Maximizing the clinical outcome with mTOR inhibitors in the renal transplant recipient: defining the role of calcineurin inhibitors

Transplant International : Official Journal of the European Society for Organ Transplantation
Björn Nashan

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.

Citations

Jan 6, 2009·Transplant International : Official Journal of the European Society for Organ Transplantation·Stefan A FarkasHans J Schlitt
Mar 4, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Y-P JinE F Reed
May 6, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Roberto Cacciola
Jun 12, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Fawaz Al AmmaryMacey L Henderson

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