Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.
Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.
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DOI：
10.1097/tp.0000000000001453
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发表时间：
2017-08
期刊：
影响因子：
6.2
通讯作者：
Advagraf-based immunosuppression regimen examining new onset diabetes mellitus in kidney transplant recipients (ADVANCE) study investigators
中科院分区：
文献类型：
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作者：
Mourad G;Glyda M;Albano L;Viklický O;Merville P;Tydén G;Mourad M;Lõhmus A;Witzke O;Christiaans MHL;Brown MW;Undre N;Kazeem G;Kuypers DRJ;Advagraf-based immunosuppression regimen examining new onset diabetes mellitus in kidney transplant recipients (ADVANCE) study investigators
Advance(NCT01304836)是一项4期、多中心、前瞻性随机、开放标签、为期24周的研究，比较了移植后糖尿病(PTDM)与2种缓释他克莫司皮质类固醇最小化方案的发病率。所有患者均接受缓释他克莫司、巴利昔单抗、霉酚酸酯和术中1次皮质类固醇(0~1000 mg)的治疗。组1的患者在第10天后停止使用锥形皮质类固醇，而组2的患者在术中推注后不接受类固醇。主要疗效变量是根据美国糖尿病协会标准(2010)在肾移植后24周内的任何时间点诊断为PTDM。次要疗效变量包括综合疗效失败的发生率(移植物丢失、活检证实的急性排斥反应或严重的移植物功能障碍：估计的肾小球滤过率(肾脏疾病中的饮食修改-4)和lt；每1.73平方米30毫升/分钟)、急性排斥反应、移植物和患者存活。完全分析组包括1081例患者(组1：n=528，组2：n=553)。两组患者的基线特征和平均他克莫司谷值相似。24周时，第1组与第2组的PTDM卡普兰-迈耶估计值相似(17.4%比16.6%；P=0.579)。两组患者的综合疗效失败率、移植物和患者存活率以及平均估计的肾小球滤过率也具有可比性。经活检证实的急性排斥反应和急性排斥反应，第2组明显高于第1组(13.6%vs8.7%，P=0.006和25.9%vs18.2%，P=0.001)。两组患者的耐受性特征具有可比性。缓释他克莫司、巴利昔单抗和霉酚酸酯免疫抑制方案是有效的，PTDM发生率低，治疗24周后耐受性可控。活检证实的急性排斥反应的发生率在接受皮质类固醇激素减量10天以上加术中皮质类固醇激素推注的患者比术中仅推注皮质类固醇激素的患者低。这项大型、多中心、前瞻性和随机研究显示，在接受巴利昔单抗、缓释他克莫司和霉酚酸酯的肾移植受者中，避免使用类固醇与不使用类固醇的急性排斥反应发生率较高，但移植后糖尿病的发生率没有差异。
ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m2), acute rejection and graft and patient survival. The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan–Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10 days plus an intraoperative corticosteroid bolus versus those receiving an intraoperative bolus only. This large, multicenter, prospective and randomized study shows no difference in the incidence of posttransplantation diabetes mellitus but higher incidence of acute rejection with a steroid avoidance versus a steroid sparing regimen in kidney transplant recipients receiving basiliximab, prolonged-release tacrolimus and mycophenolate.