mTOR Inhibition and Clinical Transplantation: Kidney
The mammalian target of rapamycin (mTOR) inhibitor class of immunosuppressive drugs were introduced more than 15 years ago as a new opportunity to create selective antirejection therapy in solid organ transplantation. In particular, absence of early nephrotoxicity seemed to provide an important opportunity to minimize or replace the calcineurin inhibitor (CNI) drugs, which were plagued by progressive nephrotoxicity when administered at doses needed to prevent rejection. Since that time, there have been dozens of single center, multicenter, international, randomized and controlled (RCT), retrospective, observational, and then registry accumulations of data on mTOR use. These studies have often confirmed an efficacy endpoint, but left conclusions incomplete due to study patient drop outs and investigator driven protocol deviations. Although the role of mTOR in limiting skin cancer (Kaposi sarcoma, squamous, and basal cell cancer) progression in transplant recipients is confirmed,1,2 a particular contraindication would be established glomerular injury and proteinuria. Both of these effects are attributed to the down regulation of vascular endothelial growth factor induced by mTOR inhibition. One can say there is no contemporary and universal agreement on the role of mTOR drugs (sirolimus [SRL] or everolimus [EVL]) in solid organ transplantation. Their use remains individual and based primarily on the comfort and experience of the clinicians who care for transplant patients.