Immunological Aspects Of Pancreas Transplantation

A. Immunosuppression for Pancreas Transplantation

The outcome of pancreas transplantation with respect to graft survival rates and rejection rates is most dependent upon the choice of immunotherapeutic agents employed. There is consensus that the risk of pancreas allograft rejection is much greater than that observed with kidney transplantation. The precise reasons are not well defined but likely involve greater immunogenicity of the pancreati-coduodenal graft. Recurrent autoimmune reactions are extremely rare. The majority of pancreas transplant programs are using induction therapy combined with microemulsion cyclosporine or tacrolimus, plus mycophenolate mofetil or sirolimus, and prednisone. This combination has significantly improved graft survival rates. The incidence of acute rejection has been reduced by more than half. The avoidance of induction therapy with this maintenance immunosuppression protocol is also associated with excellent patient graft survival rates but with a higher rate of acute rejection. There are steroid avoidance protocols described for pancreas transplantation, and reports of successful steroid withdrawal.

1. Trends in Induction Therapy in Pancreas Transplantation

Induction therapy is usually included in immunosuppressive protocols for recipients of whole-pancreas transplants. In fact, induction therapy is used with greater frequency in pancreas transplant recipients than for any other solid-organ recipients. One reason is the relatively higher risk of rejection observed for simultaneous pancreas-kidney (SPK), pancreas after kidney (PAK) and pancreas transplant alone (PTA) recipients, as compared with other solid organ transplants. The use of induction therapy in pancreas transplantation has been generally guided by practical experience, rather than by the results of formal randomized, prospective, multi-center trials. No FDA-approved immunosuppressive agents are on the market with a labeled indication to reduce rejection rates specifically in pancreas transplant recipients. Nonetheless, in 2001, ~ 81% of solitary pancreas (PAK and PTA) transplant recipients and over 75% of recipients of SPK transplants received induction therapy.i

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