Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure

We investigated the elimination of total homocysteine (tHcy) from plasma after peroral homocysteine (Hey) loading in eight patients with chronic renal failure. Data on bioavailabilitv and distribution volume were obtained from two patients and two healthy controls by performing both intravenous and peroral Hey loading. Response to high-dose folic acid 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 tHcy, but the basal tHcy level declined by 26.8%. The reduction in tHcy was particularly pronounced in three patients with low-normal serum folate, and the enhanced methionine response to I-icy loading after folic acid suggested improved Hey remethylation in tissues. In conclusion, patients with renal failure had markedly reduced clearance of tHcy from plasma, which probably accounts for their hyperhomocysteinemia. High-dose folic acid reduces fasting tHcy by improving tissue Hcy remethylation without affecting the low renal clearance of tHcy.