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Abstract
We investigated the elimination of total homocysteine (tHcy) from plasma after peroral
homocysteine (Hcy) loading in eight patients with chronic renal failure. Data on bioavailability
and distribution volume were obtained from two patients and two healthy controls by
performing both intravenous and peroral Hcy loading. Response to high-dose folic acid
was studied in six cases. Mean (SD) basal plasma tHcy was 27.4 (11.0) microM 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 Hcy loading after folic acid suggested improved Hcy
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.