Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis
Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis
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DOI：
10.1126/scitranslmed.aat4865
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发表时间：
2019-04-03
影响因子：
17.1
通讯作者：
Boor, Peter
中科院分区：
文献类型：
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作者：
Sun, Qinxue;Baues, Maike;Boor, Peter
纤维化是慢性肾脏病 (CKD) 的常见终点，也是目前进展的最佳预测指标。尽管存在一些缺点，活检仍然是专门评估肾纤维化程度的唯一可用方法。在这里，我们表明细胞外基质蛋白弹性蛋白的分子成像可以对肾纤维化进行无创分期和纵向监测。弹性蛋白在健康小鼠、大鼠和人类肾脏中几乎不表达，而在进行性 CKD 中，其在皮质、髓质和血管周围区域高度上调。与临床相关对照造影剂相比，弹性蛋白特异性磁共振成像剂 ESMA 特异性检测多种肾纤维化小鼠模型以及纤维化人类肾脏中的弹性蛋白表达。弹性蛋白成像可以对肾纤维化进行重复和可重复的评估，并且可以纵向监测治疗干预措施，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随后的纤维化，这是通过肾功能的常规评估无法识别的。因此，弹性蛋白成像有可能成为评估肾纤维化的非侵入性、特异性成像方法。
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.