Renal Hypoxia in CKD; Pathophysiology and Detecting Methods.
Renal Hypoxia in CKD; Pathophysiology and Detecting Methods.
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DOI：
10.3389/fphys.2017.00099
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发表时间：
2017
影响因子：
4
通讯作者：
Nangaku M
中科院分区：
文献类型：
--
作者：
Hirakawa Y;Tanaka T;Nangaku M
慢性肾脏病（CKD）是一个主要的公共卫生问题。越来越多的证据表明，CKD加重了肾缺氧，反过来，肾缺氧加速了CKD的进展。为了消除这种恶性循环，目前正在研究与缺氧相关的疗法，如缺氧诱导因子（HIF）激活（脯氨酰羟化酶结构域抑制）或NF-E2相关因子2激活。临床研究已经揭示了肾氧合的异质性;因此，检测具有更多缺氧肾脏的患者可用于识别对缺氧导向疗法的可能应答者。在这篇综述中，我们提供了目前的缺氧检测方法的详细描述。HIF降解与细胞内氧浓度相关;因此，需要能够检测细胞内氧张力变化的方法。微电极的使用是一种经典的技术，在定量性能方面具有上级优势;然而，其高侵入性和其反映细胞外氧张力的事实是缺点。匹莫硝唑蛋白加合物免疫组化和HIF活化检测反映细胞内氧张力，但这些技术产生定性数据。血氧水平依赖性磁共振成像具有低侵入性、高定量性能和临床应用的优点，但其最大的缺点是它只能测量脱氧血红蛋白浓度。磷光寿命测量是一种相对新颖的体内氧传感技术，具有定量的优点;然而，它有几个缺点，如磷光染料的毒性和无法评估更深的组织。了解这些缺氧检测方法的优点和缺点将有助于研究人员精确评估肾缺氧，并开发新的治疗肾缺氧相关CKD的方法。
Chronic kidney disease (CKD) is a major public health problem. Accumulating evidence suggests that CKD aggravates renal hypoxia, and in turn, renal hypoxia accelerates CKD progression. To eliminate this vicious cycle, hypoxia-related therapies, such as hypoxia-inducible factor (HIF) activation (prolyl hydroxylase domain inhibition) or NF-E2-related factor 2 activation, are currently under investigation. Clinical studies have revealed heterogeneity in renal oxygenation; therefore, the detection of patients with more hypoxic kidneys can be used to identify likely responders to hypoxia-oriented therapies. In this review, we provide a detailed description of current hypoxia detection methods. HIF degradation correlates with the intracellular oxygen concentration; thus, methods that can detect intracellular oxygen tension changes are desirable. The use of a microelectrode is a classical technique that is superior in quantitative performance; however, its high invasiveness and the fact that it reflects the extracellular oxygen tension are disadvantages. Pimonidazole protein adduct immunohistochemistry and HIF activation detection reflect intracellular oxygen tension, but these techniques yield qualitative data. Blood oxygen level-dependent magnetic resonance imaging has the advantage of low invasiveness, high quantitative performance, and application in clinical use, but its biggest disadvantage is that it measures only deoxyhemoglobin concentrations. Phosphorescence lifetime measurement is a relatively novel in vivo oxygen sensing technique that has the advantage of being quantitative; however, it has several disadvantages, such as toxicity of the phosphorescent dye and the inability to assess deeper tissues. Understanding the advantages and disadvantages of these hypoxia detection methods will help researchers precisely assess renal hypoxia and develop new therapeutics against renal hypoxia-associated CKD.