Calcineurin Inhibitor Minimization in the Symphony Study: Observational Results 3 Years after Transplantation
Calcineurin Inhibitor Minimization in the Symphony Study: Observational Results 3 Years after Transplantation
复制标题
DOI：
10.1111/j.1600-6143.2009.02726.x
复制
发表时间：
2009-08-01
影响因子：
8.8
通讯作者：
Halloran, P. F.
中科院分区：
文献类型：
--
作者：
Ekberg, H.;Bernasconi, C.;Halloran, P. F.
Symphony研究表明，在移植后1年，与其他三种方案相比，基于daclizumab诱导，2 g霉酚酸酯（MMF），低剂量他克莫司和类固醇的方案导致更好的肾功能和更低的急性排斥反应和移植物丢失率：两种低剂量环孢素或西罗莫司代替他克莫司，一种没有诱导和标准环孢素剂量。这是一项额外2年的观察性随访，终点与核心研究相同。共有958名患者参加了随访。研究期间，许多患者改变了免疫抑制方案（例如从西罗莫司改为他克莫司），但绝大多数（95%）患者仍接受MMF治疗。在随访期间，肾功能保持稳定（平均变化：-0.6 ml/min），死亡率、移植物丢失率和急性排斥反应率较低（均约为每年1%）。霉酚酸酯和低剂量他克莫司组的GFR仍然最高（68.6 +/- 23.8 ml/min vs.标准剂量环孢霉素组65.9 +/- 26.2 ml/min，低剂量环孢霉素组64.0 +/- 23.1 ml/min，低剂量西罗莫司组65.3 +/- 26.2 ml/min），但与其他组的差异不显著（总体检验中p = 0.17，配对检验中分别为0.077、0.039和0.11）。霉酚酸酯和低剂量他克莫司组也有最高的移植物存活率，但随着时间的推移，组间差异减小，急性排斥反应发生率最低。Symphony研究是有史以来规模最大的从头肾移植前瞻性研究，在3年多的时间里，达利珠单抗诱导、MMF、类固醇和低剂量他克莫司被证明是高度有效的，没有标准CNI方案通常报告的对肾功能的负面影响。
The Symphony study showed that at 1 year posttransplant, a regimen based on daclizumab induction, 2 g mycophenolate mofetil (MMF), low-dose tacrolimus and steroids resulted in better renal function and lower acute rejection and graft loss rates compared with three other regimens: two with low-doses of cyclosporine or sirolimus instead of tacrolimus and one with no induction and standard cyclosporine dosage. This is an observational follow-up for 2 additional years with the same endpoints as the core study. Overall, 958 patients participated in the follow-up. During the study, many patients changed their immunosuppressive regimen (e.g. switched from sirolimus to tacrolimus), but the vast majority (95%) remained on MMF. During the follow-up, renal function remained stable (mean change: -0.6 ml/min), and rates of death, graft loss and acute rejection were low (all about 1% per year). The MMF and low-dose tacrolimus arm continued to have the highest GFR (68.6 +/- 23.8 ml/min vs. 65.9 +/- 26.2 ml/min in the standard-dose cyclosporine, 64.0 +/- 23.1 ml/min in the low-dose cyclosporine and 65.3 +/- 26.2 ml/min in the low-dose sirolimus arm), but the difference with the other arms was not significant (p = 0.17 in an overall test and 0.077, 0.039 and 0.11, respectively, in pair-wise tests). The MMF and low-dose tacrolimus arm also had the highest graft survival rate, but with reduced differences between groups over time, and the least acute rejection rate. In the Symphony study, the largest ever prospective study in de novo kidney transplantation, over 3 years, daclizumab induction, MMF, steroids and low-dose tacrolimus proved highly efficacious, without the negative effects on renal function commonly reported for standard CNI regimens.