KIDNEY-TRANSPLANT IMMUNOSUPPRESSANTS OF TODAY .1. FROM THE IMMUNE-RESPONSE TO THERAPEUTIC APPLICATION

End-stage kidney failure is a devastating medical, social and economic al problem. With the significant improvements in diagnostic and therap eutic modalities, there has been little doubt that a functioning renal allograft is the optimum renal replacement therapy. A 1-year graft su rvival rate has increased to 90% for living related and 85% for cadave ric donors. Furthermore, a successful renal allograft is much more cos t effective than dialysis. A persisting high rate of chronic allograft loss, significant side effects and complications due to chronic immun osuppression are the major stumbling blocks to increasing the long-ter m success rate of renal transplantation. Moreover, withdrawal of immun osuppressive agents increases the risk of late graft loss due to rejec tion. There is no treatment for chronic rejection, which is the most c ommon cause of late graft loss. Therefore, a continued goal in organ t ransplantation is the development of newer immunosuppressive regimens that are associated with fewer side effects and decreased rates of lat e rejection, and that promote graft tolerance. This review focuses on the immunosuppressive agents in current use to facilitate the acceptan ce of kidney allografts and improve longterm graft function. The first part of this review is intended to orient the reader with the immunol ogical basis of the host response to a foreign allograft and the relev ant therapeutic applications. After recognition of the foreign human l eukocyte antigen present on the allograft, the host T-helper cell is a ctivated to produce a variety of cytokines necessary for stimulation o f the host cytotoxic T- and B-lymphocytes. The activated cytotoxic T- and B-lymphocytes are the effector cells by which graft rejection occu rs. Clinically, graft rejection can be immediate, acute or chronic. St rategies developed to prevent allograft rejection include blocking rec ognition of the allograft, inhibition of T-helper cell activation and inhibition of cytotoxic T- and B-lymphocyte functions. Immunosuppressi ve regimens capable of selectively inhibiting the immune response agai nst the allograft and sparing other immune responses are not yet avail able. An optimum immunosuppressive regimen should have no or limited l ong-term side effects and enhance allograft tolerance.