Therapeutic approach to organ transplantation.

Renal transplantation is firmly established as the preferred treatment for many patients suffering from endstage renal disease. Nonetheless no absolute consensus has developed on how to achieve optimal immunosuppression, and many individual centres employing somewhat different protocols report excellent graft and patient survival. Immunological considerations, including antirejection therapy, are organized around a few general principles. The first consideration is careful patient preparation and, in the circumstance of living donor renal transplantation, selection of the best available ABO compatible, human leukocyte antigen (HLA) match in the event that several potential living related donors are available for organ donation. Second is a multitiered approach to immunosuppressive therapy similar in principle to that used in chemotherapy; several agents are used simultaneously, each of which is directed at a different molecular target within the allograft response (Figure 1, Table 1). Additive/synergistic effects are achieved through application of each agent at a relatively low dose, thereby limiting the toxicity of each individual agent while increasing the total immunosuppressive effect. Third is the principle that higher immunosuppressive drug doses and/or more individual immunosuppressive drugs are required to gain early engraftment and to treat established rejection than are needed to maintain immunosuppression in the long-term. Hence intensive induction and lower dose maintenance drug protocols are used. Fourth is careful investigation of each episode of post-transplant graft dysfunction, with the realization that most of the common causes of graft dysfunction, including rejection, can (and frequently do) coexist. Successful therapy therefore often involves several simultaneous therapeutic manoeuvres. Fifth, the appropriate reduction or withdrawal of an immunosuppressive drug when that drug's toxicity exceeds its therapeutic benefit.