Reduced exposure to calcineurin inhibitors in renal transplantation
Reduced exposure to calcineurin inhibitors in renal transplantation
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DOI：
10.1056/nejmoa067411
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发表时间：
2007-12-20
影响因子：
158.5
通讯作者：
Halloran, Philip F.
中科院分区：
文献类型：
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作者：
Ekberg, Henrik;Tedesco-Silva, Helio;Halloran, Philip F.
背景：对于移植受者来说，毒性作用最小的免疫抑制方案是理想的。本研究评估了四种免疫抑制剂的疗效和相对毒性作用。方法：我们随机分配1645例肾移植受者接受标准剂量的环孢素，霉酚酸酯，和皮质类固醇，或达利珠单抗诱导，霉酚酸酯，和皮质类固醇联合低剂量环孢素，低剂量他克莫司，或低剂量西罗莫司。主要终点是移植后12个月的估计肾小球滤过率（GFR），采用Cockcroft-Gault公式计算。次要终点包括急性排斥反应和同种异体移植物survival.Results：平均计算的GFR在接受低剂量他克莫司（65.4毫升每分钟）的患者高于其他三组（范围，56.7至59.4毫升每分钟）。接受低剂量他克莫司的患者（12.3%）活检证实的急性排斥反应发生率低于接受标准剂量环孢素（25.8%）、低剂量环孢素（24.0%）或低剂量西罗莫司（37.2%）的患者。四组间移植物存活率差异显著（P=0.02），低剂量他克莫司组最高（94.2%），其次是低剂量环孢素组（93.1%），标准剂量环孢素组（89.3%）和低剂量西罗莫司组（89.3%）。严重不良事件在低剂量西罗莫司组比其他组更常见（53.2% vs.范围为43.4 - 44.3%），尽管每组中至少有1例不良事件的患者比例相似（86.3 - 90.5%）。达利珠单抗、吗替麦考酚酯和皮质类固醇联合低剂量他克莫司的方案可能有利于肾功能、同种异体移植物存活，和急性排斥率，与含有daclizumab诱导加低剂量环孢素或低剂量西罗莫司或标准剂量环孢素而不诱导的方案相比。（ClinicalTrials.gov编号，NCT 00231764.）。
Background: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.Methods: We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival.Results: The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%).Conclusions: A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764.).