, Volume 67, Issue 3, pp 369–391 | Cite as

Use of Sirolimus in Solid Organ Transplantation

  • Joshua J. Augustine
  • Kenneth A. Bodziak
  • Donald E. Hricik
Review Article


Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that inhibits cell cycle progression and has proven to be a potent immunosuppressive agent for use in solid organ transplant recipients. The drug was initially studied as an adjunct to ciclosporin (cyclosporine) to prevent acute rejection in kidney transplant recipients. Subsequent studies have shown efficacy when combined with a variety of other immunosuppressive agents. The most common adverse effects of sirolimus are hyperlipidaemia and myelosuppression. The drug has unique antiatherogenic and antineoplastic properties, and may promote immunological tolerance and reduce the incidence of chronic allograft nephropathy. Although sirolimus is relatively non-nephrotoxic when administered as monotherapy, it pharmacodynamically enhances the toxicity of calcineurin inhibitors. Ironically, the drug has been used to facilitate calcineurin inhibitor-free protocols designed to preserve renal function after solid organ transplantation. Whether sirolimus can be used safely over the long term with low doses of calcineurin inhibitors requires further study. The use of sirolimus as a corticosteroid-sparing agent also remains to be proven in controlled trials. Postmarketing studies have revealed a number of unforeseen adverse effects including impaired wound healing and possibly proteinuria, oedema, pneumonitis and thrombotic microangiopathy. Overall, sirolimus is a powerful agent when used judiciously with other available immunosuppressants. As is true for all immunosuppressive drugs available for treatment of solid organ transplant recipients, the efficacy of the drug must be balanced against its considerable adverse effects.


Tacrolimus Transplant Recipient Acute Rejection Sirolimus Kidney Transplant Recipient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported, in part, by the Leonard Rosenberg Foundation. Drs Hricik, Bodziak and Augustine have each served as either principal investigators or co-investigators on grants sponsored by Wyeth Pharmaceuticals.


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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Joshua J. Augustine
    • 1
  • Kenneth A. Bodziak
    • 1
  • Donald E. Hricik
    • 1
  1. 1.The Department of Medicine and the Transplantation ServiceCase Western Reserve University, and University Hospitals of ClevelandClevelandUSA

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