Effect of folic acid supplementation on total homocysteine levels in hemodialysis patients

Hyperhomocysteinemia is an independent risk factor for cardiovascular mortality in ESRD, but about 80% of total homocysteine (tHcy) is bound to albumin (alb). We have tried, prospectively, to reduce tHcy levels by using folic acid (f.a.) and vitamin B6 (P.P.) supplementation. All patients on HD, not receiving f.a. or P.P. and all new patients, after their third month on HD, were supplemented with f.a. 5 mg/48 hours p.o and P.P. 40 mg/week. We determined folate, P.P. (RIA), vit. B12, KTV, residual renal function (KRU), PCRn, alb and tHcy levels (HPLC). 80 patients, age 62.6 +/- 13.6 years, time on HD 16.2 +/- 25.1 months, all dialysed with AN69 or PPMA, and bicarbonate, were included. The prevalence of hyperhomocysteinemia was 84.4%, and P.P. deficit was present in 32%, with folate in the low normal range. At the beginning of the study, before supplementation, tHcy was negatively correlating only with folate (r = -0.336) (p = 0.01), and not with P.P., vitamin B12, age, albumin, KTV, KRU or PCRn. 58 patients received six months of supplementation, with normalization of P.P. levels, a significant increase of folate (7.25; I.C = 95% confidence intervals: 6.45, 8.05 vs 61.29; I.C.: 44.47, 78.11) (p < 0.001), and decrease of tHcy (24.1; IC: 21.5, 26.3 vs 19.9; I.C: 17.5, 22.4) (p < 0.05). 33 patients have received 12 months of supplementation, but in spite of a continued increase of folate (100.78; I.C: 74.81, 126.74) (p < 0.001), only 3 have normal levels of tHcy; correlating directly tHcy with albumin (r = 0.56) (p = 0.001), that had increased compared to the beginning of the study (3.39; I.C. 3.29, 3.49 vs 3.50; I.C: 3.37, 3.63) (p < 0.05). After f.a. and P.P. supplementation, though initially tHcy is reduced, this response is short lived, and tHcy directly correlates with albumin levels. Good nutrition associated with HD adequacy, in absence of B vitamin deficits, seems to be the best determinant of tHcy levels rather than its removal by dialysis tHcy levels should be interpreted taking into account the serum albumin.