Impact of new immunosuppressive agents on late graft outcome.

Several new immunosuppressive agents have recently been launched for clinical use after kidney transplantation. FK506 or tacrolimus (Prograf) has been tested as an alternative for cyclosporine A (CsA). Both tacrolimus and CsA interfere with the early stage of lymphocyte proliferation by blocking interleukin-2 synthesis. Mycophenolate mofetil (MMF) (Cell-Cept) blocks the de novo synthesis of guanine nucleotides, the pathway essential for purine synthesis in dividing T- and B-lymphocytes, and has been used in conjunction with CsA and corticosteroids. In several prospective randomized trials a significant reduction in the incidence of acute rejection has been shown. As early acute rejection and especially recurrent acute rejection, is one of the most important risk factors for chronic rejection and late graft loss, there is a growing interest in the potential beneficial effect of these drugs on the late graft survival. In the European MMF trial, a further reduction of the late graft loss after one year is seen for patients treated with 2 g MMF. A retrospective comparison of international registry data has also shown a significant increase in the graft half-life of patients receiving tacrolimus compared with CsA treated patients. Taking into account the still limited follow-up of the available trials and the fact they were not primarily designed with adequate statistical benefits of these new drugs on the late graft outcome must be made with caution.