NDT Advance Access originally published online on June 25, 2007
Nephrology Dialysis Transplantation 2007 22(11):3292-3297; doi:10.1093/ndt/gfm402
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Improvement of endothelial function in uraemic patients on peritoneal dialysis: a possible role for 5-MTHF administration
1Department of Internal Medicine, Nephrology and Dialysis Unit, Bassini Hospital, Cinisello Balsamo, Milan 2Department of Pharmacological Sciences, Center for the Study of Atherosclerosis, University of Milan, Milan, Italy
Correspondence and offprint requests to: Ivano Baragetti, Azienda Ospedaliera S. Gerardo, Presidio E. Bassini, Via Gorki 50, CAP: 20092, Cinisello Balsamo, Milan, Italy. Email: i.baragetti{at}bassini.hsgerardo.org
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Abstract |
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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.
Keywords: atherosclerosis; endothelial function; 5-methyltetrahydrofolate; plasma homocysteine; peritoneal dialysis
Received for publication: 13.12.06
Accepted in revised form: 29. 5.07
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