title: Hydroxocobalamin reduces hyperhomocysteinemia in end-stage renal disease.
abstract: 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.
authors.affiliation: School of Dietetics and Human Nutrition, and the Lady Davis Institute for Medical Research, Jewish General Hospital, Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Elian
authors.forename: L John
authors.initials: LJ
authors.lastname: Hoffer
mesh_terms: D000368:Aged; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006879:Hydroxocobalamin / Q000008:administration & dosage*; D020138:Hyperhomocysteinemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12; D006879:Hydroxocobalamin