Ponticelli Claudio
Department of Immunology, Istituto Auxologico Italiano, Milano, Italy.
Transpl Int. 2008 Jan;21(1):2-10. doi: 10.1111/j.1432-2277.2007.00524.x. Epub 2007 Jul 17.
The most frequent causes of late kidney allograft failure are chronic rejection, nonalloimmune injury and death, all of which may depend on the characteristics of the donor and recipient, but may also be influenced by the type of immunosuppression. Combining calcineurin inhibitors (CNIs) and corticosteroids offers potent immunosuppression, but may also cause side effects leading to progressive graft dysfunction or an increased risk of death. New immunosuppressive strategies may come from the availability of inhibitors of mTOR, a downstream effector of phosphatidylinositol-3 kinase that provides the signal for cell proliferation by phosphorylating a cascade of kinases. Recent trials have shown that it is possible to minimize the dose or withdraw CNIs a few weeks after transplantation when they are combined with mTOR inhibitors and their combination may also make it possible to minimize or avoid the use of corticosteroids. Moreover, by inhibiting the signal for cell proliferation, mTOR inhibitors may reduce the replication of cytomegalovirus inside host cells, prevent transplant vasculopathy, and exert anti-oncogenic activity. All of these characteristics offer a ray of hope for reducing the risk of long-term allograft failure.
晚期肾移植失败最常见的原因是慢性排斥反应、非同种免疫损伤和死亡，所有这些可能取决于供体和受体的特征，但也可能受免疫抑制类型的影响。联合使用钙调神经磷酸酶抑制剂（CNIs）和皮质类固醇可提供强效免疫抑制，但也可能导致副作用，从而导致移植肾功能进行性减退或死亡风险增加。新的免疫抑制策略可能源于雷帕霉素靶蛋白（mTOR）抑制剂的出现，mTOR是磷脂酰肌醇-3激酶的下游效应器，通过磷酸化一系列激酶为细胞增殖提供信号。近期试验表明，当与mTOR抑制剂联合使用时，有可能在移植后几周减少CNIs的剂量或停用CNIs，并且它们的联合使用还可能使减少或避免使用皮质类固醇成为可能。此外，通过抑制细胞增殖信号，mTOR抑制剂可能会减少巨细胞病毒在宿主细胞内的复制，预防移植血管病变，并发挥抗癌活性。所有这些特性为降低长期移植失败的风险带来了一线希望。
