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Sirolimus after kidney transplantation

BMJ 2014; 349 doi: (Published 26 November 2014) Cite this as: BMJ 2014;349:g6808
  1. Adnan Sharif, nephrology consultant
  1. 1Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Birmingham B15 2WB, UK
  1. Correspondence to: adnan.sharif{at}

An uncertain future for sirolimus and other mTOR inhibitors

The risk of cancer is increased after kidney transplantation and is predominantly attributed to oncogenic immunosuppression.1 It is a leading cause of death for kidney allograft recipients, and analyses of transplant registry data suggest that mortality related to cancer is on the increase.2 3 4 Strategies to reduce the risk of cancer by modifying immunosuppression are therefore desirable but must be balanced against other important adverse events such as allograft failure. An immunosuppressant that protects against cancer and avoids the nephrotoxicity of calcineurin inhibitors such as tacrolimus and ciclosporin would fulfil two important functions for kidney allograft recipients. Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR) with perceived anti-neoplastic and non-nephrotoxic properties, could potentially challenge the dominance of calcineurin inhibition for immunosuppression after kidney transplantation.

The linked article by Knoll and colleagues (doi:10.1136/bmj.g6679) examined the use of sirolimus after kidney transplantation.5 This commendable systematic review and meta-analysis has meticulous methods, with empirical data combined at an individual patient level for 5876 kidney allograft recipients from 21 randomised controlled trials of sirolimus compared with non-sirolimus immunosuppressive regimens. The authors included studies evaluating sirolimus as a …

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