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protocol consisting of an IL-2R antagonist, a calcineurin inhibitor with MMF. In both studies acute rejection occurred relatively earlier in recipients rapidly withdrawn from steroids, but was eventually equivalent at 1-year posttransplant to either historical controls or a control cohort. Matas et al,18 reported short-term results of a renal transplant pilot study in which 51 recipients were given anti-thymocyte globulin induction, with CsA and MMF. Steroids were rapidly eliminated. Rejection rates were similar to controls with respect to frequency, timing and severity. Patient and graft survival rates were similar to historical controls. Birkeland has reported long-term results on 100 consecutive renal transplant recipients that received anti-thymocyte globulin induction, CsA and MMF with follow-up of 797-1052 days posttransplant.19 Four-year graft survival is 82% and a cumulative rate of rejection is only 13%. Thus, there appears to be an important distinction between the earlier protocols involving slow steroid withdrawal (weaning) and rapid steroid elimination (avoidance).

A recent prospective, randomized study compared outcomes in recipients treated with tacrolimus (no induction) in which steroids were either rapidly eliminated (1 week) or slowly withdrawn over months.20 The incidences of acute rejection in the first 6 months posttransplant in the rapid versus slow elimination treatment arms were 29% and 33%, respectively. Rejection occurring after stopping steroids occurred in 2 recipients in the rapid elimination group and 1 recipient in the slow taper group. Patient and graft survival rates and quality of renal allograft function were the same among treatment arms.

There is speculation why completely avoiding or rapidly eliminating steroids posttransplant does not pose a risk for rejection, and may actually be associated with a decreased rate long-term.21-23 Although glucocorticoids decrease cytokine production, the effect may be offset by upregulation of proinflammatory cytokine receptor expression on T-cells. Hypothetically, disruption of the cytokine/cytokine receptor milieu may tip the balance toward T-cell activation and explain the enhanced susceptibility towards late rejection and graft loss in recipients in whom steroids are weaned off as opposed to the situation in which corticosteroids are essentially avoided. Therefore, as corticosteroids are slowly tapered the upregulation of cytokine receptor expression and proliferative capacity may create an immu-nological potential for enhanced T-cell effector function that could ensue once corticosteroid exposure falls below an individual's immunosuppression "threshold."

The alloimmune risk of graft loss in solid organ transplantation has been largely solved by application of the modern maintenance immunosuppressive agents, yet transplant recipient wellness is plagued by steroid-associated side-effects such as bone disease, cosmetic disfiguration, cataracts, gastric ulcers, increased cardiac risks, etc. The recent studies have demonstrated the feasibility of applying a prospective and flexible approach to rapid corticosteroid elimination in transplantation that gives all recipients an opportunity to have steroids permanently excluded from the maintenance immunosuppression regimen. This approach does not appear to be associated with an increased risk of rejection or graft loss in the short-or long-term.

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