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  • Title: Current approaches to the use of sirolimus in renal transplantation.
    Author: Kahan BD.
    Journal: Transplant Proc; 2009 Oct; 41(8):3011-5. PubMed ID: 19857664.
    Abstract:
    Sirolimus, a macrolide with immunosuppressive properties, was introduced into clinical practice a decade ago. The optimal use of this drug remains controversial: It displays a wide range of organ and tissue toxicities owing to the critical role of its therapeutic site- the kinase mammalian target of rapamycin-in the signal transduction pathways of numerous cytokines, growth factors, hormones, and nutrients. However, it displays unique, recognized benefits for renal transplant recipients: synergistic interactions with cyclosporine and possibly tacrolimus, allowing marked reduction in exposure to the calcineurin inhibitor; reduction in the frequency of posttransplant malignancies, particularly lymphomas, Kaposi sarcomas, and hypernephromas; and modest nephrotoxicity in comparison with calcineurin inhibitors. Because of its inhibitory effects on endothelial and smooth muscle cell proliferation, sirolimus may be a useful tool to dampen chronic vasculo-obliterative processes that attenuate graft survival. With increasing experience with the drug, the true potential of sirolimus will be realized to be a critical element in the immunosuppressive matrix.
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