Current approaches to the use of sirolimus in renal transplantation.
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.
Department of Surgery University of Texas, Division of Immunology and Organ Transplantation, 6431 Fannin, MSB 6240, Houston, TX 77030, USA.
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Kahan
D065095:Calcineurin Inhibitors; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D009369:Neoplasms / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology; D020123:Sirolimus / Q000276:immunology* / Q000633:toxicity; D016559:Tacrolimus / Q000627:therapeutic use
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus