Treatment with high-dose folic acid effectively lowers plasma homocysteine concentration in cyclosporine-treated renal transplant recipients.

Abstract

Hyperhomocysteinemia is by now an established risk factor for the development of atherosclerosis (1). Homocysteine can be effectively lowered by a safe and inexpensive agent, folic acid (2). Such treatment may reduce the incidence of atherosclerotic complications. The hyperhomocysteinemia, frequently observed in renal transplant recipients (3, 4), might be associated with the increased mortality in coronary artery disease in this group of patients (5). We recently reported data on plasma concentrations of total homocysteine (tHcy) in cyclosporine-treated renal transplant recipients (4). These patients had significantly higher tHcy than both renal transplant recipients not treated with cyclosporine, and patients without a renal graft but matched for glomerular filtration rate. Furthermore, the usual inverse correlation between tHcy and blood folate concentrations was absent in the cyclosporine-treated group. Thus, the results indicated that treatment with cyclosporine induces an increase in tHcy, possibly due to interference with the folatemediated remethylation of homocysteine. Consequently, the question arose of whether the hyperhomocysteinemia of cyclosporine-treated patients responds to treatment with folic acid. We have now studied the effect of folic acid treatment in nine cyclosporine-treated renal transplant recipients with normal levels of serum cobalamines. Blood samples for analysis of tHcy and blood folate concentrations were collected three times; the first two samples were taken before treatment, with an interval of 2 months, and the last sample was collected after the administration of 5 mg of folic acid daily for 2 months. The results are shown in Table 1. A decrease in tHcy to normal levels was observed in all study participants, ranging from 12% to 57%. The median relative reduction was 28%. In conclusion, the interference with homocysteine removal in cyclosporine-treated renal transplant recipients can be overcome by high-dose treatment with folic acid. Margret Arnadottir1,2, Björn Hultberg3 Department of Medicine; National University Hospital; Reykjavik, Iceland; Department of Clinical Chemistry; University Hospital of Lund; Lund, Sweden