Calcineurin Inhibitors in Pediatric Renal Transplant Recipients

Abstract

The calcineurin inhibitors, cyclosporine (ciclosporin) [microemulsion] and tacrolimus, are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. For pediatric patients, both drugs should be dosed per body surface area, and pharmacokinetic monitoring is mandatory. While monitoring of the trough levels may suffice for tacrolimus, cyclosporine therapy that utilizes the microemulsion formulation requires additional monitoring (e.g. determination of 2-hour post-dose levels). In a well designed randomized study in children, as in studies in adults, there was no difference in short-term patient and graft survival with cyclosporine microemulsion and tacrolimus. However, tacrolimus was significantly more effective than cyclosporine microemulsion in preventing acute rejection after renal transplantation when used in conjunction with azathioprine and corticosteroids. With regard to long-term outcome, the difference in acute rejection episodes resulted in a better glomerular filtration rate at 1 year after transplantation and eventually in better graft survival 4 years after renal transplantation. Whether this difference persists when calcineurin inhibitors are used in combination with mycophenolate mofetil has not been determined. The prevalence of hypomagnesemia was higher in the tacrolimus group whereas hypertrichosis and gingival hyperplasia occurred more frequently in the cyclosporine group. In contrast with adults, the incidence of post-transplantation diabetes mellitus was not significantly different between tacrolimus- and cyclosporine-treated patients. There was also no difference with regard to post-transplantation lymphoproliferative disorder. Medication costs were similar, but in view of the lower rejection episodes and better long-term graft survival as well as the more favorable cosmetic side effect profile, tacrolimus may be preferable. The recommendation drawn from the available data is that both cyclosporine and tacrolimus can be used safely and effectively in children. We recommend that cyclosporine should be chosen when patients experience tacrolimus-related adverse events.