Homocysteine metabolism in renal failure.
OBJECTIVE
This review focuses on recent findings (June 2002-July 2003) on the topic of homocysteine, a sulfur amino acid associated with cardiovascular disease, and its metabolism in renal failure, a condition with a high prevalence of both hyperhomocysteinemia and cardiovascular disease.


RESULTS
A large meta-analysis of prospective studies in the general population established that hyperhomocysteinemia is a risk factor for cardiovascular disease. The results of intervention trials, once available, will also have to be tested in a meta-analysis, because of predicted problems with their statistical power. In kidney patients, intervention trials, still in the recruiting stage, target transplant patients, because of their unique characteristics related to folate responsiveness. As for the cause of hyperhomocysteinemia, new findings show that in humans, renal metabolic extraction depends on renal plasma flow in the post-absorptive state. Folate absorption or interconversion seems not to be affected. Riboflavin is a determinant of plasma homocysteine levels in uraemia. The consequences of hyperhomocysteinemia in uraemia are DNA hypomethylation and altered gene expression.


CONCLUSIONS
The causes of hyperhomocysteinemia in renal failure are still not clear. However, the possibilities include defective renal or extrarenal metabolism as a result of uraemic toxicity. Renal plasma flow is important in homocysteine renal metabolism. Among the consequences of hyperhomocysteinemia in renal failure are impaired protein and DNA methylation, with an alteration in the allelic expression of genes regulated through methylation. Intervention trials are under way to test whether hyperhomocysteinemia is causally related to cardiovascular disease in this patient population.
Perna
Alessandra F
AF
First Division of Nephrology/Department of Pediatrics, School of Medicine, Second University of Naples, Naples, Italy. alessandra.perna@unina2.it
Ingrosso
Diego
D
Satta
Ersilia
E
Lombardi
Cinzia
C
Acanfora
Filomena
F
De Santo
Natale G
NG
D019175:DNA Methylation; D006710:Homocysteine / Q000378:metabolism* / Q000652:urine; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism; D051437:Renal Insufficiency / Q000378:metabolism*
D006710:Homocysteine