Homocysteine metabolism in renal failure

Of the many amino acid abnormalities that are present in chronic renal fail ure, hyperhomocysteinemia has drawn increasing attention because of its pro posed role in the development and/or progression of atherothrombotic diseas e. Renal function is a major determinant of fasting plasma homocysteine lev el, and the inverse relationship between the glomerular filtration rate (GF R) and plasma homocysteine level is present throughout the whole range of r enal function. Although this suggests an active renal homocysteine metaboli sm, no important urinary excretion or active homocysteine extraction has be en demonstrated in the human kidney. Analysis of plasma concentrations of t he various cofactors and substrates of homocysteine metabolism, and the eff ects of different therapies indicate that an abnormal folate metabolism may be the cause of hyperhomocysteinemia in uremia. This is further supported by the finding that homocysteine remethylation, as assessed by stable isoto pe techniques, is impaired in dialysis patients. It is unclear whether decr eased remethylation is also responsible for other abnormalities of homocyst eine metabolism in renal failure such as the exaggerated rise and the impai red decline of plasma homocysteine concentration after methionine or homocy steine loading. More studies are necessary to pinpoint the precise mechanis ms that lead to hyperhomocysteinemia in renal failure. This should lead to optimal treatment and, ultimately, to the prevention of cardiovascular comp lications in this vulnerable patient group.