Folic acid treatment of hyperhomocysteinemia in peritoneal dialysis patients: no change in endothelial function after long-term therapy.
BACKGROUND
Hyperhomocysteinemia occurs in renal failure and may increase the risk for cardiovascular disease, possibly by damaging the endothelium. Folic acid and betaine are required in two separate homocysteine conversion pathways and may therefore lower plasma homocysteine.


OBJECTIVE
To study the therapeutic role of betaine and the effect on endothelial function of long-term homocysteine-lowering therapy with folic acid, in peritoneal dialysis (PD) patients.


METHODS
Thirty PD patients were randomized to a 12-week treatment with 5 mg folic acid and 4 g betaine daily, or to 5 mg folic acid alone daily. They were then rerandomized to treatment with 1 or 5 mg folic acid daily for 40 weeks.


METHODS
At baseline and after 52 weeks, endothelial function was assessed by determination of endothelium-dependent vasodilatation and biochemical markers.


RESULTS
Plasma total homocysteine (tHcy) was elevated at baseline: 42.6 (5.8) micromol/L. Only 1 patient (3%) had a normal plasma homocysteine (i.e., < or = 15 micromol/L) before therapy. Normalization of plasma homocysteine occurred in 39% of the patients at 12 weeks. Betaine had no additional homocysteine-lowering effect. Plasma tHcy levels were similar during treatment with 1 or 5 mg folic acid daily. Endothelial function was impaired at baseline and had not improved after 52 weeks of treatment.


CONCLUSIONS
Peritoneal dialysis patients have hyperhomocysteinemia, which can be normalized with folic acid alone in about 40% of patients. Betaine does not further lower plasma homocysteine. A maintenance dose of 1 or 5 mg folic acid daily results in equivalent plasma homocysteine levels. Long-term reduction in plasma homocysteine did not result in improvement of endothelial function as assessed by our methods.
van Guldener
C
C
Department of Nephrology, University Hospital and Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.
Janssen
M J
MJ
Lambert
J
J
ter Wee
P M
PM
Donker
A J
AJ
Stehouwer
C D
CD
D001622:Betaine / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D013997:Time Factors
D006397:Hematinics; D006710:Homocysteine; D001622:Betaine; D005492:Folic Acid