L John Hoffer1, Kelly M Elian. 1. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Que. l.hoffer@mcgill.ca
Abstract
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.
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.
Authors: Bradley L Urquhart; David J Freeman; Murray J Cutler; Rahul Mainra; J David Spence; Andrew A House Journal: Clin J Am Soc Nephrol Date: 2008-03-12 Impact factor: 8.237