Department of Chemistry and Biomolecular Sciences, University of Ottawa, 150 Louis Pasteur Pvt., Ottawa, Ontario, K1N 6N5, Canada.
Department of Biology, University of Ottawa, 150 Louis Pasteur Pvt., Ottawa, Ontario, K1N 6N5, Canada.
Nat Commun. 2023 Jul 5;14(1):3965. doi: 10.1038/s41467-023-39720-x.
Chronic kidney disease (CKD) and acute kidney injury (AKI) are ongoing global health burdens. Glomerular filtration rate (GFR) is the gold standard measure of kidney function, with clinical estimates providing a global assessment of kidney health without spatial information of kidney- or region-specific dysfunction. The addition of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to the anatomical imaging already performed would yield a 'one-stop-shop' for renal assessment in cases of suspected AKI and CKD. Towards urography by DCE-MRI, we evaluated a class of nitrogen-centered organic radicals known as verdazyls, which are extremely stable even in highly reducing environments. A glucose-modified verdazyl, glucoverdazyl, provided contrast limited to kidney and bladder, affording functional kidney evaluation in mouse models of unilateral ureteral obstruction (UUO) and folic acid-induced nephropathy (FAN). Imaging outcomes correlated with histology and hematology assessing kidney dysfunction, and glucoverdazyl clearance rates were found to be a reliable surrogate measure of GFR.
慢性肾脏病（CKD）和急性肾损伤（AKI）是当前全球的健康负担。肾小球滤过率（GFR）是评估肾脏功能的金标准，而临床估算则可以在不提供肾脏或特定区域功能障碍的空间信息的情况下，对肾脏健康进行全球评估。在已经进行的解剖成像基础上增加动态对比增强磁共振成像（DCE-MRI），将为疑似 AKI 和 CKD 病例的肾脏评估提供“一站式”服务。为了实现 DCE-MRI 尿路造影，我们评估了一类以氮为中心的有机自由基，称为verdazyls，它们即使在高度还原的环境中也非常稳定。一种葡萄糖修饰的verdazyl，即 glucoverdazyl，仅提供肾脏和膀胱的对比度，可在单侧输尿管梗阻（UUO）和叶酸诱导的肾病（FAN）的小鼠模型中进行功能性肾脏评估。成像结果与评估肾脏功能障碍的组织学和血液学结果相关，并且发现 glucoverdazyl 清除率是 GFR 的可靠替代指标。
