Therapy of Hyperhomocysteinemia in Hemodialysis Patients: Effects of Folates and N-Acetylcysteine

Objective: Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients. Design: The study is an open, parallel, intervention study. Setting: Ambulatory chronic hemodialysis patients. Subjects: Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50). Intervention: One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47). Main Outcome Measure: Plasma homocysteine measured before and after dialysis at the first and the last treatment. Results: At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 +/- 0.94 mu mol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 +/- 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level <12 mu mol/L, compared with 19% in the MTHF group and 16% in the control group. Conclusions: NAC therapy induces a significant additional decrease in homocysteine removal during dialysis. The advantage is limited to the time of administration. (c) 2012 by the National Kidney Foundation, Inc. All rights reserved.