concentration is elevated in patients wit h end-stage renal disease (ESRD), in part because it is excreted via the ki dneys. In this study, the plasma concentrations of ADMA, symmetric dimethyl arginine, and L-arginine were determined in relation to plasma nitrate leve ls las an index of NO formation) for a group of 80 patients with ESRD. The effects of two treatment methods, i.e., hemodialysis (HD) and peritoneal di alysis (PD), and the role of the presence of atherosclerotic disease were e valuated. Forty-three patients receiving HD and 37 patients receiving PD we re compared with healthy control subjects. Plasma L-arginine and dimethylar ginine levels were determined by HPLC, using precolumn derivatization with o-phthaldialdehyde. Plasma nitrate levels were determined by gas chromatogr aphy-mass spectrometry. Predialysis ADMA concentrations in I-ID-treated pat ients were approximately sixfold higher than these in the control group (6. 0 +/- 0.5 versus 1.0 +/- 0.1 mu moI/L; P < 0.05). Plasma nitrate concentrat ions were significantly lower in I-ID-treated patients, which suggests that ADR IA may inhibit NO synthase. In contrast, plasma ADMA levels and nitrat e concentrations in PD-treated patients were similar to those in control su bjects. Plasma L-arginine concentrations were not significantly decreased i n patients with ESRD. ADMA concentrations were significantly decreased 5 h after HD, compared with baseline values. ADMA levels were significantly hig her in HD-treated patients with manifest atherosclerotic disease than in I- ID-treated patients without atherosclerotic disease (7.31 +/- 0.70 versus 3 .95 +/- 0.52 mu mol/L; P < 0.05. This study confirms that ADMA is accumulat ed in ESRD, PD-treated patients exhibit significantly lower ADMA levels tha n do HD-treated patients. Accumulation of ADMA may be a risk factor for the development of endothelial dysfunction and cardiovascular disease in patie nts with ESRD.