肾移植联合成人胰岛细胞移植治疗糖尿病肾病七例报告

Simultaneous adult islet-kidney transplantation in 7 patients of type 1 diabetes mellitus with end-stage renal failure

目的建立新型成人胰岛细胞分离纯化方法和无激素免疫抑制方案，观察肾移植联合胰岛细胞移植治疗1型糖尿病肾病的安全性与有效性。方法全氟化碳液与威斯康星大学器官保存液双层冷藏胰腺，Liberase酶消化，COBE2991型专用胰岛细胞分离机分离及连续密度梯度纯化，获取高纯度与高活性的胰岛细胞。常规方法行尸体肾移植，次日采用外科方法将短期培养的胰岛细胞经门静脉移植到肝脏内，采用无激素免疫抑制治疗。术后定期监测血糖与胰岛素用量、C肽与糖化血红蛋白水平以及肝肾功能。结果23个胰腺均成功分离胰岛细胞，平均数量30万胰岛当量（IEQ）、纯度92％、活率95％、刺激指数3．16，病原学结果均阴性。7例1型糖尿病肾病患者共行胰岛细胞移植12次（移植1次3例、2次3例、3次1例）。每次移植胰岛数量平均为11820IEQ／kg。采用阿来佐单抗诱导、西罗莫司和小剂量他克莫司、无激素免疫抑制治疗。随访1．5～3．0年，4例完全撤除胰岛素，3例胰岛素用量较术前减少〉70％。术后血糖稳定维持在正常水平，C肽均〉0．166nmol／L，糖化血红蛋白正常，肝肾功能正常。结论新型成人胰岛细胞分离纯化方法可靠，胰岛细胞联合肾移植治疗1型糖尿病肾病安全、有效。

Objective To establish a new technique of isolating pancreatic islet of langerhans and glucocorticoid-free immunosuppressive regimen and to evaluate the clinical efficacy and safety of simultaneous adult islet-kidney transplantation in the treatment of type 1 diabetes mellitus with end- stage renal failure. Methods Pancreases were stored using the ＂2-layer method＂ of the oxygenated perfluorochemical and UW solution. The pancreases were digested by Liberase collagenase enzyme and purified using continuous gradients of Ficoll-diatrizoic acid on a refrigerated COBE 2991 centrifuge to separate the islets. Cadaver kidney was transplanted by conventional method and cultured islets were infused by surgical approach to the liver via portal vasculature using glucocorticoid-free immunosuppressive regimen. Clinical metabolic data such as blood glucose, dose of insulin, C-peptide, HbAlc, liver function and renal function, were determined and compared with the pre-transplant data. Resuits Islets of langerhans were isolated successfully in 23 pancreases. The average islet yield was 300000 islet equivalents （IEQ）. Islet purity and viability were 91. 6%, 94. 6%, respectively. The stimulation index as assessing function of human islet was 3.16 and etiology results in vivo were negative. Twelve islet transplant infusions were carried out in 7 patients after kidney transplantation. Three recipients received 2 islet infusions, 1 patient had 3 transplants, and 3 patients received 1 transplant only. The average islet mass for infusion was 11820 IEQ/kg. The immunosuppressive regimen was to give campath-lH induction, sirolimus and low-dose tacrolimus maintenance therapy without glucocortieoid. During 18 months to 3 years＇ follow-up, 4 recipients had insulin independence, the dosage of insulin decreased by 70% in 3 patients. The level of blood glucose and HbAlc, liver and renal function were normal throughout follow-up period. C-peptide of all patients was positive after islet transplantation. No adverse effects and complications related to islet infusion procedure were found. Conclusions New technique has proved to be suitable for isolating pancreatic islet of langerhans. Simultaneous adult islet-kidney transplantation could be used as an effective and safe way for treating type 1 diabetes mellitus with end-stage renal failure.