Jordan M L, Shapiro R, Gritsch H A, Egidi F, Khanna A, Vivas C A, Scantlebury V P, Fung J J, Starzl T E, Corry R J
Division of urologic Surgery and Transplantation and the Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Transplantation. 1999 Jan 27;67(2):266-72. doi: 10.1097/00007890-199901270-00014.
The long-term safety and efficacy of tacrolimus in pancreas transplantation has not yet been demonstrated. The observation of prolonged pancreatic graft function under tacrolimus would indicate that any potential islet toxicity is short-lived and clinically insignificant. We report herein the results of pancreas transplantation in patients receiving primary tacrolimus immunosuppression for a minimum of 2 years.
From July 4, 1994 until April 18, 1996, 60 patients received either simultaneous pancreas-kidney transplant (n=55), pancreas transplant only (n=4), or pancreas after kidney transplantation (n=1). Baseline immunosuppression consisted of tacrolimus and steroids without antilymphocyte induction. Azathioprine was used as a third agent in 51 patients and mycophenolate mofetil in 9. Rejection episodes within the first 6 months occurred in 48 (80%) patients and were treated with high-dose corticosteroids. Antilymphocyte antibody was required in eight (13%) patients with steroid-resistant rejection.
With a mean follow-up of 35.1+/-5.9 months (range: 24.3-45.7 months), 6-month and 1-, 2-, and 33-year graft survival is 88%, 82%, 80%, and 80% (pancreas) and 98%, 96%, 93%, and 91% (kidney), respectively. Six-month and 1-, 2-, and 3-year patient survival is 100%, 98%, 98%, and 96.5%. Mean fasting glucose is 91.6+/-13.8 mg/dl, and mean glycosylated hemoglobin is 5.1+/-0.7% (normal range: 4.3-6.1%). Mean tacrolimus dose is 6.5+/-2.6 mg/day and mean prednisone dose 2.0+/-2.9 mg/day at follow-up. Complete steroid withdrawal was possible in 31 (65%) of the 48 patients with functioning pancreases.
These data show for the first time that tacrolimus is a safe and effective long-term primary agent in pancreas transplantation and provides excellent long-term islet function without evidence of toxicity while permitting steroid withdrawal in the majority of patients.
他克莫司在胰腺移植中的长期安全性和有效性尚未得到证实。观察他克莫司作用下延长的胰腺移植功能，将表明任何潜在的胰岛毒性都是短暂的，且在临床上无显著意义。我们在此报告接受他克莫司作为初始免疫抑制剂至少2年的患者的胰腺移植结果。
从1994年7月4日至1996年4月18日，60例患者接受了同期胰肾联合移植（n = 55）、单纯胰腺移植（n = 4）或肾移植后胰腺移植（n = 1）。基线免疫抑制方案包括他克莫司和类固醇，未进行抗淋巴细胞诱导治疗。51例患者使用硫唑嘌呤作为第三种药物，9例患者使用霉酚酸酯。48例（80%）患者在最初6个月内发生排斥反应，采用大剂量皮质类固醇治疗。8例（13%）对类固醇耐药的排斥反应患者需要使用抗淋巴细胞抗体。
平均随访35.1±5.9个月（范围：24.3 - 45.7个月），胰腺移植6个月及1年、2年和3年的移植物存活率分别为88%、82%、80%和80%，肾移植分别为98%、96%、93%和91%。患者6个月及1年、2年和3年的存活率分别为100%、98%、98%和96.5%。平均空腹血糖为91.6±13.8 mg/dl，平均糖化血红蛋白为5.1±0.7%（正常范围：4.3 - 6.1%）。随访时他克莫司平均剂量为6.5±2.6 mg/天，泼尼松平均剂量为2.0±2.9 mg/天。48例胰腺功能正常的患者中，31例（65%）实现了完全停用类固醇。
这些数据首次表明，他克莫司在胰腺移植中是一种安全有效的长期初始药物，可提供出色的长期胰岛功能，无毒性证据，同时多数患者可停用类固醇。
