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Calcineurin activity in children with renal transplants receiving cyclosporine
R M Quien1, B A Kaiser, S P Dunn
1Department of Pediatrics, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, USA.
Insights
Cyclosporine (CsA) inhibits calcineurin, crucial for T cell activation. This study shows CsA blood levels correlate with calcineurin inhibition in pediatric kidney transplant patients.
Area of Science:
- Immunopharmacology
- Transplantation Immunology
Background:
- Cyclosporine (CsA) is a key immunosuppressant.
- Its mechanism involves inhibiting calcineurin, essential for T lymphocyte activation.
- Pediatric studies on calcineurin activity and CsA inhibition were lacking.
Purpose of the Study:
- To investigate calcineurin activity and its inhibition by CsA in pediatric renal transplant recipients.
- To determine the relationship between CsA blood concentrations and calcineurin inhibition.
Main Methods:
- Measured calcineurin activity in pediatric renal transplant patients and healthy controls.
- Quantified whole blood CsA concentrations using radioimmunoassay.
- Assessed simultaneous calcineurin and CsA levels at multiple time points post-dose.
Main Results:
- Calcineurin activity was ~50% inhibited at trough CsA levels (~148 microg/L).
- Inhibition increased with CsA concentration, reaching ~70% at ~431 microg/L.
- Significant correlation found between CsA blood concentration and calcineurin inhibition (P=0.005).
Conclusions:
- CsA effectively inhibits calcineurin activity in pediatric renal transplant recipients.
- This inhibition is directly correlated with CsA blood concentrations.
- Findings support therapeutic drug monitoring of CsA in pediatric transplantation.
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).
Conclusion:
We conclude that inhibition of calcineurin activity by CsA in pediatric renal transplant recipients correlates with CsA blood concentrations.