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


METHODS
We examined the effect of oral treatment with 15 mg/daily of 5-methyltetrahydrofolate (5-MTHF) for 12 weeks, on homocysteinaemia and endothelial function in 19 patients undergoing peritoneal dialysis and compared them, for the same period of time, to a control group of patients on peritoneal dialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by the inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after sublingual administration of glyceryl trinitrate. Finally, oxidative stress was assessed by evaluating the conjugated dienes plasma levels.


RESULTS
Plasma homocysteine concentrations fell by 30% after oral treatment with 5-MTHF. Endothelial function improved significantly after oral 5-MTHF treatment (13.8 +/- 1.2% vs 11.4 +/- 1.4%; P < 0.02) while in the control group we observed a worsening of basal values from 12.1 +/- 2.66% to 8.7 +/- 2.90% (P < 0.02). The conjugated dienes plasma levels did not change either.


CONCLUSIONS
Our study demonstrated that 5-MTHF administration improves endothelial dysfunction in patients undergoing peritoneal dialysis. This effect appears to be independent of the reduction in homocysteine plasma levels.
Baragetti
Ivano
I
Department of Internal Medicine, Nephrology and Dialysis Unit, Bassini Hospital, Cinisello Balsamo, Milan, Italy. i.baragetti@bassini.hsgerardo.org
Raselli
Sara
S
Stucchi
Andrea
A
Terraneo
Veronica
V
Furiani
Silvia
S
Buzzi
Laura
L
Garlaschelli
Katia
K
Alberghini
Elena
E
Catapano
Alberico L
AL
Buccianti
Gherardo
G
D000368:Aged; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000628:therapy*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D013763:Tetrahydrofolates / Q000627:therapeutic use*; D014463:Ultrasonography; D014511:Uremia / Q000188:drug therapy / Q000628:therapy*; D014664:Vasodilation / Q000187:drug effects
D013763:Tetrahydrofolates; D006710:Homocysteine; D005492:Folic Acid; C005984:5-methyltetrahydrofolate