CALCINEURIN ACTIVITY IN CHILDREN WITH RENAL-TRANSPLANTS RECEIVING CYCLOSPORINE

Background. The major immunosuppressive effect of cyclosporine is thro ugh the inhibition of calcineurin, an enzyme important in the activati on of T lymphocytes. In children, neither calcineurin activity nor its inhibition by cyclosporine (CsA) has been investigated. Methods. Calc ineurin activity, was measured in stable pediatric renal transplant pa tients, with healthy children used as controls. Whole blood CsA concen trations were measured by monoclonal radioimmunoassay, Simultaneous ca lcineurin and CsA levels were measured before and 1, 2, 3.5, 5, and 12 hr after their routine morning CsA dose. Results. Calcineurin activit y was approximately 50% inhibited at trough blood concentrations (148 mu g/L); moreover, inhibition increased as CsA concentrations rose and declined as concentrations fell. Maximum calcineurin inhibition was a bout 70% at concentrations of about 431 mu g/L. Linear regression anal ysis revealed a significant correlation between mean CsA blood concent ration and the mean degree of inhibition of calcineurin activity (P=0. 005, one-tailed). Conclusion. We conclude that inhibition of calcineur in activity by CsA in pediatric renal transplant recipients correlates with CsA blood concentrations.