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).

中文翻译：

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胰腺和肾脏同时移植后他克莫司与基于西罗莫司的免疫抑制：一项随机试验的 5 年结果。

他克莫司是同时进行胰腺和肾脏 (SPK) 移植后免疫抑制的基石，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基于西罗莫司的免疫抑制方案。在手术时使用允许盲分配的区组方法进行随机化。所有患者均接受抗胸腺细胞球蛋白和他克莫司、霉酚酸酯和类固醇的维持治疗。第 3 个月时，继续使用他克莫司或用西罗莫司代替。主要终点是肾脏和胰腺移植物在 1 年和 5 年的存活率。每组 50 名患者被纳入最终分析。1 岁时，西罗莫司和他克莫司之间肾脏和胰腺移植存活率的差异分别为 0%（90% 置信区间 -4.61% 至 4.61%）和 6%（90% 置信区间 -6.32% 至 18.32%）。肾脏和胰腺移植物的 5 年存活率没有差异。西罗莫司组中有 34 名患者 (68%) 与他克莫司组中的 3 名患者 (6%) 需要明确停用研究药物。尽管与他克莫司相比，西罗莫司在肾脏和胰腺移植物存活率方面非劣效性，但西罗莫司的停药率很高，不利于将其用作 SPK 移植后的基石治疗 (NCT00693446)。西罗莫司组中有 34 名患者 (68%) 与他克莫司组中的 3 名患者 (6%) 需要明确停用研究药物。尽管与他克莫司相比，西罗莫司在肾脏和胰腺移植物存活率方面非劣效性，但西罗莫司的停药率很高，不利于将其用作 SPK 移植后的基石治疗 (NCT00693446)。西罗莫司组中有 34 名患者 (68%) 与他克莫司组中的 3 名患者 (6%) 需要明确停用研究药物。尽管与他克莫司相比，西罗莫司在肾脏和胰腺移植物存活率方面非劣效性，但西罗莫司的停药率很高，不利于将其用作 SPK 移植后的基石治疗 (NCT00693446)。