New immunosuppressive drugs for prevention and treatment of rejection in renal transplant.

Rejection prevention and control have been pivotal aims of medical research since the time that renal transplant was first developed. While acute rejection rates have generally fallen to 10%-15% at 1 year, chronic rejection and chronic allograft nephropathy (CAN) still erode long-term transplant potential. Furthermore, drug tolerability and their 'secondary' effects other than immunosuppression have become as important as their effectiveness in a recipient population that is increasingly old and burdened by cardiovascular morbidity. We review the state of the art of new immunosuppressive drugs: some of them have already entered clinical practice (e.g., mycophenolate mofetil, anti-CD25 monoclonal antibodies and sirolimus [SRL]); others are at different stages of the pre-registration phase (everolimus, mycophenolic acid, FTY 720, leflunomide-FK 778 and Campath-1H), and many others show promising potential for the future (rituximab, monoclonal antibodies against costimulatory molecules). Especially, new drugs with antiproliferative and antifibrogenic effects (SRL, everolimus, leflunomide and mycophenolic acid) could to be decisive in still challenging areas such as CAN and cardiovascular and neoplastic transplant complications. The key to solving these open issues probably lies in the possibility of relying on a wide repertoire of drugs with different profiles, to be exploited in several associations, and in our capacity to integrate new and old immunosuppressive drugs.