Folic Acid Treatment of Hyperhomocysteinemia in Peritoneal Dialysis Patients: No Change in Endothelial Function after Long Term Therapy

Abstract

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-Iowering therapy with folic acid, in peritoneal dialysis (PO) patients.

Patients and Design

Thirty PO 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.

Measurements

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) μmol/L. Only 1 patient (3%) had a normal plasma homocysteine (i.e., ≤ 15 μmol/L) before therapy. Normalization of plasma homocysteine occurred in 39% of the patients at 12 weeks. Betaine had no additional homocysteine-Iowering 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.