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

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...

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Bibliographic Details
Published in:American journal of transplantation 2017-09, Vol.17 (9), p.2444-2450
Main Authors: Wisel, S. A., Gardner, J. M., Roll, G. R., Harbell, J., Freise, C. E., Feng, S., Kang, S. M., Hirose, R., Kaufman, D. B., Posselt, A. M., Stock, P. G.
Format: Article
Language:English
Subjects:
Adult
Antigens
Beta cells
clinical research/practice
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 1 - surgery
diabetes: type 1
Female
Follow-Up Studies
Graft rejection
Graft Rejection - prevention & control
Graft Survival
Hemoglobin
Humans
Immunosuppression
Immunosuppressive Agents - therapeutic use
immunosuppressive regimens
Insulin
Insulin - blood
Islet cells
islet transplantation
Islets of Langerhans Transplantation
Kidney transplantation
Male
Methylprednisolone
Middle Aged
Pancreas
Pancreas Transplantation
pancreas/simultaneous pancreas‐kidney transplantation
Pancreatic islet transplantation
patient characteristics
Prognosis
protocol biopsy
Renal function
Risk Factors
Thymoglobulin
Transplantation
Transplants & implants
Xenografts
Young Adult
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Description
Summary: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. This observational study explores pancreas‐after‐islet transplantation as a modality to re‐establish insulin independence following failed islet transplant, with all patients achieving and maintaining insulin independence at a mean of 6.7 years posttransplant.
ISSN:1600-6135
1600-6143
DOI:10.1111/ajt.14344