Oberbauer Rainer, Segoloni Giuseppe, Campistol Josep M, Kreis Henri, Mota Alfredo, Lawen Joseph, Russ Graeme, Grinyó Josep M, Stallone Giovanni, Hartmann Anders, Pinto Jose R, Chapman Jeremy, Burke James T, Brault Yves, Neylan John F
Allgemeines Krankenhaus-Wien, Innere Medizin III-Nephrologie, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Transpl Int. 2005 Jan;18(1):22-8. doi: 10.1111/j.1432-2277.2004.00052.x.
We report the 48-month results of a trial testing whether withdrawal of cyclosporine (CsA) from a sirolimus (SRL)-CsA-steroid (ST) regimen would impact renal allograft survival. Eligible patients receiving SRL-CsA-ST from transplantation were randomly assigned at 3 months to remain on triple therapy (SRL-CsA-ST, n = 215) or to have CsA withdrawn and SRL trough concentrations increased (SRL-ST, n = 215). SRL-ST therapy resulted in significantly better graft survival, either when including death with a functioning graft as an event (84.2% vs. 91.5%, P = 0.024) or when censoring it (90.6% vs. 96.1%, P = 0.026). Calculated glomerular filtration rate (43.8 vs. 58.3 ml/min, P < 0.001) and mean arterial blood pressure (101.3 vs. 97.1 mmHg, P = 0.047) were also improved with SRL-ST. Differences in the incidences of biopsy-proven acute rejection after randomization (6.5% vs. 10.2%, SRL-CsA-ST versus SRL-ST, respectively) and mortality (7.9% vs. 4.7%) were not significant. SRL-CsA-ST-treated patients had significantly higher incidences of adverse events generally associated with CsA, whereas those in the SRL-ST group experienced greater frequencies of events commonly related to higher trough levels of SRL. In conclusion, early withdrawal of CsA from a SRL-CsA-ST regimen rapidly improves renal function and ultimately results in better graft survival.
我们报告了一项试验的48个月结果，该试验旨在测试从西罗莫司（SRL）-环孢素（CsA）-类固醇（ST）方案中撤掉环孢素是否会影响肾移植受者的存活。符合条件且自移植后接受SRL-CsA-ST治疗的患者在3个月时被随机分组，一组继续接受三联疗法（SRL-CsA-ST，n = 215），另一组撤掉CsA并提高SRL谷浓度（SRL-ST，n = 215）。SRL-ST疗法使移植肾存活显著改善，无论是将带功能移植物死亡作为事件纳入分析（84.2%对91.5%，P = 0.024）还是将其作为截尾数据处理（90.6%对96.1%，P = 0.026）。采用SRL-ST治疗时，计算的肾小球滤过率（43.8对58.3 ml/分钟，P < 0.001）和平均动脉血压（101.3对97.1 mmHg，P = 0.047）也有所改善。随机分组后，活检证实的急性排斥反应发生率（分别为6.5%对10.2%，SRL-CsA-ST组对SRL-ST组）和死亡率（7.9%对4.7%）的差异不显著。接受SRL-CsA-ST治疗的患者中，通常与CsA相关的不良事件发生率显著更高，而SRL-ST组患者中与SRL较高谷浓度通常相关的事件发生频率更高。总之，从SRL-CsA-ST方案中早期撤掉CsA可迅速改善肾功能，并最终带来更好的移植肾存活。
