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islet transplant trials, and the very low incidence of treated rejection episodes in islet recipients immunosuppressed with sirolimus and reduced-dose tacrolimus.

For recipients of an islet-after-kidney transplant procedure, there are special considerations for immunosuppression. Recipients that have a successful kidney transplant may be prescribed an immunosuppressive regimen that differs from the corticosteroid-free protocol described by the Edmonton group. Conversion of immunosuppression to the Edmonton protocol prior to islet transplantation may be necessary to improve results over those previously reported.60,71,72 In those three series, IAK recipients were continued on cyclosporine-based immunosuppression with an antimetabolite adjuvant. At the time of IAK, prednisone boluses were administered—typically 500-1000 mg of prednisolone, with or without an antibody induction agent. The detrimental effects of steroids, and the beneficial effects of induction therapy have been well documented in preclinical large animal models of islet transplantation.23 Therefore, modifications and consistent application of the newer immunosuppression approaches to islet transplantation may be needed to achieve insulin independence following IAK.

There are at least two situations that describe approaches to kidney transplant immunosuppression that have implications with respect to preparation for a subsequent IAK transplant. The first scenario includes renal transplant recipients with Type I diabetes that were initially prescribed a "conventional" immuno-suppression regimen including corticosteroids at the time of kidney transplantation prior to any consideration of an IAK procedure. A typical immunosuppression protocol might entail cyclosporine, azathioprine (or mycophenolate mofetil) and prednisone. This situation in which immunosuppression was initially prescribed in consideration of the kidney transplant only is referred to as a "casual approach" In this circumstance the patient would undergo immunotherapy conversion to that resembling the Edmonton protocol of tacrolimus and sirolimus without corticosteroids prior to the IAK transplant.

The second scenario includes renal transplant recipients with type I diabetes that are prescribed an immunosuppression regimen in which the corticosteroids are avoided or immediately rapidly eliminated following the kidney transplantation in anticipation of the subsequent islet transplant. This approach is referred to as "expectant immunosuppression." The combined use of tacrolimus and MMF with an IL-2 receptor antagonist allows corticosteroids to be withdrawn within 3 days of renal transplantation.73 The risk of a renal allograft rejection episode is approximately 13%, (85-90% of occurring within 3 weeks of transplantation), and 100% were reversible with appropriate anti-rejection therapy. One of the criticisms of steroid avoidance protocols is that the long-term results are not known. The long-term outcome of steroid avoidance was addressed by Birkeland.74 A 5-year follow-up of 100 kidney transplant recipients indicated that renal allograft survival was not compromised by omitting chronic steroid exposure.

The ability to coordinate the approach of renal transplant immunotherapy with subsequent medical conversion including possible corticosteroid withdrawal in preparation of the islet transplant requires that there is integration of the kidney and islet transplant programs. A functionally integrated program also assumes

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