Abstract:
Cardiorenal syndrome (CRS) denotes the bidirectional interaction of chronic kidney disease and heart failure with an adverse prognosis but with a limited understanding of its pathogenesis. This study correlates biochemical blood markers, histopathological and immunohistochemistry features, and 2-deoxy-2-fluoro-D-glucose positron emission tomography (18F-FDG PET) metabolic data in low-dose doxorubicin-induced heart failure, cardiorenal syndrome, and renocardiac syndrome induced on Wistar male rats. To our knowledge, this is the first study that investigates the underlying mechanisms for CRS progression in rats using 18F-FDG PET. Clinical, metabolic cage monitoring, biochemistry, histopathology, and immunohistochemistry combined with PET/MRI (magnetic resonance imaging) data acquisition at distinct points in the disease progression were employed for this study in order to elucidate the available evidence of organ crosstalk between the heart and kidneys. In our CRS model, we found that chronic treatment with low-dose doxorubicin followed by acute 5/6 nephrectomy incurred the highest mortality among the study groups, while the model for renocardiac syndrome resulted in moderate-to-high mortality. 18F-FDG PET imaging evidenced the doxorubicin cardiotoxicity with vascular alterations, normal kidney development damage, and impaired function. Given the fact that standard clinical markers were insensitive to early renal injury, we believe that the decreasing values of the 18F-FDG PET-derived renal marker across the groups and, compared with their age-matched controls, along with the uniform distribution seen in healthy developing rats, could have a potential diagnostic and prognostic yield in cardiorenal syndrome.
摘要:
心肾综合征(CRS)表示慢性肾脏疾病和心力衰竭的双向相互作用,预后不良,但对其发病机理的了解有限。这项研究与生化血液标志物相关,组织病理学和免疫组织化学特征,和2-脱氧-2-氟-D-葡萄糖正电子发射断层扫描(18F-FDGPET)在低剂量阿霉素诱导的心力衰竭的代谢数据,心肾综合征,和Wistar雄性大鼠诱发的肾心综合征。据我们所知,这是第一项使用18F-FDGPET研究大鼠CRS进展的潜在机制的研究.临床,代谢笼监测,生物化学,组织病理学,本研究采用免疫组织化学和PET/MRI(磁共振成像)数据采集在疾病进展的不同点进行,以阐明心脏和肾脏之间器官串扰的可用证据。在我们的CRS模型中,我们发现,在研究组中,低剂量阿霉素和急性5/6肾切除术的慢性治疗死亡率最高。而肾心综合征模型导致中度至高度死亡率。18F-FDGPET显像证实阿霉素心脏毒性伴血管改变,正常的肾脏发育损伤,和功能受损。鉴于标准临床标志物对早期肾损伤不敏感,我们认为,18F-FDGPET衍生的肾脏标志物的值在各组之间下降,与他们年龄匹配的对照组相比,以及在健康发育的大鼠中看到的均匀分布,在心肾综合征中可能具有潜在的诊断和预后结果。