Sustained reduction of hyperhomocysteinaemia with folic acid supplementation in predialysis patients

Background. Moderate hyperhomocysteinaemia, as occurs in chronic renal failure patients, is an established independent risk factor for atherosclerotic arterial occlusive accidents, the incidence of which is abnormally high in such patients. Folic acid supplementation has been shown to reduce plasma homocysteine level in end-stage renal disease patients treated with haemodialysis or peritoneal dialysis, but its long-term effects in predialysis patients had not been assessed. Methods. We prospectively treated a total of 78 predialysis patients with folic acid for at least 1 year (range 12-74 months) together with oral pyridoxine and vitamin B12 supplements. Of the patients, 67 received 5 mg folic acid three times per week, whereas the other 11 patients who were treated with recombinant erythropoietin received 5 mg/day. Plasma fasting total homocysteine concentration was determined at baseline, after 3 months and at the end of follow-up. Results. Mean (±SD) plasma total homocysteine level decreased from 21.2±6.4 μmol/l at baseline to 14.2±4.6 at 3 months and remained at 12.8±3.7 μmol/l at the end of follow-up (average duration 2.8 years), whereas plasma creatinine rose from 268±129 to 399±234 μmol/l. Mean plasma folate concentration rose from 19±12 to 47±13 nmol/l and mean plasma vitamin B12 rose from 237±119 to 347±191 pmol/l from baseline to end of follow-up. Conclusions. Moderate folic acid supplementation (2.15 mg/day) allows a substantial (40% as a mean) and sustained (up to 6 years) reduction of plasma total homocysteine level in predialysis uraemic patients without any detectable side effect. Folic acid supplementation may thus contribute to lower the risk of accelerated atherosclerosis in such patients.