Journal
TRANSPLANT INTERNATIONAL
Volume 23, Issue 5, Pages 447-460Publisher
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1432-2277.2010.01051.x
Keywords
graft survival; kidney; mTOR inhibition; rejection; transplantation
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Funding
- Wyeth Pharmaceuticals
- MediMedia Educational Group, LLC
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P>All immunosuppressive medications require a learning curve that enables clinicians to improve the therapeutic index of agents. Mammalian target of rapamycin (mTOR) inhibitors are potentially a less nephrotoxic form of immunosuppression than calcineurin inhibitors (CNIs) that has been used in kidney transplant recipients for more than two decades. This drug class has a novel immunosuppressive action, probably mediated in part through inhibition of growth receptor signaling mechanisms. In addition, it has a unique drug toxicity, which is partially dose-related. This medication class also possesses antiproliferative activity, which may be useful in-post-transplant patients with increased atherosclerotic and malignancy risks. mTOR inhibitors have been utilized for de novo immunosuppression with CNIs, corticosteroids, and antimetabolites. mTOR inhibitors also have been used as CNI-sparing agents both early and late post-transplant. Much debate remains over how to best utilize mTOR inhibition in kidney transplantation.
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