Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany.
Department of Radiology, Ningbo Medical Center Li Huili Hospital, 315040 Ningbo, China.
Sci Transl Med. 2019 Apr 3;11(486). doi: 10.1126/scitranslmed.aat4865.
Fibrosis is the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically assess the extent of renal fibrosis. Here, we show that molecular imaging of the extracellular matrix protein elastin allows for noninvasive staging and longitudinal monitoring of renal fibrosis. Elastin was hardly expressed in healthy mouse, rat, and human kidneys, whereas it was highly up-regulated in cortical, medullar, and perivascular regions in progressive CKD. Compared to a clinically relevant control contrast agent, the elastin-specific magnetic resonance imaging agent ESMA specifically detected elastin expression in multiple mouse models of renal fibrosis and also in fibrotic human kidneys. Elastin imaging allowed for repetitive and reproducible assessment of renal fibrosis, and it enabled longitudinal monitoring of therapeutic interventions, accurately capturing anti-fibrotic therapy effects. Last, in a model of reversible renal injury, elastin imaging detected ensuing fibrosis not identifiable via routine assessment of kidney function. Elastin imaging thus has the potential to become a noninvasive, specific imaging method to assess renal fibrosis.
纤维化是慢性肾脏病(CKD)进展的共同终点,也是目前最好的预测指标。尽管存在一些缺点,但活检仍然是唯一可用的方法,可特异性评估肾脏纤维化的程度。在这里,我们展示了细胞外基质蛋白弹性蛋白的分子成像可实现对肾脏纤维化的非侵入性分期和纵向监测。健康的小鼠、大鼠和人肾脏中几乎不表达弹性蛋白,而在进行性 CKD 的皮质、髓质和血管周围区域中则高度上调。与临床相关的对照造影剂相比,弹性蛋白特异性磁共振成像造影剂 ESMA 特异性地在多种小鼠肾脏纤维化模型以及纤维化的人类肾脏中检测到弹性蛋白的表达。弹性蛋白成像可重复、可重现地评估肾脏纤维化,并能进行治疗干预的纵向监测,准确捕捉抗纤维化治疗效果。最后,在可逆性肾损伤模型中,弹性蛋白成像检测到了通过常规肾功能评估无法识别的后续纤维化。因此,弹性蛋白成像有可能成为一种非侵入性、特异性的评估肾脏纤维化的成像方法。