KINETIC BASIS OF HYPERHOMOCYSTEINEMIA IN PATIENTS WITH CHRONIC-RENAL-FAILURE

We investigated the elimination of total homocysteine (tHcy) from plas ma after peroral homocysteine (Hey) loading in eight patients with chr onic renal failure. Data on bioavailabilitv and distribution volume we re obtained from two patients and two healthy controls by performing b oth intravenous and peroral Hey loading. Response to high-dose folic a cid was studied in six cases. Mean (SD) basal plasma tHcy was 27.4 (11 .0) mu M at inclusion. The half-life and the area under the curve were about four times higher, and clearance was reduced to 29.8% compared to controls. High-dose folic acid had no influence on half-life for tH cy, but the basal tHcy level declined by 26.8%. The reduction in tHcy was particularly pronounced in three patients with low-normal serum fo late, and the enhanced methionine response to I-icy loading after foli c acid suggested improved Hey remethylation in tissues. In conclusion, patients with renal failure had markedly reduced clearance of tHcy fr om plasma, which probably accounts for their hyperhomocysteinemia. Hig h-dose folic acid reduces fasting tHcy by improving tissue Hcy remethy lation without affecting the low renal clearance of tHcy.