Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy

Background. Folic acid supplementation is only partially efficacious in correcting moderate elevation of plasma total homocysteine (tHcy) concentrations observed in hemodialysis (HD) patients. Experimental and clinical data have suggested that this partial efficacy may be due to impairment of folic acid metabolism to 5-methyltetrahydrofolate (MTHF) and of MTHF transmembrane transport as well. To bypass these difficulties, we assessed the efficacy of intravenous (i.v.) folinic acid, a ready precursor of MTHF, on reducing plasma tHcy concentrations in HD patients. Methods. In a cohort of 37 patients on intermittent HD treatment, plasma tHcy concentrations were determined before and during i.v. supplementation of folinic acid (50 mg once per week), together with i.v. pyridoxine (250 mg 3 times per week), to prevent vitamin deficiency, particularly in those treated by recombinant erythropoietin. Results. Folinic acid and pyridoxine i.v. supplementation was given for 11.2 +/- 2.45 months (range 7.5 to 17 months). The mean plasma tHcy levels decreased significantly from 37.3 +/- 5.8 mu M at baseline to 12.3 +/- 5.4 mu M on folinic acid treatment (P < 0.001). Moreover, 29 of the 37 patients (78%) had normal plasma tHcy levels at the end of follow-up (that is, <14.1 mu M. mean 9.8 mu M. range 6.2 to 13 mu M). No adverse effects attributable to folinic acid treatment were observed during this time. Conclusions. Intravenous folinic acid therapy (50 mg) once per week associated with pyridoxine supplementation appears to be an effective and safe strategy to normalize plasma tHcy levels in the majority of chronic HD patients.