Kishimoto Shun, Horie Kazumasa, Devasahayam Nallathamby, Yamashita Kota, Gadisetti Chandramouli, Yamamoto Kazutoshi, Brender Jeffrey R, Mitchell James B, Krishna Murali C, Linehan W Marston, Crooks Daniel R
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Clinical Cancer Metabolism Facility, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
bioRxiv. 2025 Jan 25:2025.01.22.634393. doi: 10.1101/2025.01.22.634393.
Renal oxygenation is essential for maintaining kidney function. Disruptions in oxygen delivery can lead to renal hypoxia, which can exacerbate kidney injury through multiple pathways, including inflammation, oxidative stress, and ischemia-reperfusion injury. Despite the recognized importance of oxygenation in renal pathology, non-invasive and reliable methods for assessing kidney oxygen levels are limited. Current techniques either lack sensitivity or involve invasive procedures, restricting their use in routine monitoring. Therefore, there is a pressing need for innovative approaches to assess renal oxygenation, particularly in kidney injury. This study evaluated Electron Paramagnetic Resonance (EPR)-based oxygen imaging using the paramagnetic tracer Ox071 to assess kidney oxygen levels in mice with cyclophosphamide-induced kidney injury. Urine pO2 was also assessed as a potential surrogate marker. EPR oximetry accurately measured kidney oxygen distribution, revealing a temporary increase in pO2 post-injury. Urine oximetry, however, did not reliably reflect changes in kidney oxygenation. Furthermore, EPR oximetry provided high-resolution spatial mapping of oxygen levels within the kidney, allowing for a detailed understanding of the impact of hypoxia on renal tissue. EPR oximetry is a promising, non-invasive tool for monitoring renal oxygenation, offering high-resolution mapping and longitudinal assessment. Its ability to provide detailed information about oxygen distribution within the kidney makes it a valuable tool for studying the pathophysiology of renal diseases and for developing novel therapeutic strategies.
肾脏氧合作用对于维持肾脏功能至关重要。氧输送的中断可导致肾脏缺氧,进而通过多种途径加重肾损伤,包括炎症、氧化应激和缺血再灌注损伤。尽管氧合作用在肾脏病理学中的重要性已得到认可,但评估肾脏氧水平的非侵入性可靠方法却很有限。目前的技术要么缺乏敏感性,要么涉及侵入性操作,限制了它们在常规监测中的应用。因此,迫切需要创新方法来评估肾脏氧合作用,尤其是在肾损伤方面。本研究使用顺磁性示踪剂Ox071评估基于电子顺磁共振(EPR)的氧成像,以评估环磷酰胺诱导的肾损伤小鼠的肾脏氧水平。尿pO2也作为一种潜在的替代标志物进行了评估。EPR血氧测定法准确测量了肾脏的氧分布,显示损伤后pO2暂时升高。然而,尿血氧测定法并不能可靠地反映肾脏氧合作用的变化。此外,EPR血氧测定法提供了肾脏内氧水平的高分辨率空间图谱,有助于详细了解缺氧对肾组织的影响。EPR血氧测定法是一种有前景的非侵入性工具,可用于监测肾脏氧合作用,提供高分辨率图谱和纵向评估。它能够提供有关肾脏内氧分布的详细信息,使其成为研究肾脏疾病病理生理学和开发新治疗策略的有价值工具。