Islet and Pancreas Transplantation

Islet allotransplantation for patients with brittle type 1 diabetes mellitus (T1DM) is a minimally invasive and relatively safe procedure that can induce sustained, normalized glucose control and restore C-peptide secretion, with reduction of hypoglycemic episodes, stabilization or delay of chronic complications, and better quality of life. Current immunosuppressive protocols have significantly improved short-term outcomes, whereas long-term results are still inadequate (from 80% to 10% insulin-independence from 1 to 5 years post-transplant). Principal limitations include: imperfections in the islet isolation process, auto- and alloimmunity, allosensitization, immunosuppression-related toxicity, and unsuitability of the intrahepatic implantation site. More efficient isolation methods, safer and more efficient immunosuppressive agents in tolerogenic strategies, and alternative transplant site(s) may resolve these limitations in the near future. Simultaneous pancreas–kidney (SPK) transplantation is the optimal treatment for patients with T1DM with end-stage renal disease. Restoration of normoglycemia after pancreas transplant, as well as of renal function after kidney transplant, results in significant improvement of neuropathy, retinopathy, and nephropathy. Novel immunosuppressive therapies, improvements in surgical techniques, and better understanding of postoperative recipient care have improved results of SPK transplants consistently over the past decade. Future directions include optimization of immunosuppression, allowing freedom from insulin injection therapy while maintaining normoglycemia, and avoidance of chronic transplant glomerulopathy, with durable normalization of kidney function, thus improving quality of life as well as extending patient survival.