HIGHER MAINTENANCE CYCLOSPORINE DOSE DECREASES THE RISK OF GRAFT FAILURE IN NORTH-AMERICAN CHILDREN - A REPORT OF THE NORTH-AMERICAN PEDIATRIC RENAL-TRANSPLANT COOPERATIVE STUDY

Because of changing cyclosporine dosing patterns over the years, maint enance doses in 1469 living donor and 1486 cadaver donor index renal t ransplants in patients who were 0 to 20 yr of age at the time of trans plantation were reviewed. All grafts had at least 30 days' function. E ighty-nine percent of living donor patients and 95% of cadaver donor p atients were maintained on cyclosporine for 12 months after transplant ation. Among patients receiving cyclosporine, the maintenance 12-month dose in living donor graft recipients increased from 6.4 mg/kg per da y for patients who had transplants done in 1987 to 7.9 mg/kg per day f or patients who had transplants done in 1992 (P = 0.02), Among cadaver donor graft recipients, the mean 12-month maintenance dose increased from 6.4 mg/kg per day in 1987 to 7.8 mg/kg per day in 1992 (P = 0.01) , At 6 months after transplantation, the maintenance cyclosporine dose in 1103 living donor graft recipients who retained graft function dur ing the subsequent 6-month period was 7.1 mg/kg per day, compared with a 6-month dose of 3.9 mg/kg per day in 28 patients who lost their gra ft in the subsequent 6-month period. For 1041 recipients of cadaver do nor grafts who retained graft function through 12 months after transpl antation, the 6-month maintenance cyclosporine dose was 7.4 mg/kg per day, compared with 5.4 mg/kg per day in 59 patients whose graft failed in the subsequent 6 months. In patients who did not have an acute rej ection episode during the first 12 months after transplantation, the r ate of subsequent ''late'' rejections was 22% for patients with a 12-m onth maintenance cyclosporine dose less than or equal to 4.0 mg/kg per day, and 16% for patients whose 12-month maintenance cyclosporine dos e exceeded 8.6 mg/kg per day. A proportional hazards regression analys is, using cyclosporine dose as a time-dependent covariate, showed that the hazard of graft failure was reduced 5 to 6% for each incremental increase of 1 mg/kg maintenance dose of cyclosporine (within the dose range studied) for both living and cadaver donor source transplants.