Pancreas-After-Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence.

Abstract

Islet transplantation offers a minimally invasive approach for β cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long-term follow-up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow-up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas-after-islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure.

• Authors: S A Wisel, J M Gardner, G R Roll, J Harbell, C E Freise, S Feng, S M Kang, R Hirose, D B Kaufman, A M Posselt, P G Stock
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 17 Issue 9 Pg. 2444-2450 (Sep 2017) ISSN: 1600-6143 [Electronic] United States
• PMID: 28489277 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Immunosuppressive Agents
• Insulin

Topics

• Adult
• Diabetes Mellitus, Type 1 (surgery)
• Female
• Follow-Up Studies
• Graft Rejection (prevention & control)
• Graft Survival
• Humans
• Immunosuppressive Agents (therapeutic use)
• Insulin (blood)
• Islets of Langerhans Transplantation
• Male
• Middle Aged
• Pancreas Transplantation
• Prognosis
• Risk Factors
• Young Adult