Ekberg Henrik, Tedesco-Silva Helio, Demirbas Alper, Vítko Stefan, Nashan Björn, Gürkan Alp, Margreiter Raimund, Hugo Christian, Grinyó Josep M, Frei Ulrich, Vanrenterghem Yves, Daloze Pierre, Halloran Philip F
Lund University, Malmö, Sweden.
N Engl J Med. 2007 Dec 20;357(25):2562-75. doi: 10.1056/NEJMoa067411.
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.
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.
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%).
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 [ClinicalTrials.gov].).
对于移植受者而言，希望采用毒性作用尽可能小的免疫抑制方案。本研究评估了四种免疫抑制方案的疗效及相对毒性作用。
我们将1645例肾移植受者随机分组，分别接受标准剂量环孢素、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治疗。主要终点为移植后12个月时根据Cockcroft - Gault公式计算的估计肾小球滤过率（GFR）。次要终点包括急性排斥反应和移植物存活情况。
接受低剂量他克莫司治疗的患者计算得出的平均GFR（65.4毫升/分钟）高于其他三组（范围为56.7至59.4毫升/分钟）。经活检证实的急性排斥反应发生率在接受低剂量他克莫司治疗的患者中（12.3%）低于接受标准剂量环孢素治疗的患者（25.8%）、低剂量环孢素治疗的患者（24.0%）或低剂量西罗莫司治疗的患者（37.2%）。四组间移植物存活情况存在显著差异（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% 对43.4%至44.3%的范围），尽管每组中相似比例的患者在治疗期间至少发生了一次不良事件（86.3%至90.5%）。
与包含达利珠单抗诱导加低剂量环孢素或低剂量西罗莫司的方案或无诱导的标准剂量环孢素方案相比，达利珠单抗、霉酚酸酯和皮质类固醇联合低剂量他克莫司的方案可能在肾功能、移植物存活及急性排斥反应发生率方面具有优势。（ClinicalTrials.gov编号，NCT00231764 [ClinicalTrials.gov]。）
