Cyclosporine vs. tacrolimus immunosuppression does not effect plasma homocysteine levels in cardiac transplant recipients

Abstract

Introduction: Elevated plasma levels of homocysteine have been associated with hypercoagulability, myocardial infarction, cerebral and peripheral vascular disease, and increased mortality in patients with known coronary artery disease. In cardiac transplant recipients and in murine models, elevated plasma levels of homocysteine have been linked to accelerated transplant coronary artery disease. An association has been suggested between the type of calcineurin inhibitor (cyclosporine or tacrolimus) used for immunosuppression and plasma levels of homocysteine following non-cardiac solid organ transplantation, specifically that cyclosporine use may lead to higher homocysteine levels. Our hypothesis was that cardiac transplant recipients taking cyclosporine would have higher levels of plasma homocysteine than those taking tacrolimus. Methods: We conducted a retrospective review of 68 adult cardiac transplant recipients with available homocysteine levels. Homocysteine levels were compared between patients taking cyclosporine versus tacrolimus both with and without correction for renal function, multivitamin use, and B-12/folate supplementation. Results: 17 patients were on tacrolimus and 51 on cyclosporine immunosuppression, and patients were an average of 63 months post-transplant. Average patient age was 59, and 57 (84%) patients were male. Average homocysteine levels were 16.1 μmol/L and 15.4 μmol/L in the tacrolimus and cyclosporine groups respectively (p=0.66). In a multivariate analysis, controlling for multivitamin use, vitamin B-12/folate supplementation, and renal function did not change the above association. The only significant association observed was a direct effect of serum creatinine on homocysteine levels, with higher serum creatinine being associated with higher levels of homocysteine in both groups (p=<0.001). Conclusion: Cyclosporine vs. tacrolimus immunosuppression does not have a significant effect on plasma homocysteine levels in this group of adult cardiac transplant recipients. The choice of immunosppressant agent should therefore be made based on clinical factors other than the effects of the drug on plasma homocysteine levels. Elevated serum creatinine appears to be the strongest risk factor for elevation of plasma homocysteine in cardiac transplant recipients.