Calcineurin activity in children with renal transplants receiving cyclosporine.
BACKGROUND
The major immunosuppressive effect of cyclosporine is through the inhibition of calcineurin, an enzyme important in the activation of T lymphocytes. In children, neither calcineurin activity nor its inhibition by cyclosporine (CsA) has been investigated.


METHODS
Calcineurin activity, was measured in stable pediatric renal transplant patients, with healthy children used as controls. Whole blood CsA concentrations were measured by monoclonal radioimmunoassay. Simultaneous calcineurin and CsA levels were measured before and 1, 2, 3.5, 5, and 12 hr after their routine morning CsA dose.


RESULTS
Calcineurin activity was approximately 50% inhibited at trough blood concentrations (148 microg/L); moreover, inhibition increased as CsA concentrations rose and declined as concentrations fell. Maximum calcineurin inhibition was about 70% at concentrations of about 431 microg/L. Linear regression analysis revealed a significant correlation between mean CsA blood concentration and the mean degree of inhibition of calcineurin activity (P=0.005, one-tailed).


CONCLUSIONS
We conclude that inhibition of calcineurin activity by CsA in pediatric renal transplant recipients correlates with CsA blood concentrations.
Quien
R M
RM
Department of Pediatrics, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, USA.
Kaiser
B A
BA
Dunn
S P
SP
Kulinsky
A
A
Polinsky
M
M
Baluarte
H J
HJ
Batiuk
T D
TD
Halloran
P F
PF
D000293:Adolescent; D000328:Adult; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002648:Child; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019703:Calcineurin