Maximizing the clinical outcome with mTOR inhibitors in the renal transplant recipient: defining the role of calcineurin inhibitors |
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Authors: | Email author" target="_blank">Bj?rn?NashanEmail author |
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Institution: | (1) Multi Organ Transplant Program, QEII Health Sciences Centre, Dalhousie University, VG Site, 1278 Tower Road 6S-202 Victoria Building, Halifax, Nova Scotia, B3H 2Y9, Canada |
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Abstract: | The synergistic action of mTOR inhibitors and calcineurin inhibitors (CNIs) provide a rationale for combination therapy, with the potential for CNI-dose reduction and corresponding clinical benefits. CNI therapy is necessary in the early post-transplant phase to deliver sufficient immunosuppressive potency, but use of standard-dose cyclosporine (CsA) with either sirolimus or everolimus has been associated with inferior renal function. Withdrawal of CsA from an mTOR-based regimen reduces renal toxicity, but this may be achieved at the price of increased late rejection and sirolimus-related adverse events. Use of a concentration-controlled mTOR inhibitor with low-exposure CsA seems to be effective in preventing rejection with good renal function. Currently, routine withdrawal of CNIs from an mTOR-inhibitor based regimen, or substitution of an mTOR inhibitor for a CNI, is not justified except in patients who experience toxicity (particularly nephrotoxicity) and who do not respond to CNI dose optimization. |
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Keywords: | Sirolimus Everolimus Cyclosporin A mTOR inhibitor Calcineurin inhibitor Rejection |
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