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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 hemodialysis 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 micromol/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 supplemented 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.

Renal failure causes hyperhomocysteinemia, an important risk factor for cardiovascular disease and venous access thrombosis in end-stage renal disease (ESRD). Folic acid is necessary for homocysteine (Hcy) metabolism, and therapy with 1 mg/d or more of folic acid reduces plasma total Hcy (tHcy) concentrations in ESRD, although seldom to normal. In contrast to folic acid, the Hcy-lowering effect of vitamin B(12) has not been well studied in ESRD. We performed a prospective randomized controlled clinical trial involving 24 maintenance hemodialysis patients with normal or supranormal serum folate and vitamin B(12) concentrations who received either standard therapy, which included 5 to 6 mg folic acid, 5 to 10 mg pyridoxine, and 6 to 10 microg oral vitamin B(12) per day, or standard therapy plus 1 mg hydroxocobalamin administered subcutaneously once per week after dialysis. Plasma tHcy and serum methylmalonic acid (MMA) concentrations were measured before and after 8 and 16 weeks of continuous treatment. Hydroxocobalamin reduced plasma tHcy by an average of 32% (P <.005) and serum MMA by an average of 19% (P <.001). The Hcy-lowering effect of hydroxocobalamin was independent of baseline serum vitamin B(12), folic acid, and MMA concentrations. Patients with higher baseline plasma tHcy concentrations had the greatest response (r = 0.80; P <.002). These results show that parenteral hydroxocobalamin reduces plasma tHcy dramatically in vitamin B(12)-replete hemodialysis patients. Persons with considerable persisting hyperhomocysteinemia despite high-dose folic acid therapy are likely to respond to the addition of hydroxocobalamin, irrespective of their serum vitamin B(12) concentrations., (Copyright 2002, Elsevier Science (USA). All rights reserved.)