An ideal nondiabetogenic, nonnephrotoxic immunosuppressive protocols for pancreas transplantation

Calcineurins and steroids have been the foundation in immunosuppression regimens for pancreas transplants since the introduction of the procedure. Although steroids have several side effects such as hypertension, osteoporosis, and gastric ulcerations while calcineurins can cause hyperglycemia, hirsutism, and hyperlipidemia, these immunosuppressive regimens in combination have resulted in a significant reduction in acute rejection rates. In recent reports, steroid withdrawal or avoidance in kidney transplantation has been associated with excellent rejection-free graft survival, particularly when induction therapy is used. Although there is no clear evidence of the ability of steroid-free protocols in pancreas transplants to achieve success, early results in pancreas kidney patients are extremely encouraging. With more studies, the use of nontoxic immunosuppressants will be possible and will result in further improvement in patients' quality of life after pancreas transplantation. For many years, pancreas transplantation results have lagged behind those of other solid organ transplants, particularly for pancreas alone and pancreas after kidney recipients. This was related to an increased graft loss following pancreatic transplantation, secondary to a high technical failure rate and an increased incidence of loss to acute rejection. Consequently, immunosuppressive and surveillance strategies that target the increased rejection rates evolved over the years and emphasized combinations of immunosuppressants, mandatory induction therapy, and reluctance for withdrawal of immunosuppressants in long-term care. [1] More recently, with improvements in preservation, donor selection criteria, and technical aspects of the procedure, graft failure rates have been reduced substantially. In addition, the introduction of antithymocyte globulin (Thymoglobulin, Sangstat, Freemont, CA), humanized anti-CD25 antibodies, and several newer maintenance drugs has led to a significant decline in acute rejection and graft loss rates [2]. The question now is whether the newer combinations of immunosuppressants could allow steroid withdrawal or the use of nonnephrotoxic regimens routinely in pancreatic transplantation. Calcineurins and steroids have been the mainstay in maintenance regimens for pancreas transplants since the introduction of the procedure. Combination therapy of calcineurins, mycophenolate mofetil, and steroids after induction therapy has been shown to reduce acute rejection rates to the 15 to 30% rate [3–5]. In view of these excellent results, it is reasonable to examine whether there is justification for modifying these successful regimens by removing steroid or calcineurins. The answer to the question is, however, dependent to a large degree on the setting in which the procedures are performed, on the donor and recipient selection criteria, and on the diligence in managing the complex immunosuppression and drug regimens of these patients.