Efficacy and safety of early cyclosporine conversion to sirolimus with continued MMF-four-year results of the Postconcept study

Am J Transplant. 2011 Aug;11(8):1665-75. doi: 10.1111/j.1600-6143.2011.03637.x.

Abstract

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function. We previously reported that conversion from cyclosporine A (CsA) to sirolimus (SRL) 3 months after transplantation significantly improved renal function at 1 year. In the Postconcept trial, 77 patients in the SRL group and 85 in the CsA group were followed for 48 months. Renal function (Cockcroft and Gault) was significantly better at month 48 (M48) in the SRL group both in the intent-to-treat population (ITT): 62.6 mL/min/1.73 m(2) versus 57.1 mL/min/1.73 m(2) (p = 0.013) and in the on-treatment population (OT): 67.5 mL/min/1.73 m(2) versus 57.4 mL/min/1.73 m(2) (p = 0.002). Two biopsy proven acute rejection episodes occurred after M12 in each group. Graft and patient survival were comparable (graft survival: 97.4 vs. 100%; patient survival: 97.4 vs. 97.6%, respectively). The incidence of new-onset diabetes was numerically increased in the SRL group (7 vs. 2). In OT, three cancers occurred in the SRL group versus nine in the CsA group and mean proteinuria was increased in the SRL group (0.42 ± 0.44 vs. 0.26 ± 0.37; p = 0.018). In summary, the renal benefits associated with conversion of CsA to SRL, at 3 months posttransplantation, in combination with MMF were maintained for 4 years posttransplantation.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cyclosporine / adverse effects
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use*
  • Female
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Failure, Chronic / drug therapy
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Sirolimus / adverse effects
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use*
  • Survival Rate

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Sirolimus