Maximizing the clinical outcome with mTOR inhibitors in the renal transplant recipient: defining the role of calcineurin inhibitors
Author:
Open Access
- 1 July 2004
- journal article
- Published by Frontiers Media SA in Transplant International
- Vol. 17 (6) , 279-285
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.Keywords
This publication has 32 references indexed in Scilit:
- Clinical outcomes during the first three months posttransplant in renal allograft recipients managed by C2 monitoring of cyclosporine microemulsionTransplantation, 2003
- Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the rapamune maintenance regimen study1 2Transplantation, 2003
- Clinical benefits of neoral C2 monitoring in the long-term management of renal transplant recipients1Transplantation, 2003
- A prospective, randomized clinical trial of cyclosporine reduction in stable patients greater than 12 months after renal transplantationTransplantation, 2003
- A phase III prospective, randomized study to evaluate concentration-controlled sirolimus (rapamune) with cyclosporine dose minimization or elimination at six months in de novo renal allograft recipients1,2Transplantation, 2003
- Cyclosporin withdrawal with concomitant conversion from azathioprine to mycophenolate mofetil in renal transplant recipients with chronic allograft nephropathy: a 2-year follow-upTransplant International, 2002
- Cyclosporine Microemulsion (Neoral®) Absorption Profiling and Sparse-sample Predictors During the First 3 Months after Renal TransplantationAmerican Journal of Transplantation, 2002
- SIROLIMUS (RAPAMYCIN)-BASED THERAPY IN HUMAN RENAL TRANSPLANTATIONTransplantation, 1999
- LONG-TERM RENAL ALLOGRAFT SURVIVALTransplantation, 1997
- Rapamune (Sirolimus, Rapamycin): An Overview and Mechanism of ActionTherapeutic Drug Monitoring, 1995