Clinical Nephrology - Epidemiology - Clinical Trials

Kidney International (1997) 52, 495–502; doi:10.1038/ki.1997.359

Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure

Anne B Guttormsen1, Per M Ueland1, Einar Svarstad1 and Helga Refsum1

1Department of Pharmacology, University of Bergen, and Department of Medicine, Haukeland University Hospital, Bergen, Norway

Correspondence: Dr Anne B Guttormsen, Department of Pharmacology, University of Bergen, Armauer Hansens Hus, 5021 Bergen, Norway. E-mail: Anne.Guttormsen@farm.uib.no

Received 31 December 1996; Revised 24 March 1997; Accepted 24 March 1997.

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Abstract

Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. 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.

Keywords:

chronic renal failure, folic acid, clearance, homocysteine, cardiovascular disease

Abbreviations:

Hcy, homocysteine; tHcy, total homocysteine; GFR, glomerular filtration rate; Vd, distribution volume; fHcy, free homocysteine; tCys, total cysteine; AUC, area under the curve

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