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一个中心在胰肾联合移植中使用包括抗胸腺细胞球蛋白(ATG)或白细胞介素2抗体以及霉酚酸酯在内的四联免疫抑制方案的临床经验。

A single center's clinical experience with quadruple immunosuppression including ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas-kidney transplants.

作者信息

Hesse U J, Troisi R, Jacobs B, Van Vlem B, de Hemptinne B, Van Holder R, Vermassen F, De Roose J, Lameire N

机构信息

Department of Surgery, Ghent University Hospital, Belgium.

出版信息

Clin Transplant. 2000 Aug;14(4 Pt 1):340-4. doi: 10.1034/j.1399-0012.2000.140410.x.

Abstract

UNLABELLED

Acute rejection remains a major problem in simultaneous pancreas-kidney (SPK) transplant and occurs in 60-100% of the cases. With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving antithymocyte globulin (ATG) or Basiliximab induction therapy and cyclosporine Neoral (CyA), MMF, steroid basis immunosuppression. Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean +/- standard deviation (SD) age of 42 +/- 6 yr. Of these, 14 patients were treated with anti-thymocyte globulin (ATG) Fresenius (rabbit) 3-5 mg/kg for 6 +/- 2 d, cyclosporine Neoral (CyA) (trough levels 350-400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect, Novartis 20 mg on d 0 and d 4 post-transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean +/- SD cold ischemia time (CIT) of the organs was 10.1 +/- 2.4 h for the pancreas and 10.5 +/- 2.6 h for the kidney.

RESULTS

Biopsy-proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6-d course of anti-CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA1C) of 5.1 +/- 0.7%, and serum creatinine with a mean of 1.24 +/- 0.24 mg/dL in a mean follow-up period of 17 +/- 15 months (median 12, range 2 37).

CONCLUSION

Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas-kidney transplant (PKT) with a marked reduction in the incidence of rejection.

摘要

未标记

急性排斥反应仍是同期胰肾联合移植(SPK)中的一个主要问题,发生率为60% - 100%。随着霉酚酸酯(MMF)取代硫唑嘌呤(AZA)作为基础免疫抑制剂的应用,排斥反应发生率有所降低。本研究调查了接受抗胸腺细胞球蛋白(ATG)或巴利昔单抗诱导治疗以及环孢素新山地明(CyA)、MMF、类固醇基础免疫抑制的SPK患者中移植肾排斥反应的频率及临床相关性。1996年12月至1999年10月,21例连续患者(15例男性,6例女性)在我院接受了SPK移植,平均年龄为42 ± 6岁(均值 ± 标准差)。其中,14例患者接受了Fresenius抗胸腺细胞球蛋白(兔)3 - 5 mg/kg治疗6 ± 2天,环孢素新山地明(CyA)(谷浓度350 - 400 ng/mL)、MMF 3 g/d及低剂量类固醇治疗。7例SPK患者接受巴利昔单抗(舒莱,诺华公司,移植后第0天和第4天各20 mg)替代ATG治疗。患者平均人类白细胞抗原(HLA)错配率为3.9/6,交叉配型阴性。所有患者均维持三联药物治疗。3例患者因不耐受CyA而改用他克莫司替代新山地明。器官的平均 ± 标准差冷缺血时间(CIT)为:胰腺10.1 ± 2.4小时,肾脏10.5 ± 2.6小时。

结果

1例接受ATG治疗的患者(8%)肾活检证实发生排斥反应,经类固醇冲击治疗后缓解。1例接受巴利昔单抗诱导治疗的患者(14%)发生了移植肾排斥反应,经6天抗CD3单克隆抗体(OKT3)治疗后缓解。通过尿淀粉酶水平及血糖控制情况衡量,所有患者(100%)胰腺均未发生排斥反应,无需外源性胰岛素,平均糖化血红蛋白(HBA1C)为5.1 ± 0.7%,血清肌酐平均为1.24 ± 0.24 mg/dL,平均随访期为17 ± 15个月(中位数12个月,范围2 - 37个月)。

结论

包括环孢素、MMF和低剂量类固醇以及ATG或白细胞介素2(IL2)受体抗体诱导治疗的三联药物免疫抑制方案似乎是胰肾联合移植(PKT)非常合适的免疫抑制方案,可显著降低排斥反应的发生率。

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