Cyclosporine dosing and its relationship to outcome in pediatric renal transplantation

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) contains information on more than 2,000 pediatric renal transplants performed since 1987. We reviewed the NAPRTCS database to determine the long-term trends in cyclosporine dosing for pediatric recipients of renal transplants and to determine whether there is a relationship between cyclosporine doses and graft outcome. More than 90% of all patients in the NAPRTCS registry received cyclosporine as initial therapy, with a slightly higher percentages of cadaver donor recipients than living-related donor recipients. Cyclosporine doses is all patients decreased from a median of 9 mg/kg/day at one month following transplant to 4.3 mg/kg/day at 36 months. Cyclosporine doses were generally higher in younger patients, particularly during the first year following transplantation. The relationships between cyclosporine doses and both rejection episodes and graft losses were assessed. Between 6 months and 36 months following transplantation, patients who had first rejection episodes or lost their grafts had lower median cyclosporine doses than those who did not. Proportional hazards regression analysis of the risk of having a first rejection episode more than one year after the transplant indicated that the cyclosporine dose was negatively correlated with risk of rejection (RR = 0.9, P = 0.02). We conclude that cyclosporine doses are routinely decreased following renal transplantation in children. Lower doses of cyclosporine are associated with rejection episodes, particularly late rejections. Cyclosporine doses of pediatric recipients of renal transplants should not be tapered.