Can mTOR inhibitors reduce the risk of late kidney allograft failure?
Ponticelli C Transpl Int 2008; 21(1):2-10. [Full text] (PMID: 17635837) 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 corticoste