Other side effects associated with tacrolimus were a greater incidence of deep venous thrombophlebitis and neurotoxicity. There was no difference in the incidence of nephrotoxicity or hypertension between cyclosporine and tacrolimus. A significant benefit of tacrolimus therapy was a marked decrease in the incidence of hyperlipidemia. The results of this study, although showing no differences in patient and graft survivals, suggested that tacrolimus was superior in reducing the incidence of acute rejection and antilymphocyte therapy in kidney transplant recipients. The introduction of these three agents in clinical transplantation increases the available options for post-transplant immunosuppression.
Several questions remain to be answered.
The first is whether the increased efficacy of these agents will allow discontinuation of corticosteroids. There is near universal agreement in the transplant community that corticosteroids, although a mainstay of immunosuppression for decades, cause the greatest long-term morbidity for transplant recipients. Similarly, the introduction of mycophenolate mofetil may allow reduction in cyclosporine or tacrolimus usage, both of which can cause long-term nephrotoxicity. Finally, the role of combination therapy with mycophenolate mofetil and tacrolimus remains to be defined. A recent study from The University of Miami suggests that the AUC for mycophenolic acid may be increased when used in combination with tacrolimus, which could result in increased toxicity.