Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients
Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients
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DOI：
10.1097/00007890-200004150-00009
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发表时间：
2000-04-15
期刊：
影响因子：
6.2
通讯作者：
Vialtel, P
中科院分区：
文献类型：
--
作者：
Kreis, H;Cisterne, JM;Vialtel, P
导论.先前的一项肾移植试验比较了西罗莫司（雷帕霉素）与环孢素（CsA）在硫唑嘌呤和皮质类固醇三联药物治疗方案中的作用，发现急性排斥反应的发生率相似（约40%），西罗莫司有改善肾功能的趋势。在14个欧洲中心，第一个尸体肾移植受者随机接受西罗莫司（n=40）或CsA（n=38）在开放标签设计。所有患者均接受皮质类固醇和吗替麦考酚酯2 g/d。西罗莫司和CsA的浓度控制;谷浓度的霉酚酸和泼尼松龙也进行了测量。12个月时，移植物存活率（西罗莫司92.5% vs. CsA 89.5%）、患者存活率（西罗莫司97.5% vs. CsA 94.7%）和活检证实的急性排斥反应发生率（西罗莫司27.5% vs. CsA 18.4%）无统计学差异。使用抗体治疗疑似排斥事件也相似（西罗莫司7.5% vs. CsA 5.3%）。西罗莫司组接受类固醇推注治疗的患者更多（20 vs. 11，P=0.068）。从第2个月开始，西罗莫司治疗的患者计算的肾小球滤过率始终较高。西罗莫司组报告频率更高的不良事件为血小板减少（45% vs. 8%）和腹泻（38% vs. 11%）。在CsA组中，肌酐升高（18% vs. 39%）、高尿酸血症（3% vs. 18%）、巨细胞病毒感染（5% vs. 21%）和震颤（5% vs. 21%）的发生率显著更高。西罗莫司和CsA的患者和移植物存活率以及12个月时活检证实的急性排斥反应发生率相当，而安全性特征不同。这些数据表明，西罗莫司可作为预防急性排斥反应的主要治疗方法。
Introduction. A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) ina triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus.Methods. In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n=40) or CsA (n=38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured.Results. At 12 months, graft survival(92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P=0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often.Discussion. Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.