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Sirolimus - Challenging Current Perspectives

Buhaescu, Irina MD*; Izzedine, Hassan MD, PhD; Covic, Adrian MD, PhD*

doi: 10.1097/01.ftd.0000245377.93401.39
Review Article

Sirolimus is a potent immunosuppressant drug with a novel mechanism of action. It inhibits the mammalian target of rapamycin (mTOR) and blocks the cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus is widely used as a maintenance immunosuppressive agent in organ transplantation. Also, a potentially benefit of this valuable drug in some immunologic and malignant diseases is currently under scrutiny.

Classical side effects: hematological (anaemia, leucopenia, thrombocytopenia), hypercholesterolemia, arthralgias, extremity oedema and impaired wound healing have been frequently associated with the use of sirolimus. Additionally with its increased use, transplant professionals are encountering a variety of previously unreported and potentially more severe side effects.

Here, we review the most recent data on sirolimus unexpected side effects (with an emphasis on pulmonary and renal toxicity), its use in renal transplantation and its new potential therapeutic indications (chronic glomerulopathies, polycystic kidney disease, different types of cancer). A brief description of the current knowledge of sirolimus therapeutic drug monitoring, methods of analysis, pharmacokinetics and drug interactions with calcineurin inhibitors is also included.

From the *Dialysis and Renal Transplantation Center, Parhon University Hospital, Iasi, Romania; and †Nephrology Unit, Pitie Salpetriere Hospital, Paris, France.

Reprints: Irina Buhaescu, MD, Dialysis and Renal Transplantation Center Parhon University Hospital, 50 Carol 1st Blvd, IASI 6600, Romania (e-mail: irinabuhaescu@yahoo.fr).

© 2006 Lippincott Williams & Wilkins, Inc.