Induction and Immunosuppressive Management of Pancreas Transplant Recipients

Abstract

Background: Despite improved overall outcomes, rejection continues to occur frequently after pancreas transplantation.

Objective: To review the literature and to provide a state-of-the-art assessment of current practice and developments of immunosuppressive regimens in pancreas transplantation.

Methods: The literature was reviewed and relevant articles were retrieved and analyzed.

Results: Induction therapy is used in approximately 90% of the transplants, with T-cell depleting antibodies being the prevalent therapy (>90%). Despite the initial enthusiasm on steroid-free regimens, maintenance protocols continue to be mostly based on a combination of steroids, tacrolimus, and mycophenolate mofetil. Tacrolimus is used in the majority of recipients. Sirolimus is rarely used at the time of transplant and is introduced later on in approximately 10% of the recipients, mostly in the context of a switching strategy to address the side effects of calcineurin inhibitors. The overall quality of published studies was quite low, because of the retrospective design, the heterogeneity of study groups with respect to PTx categories, the inclusion of mixed recipient categories with respect to immunologic risk profile, and the use of non-standardized concurrent immunosuppressive therapies. In addition, most reported studies were clearly underpowered, and treatment outcomes were not standardized.

Conclusion: Since approximately two decades, immunosuppression in pancreas transplantation mostly consists of induction with depleting antibodies and maintenance therapy using a combination of steroids, tacrolimus, and mycophenolate mofetil. While true novelty would be very much needed, this review confirms the wide use and the clinical efficacy of this regimen.

Keywords: Pancreas transplantation; acute rejection; adverse events; autoimmune recurrence; chronic rejection; graft survival; immunosuppression; patient survival.