Response of homocysteine, cystathionine, and methylmalonic acid to vitamin treatment in dialysis patients

Abstract

Background: Hyperhomocysteinemia is observed in >80% of hemodialysis patients and is considered a risk factor for cardiovascular disease. Vitamin treatment lowers total homocysteine (tHcy) concentrations in plasma and may therefore reduce the associated risk. Current treatment strategies have not achieved normalization of tHcy in the majority of dialysis patients. Methods: We administered folic acid (5 mg) plus vitamin B6 (50 mg) and B 12 (0.7 mg) intravenously to 38 hyperhomocysteinemic patients (tHcy >18 μmol/L) after each dialysis treatment. The treatment phase lasted 1 month, and serum concentrations of tHcy, methylmalonic acid (MMA), and cystathionine were measured at weeks 0, 2, 4, 6, 8, and 24. Results: The median serum tHcy concentration decreased significantly, from 26.1 μmol/L at baseline to 13.2 μmol/L at week 4. The median change in tHcy after 4 weeks was 13.4 μmol/L (-51%) compared with baseline. Serum MMA and cystathionine concentrations were reduced by 28% and 26%, respectively, but neither was normalized at 4 weeks. Backward-elimination stepwise regression analysis revealed that higher concentrations of tHcy, MMA, and cystathionine and lower folate at baseline predict changes of tHcy after treatment. Twenty weeks after vitamin withdrawal, tHcy concentrations returned to values comparable to baseline (median, 24.8 μmol/L). Conclusions: The combination of folic acid, vitamin B12, and vitamin B6 used in this study normalized serum concentrations of tHcy in almost all of our hyperhomocysteinemic dialysis patients. This regimen may be used to investigate the effects of homocysteine normalization on cardiovascular outcomes in hemodialysis patients. © 2005 American Association for Clinical Chemistry.