Semin Thromb Hemost 2000; Volume 26(Number 03): 313-324
DOI: 10.1055/s-2000-8407
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Homocysteine and Renal Disease

  • 1Department of Internal Medicine, University Hospital and Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands
  • 2Department of Medicine/Cardiology, Wake Forest University, Winston Salem, North Carolina
Further Information

Publication History

Publication Date:
31 December 2000 (online)


Hyperhomocysteinemia refers to an elevated circulating level of the sulfur-containing amino acid homocysteine and has been shown to be a risk factor for vascular disease in the general population. In patients with renal failure, hyperhomocysteinemia is a common feature. The underlying pathophysiological mechanism for this phenomenon is unknown. Proposed mechanisms include reduced renal elimination of homocysteine and impaired nonrenal disposal, possibly because of inhibition of crucial enzymes in the methionine-homocysteine metabolism by the uremic milieu. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Several case-control and prospective studies have now indicated that hyperhomocystenemia is an independent risk factor for atherothrombotic disease in patients with predialysis and end-stage renal disease. In renal patients, plasma homocysteine concentration can be reduced by administration of folic acid in doses ranging from 1 to 15 mg per day. In more than 50% of the cases, however, the homocysteine concentration remains above 15 μmol/L. The effects of vitamin B12 or vitamin B6 are unclear. Large intervention trials are now needed to establish whether homocysteine-lowering therapy will reduce athero-thrombotic events in patients with renal failure. These studies are now planned or are ongoing.