소아 신장이식 환자에서 칼시뉴린억제제의 약력학적 모니터링

Background: Introduction of calcineurin inhibitor (CNI) has markedly improved the outcome of kidney transplantation. While therapeutic drug monitoring is used to adjust the dosage of CNI, some patients, particularly children, still suffer from rejection, infection, and CNI toxicity. This study was conducted in order to assess the adequacy of immunosuppression using pharmacodynamic monitoring. Methods: Pharmacodynamic monitoring was performed for 64 pediatric kidney allograft recipients. Expression of nuclear factor of activated T lymphocytes (NFAT)-regulated genes in patients` mononuclear cells was measured by quantitative polymerase chain reaction of interleukin-2, interferon-gamma (IFN-g), and granulocyte-macrophage colony stimulating-factor before (trough) and 1.5 hour (peak) after ingestion of tacrolimus and the residual gene expression (RGE) was calculated. Global immune response was assessed by Cylex-ImmuKnow assay. Trough and peak levels of tacrolimus were measured and clinical findings of rejection episodes and infectious complications were reviewed retrospectively. Results: Global immune response measured byImmuKnow did not show correlation with trough and peak levels of tacrolimus. Adenosine triphosphate level of ImmuKnow was higher in patients with Epstein-Barr virus (EBV) infection than in those without infectious complications (515.4±149.0 ng/mL vs. 342.7±155.3 ng/mL, P=0.006). Mean RGE of the three NFAT-regulated genes showed negative correlation with tacrolimus peak levels. RGE of IFN-g was lower in patients with other infections except EBV than in those without infectious complications (34.0%±7.5% vs. 56.0%±30.2%, P＜0.001). Conclusions: RGE of NFAT-regulated genes and ImmuKnow did not show significant correlation with clinical manifestation of under- or over-suppression of immune function in pediatric kidney allograft recipients. Further studies are required for development of optimal pharmacodynamic monitoring for pediatric kidney transplantation recipients.