Morath Christian, Arns Wolfgang, Schwenger Vedat, Mehrabi Arianeb, Fonouni Hamidreza, Schmidt Jan, Zeier Martin
Department of Nephrology, University of Heidelberg, Im Neuenheimer Feld 162, 69120 Heidelberg, Germany.
Nephrol Dial Transplant. 2007 Sep;22 Suppl 8:viii61-viii65. doi: 10.1093/ndt/gfm652.
Acute rejection episodes are now as low as 5-20% in the first year after renal transplantation; however, graft half-life has remained almost unchanged in the last decade. This statistic is mainly attributable to the side effects of immunosuppression, with loss of allografts due to the chronic allograft nephropathy that is a consequence of calcineurin inhibitor toxicity or hypertension. Patient death due to cardiovascular events, infections and malignancy also contribute to allograft loss. The introduction of the inhibitors of the mammalian target of rapamycin sirolimus and everolimus in renal transplantation has increased the repertoire of immunosuppressive protocols substantially. They have a different mode of action and a different side effect profile (i.e. lower nephrotoxicity, less hypertension and less neoplastic potential) than the calcineurin inhibitors. The inhibitors of the mammalian target of rapamycin therefore provide an especially promising alternative for the maintenance immunosuppression after renal transplantation. This overview provides a summary of the current literature on inhibitors of the mammalian target of rapamycin, with a special focus on sirolimus.
肾移植术后第一年急性排斥反应发生率目前低至5%-20%;然而,在过去十年中移植物半衰期几乎没有变化。这一统计数据主要归因于免疫抑制的副作用,因钙调神经磷酸酶抑制剂毒性或高血压导致的慢性移植肾肾病会造成同种异体移植物丢失。心血管事件、感染和恶性肿瘤导致的患者死亡也会造成同种异体移植物丢失。雷帕霉素靶蛋白抑制剂西罗莫司和依维莫司应用于肾移植,极大地增加了免疫抑制方案的种类。与钙调神经磷酸酶抑制剂相比,它们具有不同的作用方式和不同的副作用谱(即肾毒性较低、高血压较少和肿瘤发生可能性较小)。因此,雷帕霉素靶蛋白抑制剂为肾移植后维持免疫抑制提供了一个特别有前景的选择。本综述总结了目前关于雷帕霉素靶蛋白抑制剂的文献,特别关注西罗莫司。