Hirakawa Yosuke, Tanaka Tetsuhiro, Nangaku Masaomi
Division of Nephrology, The University of Tokyo School of Medicine Hongo, Japan.
Front Physiol. 2017 Feb 21;8:99. doi: 10.3389/fphys.2017.00099. eCollection 2017.
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 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.
慢性肾脏病（CKD）是一个重大的公共卫生问题。越来越多的证据表明，CKD会加重肾脏缺氧，而反过来，肾脏缺氧又会加速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治疗方法，如缺氧诱导因子（HIF）激活（脯氨酰羟化酶结构域抑制）或核因子E2相关因子2激活。临床研究已经揭示了肾脏氧合的异质性；因此，检测肾脏缺氧程度更高的患者可用于识别可能对以缺氧为导向的治疗有反应的患者。在这篇综述中，我们详细描述了当前的缺氧检测方法。HIF降解与细胞内氧浓度相关；因此，能够检测细胞内氧张力变化的方法是可取的。使用微电极是一种经典技术，在定量性能方面具有优势；然而，其高侵入性以及它反映细胞外氧张力这一事实是其缺点。匹莫硝唑蛋白加合物免疫组织化学和HIF激活检测反映细胞内氧张力，但这些技术产生的是定性数据。血氧水平依赖的磁共振成像具有低侵入性、高定量性能以及可应用于临床的优点，但其最大的缺点是它仅测量脱氧血红蛋白浓度。磷光寿命测量是一种相对新颖的氧传感技术，具有定量的优点；然而，它有几个缺点，如磷光染料的毒性以及无法评估更深层组织。了解这些缺氧检测方法的优缺点将有助于研究人员精确评估肾脏缺氧，并开发针对与肾脏缺氧相关的CKD的新疗法。
