Plasma homocysteine levels in renal transplanted patients on cyclosporine or tacrolimus therapy: effect of treatment with folic acid

Abstract

Hyperhomocysteinemia, an independent risk cardiovascular factor, has been reported in renal transplanted patients (RTP). The aim of the present study was to evaluate homocysteine levels in RTP treated with cyclosporine or tacrolimus, and the changes observed in the two groups of patients after treatment with folic acid. Forty-two RTP with stable function (21 treated with cyclosporine and 21 with tacrolimus, matched by gender and age) were studied. Forty healthy control subjects were matched by age and gender with the patients. In RTP, homocysteine was increased compared with the controls (16.4 +/-5.2 vs 8.0 +/- 1.8 micromol/L; p < 0.001), but there was no difference in vitamin B12 and folic acid levels. Thirty-three patients and one control showed hyperhomocysteinemia (78.5 vs 2.5%; p < 0.001). Homocysteine correlated negatively with creatinine clearance in the patients (p = 0.04), but no correlation was found with vitamin B12, folic acid and lipoproteins. By univariate analysis, patients treated with cyclosporine had higher homocysteine than those treated with tacrolimus (p = 0.03), but multivariate analysis did not confirm these results. In 21 patients with hyperhomocysteinemia and folate levels similar to those of the controls, folic acid (5 mg/d for 3 months) was administered. Homocysteine decreased significantly (19.1 +/- 4.8 vs 13.2 +/- 3.4 micromol/L; p < 0.001), with a median reduction of 31% and with no differences observed in patients treated with either cyclosporine or tacrolimus. We concluded that hyperhomocysteinemia is very frequent in RTP, but homocysteine levels are not different in patients treated with cyclosporine or tacrolimus. Folic acid therapy produces a significant decrease in homocysteine concentrations, in the absence of clear folate deficiency, without differences in relation to immunosuppressant therapy.

Plasma total homocysteine and cardiovascular risk in patients submitted to liver transplantation

“…Mildly elevated Hcy is frequently associated to nutritional abnormalities (pyridoxal phosphate, folate, and/or cyanocobalamin deficiency) and/or to pathological conditions, namely kidney failure, or to the use of some classes of drugs, including calcineurin inhibitors 10. CyA, as well as other calcineurin inhibitors, are known to interfere with the folate‐dependent remethylation of homocysteine to methionine,10, 33 but conflicting data have been reported on the relation between folate and Hcy in renal transplant patients 10, 28, 30, 34. In the present series, nutritional defects were not clinically apparent, thus making a role of folate deficiency unlike.…”

Therapeutic potential of total homocysteine-lowering drugs on cardiovascular disease

“…In a recent Austrian-US-American study, the use of cyclosporin A was not associated with increased tHcy plasma levels [112]. There was also no difference in the effect of folic acid on tHcy levels in patients treated with cyclosporin A or tacrolimus in the study of Fernandez-Miranda et al [113]. An in vitro study also showed that cyclosporin A has no effect on tHcy export from human proximal tubule epithelial cells [114].…”

The association of homocysteine and coronary artery disease

“…[34][35][36][37] Immunosuppressive medications such as azathioprine, prednisone, and tacrolimas do not appear to affect Hcy in either cardiac or renal transplant patients. 33,38,39 Cyclosporin is associated with elevated Hcy in heart transplants, but the data in renal transplants are conflicting. 33-35, 40, 41 Certain demographic features are associated with elevated Hcy concentrations.…”