5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis.
BACKGROUND
Hyperhomocysteinaemia is an independent risk factor for the development of atherosclerosis. In patients with chronic renal failure, the administration of folic acid or its metabolites reduces but does not normalize plasma homocysteine concentrations. Furthermore, homocysteine induces endothelial dysfunction by an increased inactivation of nitric oxide.


METHODS
We examined the effect of the active metabolite of folic acid, 5-methyltetrahydrofolate (5-MTHF), 45 mg/week i.v. for 10 weeks, combined during the last 2 weeks with vitamin B12, 500 microg s.c. twice weekly, on homocysteinaemia and endothelial function in 15 patients undergoing convective haemodialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after administration of isosorbide dinitrate. Finally, the presence of the thermolabile variant of methyltetrahydrofolate reductase (t-MTHFR) was assessed by genotype analysis.


RESULTS
Plasma homocysteine concentrations fell by 47% after treatment with 5-MTHF alone and by a further 13.6% after the addition of vitamin B12. The reduction was more marked in homo- and heterozygous patients than in normal genotypes for t-MTHFR. Flow-mediated endothelial vasodilation, measured by ultrasonography of the brachial artery, improved after administration of 5-MTHF (12.52+/- 2.47% vs. 7.03+/-1.65%; P<0.05), but there were no further changes following the addition of vitamin B12.


CONCLUSIONS
Our study demonstrated that 5-MTHF administration not only reduced plasma homocysteine but also improved endothelial function in uraemic patients undergoing convective haemodialysis.
Buccianti
Gherardo
G
Department of Internal Medicine, Nephrology and Dialysis Unit, Bassini Hospital, Cinisello Balsamo, Milan, Italy. ghbucci@hotmail.com
Raselli
Sara
S
Baragetti
Ivano
I
Bamonti
Fabrizia
F
Corghi
Enzo
E
Novembrino
Cristina
C
Patrosso
Cristina
C
Maggi
Franco M
FM
Catapano
Alberico L
AL
D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood; D006720:Homozygote; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013763:Tetrahydrofolates / Q000008:administration & dosage / Q000627:therapeutic use*; D014463:Ultrasonography; D014511:Uremia / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D014664:Vasodilation / Q000187:drug effects; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use
D013763:Tetrahydrofolates; D006710:Homocysteine; D014805:Vitamin B 12; C005984:5-methyltetrahydrofolate