Report of the first international liver transplantation society expert panel consensus conference on renal insufficiency in liver transplantation

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64330/1/21877_ftp.pd

Pig-to-Nonhuman Primates Pancreatic Islet Xenotransplantation: An Overview

The therapy of type 1 diabetes is an open challenging problem. The restoration of normoglycemia and insulin independence in immunosuppressed type 1 diabetic recipients of islet allotransplantation has shown the potential of a cell-based diabetes therapy. Even if successful, this approach poses a problem of scarce tissue supply. Xenotransplantation can be the answer to this limited donor availability and, among possible candidate tissues for xenotransplantation, porcine islets are the closest to a future clinical application. Xenotransplantation, with pigs as donors, offers the possibility of using healthy, living, and genetically modified islets from pathogen-free animals available in unlimited number of islets. Several studies in the pig-to-nonhuman primate model demonstrated the feasibility of successful preclinical islet xenotransplantation and have provided insights into the critical events and possible mechanisms of immune recognition and rejection of xenogeneic islet grafts. Particularly promising results in the achievement of prolonged insulin independence were obtained with newly developed, genetically modified pigs islets able to produce immunoregulatory products, using different implantation sites, and new immunotherapeutic strategies. Nonetheless, further efforts are needed to generate additional safety and efficacy data in nonhuman primate models to safely translate these findings into the clinic

Minimization protocols in pancreas transplantation

Diagnosis of immunologic injury (acute and chronic) is much more difficult in pancreas transplants when compared with transplants of other organs. Currently, the immunosuppressive regimen for induction involves calcineurin inhibitors (CNI), antimetabolites and corticosteroids (Cs). This strong and nonspecific regimen does not take into consideration pancreas specificities (i.e. the need to avoid diabetogenic compounds). For obvious reasons, CNI might be calling for review, if permanently indicated in recipients of solitary pancreas with mild renal dysfunction. CNI as well as corticosteroids may induce hyperglycemia and contribute to differential diagnosis of a rejection process. However, in spite of the benefits accruing from withdrawal of above immunosuppressive agents, minimization or avoidance of these drugs could be dangerous and may end up with graft loss (i.e. antibody-mediated process). Long-term results of pancreas transplantation are now achieving comparable survival rates similar to the transplant of traditional organs such as kidney and liver. As a consequence, the physicians’ objectives are to prolong the patient’s quality of life and organ function as long as possible. Weaning strategies in regard to CNI and steroids are tested. Sirolimus, everolimus, CTLA-4 Ig, etc, are agents known to be either both nonnephrotoxic and nondiabetogenic or less so when compared with CNI. Their impact on pancreas transplantation is beginning to be evaluated. Large randomized trials in all pancreas categories, with long-term clinical and histologic results, are mandatory to establish new guidelines for immunosuppressive regimens for pancreas transplantation

A Multicenter, Prospective and Randomized Trial Comparing Pancreas versus Islet Transplantation: Should We Do It Now?

International audienc