David Cucchiari1, José Ríos2,3, Alicia Molina-Andujar4, Enrique Montagud-Marrahi4, Ignacio Revuelta4,5,6, Pedro Ventura-Aguiar4, Gastón J Piñeiro4, Erika De Sousa-Amorim4, Nuria Esforzado4, Frederic Cofán4, Jose-Vicente Torregrosa4, Jessica Ugalde-Altamirano4, Maria José Ricart4, Jordi Rovira5,6, Ferran Torres2,3, Manel Solè7, Josep M Campistol4, Fritz Diekmann8,9,10, Frederic Oppenheimer4. 1. Renal Transplant Unit, Hospital Clínic, Carrer Villaroel 170, 08023, Barcelona, Spain. cucchiari@clinic.cat. 2. Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 3. Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. 4. Renal Transplant Unit, Hospital Clínic, Carrer Villaroel 170, 08023, Barcelona, Spain. 5. Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 6. Red de Investigación Renal (REDINREN), Madrid, Spain. 7. Pathology Unit, Hospital Clínic, Barcelona, Spain. 8. Renal Transplant Unit, Hospital Clínic, Carrer Villaroel 170, 08023, Barcelona, Spain. fdiekman@clinic.cat. 9. Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. fdiekman@clinic.cat. 10. Red de Investigación Renal (REDINREN), Madrid, Spain. fdiekman@clinic.cat.
Abstract
INTRODUCTION: The TRANSFORM study demonstrated that an immunosuppression based on a combination of calcineurin inhibitors and de-novo mTOR inhibitors (mTORi) is safe and effective in kidney transplant recipients. However, data that validate this approach in clinical practice are currently missing. MATERIALS AND METHODS: Analysis of 401 kidney transplant recipients transplanted from June 2013 to December 2016. All patients received tacrolimus with prednisone in combination with either mycophenolate (n = 186) or mTORi (either everolimus or sirolimus, n = 215). A propensity score to receive mTORi was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age and sex of donor and recipient, BMI, previous transplants, diabetes, cPRA, dialysis before transplantation, dialysis vintage, type of donor, ABO-incompatibility, HLA-mismatches, induction and ischemia time. Median follow-up was 2.6 [1.9; 3.7] years. RESULTS: Cox-regression analysis suggests good results for mTORi versus MPA in terms of 1-year biopsy-proven acute rejection (BPAR, P = 0.063), 1-year graft loss (P = 0.025) and patient survival (P < 0.001). Results observed for BPAR and graft failure were largely attributed to those patients that would have been excluded by the TRANSFORM because of some exclusion criteria (52.9% of the population, P = 0.003 for 1-year BPAR and P = 0.040 for graft loss). In patients who met selection criteria for TRANSFORM, no effect of treatment for BPAR or graft failure was observed, while the beneficial effect on overall survival persisted. CONCLUSIONS: In a real-life setting, a protocol based on de-novo mTORi with tacrolimus and prednisone could be employed as a standard immunosuppressive regimen and was associated with good outcomes.
INTRODUCTION: The TRANSFORM study demonstrated that an immunosuppression based on a combination of calcineurin inhibitors and de-novo mTOR inhibitors (mTORi) is safe and effective in kidney transplant recipients. However, data that validate this approach in clinical practice are currently missing. MATERIALS AND METHODS: Analysis of 401 kidney transplant recipients transplanted from June 2013 to December 2016. All patients received tacrolimus with prednisone in combination with either mycophenolate (n = 186) or mTORi (either everolimus or sirolimus, n = 215). A propensity score to receive mTORi was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age and sex of donor and recipient, BMI, previous transplants, diabetes, cPRA, dialysis before transplantation, dialysis vintage, type of donor, ABO-incompatibility, HLA-mismatches, induction and ischemia time. Median follow-up was 2.6 [1.9; 3.7] years. RESULTS: Cox-regression analysis suggests good results for mTORi versus MPA in terms of 1-year biopsy-proven acute rejection (BPAR, P = 0.063), 1-year graft loss (P = 0.025) and patient survival (P < 0.001). Results observed for BPAR and graft failure were largely attributed to those patients that would have been excluded by the TRANSFORM because of some exclusion criteria (52.9% of the population, P = 0.003 for 1-year BPAR and P = 0.040 for graft loss). In patients who met selection criteria for TRANSFORM, no effect of treatment for BPAR or graft failure was observed, while the beneficial effect on overall survival persisted. CONCLUSIONS: In a real-life setting, a protocol based on de-novo mTORi with tacrolimus and prednisone could be employed as a standard immunosuppressive regimen and was associated with good outcomes.