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

Hyperhomocysteinemia is an independent risk factor for cardiovascular morta lity in ESRD, but about 80% of total homocysteine (tHcy) is bound to albumi n (alb). We have tried, prospectively, to reduce tHcy levels by using folic acid (f.a.) and vitamin B-6 (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. B-12, KTV, residual renal function (KRU), PCRn, alb and tHcy levels (HPLC). 80 patients, age 62.6 +/- 73.6 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%, wit h folate in the low normal range. At the beginning of the study, before sup plementation, tHcy was negatively correlating only with folate (r = -0.336) (p = 0.01), and not with P.P., vitamin B-12, age, albumin, KTV, KRU or PCR n. 58 patients received six months of supplementation, with normalization of P .P. levels, a significant increase of folate (7.25; I.C = 95% confidence in tervols: 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 c ontinued 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). Conclusion: After f.a. and P.P. supplementation, though initially tHcy is r educed, this response is short lived, and tHcy directly correlates with alb umin levels. Good nutrition associated with HD adequacy, in absence of B vi tamin deficits, seems to be the best determinant of tHcy levels rather than its removal by dialysis tHcy levels should be interpreted Taking into acco unt the serum albumin.