Plasma reduced homocysteine and other aminothiol concentrations in patients with CKD

Background: Hyperhomocysteinemia, a risk factor for cardiovascular disease, is present in the majority of patients with chronic kidney disease (CKD). Several studies indicated that the moiety of homocysteine (Hcy) with an unbound -SH group (reduced Hcy [rHcy]) is the atherogenic molecule. This study is designed to examine the relation between different forms of Hcy and other aminothiols in hemodialysis (HD) patients, peritoneal dialysis (PD) patients, and nondialyzed patients with CKD. Methods: rHcy, free Hcy (fHcy), and total Hcy (tHcy), as well as different forms of cysteine, cysteinyl-glycine, and glutathione, were studied by using a high-performance liquid chromatography technique in 19 HD patients, 12 PD patients, 47 patients with CKD, and 15 control subjects. Results: In PD patients, tHcy levels were 2.8 times greater compared with controls, and in HD patients and those with CKD, 2.1 and 1.9 times greater, respectively. Mean rHcy/tHcy ratios were significantly greater in both HD (P < 0.05) and PD patients (P < 0.01), but did not differ in patients with CKD compared with controls. The decrease in rHcy levels during 1 HD treatment was smaller than that in tHcy and fHcy levels, and rHcy/tHcy ratio increased (before HD, 1.25% +/- 0.44%; after HD, 1.44% +/- 0.66%; P < 0.05). Conclusion: Levels of rHcy and other aminothiols are markedly increased in patients with impaired renal function. In dialysis patients, rHcy/tHcy ratio is markedly elevated and shows greater variability than in patients with CKD and controls. We conclude that because rHcy is believed to induce endothelial dysfunction and may be part of the accelerated atherogenic process in patients with CKD, plasma rHcy level could be a more relevant marker of cardiovascular disease risk than tHcy level.