Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes
Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes
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DOI：
10.1111/j.1600-6143.2008.02404.x
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发表时间：
2008-11-01
影响因子：
8.8
通讯作者：
Hering, B. J.
中科院分区：
文献类型：
--
作者：
Bellin, M. D.;Kandaswamy, R.;Hering, B. J.
我们试图确定1型糖尿病患者接受改良免疫抑制方案的门静脉同种异体胰岛移植的长期结局。6例低血糖无意识的受者接受了1至2次胰岛输注。诱导治疗采用抗胸腺细胞球蛋白（ATG）加依那西普（用于肿瘤坏死因子-α阻断）。移植后第一年接受环孢素和依维莫司维持免疫抑制，随后用麦考酚酸或麦考酚酸酯代替依维莫司。接受者自末次输注后随访1173 +/- 270天，以了解胰岛移植物功能（胰岛素依赖性、血红蛋白A（1c）水平和C肽产生）以及与研究方案相关的不良事件。在6名受者中，5名在1年时不依赖胰岛素，4名在移植后平均3.4 +/- 0.4年时继续不依赖胰岛素。6名受试者均未出现严重低血糖复发。肾小球滤过率从移植前的110.5 ± 21.2 mL/min/1.73 m2下降到移植后1年的82.6 ± 19.1 mL/min/1.73 m2。总之，6例接受ATG和依那西普诱导治疗并接受环孢霉素和依维莫司维持治疗的受者中，4例接受胰岛移植后平均胰岛素依赖性恢复> 3年。我们的研究结果表明，这种免疫抑制方案可能使移植物长期存活。
We sought to determine the long-term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received one to two islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor-alpha blockade. Recipients received cyclosporine and everolimus for maintenance immunosuppression for the first year posttransplant, with mycophenolic acid or mycophenolate mofetil subsequently substituted for everolimus. Recipients have been followed for 1173 +/- 270 days since their last infusion for islet graft function (insulin independence, hemoglobin A(1c) levels and C-peptide production) and for adverse events associated with the study protocol. Of the six recipients, five were insulin-independent at 1 year, and four continue to be insulin-independent at a mean of 3.4 +/- 0.4 years posttransplant. None of the six recipients experienced recurrence of severe hypoglycemia. Measured glomerular filtration rate decreased from 110.5 +/- 21.2 mL/min/1.73 m(2) pretransplant to 82.6 +/- 19.1 mL/min/1.73 m(2) at 1 year posttransplant. In conclusion, islet transplants restored insulin independence for a mean of > 3 years in four of six recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance. Our results suggest this immunosuppressive protocol may allow long-term graft survival.