背景:对比剂相关急性肾损伤(CA-AKI)的特征在于放射性对比剂施用后肾功能丧失。虽然所有造影剂在体外诱导微血管内皮细胞的可变变化,只有少数研究报告其发现的临床意义。全面评估碘化造影剂对体外和体内肾功能的影响至关重要。我们研究的目的是通过形态学量化两种不同的造影剂(Iobitridol和Iodixanol)对体外血管内皮毛细血管的影响,并分析其对接受心脏导管插入术(包括动脉内)的患者的肾功能的影响。通过测量血清肌酐浓度(SCr),肌肉新陈代谢的副产品,主要由肾脏排泄。我们的假设表明,对两种结果进行定性比较将能够识别体外和体内暴露之间的差异和相似性。
方法:体外,将形成毛细血管床的人真皮成纤维细胞和人真皮微血管内皮细胞的共培养物暴露于磷酸盐缓冲盐水和Iobitridol的混合物中,碘克沙醇,或他们的补充剂EDTA或Trometamol之一1.5或5分钟。将阴性对照共培养物专门暴露于磷酸盐缓冲盐水。共培养物直接固定或经历1、3或7天的再生时间。训练人工智能软件以在光学显微镜图像上检测标记的内皮毛细血管(CD31)并测量形态参数。在体内,我们回顾性分析了接受动脉内对比剂给药的患者的数据,这些患者的SCr值在对比暴露前后(术后1,3和7天)均可获得.评估SCr的时间发展和CA-AKI的发生率。定性比较了两种暴露类型。
结果:体外,Iobitridol,再生3天后,碘克沙醇和EDTA引起两个形态参数的强烈降低。在体内,在造影剂后患者中,术后3天观察到SCr和CA-AKI发生率显著升高.组间没有观察到差异。
结论:两个形态测量参数与患者的SCr成反比。如果体外观察到的内皮损伤发生在体内,它可能会导致肾脏缺氧,诱导肾功能丧失临床转化为SCr增加。我们的体外模型的进一步发展可以更紧密地复制肾脏的内部结构,并弥合体外研究与其临床发现之间的差距。
Contrast-associated acute kidney injury (CA-AKI) is characterized as a loss of renal function following radiological contrast media administration. While all contrast media induce variable changes in microvascular endothelial cells in vitro, only few studies report clinical significance of their findings. A comprehensive assessment of the effect of iodinated contrast media on the renal function in vitro and in vivo is essential. The aim of our study was to morphometrically quantify the effect of two different contrast media (Iobitridol and Iodixanol) on vascular endothelial capillaries in vitro and to analyze their effect on the renal function of patients who underwent cardiac catheterization including the intra-arterial administration of contrast media, by measuring serum creatinine concentration (SCr), a byproduct of muscle metabolism, primarily excreted by the kidneys. Our hypothesis suggests that conducting a qualitative comparison of both outcomes will enable identification of differences and similarities between in vitro and in vivo exposure.
In vitro, co-cultures of human dermal fibroblasts and human dermal microvascular endothelial cells forming capillary beds were exposed to a mixture of phosphate buffered saline and either Iobitridol, Iodixanol, or one of their supplements EDTA or Trometamol for 1.5 or 5 min. Negative control co-cultures were exposed exclusively to phosphate buffered saline. Co-cultures were either directly fixed or underwent a regeneration time of 1, 3 or 7 days. An artificial intelligence software was trained for detection of labeled endothelial capillaries (CD31) on light microscope images and measurements of morphometric parameters. In vivo, we retrospectively analyzed data from patients who underwent intra-arterial administration of contrast media and for whom SCr values were available pre- and post-contrast exposition (1, 3, and 7 days following procedure). Temporal development of SCr and incidence of CA-AKI were assessed. Both exposure types were qualitatively compared.
In vitro, Iobitridol, Iodixanol and EDTA induced a strong decrease of two morphometric parameters after 3 days of regeneration. In vivo, a significant increase of SCr and incidence of CA-AKI was observed 3 days following procedure in the post-contrast media patients. No difference was observed between groups.
Two of the morphometric parameters were inversely proportional to the SCr of the patients. If the endothelial damages observed in vitro occur in vivo, it may result in renal hypoxia, inducing a loss of kidney function clinically translated into an increase of SCr. Further development of our in vitro model could allow closer replication of the internal structure of a kidney and bridge the gap between in vitro studies and their clinical findings.