Pharmacodynamic monitoring of cyclosporine A by NFAT‐regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients

摘要: Pharmacokinetic monitoring of CsA is unsatisfactory, because at comparable blood concentrations, the frequency and severity adverse effects vary considerably among patients. We have therefore recently developed a precise, reliable, robust whole-blood pharmacodynamic assay that measures suppression CsA-target genes in T lymphocytes. Because different characteristics pharmacokinetics children higher propensity for infectious complications, this requires validation pediatric patient population. quantified prospective study 45 renal transplant recipients residual expression NFAT-regulated lymphocytes by RT-PCR correlated these findings with recurrent infections maintenance period post-transplant. Patients showed significantly stronger inhibition gene (18.2%) than patients without (31.7%; p = 0.012). This difference was specific, various PK parameters concomitant immunosuppressive therapy were between Multivariate regression analysis age only independent determinants infections. By ROC curve analysis, cutoff value 23% had highest sensitivity (71.1%) specificity (65.4%) discrimination Pharmacodynamic measurement has potential to identify over-immunosuppressed useful tool optimization therapy.