Cyclosporine and long-term kidney graft survival

BACKGROUND: Previous analysis of kidney transplant data from the Collaborative Transplant Study database showed that patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 7 years posttransplantation. Longer-term and additional analyses have now been performed. METHODS: Data from cadaver kidney transplants performed between 1985 and 1998 were analyzed retrospectively. Patients were included if they had a functioning graft 1 year posttransplantation, and the daily cyclosporine dose administered 1 year posttransplantation was reported. Data on cyclosporine dose, serum creatinine concentration, and systolic blood pressure were recorded 1 and 5 years after transplantation; information on graft survival was documented at yearly intervals. RESULTS: Patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 10 years posttransplantation. Cyclosporine <2 mg/kg/day was least beneficial overall and in subanalyses based on age, risk level, and 1-year serum creatinine concentration. The microemulsion cyclosporine formulation (Neoral) was associated with a significantly higher 4-year graft survival rate than the conventional formulation (Sandimmune; P=0.0001). Median systolic blood pressure 5 years posttransplantation was similar in each 1-year cyclosporine dose category (range of medians 139.0-140.0 mmHg). The percentages of patients with serum creatinine concentrations of <130, 130-260, 260-400, or >400 micromol/L 1 and 5 years posttransplantation were similar across 1-year cyclosporine dose categories, with the exception of >6 mg/kg/day, where there was a shift toward a less favorable serum creatinine concentration over time. CONCLUSIONS: The 1-year cyclosporine dose was significantly associated with long-term graft survival, with evidence of underimmunosuppression at doses <3 mg/kg/day and overimmunosuppression at doses >6 mg/kg/day, but had little influence on systolic blood pressure or serum creatinine concentration at doses up to 6 mg/kg/day.