Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36months after transplantation

Transpl Int. 2012 Apr;25(4):416-23. doi: 10.1111/j.1432-2277.2012.01432.x. Epub 2012 Feb 10.

Abstract

Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36months. At 36months, renal function continued to be superior in SRL-treated patients [ITT-eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73m(2) , P=0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36months was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60years, S-creatinine at conversion >2mg/dl, CMV naïve(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36months. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36months after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcineurin Inhibitors*
  • Creatinine / blood
  • Cyclosporine / administration & dosage
  • Female
  • Follow-Up Studies
  • Graft Rejection / epidemiology
  • Humans
  • Immunosuppression Therapy / methods*
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / physiology*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Sirolimus / administration & dosage*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Creatinine
  • TOR Serine-Threonine Kinases
  • Mycophenolic Acid
  • Sirolimus