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Background: End-stage renal disease (ESRD) is associated with moderately severe hyperhomocysteinemia that is incompletely normalized by oral folic acid therapy and vitamin B12. Method: We administered 1 mg hydroxocobalamin parenterally at 14-day intervals to vitamin B12--replete hemo-dialysis patients who were already consuming 6 mg folic acid daily by mouth. Plasma total homocysteine (tHcy), serum folate, vitamin B12 and methylmalonate were measured immediately before and after 4 and 8 weeks of therapy. Results: Serum folate concentrations were consistently over 25 times the upper normal limit. Hydroxocobalamin therapy increased serum vitamin B12 concentrations 14-fold (p < 0.001) and reduced plasma tHcy by 23% from 29.7 ± 2.9 to 22.8 ± 2.5 µmol/L (p < 0.01); serum methylmalonate decreased by one-third (p < 0.05). Conclusions: These results demonstrate the Hcy-lowering potential of parenteral vitamin B12 in folic acid supple-mented vitamin B12--replete hemodialysis patients, and indicate the need for formal dose-optimization studies of this simple, inexpensive and promising approach to Hcy reduction in end-stage renal disease. [ABSTRACT FROM AUTHOR]