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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.

1996 Apr

Journal Article

Tejani, A.; Sullivan, E.K.

J Am Soc Nephrol





Adolescent; Adult; Child; Child, Preschool; Cyclosporine; Dose-Response Relationship, Drug; Follow-Up Studies; Graft Rejection; Humans; Infant; kidney transplantation; North America; Tissue Donors

Because of changing cyclosporine dosing patterns over the years, maintenance doses in 1469 living donor and 1486 cadaver donor index renal transplants in patients who were 0 to 20 yr of age of the time of transplantation were reviewed. All grafts had at least 30 days' function. Eighty-nine percent of living donor patients and 95% of cadaver donor patients were maintained on cyclosporine for 12 months after transplantation. Among patients receiving cyclosporine, the maintenance 12-month dose in living donor graft recipients increased from 6.4 mg/kg per day for patients who had transplants done in 1987 to 7.9 mg/kg per day for 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 during 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 graft in the subsequent 6-month period. For 1041 recipients of cadaver donor grafts who retained graft function through 12 months after transplantation, 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 rejection episode during the first 12 months after transplantation, the rate of subsequent "late" rejections was 22% for patients with a 12-month maintenance cyclosporine dose < or = 4.0 mg/kg per day, and 16% for patients whose 12-month maintenance cyclosporine dose exceeded 8.6 mg/kg per day. A proportional hazards regression analysis, 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.

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