The kidney and homocysteine metabolism

A. N. Friedman, A. G. Bostom, J. Selhub, A. S. Levey, I. H. Rosenberg

Research output: Contribution to journalReview article

204 Scopus citations


Homocysteine (Hcy) is an intermediate of methionine metabolism that, at elevated levels, is an independent risk factor for vascular disease and atherothrombosis. Patients with renal disease, who exhibit unusually high rates of cardiovascular morbidity and death, tend to be hyperhomocysteinemic, particularly as renal function declines. This observation and the inverse relationship between Hcy levels and GFR implicate the kidney as an important participant in Hcy handling. The normal kidney plays a major role in plasma amino acid clearance and metabolism. The existence in the kidney of specific Hcy uptake mechanisms and Hcy-metabolizing enzymes suggests that this role extends to Hcy. Dietary protein intake may affect renal Hcy handling and should be considered when measuring Hcy plasma flux and renal clearance. The underlying cause of hyperhomocysteinemia in renal disease is not entirely understood but seems to involve reduced clearance of plasma Hcy. This reduction may be attributable to defective renal clearance and/or extrarenal clearance and metabolism, the latter possibly resulting from retained uremic inhibitory substances. Although the currently available evidence is not conclusive, it seems more likely that a reduction in renal Hcy clearance and metabolism is the cause of the hyperhomocysteinemic state. Efforts to resolve this important issue will advance the search for effective Hcy-lowering therapies in patients with renal disease.

Original languageEnglish (US)
Pages (from-to)2181-2189
Number of pages9
JournalJournal of the American Society of Nephrology
Issue number10
StatePublished - Oct 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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    Friedman, A. N., Bostom, A. G., Selhub, J., Levey, A. S., & Rosenberg, I. H. (2001). The kidney and homocysteine metabolism. Journal of the American Society of Nephrology, 12(10), 2181-2189.