Fig. 6.7. Transplant nephrectomy utilizing the intracapsular surgical technique.

mediately posttransplant. The rationale for using induction agents pertains to its potent anti-T-cell immunosuppressive properties. In this context, induction therapy is used in conjunction with maintenance agents for the purpose of minimizing the risks of early rejection episodes, often with aims to accelerate renal allograft function, and perhaps, even inducing a tolerogenic effect to donor allo-antigen.

This strategy of using induction therapy is most often applied to recipients at relatively "high risk" for rejection. Some recipient characteristics associated with a high risk of rejection include: HLA Class I antigen sensitization, elevated PRA status, re-transplantation, and African American race. In those settings, induction therapy is used to prevent or delay early acute rejection. Induction therapy is applied in other situations, as well. For example, for recipients receiving a kidney with delayed graft function, induction therapy is often used to "cover" the recipient with effective anti-T-cell therapy (using blocking or deleting agents), to delay the application of calcineurin inhibitors. This strategy serves to avoid the renal vasoconstrictive and injurious tubular effects that can occur with calcineurin inhibitors until adequate renal function occurs.

Another reason to use induction therapy is that it will provide a short course of potent immunosuppression that permits immediate and permanent elimination of one (or more) of the maintenance agents required posttransplant. This has been successfully used to immediately eliminate corticosteroid usage in kidney transplant recipients. The fourth context in which induction therapy is discussed relates to its theoretical "conditioning" effects to induce host immunological hyporesponsiveness (or tolerance) to alloantigen.

With respect to the use of induction therapy, it is estimated is that is is routinely used in approximately 50% of transplant centers for cadaveric kidney transplantation. There has not been any documented substantial effect of induction therapy on patient and graft survival rates. However, there is a significant difference in the incidence of rejection within the first six months posttransplant in recipients receiving anti-IL-2R induction agents with double or triple maintenance immuno-therapy with or without azathioprine. Of note is that the incidence of rejection the first six months has also been reduced with the application of the new agents, microemulsion cyclosporine or tacrolimus in combination with MMF or sirolimus, versus the old combinations involving standard cyclosporine and azathioprine.

Trends in induction therapy. Since 1995 the proportion of kidney transplant recipients receiving induction therapy has doubled from under 30% to approximately 60%. Figure 6.8 shows the number of recipients receiving the various types of induction agents by year of transplantation. OKT3 and equine antithymocyte globulin were the predominant induction agents used through 1997. After that there has been a marked shift to the use of the anti-interleukin 2 receptor antibodies (daclizumab and basiliximab) in 1998. In 2001, 26% of the 13,109 transplants for which information is available used basiliximab and 15% used daclizumab. Rabbit antithymocyte globulin began being incorporated in 1999. The use of this agent has grown rapidly to 18% of kidney transplants in 2001. OKT3 use has dropped to <1% of transplants, and equine antithymocyte globulin, which peaked in 1997, to 2%.

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