Early conversion to a CNI-free immunosuppression with SRL after renal transplantation—Long-term follow-up of a multicenter trial

Abstract

Introduction Early conversion to a CNI-free immunosuppression with SRL was associated with an improved 1-and 3-yr renal function as compared with a CsA-based regimen in the SMART-Trial. Mixed results were reported on the occurrence of donor specific antibodies under mTOR-Is. Here, we present long-term results of the SMART-Trial. Methods and materials N = 71 from 6 centers (n = 38 SRL and n = 33 CsA) of the original SMART-Trial (ITT n = 140) were enrolled in this observational, non-interventional extension study to collect retrospectively and prospectively follow-up data for the interval since baseline. Primary objective was the development of dnDSA. Blood samples were collected on average 8.7 years after transplantation. Results Development of dnDSA was not different (SRL 5/38, 13.2% vs. CsA 9/33, 27.3%; P = 0.097). GFR remained improved under SRL with 64.37 ml/min/1.73m 2 vs. 53.19 ml/min/ 1.73m 2 (p = 0.044). Patient survival did not differ between groups at 10 years. There was a

Dual-Organ Transplantation: Indications, Evaluation, and Outcomes for Heart-Kidney and Heart-Liver Transplantation: A Scientific Statement From the American Heart Association

“…However, when used in place of the CNI within 3 to 6 months of transplantation, PSIs may prevent progression of renal dysfunction in both HT 77,78 and KT recipients. 79 In HT recipients in the SCHEDULE trial 77 (Scandinavian Heart Transplant Everolimus De Novo Study With Early Calcineurin Inhibitor [CNI] Avoidance) and MANDELA trial 78 (A Study Investigating the Renal Tolerability, Efficacy, and Safety of a CNI-Free Versus a Standard Regimen in De Novo Heart Transplant [HTx] Recipients), when the CNI was withdrawn 3 to 6 months after transplantation with conversion to PSI in addition to mycophenolate mofetil, patients had improved renal function by 1 year; however, more frequent episodes of biopsy-proven rejection were observed. This concern has limited the widespread implementation of CNI-free regimens, which are generally tailored to those patients who are >1 year after transplantation with significant renal dysfunction and lower risk for rejection.…”

Sarcoma de Kaposi en orofaringe en paciente postrasplante renal y manejo con inhibidor de señal de coestimulación e inhibidor de mTOR

“…Otros ensayos clínicos, comparando terapia inmunosupresora basada en inhibidores de calcineurina vs. inhibidores m-TOR, han demostrado una reducción en la incidencia de cáncer pos trasplante en la población que recibe terapia basada en inhibidores m-TOR en el seguimiento a largo plazo [30]. Los inhibidores de m-TOR como el sirolimus y el everolimus inhiben la producción de VEGF y la respuesta de las células endoteliales al VEGF.…”

The SMART trial; does it make us wiser in choosing between sirolimus in preference to cyclosporine – A postrenal transplant?

“…The follow-up analysis of the SMART trial[ 1 ] assessed the role of sirolimus (mTOR inhibitor) as an alternative option to cyclosporin A (calcineurin inhibitor) in the renal transplant patients’ maintenance regimen in a randomized controlled multicenter trial. Induction was given with anti-thymocyte globulin and methylprednisolone.…”