F Gonzalez-Vilchez1, J A Vazquez de Prada2, M J Paniagua3, M Gomez-Bueno4, J M Arizon5, L Almenar6, E Roig7, J Delgado8, J L Lambert9, F Perez-Villa10, M L Sanz-Julve11, M Crespo-Leiro3, J Segovia4, A Lopez-Granados5, L Martinez-Dolz6, S Mirabet7, P Escribano8, B Diaz-Molina9, M Farrero10, T Blasco11. 1. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Marques de Valdecilla, Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain. Electronic address: cargvf@gmail.com. 2. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Marques de Valdecilla, Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain. 3. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital de La Coruña, La Coruña, Spain. 4. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Puerta de Hierro, Majadahonda, Madrid, Spain. 5. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Reina Sofia, Cordoba, Spain. 6. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital La Fe, Valencia, Spain. 7. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Santa Creu i Sant Pau, Barcelona, Spain. 8. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital 12 de Octubre, Madrid, Spain. 9. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Central de Asturias, Oviedo, Spain. 10. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Clinic de Barcelona, Barcelona, Spain. 11. Heart Failure and Cardiac Transplantation Unit, Cardiology Service, University Hospital Miguel Servet, Zaragoza, Spain.
Abstract
BACKGROUND: In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. METHODS: In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. RESULTS: Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07). CONCLUSION: In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.
BACKGROUND: In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. METHODS: In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. RESULTS: Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07). CONCLUSION: In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.
Authors: Nicolás Manito; Juan F Delgado; María G Crespo-Leiro; José María Arizón; Javier Segovia; Francisco González-Vílchez; Sònia Mirabet; Ernesto Lage; Domingo Pascual-Figal; Beatriz Díaz; Jesús Palomo; Gregorio Rábago; Marisa Sanz; Teresa Blasco; Eulàlia Roig Journal: World J Transplant Date: 2015-12-24
Authors: Natalia Kamieńska; Michał Zakliczyński; Alicja Kasperska-Zając; Marta Szewczyk; Dominika Trybunia-Orzeszek; Jerzy Nożyński; Marta Pijet; Tomasz Hrapkowicz; Marian Zembala Journal: Kardiochir Torakochirurgia Pol Date: 2014-06-29