Introduction: The aim of this study was to evaluate long-term safety outcomes of de novo kidney transplant recipients who received MTORi [sirolimus (SRL) or Everolimus (EVR)] in association with calcineurin inhibitors [tacrolimus (TAC) or cyclosporine (CsA)] and steroids.
Methods: This was a retrospective cohort study including 457 de novo kidney transplant recipients (31/Mar/99 to 11/Feb/08) who received CsA/SRL (n=234), CsA/EVR (n=110), TAC/SRL (n=95) and TAC/EVR (n=17). The mean follow up time of was 9.7 ± 7.4 years. Results: Mean age was 38.5±11.5 years, 50.8% were Caucasian, 65.6% were males and 9.0% received a deceased donor allograft. Only 18% received antibody induction with anti-IL-2R. Mean SRL through blood concentrations were 10.8±6.0, 10.0±5.6 and 8.8±4.9 ng/ml and mean EVR through blood concentrations 6.3±2.5 ng/ml; 7.9±2.1 and 6.6±2.5 ng/ml at 1, 5 and 10 years, respectively. Overall incidence of biopsy-proven acute rejection was 26.9% (SRL, 30.1%; EVR, 18.75%). Mean creatinine values at 1, 5 and 10 years were 1.6±0.9, 1.7±0.8, and 1.8±0.8 mg/dL, respectively. mTORi was replaced by other immunosuppressive agent in 184 (40%) patients: due to lack of efficacy in 15 (8.2%) patients at a mean time of 1.7±1.4 years and due to adverse effects in 169 (91.8%) patients at mean time of 2.7 ± 2.6 years. The main reasons for mTORi discontinuation were proteinuria (22.8%), dyslipidemia (14.7%) and infection (8.2%). Logistic regression analysis showed both early acute rejection (incidence of acute rejection within first year of transplantation) and pre-transplant obesity (body mass index above 30 kg/m2) as factors associated to mTORi discontinuation. At 10 years, mean hemoglobin, cholesterol and triglycerides levels were 13.03±1.87 g/dL, 204.47±57.9 mg/dL and 217.48±91.9 mg/dL, respectively. The incidence of malignancies and viral infections were low over this period (4% and 13.6%, respectively). Patient, graft and death-censored graft survival rates were 83%; 72% and 88%, respectively. The mTORi discontinuation-free survival rate was 58%. Conclusion: mTORi combined with CNi is associated with acceptable 10-year outcomes with reasonable retention in the initial regimen (58%). Safety profile is characteristic, including low incidence if viral infection and cancer, and with no new events in the long-term.
Tedesco, H.: Grant/Research Support, Sirolius, Everolimus. Medina- Pestana, J.: Grant/Research Support, Sirolimus.
To cite this abstract in AMA style:Paula M, Hannun P, Felipe C, Tedesco H, Medina- J. Long-Term Safety and Effectiveness of Inhibitors of the Mammalian Target of Rapamycin in De Novo Kidney Transplantation: 10 Years of a Single Center Experience [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/long-term-safety-and-effectiveness-of-inhibitors-of-the-mammalian-target-of-rapamycin-in-de-novo-kidney-transplantation-10-years-of-a-single-center-experience/. Accessed September 23, 2017.
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