Observations on the use of sirolimus and tacrolimus in high-risk renal transplant recipients

Sirolimus is the first of a group of mammalian target of rapamycin inhibitors to be introduced for clinical use in the United States. At the University of Tennessee in Memphis, we have evolved strategies for the use of sirolimus in kidney transplant recipients; which utilize the drug as a primary immunosuppressant and exploit its potential for preserving renal function. Conversions from the calcineurins to sirolimusbased immunosuppression established the efficacy of calcineurin-free immunosuppressants in selected high-risk patients. The conversion experience stimulated the design of protocols for primary use of sirolimus. Posttransplant use of sirolimus was associated with low incidence of rejection whether sirolimus was used with low-dose Prograf or in calcineurin-free protocols. Primary use with full-dose Prograf was associated with a high incidence of calcineurin-related nephrotoxicity and was abandoned in our program. Hematologic and lipid side effects were manageable, as was an observed increase in wound-healing problems and lymphocele formation. Continuous modifications of the sirolimus protocols to increase our benefit-to-risk ratio are ongoing and indicate a continued role for the drug in posttransplant immune suppression.