Early conversion to a sirolimus‐based, calcineurin‐inhibitor‐free immunosuppression in the SMART trial: observational results at 24 and 36 months after transplantation
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 36 months. At 36 months, renal function continued to be superior in SRL‐treated patients [ITT‐eGFR@36m: 60.88 vs. 53.72 (CsA) ml/min/1.73 m2, 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 36 months 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 >60 years, S‐creatinine at conversion >2 mg/dl, CMV naïve(‐) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36 months. Early conversion to a CNI‐free SRL‐based immunosuppression is associated with a sustained improvement of renal function up to 36 months after transplantation. Patient selection will be key to derive long‐term benefit and avoid treatment failure using this mTOR‐inhibitor‐based immunosuppressive regimen.
Document Type: Research Article
Affiliations: 1: Department of Surgery, Munich University Hospital, Campus Grosshadern, Munich, Germany 2: Department of Transplantation, Visceral- and Thoracic Surgery, University of Innsbruck, Innsbruck, Austria 3: Department of Medicine III, Carl Gustav Carus University Hospital, Technical University Dresden, Dresden, Germany 4: Department of Medicine V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany 5: Department of General, Visceral, and Transplantation Surgery, Charité, Campus Virchow-Clinic, Berlin, Germany 6: Department of Medicine, Division of Nephrology, University of Erlangen, Erlangen, Germany 7: Department of Urology, University of Rostock, Rostock, Germany 8: Department of Medicine I, Munich University Hospital, Campus Grosshadern, Munich, Germany 9: Department of Transplantation and Visceral Surgery, University of Zürich, Zürich, Switzerland 10: Internal Medicine II, Nephrology and Transplantation, University Medical Center, Regensburg, Germany
Publication date: April 1, 2012