BACKGROUND: Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established. METHODS: This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroidsin their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration-time curve (AUC)(0-12 h) (usual exposure, n = 104) or 50% of the study standard AUC(0-12 h) (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/nephrotoxicity/>15% serum creatinine level increase). RESULTS:Treatment failure was reported in 37 out of 101 (37%) patients in the usual-exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively). CONCLUSION: In renal transplant recipients receivingmaintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.
RCT Entities:
BACKGROUND: Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established. METHODS: This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroids in their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration-time curve (AUC)(0-12 h) (usual exposure, n = 104) or 50% of the study standard AUC(0-12 h) (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/nephrotoxicity/>15% serum creatinine level increase). RESULTS: Treatment failure was reported in 37 out of 101 (37%) patients in the usual-exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively). CONCLUSION: In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.
Authors: L Frimat; E Cassuto-Viguier; F Provôt; L Rostaing; B Charpentier; K Akposso; M C Moal; P Lang; D Glotz; S Caillard; D Ducloux; C Pouteil-Noble; S Girardot-Seguin; M Kessler Journal: J Transplant Date: 2010-07-28