Impact of vitamin E on plasma asymmetric dimethylarginine (ADMA) in chronic kidney disease (CKD): a pilot study

Background. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase and a proposed cardiovascular risk factor, is elevated in chronic kidney disease (CKD). Pharmacological strategies that lower plasma concentration of ADMA may be expected to increase nitric oxide (NO� ) bioavailability and potentially limit atherosclerosis. We hypothesized that the antioxidant -tocopherol (vitamin E) reduces ADMA levels in CKD. Methods. An open-label pilot interventional study using 800 IU of vitamin E was undertaken in eight stable out-patients with non-diabetic CKD (creatinine clearance <30 ml/min/1.73 m 2 ) and six healthy controls, with the objective of measuring plasma ADMA levels at baseline and after 8 weeks of treatment. Plasma ADMA, symmetric dimethylarginine (SDMA) and -tocopherol concentrations were determined at study entry and exit using high-performance liquid chromatography, while plasma total F2-isoprostanes, an index of oxidative stress, were measured using a commercially available enzyme-linked immunosorbent assay kit. Results. ADMA and SDMA concentrations were significantly higher in the plasma of patients compared with that of controls (P � 0.001). After treatment with vitamin E, ADMA decreased by 23% in six of eight patients (P <0.001). The remaining two patients showed either an increase or no change (overall, P ¼ 0.16). There was no significant change in plasma F2-isoprostanes with vitamin E treatment for 8 weeks. Conclusions. Antioxidant therapy with vitamin E has the potential to lower ADMA levels in CKD patients,