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Q J Med 2003; 96: 401-409
© 2003 Association of Physicians

Review

The evolving role of sirolimus in renal transplantation

P. Dupont and A.N. Warrens

From the Division of Medicine, Imperial College London, London, UK

The first 150 words of the full text of this article appear below.


   Introduction
 
Sirolimus (rapamycin) is a macrolide antibiotic isolated from the fungus Streptomyces hygroscopicus1 first identified in soil samples from Easter Island. Structurally similar to the calcineurin inhibitor (CNI) tacrolimus (Figure 1), it shares its potent immunosuppressive properties, but with a novel mechanism of action (Figure 2). Initial clinical trials have focussed on its use as adjunctive therapy, substituting for the anti-metabolite azathioprine. However, given that it lacks the nephrotoxicity of the CNIs (cyclosporin and tacrolimus), it has the potential to supplant these agents as baseline immunosuppressive therapy following renal transplantation, and offers the added potential benefit of promoting immunological tolerance.


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  		Figure 1. Structure of sirolimus. Sirolimus (rapamycin) is a macrocyclic lactone structurally similar to tacrolimus (FK506).

 

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  		Figure 2. Mechanism of action of sirolimus (rapamycin). CD4-positive T cells recognize a complex of class II MHC and peptide present on the surface of antigen-presenting cells (APCs). This results in signalling via the T . . . [Full Text of this Article]

 

   Pharmacology
 

   Pre-clinical data
 
Effectiveness of sirolimus in transplantation
Sirolimus and vascular disease
Sirolimus and tolerance

   Clinical experience in renal transplantation
 
As an adjunct to a CNI
CNI replacement (primary therapy)
Other roles for sirolimus—drug-eluting coronary stents
Adverse effects

   Pharmacodynamics and drug monitoring
 

   Potential roles for sirolimus therapy
 
Nephrotoxicity due to calcineurin inhibitors
Intolerance of mycophenolate mofetil (MMF)
Haemolytic uraemic syndrome (HUS)
Delayed graft function (DGF)

   Conclusions
 

Address correspondence to: Dr A.N Warrens, Department of Immunology, Commonwealth Building, Hammersmith Hospital, Ducane Road, London W12 0NN. e-mail: a.warrens@ic.ac.uk


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L. Champion, M. Stern, D. Israel-Biet, M.-F. Mamzer-Bruneel, M.-N. Peraldi, H. Kreis, R. Porcher, and E. Morelon
Brief Communication: Sirolimus-Associated Pneumonitis: 24 Cases in Renal Transplant Recipients
Ann Intern Med, April 4, 2006; 144(7): 505 - 509.
[Abstract] [Full Text] [PDF]