title: An evaluation of  sirolimus  in renal transplantation.
abstract: BACKGROUND
  Sirolimus is a powerful antiproliferative immunosuppressive drug approved for the prevention of kidney allograft rejection. By its unique mechanism of action, sirolimus provides a multitude of clinical potential and has been used effectively in different drug combinations. Extensive experience has been gained regarding the best timing of its application, side effect profile and potential benefits and limitations compared with other immunosuppressive drugs.
  
  
  METHODS
  The authors evaluate the recent experience with sirolimus in kidney transplantation. Pivotal randomized controlled trials were used to provide an overview with special attention to pharmacokinetic and dynamic aspects of sirolimus, its current clinical use as well as perspectives for its future role.
  
  
  CONCLUSIONS
  Sirolimus enriches the possibilities of immunosuppressive therapies after renal transplantation. Beneficial effects toward kidney function by allowing CNI sparing, lower incidence of malignancies and less viral infections have been suggested. Sirolimus should be used cautiously in de novo patients for reasons of wound healing. An early conversion to a sirolimus-based CNI-free regimen has shown promising results, whereas late conversion is more challenging. Finally, sirolimus-associated side effects are causing tolerability concerns and frequent discontinuations. Future research should aim to better define the therapeutic window and those patients most likely to benefit.
authors.affiliation: Department of Nephrology, Charité Universitätsmedizin, Berlin, Germany. fabian.halleck@charite.de
authors.forename: Fabian
authors.initials: F
authors.lastname: Halleck
authors.forename: Michael
authors.initials: M
authors.lastname: Duerr
authors.forename: Johannes
authors.initials: J
authors.lastname: Waiser
authors.forename: Lu
authors.initials: L
authors.lastname: Huber
authors.forename: Mareen
authors.initials: M
authors.lastname: Matz
authors.forename: Susanne
authors.initials: S
authors.lastname: Brakemeier
authors.forename: Lutz
authors.initials: L
authors.lastname: Liefeldt
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D019703:Calcineurin / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D016030:Kidney Transplantation; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D019703:Calcineurin; D020123:Sirolimus