Background/Aim: Endothelial dysfunction due to reduced nitric oxide (NO) availability precedes the development of atherosclerosis. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is not only a cause of endothelial dysfunction, but also a predictor of the cardiovascular outcome in end-stage renal disease (ESRD) patients on hemodialysis (HD). α-Lipoic acid (ALA), a strong antioxidant, increases NO-mediated vasodilation in diabetic patients. We investigated whether ALA could decrease the plasma level of ADMA in diabetic ESRD patients on HD. Methods: Fifty patients undergoing HD three times per week were randomized to a treatment group receiving ALA 600 mg/day for 12 weeks or a control group. We measured the plasma levels of cholesterol, albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A1c, and ADMA in both groups at baseline and at 12 weeks. Results: In the control group, the levels of total cholesterol, serum albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A1c, and ADMA did not change. In the treatment group, the plasma levels of ADMA decreased significantly from a median of 1.68 (range 0.45–3.78) µM to a median of 1.31 (range 0.25–3.19) µM (p = 0.001). Conclusion: Considering that ADMA is an independent risk factor for cardiovascular outcome in ESRD patients, ALA may have the potential of a beneficial effect in them, in part by decreasing the plasma level of ADMA.

1.
Comorbid conditions and correlations with mortality risk among 3,399 incident hemodialysis patients. Am J Kidney Dis 1992;20(5 Suppl 2):32–38.
2.
Cooke JP: Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000;20:2032–2037.
3.
Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, Imaizumi T: Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999;99:1141–1146.
4.
Xiong Y, Fu YF, Fu SH, Zhou HH: Elevated levels of the serum endogenous inhibitor of nitric oxide synthase and metabolic control in rats with streptozotocin-induced diabetes. J Cardiovasc Pharmacol 2003;42:191–196.
5.
Kielstein JT, Boger RH, Bode-Boger SM, Schaffer J, Barbey M, Koch KM, Frolich JC: Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol 1999;10:594–600.
6.
Zoccali C, Bode-Boger S, Mallamaci F, Benedetto F, Tripepi G, Malatino L, Cataliotti A, Bellanuova I, Fermo I, Frolich J, Boger R: Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 2001;358:2113–2117.
7.
Rosen P, Nawroth PP, King G, Moller W, Tritschler HJ, Packer L: The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a congress series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 2001;17:189–212.
8.
Terawaki H, Yoshimura K, Hasegawa T, Matsuyama Y, Negawa T, Yamada K, Matsushima M, Nakayama M, Hosoya T, Era S: Oxidative stress is enhanced in correlation with renal dysfunction: examination with the redox state of albumin. Kidney Int 2004;66:1988–1993.
9.
Descamps-Latscha B, Drueke T, Witko-Sarsat V: Dialysis-induced oxidative stress: biological aspects, clinical consequences, and therapy. Semin Dial 2001;14:193–199.
10.
Sydow K, Munzel T: ADMA and oxidative stress. Atheroscler Suppl 2003;4:41–51.
11.
Heitzer T, Finckh B, Albers S, Krohn K, Kohlschütter A, Meinertz T: Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Free Radic Biol Med 2001;31:53–61.
12.
Vallance P, Leone A, Calver A, Collier J, Moncada S: Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992;339:572–575.
13.
Masuda H, Goto M, Tamaoki S, Azuma H: Accelerated intimal hyperplasia and increased endogenous inhibitors for NO synthesis in rabbits with alloxan-induced hyperglycaemia. Br J Pharmacol 1999;126:211–218.
14.
Scalera F, Kielstein JT, Martens-Lobenhoffer J, Postel SC, Tager M, Bode-Boger SM: Erythropoietin increases asymmetric dimethylarginine in endothelial cells: role of dimethylarginine dimethylaminohydrolase. J Am Soc Nephrol. 2005;16:892–898.
15.
Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven GM, Cooke JP: Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002;106:987–992.
16.
Saran R, Novak JE, Desai A, Abdulhayoglu E, Warren JS, Bustami R, Handelman GJ, Barbato D, Weitzel W, D’Alecy LG, Rajagopalan S: Impact of vitamin E on plasma asymmetric dimethylarginine (ADMA) in chronic kidney disease (CKD): a pilot study. Nephrol Dial Transplant 2003;18:2415–2420.
17.
Zoccali C: Cardiovascular risk in uraemic patients – is it fully explained by classical risk factors? Nephrol Dial Transplant 2000;15:454–457.
18.
Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C: Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648–658.
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