IMMUNOSUPPRESSION IN RENAL-TRANSPLANTATION - CURRENT STATUS AND PROSPECTS

Introduction of cyclosporin A has markedly improved the results of renal transplantation. Currently, nearly all immunosuppression regimens are cyclosporin-based. To avoid cyclosporin-associated nephrotoxicity and to reduce undesirable side effects of other immunosuppressive drugs a variety of treatment strategies has been developed ranging from cyclosporin monotherapy to triple therapy or to later conversion to azathioprine. FK 506 is a promising new immunosuppressant that has properties similar to cyclosporin. Its definite value for renal transplanation is under evaluation. A number of new immunosuppressive agents has been developed with molecular mechanisms of action that are different from cyclosporin A. Rapamycine blocks the transduction of the interleukin 2/IL-2 receptor signal. Antiproliferative drugs such as RS-61443 and brequinar may inhibit lymphocytic DNA synthesis more effectively than does azathioprine. 15-Deoxyspergualin suppresses macrophage function, inhibits lymphocyte clonal expansion and suppresses antibody production by B cells. A large array of new monoclonal antibodies has been developed, that can be used in prophylaxis and treatment of acute rejection. Murine monoclonal antibodies of the IgA class specifically directed at the CD3 molecular complex may have fewer side effects than OKT 3. Other antibodies directed at the T cell receptor, at the IL-2 receptor or at adhesion molecules are being evaluated, but as yet, their future impact on the success rate of renal transplanation is uncertain.