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
Department of Surgery, University of California, San Francisco, San Francisco, CA.
Department of Surgery, University of Wisconsin, Madison, WI.
Am J Transplant. 2017 Sep;17(9):2444-2450. doi: 10.1111/ajt.14344. Epub 2017 Jun 6.
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.
胰岛移植为低血糖无感知的糖尿病患者提供了一种微创的β细胞替代方法。实现胰岛素自主分泌可能需要多次输注来自不同供体的胰岛，这会增加同种异体致敏的风险。目前，在美国，胰岛移植失败后，实体器官胰腺移植是唯一剩下的手术选择；然而，反复接触供体抗原对后续胰腺移植的免疫影响尚不清楚。我们描述了一个病例系列，包括7例胰岛移植失败后接受实体器官胰腺移植的患者，并对胰腺移植存活情况和肾功能进行了长期随访。尽管胰腺移植前群体反应性抗体水平差异很大（平均27±35%），但所有7例患者均实现了稳定且持久的胰岛素自主分泌，平均随访6.7年。糖化血红蛋白（HbA1c）平均值从胰岛移植后、胰腺移植前水平（平均8.1±1.5%）显著改善至胰腺移植后水平（平均5.3±0.1%；p = 0.0022）。3例患者发生急性排斥反应，经兔抗胸腺细胞球蛋白和甲泼尼龙成功处理，这些尿毒症前期1型糖尿病受者术后均未发展为4期或5期慢性肾脏病。这些结果支持在胰岛移植失败后进行积极免疫抑制和方案活检的胰岛后胰腺移植，作为恢复胰岛素自主分泌的可行策略。
