Homocysteine in uremia.
Hyperhomocysteinemia is an independent cardiovascular risk factor that possibly accounts for about one of 5 cardiovascular deaths. It is conceivable that the importance of hyperhomocysteinemia will increase when other risk factors, such as hypertension or hypercholesterolemia, will become less prevalent in the general population. In chronic renal failure (CRF), high plasma homocysteine levels are a common finding and in uremia almost the rule. However, a small subset of patients remains normohomocysteinemic. The cause of hyperhomocysteinemia in CRF, whether it lies in an impaired renal or extrarenal metabolism or through uremic retention toxins, is still under intensive scrutiny. As for the consequences of high homocysteine levels in the general population and in patients with CRF, these are many-fold and linked to the mechanism of homocysteine toxic action. In fact, homocysteine can be harmful to cells because (1) it evokes oxidative stress (through the production of reactive oxygen species), (2) binds to nitric oxide, (3) produces homocysteinylated proteins, or (4) leads to the accumulation of its precursor, S-adenosylhomocysteine, a potent inhibitor of biological transmethylations. Macromolecule hypomethylation is a common feature in CRF and uremia with possible functional consequences. Nutritional or pharmacologic interventions have been proposed in the treatment of hyperhomocysteinemia, while the results of large clinical trials designed to assess if lowering homocysteine levels is effective in reducing cardiovascular risk, are pending.
Perna
Alessandra F
AF
First Division of Nephrology/Department of Pediatrics, School of Medicine, Second University of Naples (SUN), Naples, Italy. alessandra.perna@unina2.it
Ingrosso
Diego
D
Lombardi
Cinzia
C
Cesare
Concetta Maria
CM
Acantora
Filomena
F
Satta
Ersilia
E
De Santo
Natale G
NG
D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology / Q000473:pathology; D014511:Uremia / Q000097:blood*
D006710:Homocysteine