Cantarovich Diego, Kervella Delphine, Karam Georges, Dantal Jacques, Blancho Gilles, Giral Magali, Garandeau Claire, Houzet Aurélie, Ville Simon, Branchereau Julien, Delbos Florent, Guillot-Gueguen Cécile, Volteau Christelle, Leroy Maxime, Renaudin Karine, Soulillou Jean-Paul, Hourmant Maryvonne
CHU Nantes, Université de Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes, France.
CHU Nantes, Université de Nantes, Institut de Transplantation, Urologie, Néphrologie, Nantes, France.
Am J Transplant. 2020 Jun;20(6):1679-1690. doi: 10.1111/ajt.15809. Epub 2020 Feb 28.
Tacrolimus, the cornerstone immunosuppression after simultaneous pancreas and -kidney (SPK) transplantation, may exert nephrotoxic and diabetogenic effects. We therefore prospectively compared in an open-label, randomized, monocentric, 5-year follow-up study, a tacrolimus- and a sirolimus-based immunosuppressive regimen. Randomization using the block method allowing a blind allocation was done at the time of surgery. All patients received anti-thymocyte globulin and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids. At month 3, tacrolimus was continued or replaced by sirolimus. The primary endpoint was kidney and pancreas graft survival at 1 and 5 years. Fifty patients were included in the final analysis in each group. At 1 year, differences for kidney and pancreas graft survival between sirolimus and tacrolimus were 0% (90% confidence interval -4.61% to 4.61%) and 6% (90% confidence interval -6.32% to 18.32%), respectively. There was no difference in renal and pancreas graft survival at 5 years. Thirty-four patients (68%) in the sirolimus group vs three (6%) in the tacrolimus group needed definitive withdrawal of the study drug. Despite noninferiority of sirolimus compared to tacrolimus for kidney and pancreas graft survival, the high rate of sirolimus discontinuation does not favor its use as cornerstone therapy after SPK transplantation (NCT00693446).
他克莫司是胰肾联合移植（SPK）术后免疫抑制的基石，但可能会产生肾毒性和致糖尿病作用。因此，我们在一项开放标签、随机、单中心、为期5年的随访研究中，前瞻性地比较了基于他克莫司和西罗莫司的免疫抑制方案。手术时采用允许盲法分配的区组法进行随机分组。所有患者均接受抗胸腺细胞球蛋白治疗，并使用他克莫司、霉酚酸酯和类固醇进行维持治疗。在第3个月时，继续使用他克莫司或用西罗莫司替代。主要终点是1年和5年时肾和胰腺移植物的存活情况。每组最终分析纳入50例患者。1年时，西罗莫司组和他克莫司组肾和胰腺移植物存活的差异分别为0%（90%置信区间为-4.61%至4.61%）和6%（90%置信区间为-6.32%至18.32%）。5年时肾和胰腺移植物存活无差异。西罗莫司组有34例患者（68%）与他克莫司组的3例患者（6%）需要明确停用研究药物。尽管在肾和胰腺移植物存活方面西罗莫司不劣于他克莫司，但西罗莫司停药率高不利于其在SPK移植后作为基石治疗药物使用（NCT00693446）。
