Comparison of the portal vein and kidney subcapsule as sites for primate islet autotransplantation.

To date, the portal vein has been the primary site for clinical islet transplantation. Despite success, potential complications such as portal vein thrombosis still exist. The kidney subcapsule has been used successfully in rodent models of islet transplantation. We hypothesized that the kidney subcapsule as a site for islet transplantation in the nonhuman primate model would be as effective as the portal vein. Diabetes was induced in the primate Macaca fascicularis via a total pancreatectomy. Animals were kept under anesthesia during the isolation procedure. Islet isolation was performed using intraductal infusion with Liberase HI and mechanical digestion in the Ricordi chamber, and were purified using a continuous Ficoll gradient. Purified islets were autotransplanted either into the portal vein (n = 6) or the left kidney subcapsule (n = 5) of pancreatectomized animals. Intravenous glucose tolerance tests were performed prior to pancreatectomy and 10 days following transplantation. Three animals underwent pancreatectomy and served as diabetic controls. Of the six animals receiving islets in the portal vein, one developed portal vein thrombosis. All remaining autotransplanted animals in this group remained normoglycemic with glucose-induced insulin secretion that was not different from that prior to pancreatectomy. Of the five animals undergoing transplantation into the kidney subcapsule, only one maintained normoglycemia and elicited insulin secretion in response to glucose stimulation. The other four animals remained hyperglycemic. We conclude that the portal vein is superior to the kidney subcapsule as a site for islet transplantation in nonhuman primates 10 days posttransplantation.

Glucose metabolism after pancreas-kidney transplantation.

Simultaneous pancreas-kidney (SPK) transplantation is a promising treatment option for patients with type 1 diabetes and end-stage renal disease. Most of these patients can achieve normalization of glucose and hemoglobin A(1c) levels. Patient and graft survival continues to improve; however, defects in beta-cell function and insulin resistance can be seen over time after transplant. Various methods can be used to assess the SPK recipient for the development of hyperglycemia and graft dysfunction, with treatment aimed at minimizing diabetogenic immunosuppression, using agents that may preserve beta-cell function, and improving insulin resistance.