Four-year data after pediatric renal transplantation: A randomized trial of tacrolimus vs. cyclosporin microemulsion
Four-year data after pediatric renal transplantation: A randomized trial of tacrolimus vs. cyclosporin microemulsion
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DOI：
10.1111/j.1399-3046.2005.00334.x
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发表时间：
2005-08-01
影响因子：
1.3
通讯作者：
Trompeter, R
中科院分区：
文献类型：
--
作者：
Filler, G;Webb, NJA;Trompeter, R
本研究旨在比较他克莫司 (Tac) 与环孢菌素微乳 (CyA) 在儿童肾移植受者中的疗效和安全性。来自 9 个欧洲国家的 18 个中心进行了一项为期 6 个月的随机、前瞻性、开放、平行小组研究以及开放扩展阶段。总共 196 名儿童患者（< 18 岁）被随机分配（1:1）接受 Tac（n = 103）或 CyA（n = 93）联合硫唑嘌呤和皮质类固醇治疗。主要终点是发生率和首次急性排斥反应（意向治疗）的时间。治疗组之间的基线特征具有可比性。排除已故患者 (n = 9) 和失访患者 (n = 31，大部分转入成人护理)，检索到 95% 的 2 年数据（167 名可能患者中的 159 名）、87% 的 3 年数据（163 名患者中的 142 名）和 73% 的 4 年数据（156 名患者中的 114 名）。 1 年时，与 CyA 治疗 (59.1%，p = 0.003) 相比，Tac 治疗的急性排斥反应发生率 (36.9%) 显着降低。 Tac 的皮质类固醇耐药性排斥反应发生率也显着降低（7.8% vs. 25.8%，p = 0.001）。 4 年时，患者存活率相似（94% vs. 92%，p = 0.86），但移植物存活率明显有利于 Tac（86% vs. 69%；p = 0.025，对数秩检验）。 1 年时，平均肾小球滤过率 (GFR)（Schwartz 公式，ml/min/1.73 m(2)）为 64.9 +/- 20.7 (n = 84) 对比 57.8 +/- 21.9 (n = 77，p = 0.0355)，2 年时为 64.9 +/- 19.8 (n = 71) 对比 1 年。 51.7 +/- 20.3 (n = 66, p = 0.0002)，3 年时 66.7 +/- 26.4 (n = 81) 对比 53.0 +/- 23.3 (n = 55, p = 0.0022)，4 年时 71.5 +/- 22.9 (n = 51) 对比 53.0 Tac 与 CyA 分别为 +/- 21.6 (n = 44，p = 0.0001)。在整个随访过程中，CyA 治疗后的胆固醇水平仍显着升高。每组有三名患者出现移植后淋巴增殖性疾病。胰岛素依赖型糖尿病的发病率没有差异。 Tac 在预防儿童肾移植者的急性排斥反应方面比 CyA 显着更有效。 Tac 的肾功能和移植物存活率也较高。肾小球滤过率似乎是长期结果的有用替代指标。
This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (< 18 yr) were randomly assigned (1:1) to receive either Tac (n = 103) or CyA (n = 93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection (intent-to-treat). Baseline characteristics were comparable between treatment groups. Excluding deceased patients (n = 9) and patients lost to follow-up (n = 31, mostly transferred to adult care), 95% of 2-yr data (159 of 167 possible patients), 87% of 3-yr data (142 of 163) and 73% of 4-yr data (114 of 156) were retrieved. At 1 yr Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA (59.1%, p = 0.003). The incidence of corticosteroid-resistant rejection was also significantly lower with Tac (7.8% vs. 25.8%, p = 0.001). At 4 yr, patient survival was similar (94% vs. 92%, p = 0.86) but graft survival significantly favored Tac (86% vs. 69%; p = 0.025, log-rank test), respectively. At 1 yr, the mean glomerular filtration rate (GFR) (Schwartz formula, ml/min/1.73 m(2)) was 64.9 +/- 20.7 (n = 84) vs. 57.8 +/- 21.9 (n = 77, p = 0.0355), at 2 yr 64.9 +/- 19.8 (n = 71) vs. 51.7 +/- 20.3 (n = 66, p = 0.0002), at 3 yr 66.7 +/- 26.4 (n = 81) vs. 53.0 +/- 23.3 (n = 55, p = 0.0022), and at 4 yr 71.5 +/- 22.9 (n = 51) vs. 53.0 +/- 21.6 (n = 44, p = 0.0001) for Tac vs. CyA, respectively. Cholesterol remained significantly higher with CyA throughout follow-up. Three patients in each arm developed post-transplant lymphoproliferative disease. Incidence of insulin-dependent diabetes mellitus was not different. Tac was significantly more effective than CyA in preventing acute rejection in pediatric renal recipients. Renal function and graft survival were also superior with Tac. Glomerular filtration rate appears to be an useful surrogate marker for long-term outcome.