CORRELATION BETWEEN TOTAL HOMOCYSTEINE AND CYCLOSPORINE CONCENTRATIONS IN CARDIAC TRANSPLANT RECIPIENTS

Increased circulating total homocysteine (tHcy) has been implicated as an independent risk factor for atherosclerotic disease. In cardiac tr ansplant patients, accelerated coronary atherosclerosis is an importan t cause of late allograft failure; however, studies of tHcy in this at -risk group are limited. We sampled a cohort of 72 subjects 3.95 +/- 3 .14 (mean +/- SD) years after transplantation and found that all had t Hcy concentrations above our upper reference limit (15.0 mu mol/L). Th e mean tHcy in the transplant group (25.4 +/- 7.1 mu mol/L) was signif icantly greater than in our reference group (9.0 +/- 4.3 mu mol/L; n = 457; P <0.001). We also examined the effect of age, gender, time sinc e transplant, serum folate and cobalamin, total protein, urate, creati nine, albumin, and trough whole blood cyclosporine concentrations. In a multiple linear regression model, only creatinine (mean 144 +/- 52 m u mol/L; P = 0.021) and trough cyclosporine concentrations (191 +/- 16 3 mu g/L; P = 0.015) were independent positive predictors of tHcy, whe reas serum folate (8.35 +/- 7.43 nmol/L; P = 0.018) and time since tra nsplant (P = 0.049) were significant negative predictors. We conclude that hyperhomocysteinemia is a common characteristic of cardiac transp lant recipients. Our analysis suggests that folate and renal glomerula r dysfunction are important contributory factors; however, whole blood cyclosporine concentrations may also predict the degree of hyperhomoc ysteinemia in this population and therefore influence interpretation o f any apparent response to treatment.