Mapping single nephron glomerular filtration rate with mechanisms of autoregulation in the kidney using magnetic resonance imaging

使用磁共振成像绘制单肾单位肾小球滤过率与肾脏自动调节机制

• 批准号: 10732632
• 负责人: Kevin M Bennett
• 金额: $ 7.69万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10732632
• 关键词: 3-Dimensional; Address; Allografting; Anatomy; Animal Model; Animals; Biological Markers; Blood Pressure; Blood Vessels; Blood flow; Brain; Clinical; Coupling; Development; Diabetes Mellitus; Diabetic Nephropathy; Diameter; Disease; Disease Progression; Dysbarism; Experimental Designs; Failure; Feedback; Frequencies; Functional disorder; Furosemide; Genetic Engineering; Genetic Models; Glomerular Capillary; Glomerular Filtration Rate; Goals; Health; Homeostasis; Human; Hypertension; Image; Imaging Device; Impairment; Inbred SHR Rats; Individual; Kidney; Kidney Diseases; Knowledge; Life; Life Cycle Stages; Location; Longevity; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Microscopy; Modeling; Monitor; Nephrons; Optics; Outcome; Pathology; Patients; Pattern; Perfusion; Physiological Processes; Rattus; Regulation; Renal Blood Flow; Renal Hypertension; Renal function; Reproducibility; Rest; Scanning; Signal Transduction; Source; Systemic blood pressure; Testing; Time; Transplantation; Work; aging population; cohort; experimental study; glomerular filtration; in vivo; kidney allograft; lens; non-invasive imaging; novel therapeutics; pharmacologic; predictive marker; pressure; respiratory; response; therapy development; tool; treatment response

Project Summary/Abstract The kidney maintains glomerular filtration, despite constant and potentially damaging natural fluctuations in systemic blood pressure. This autoregulation is critical to maintaining the structural and functional integrity of the kidney, and failure of autoregulation is strongly implicated in progression of kidney pathologies associated with diabetic and hypertensive nephropathy. There are several identified mechanisms of autoregulation of local blood pressure and flow, including a myogenic response and tubuloglomerular feedback (TGF). These mechanisms are associated with distinct bands of low frequencies of oscillation in perfusion pressure, but there are currently no tools to investigate the spatial localization of these mechanisms or develop them for potential clinical use. Here we develop the tool of resting- state magnetic resonance imaging (MRI) to measure and map oscillations in vascular diameters associated with these two mechanisms. This is based on our recent observations of reproducible resting- state fluctuations in MRI with frequency bands consistent with myogenic and TGF mechanisms. We will first investigate this tool in the healthy rat kidney and measure patterns in the spectra within and between kidneys during the life course of the animal. We will validate the MRI measurements using optical microscopy, and determine whether the detected autoregulation is eliminated or reduced with administration of furosemide. Finally, we will investigate the use of resting- state MRI to measure a decrease in autoregulation during development of nephropathy in the spontaneously hypertensive rat model. If successful, this work will provide a noninvasive tool to more completely understand mechanisms and develop predictive markers to investigate genetic models, guide new therapies, inform allograft transplantation, and monitor kidney health.

项目概要/摘要 尽管肾小球滤过率存在持续且具有潜在破坏性的自然波动，但肾脏仍能维持肾小球滤过。 全身血压。这种自动调节对于维持结构和功能的完整性至关重要 肾脏，自动调节的失败与相关肾脏病理的进展密切相关 患有糖尿病和高血压肾病。有几种已确定的局部自动调节机制 血压和血流，包括肌源性反应和肾小球反馈（TGF）。这些 机制与灌注压中不同的低频振荡频带相关，但也有 目前还没有工具可以研究这些机制的空间定位或开发它们的潜力 临床使用。在这里，我们开发了静息态磁共振成像 (MRI) 工具来测量和绘制地图 与这两种机制相关的血管直径振荡。这是根据我们最近 MRI 中可重复静息态波动的观察，频带与肌源性一致 和TGF机制。我们将首先在健康大鼠肾脏中研究该工具并测量 动物生命过程中肾脏内部和肾脏之间的光谱。我们将验证 MRI 使用光学显微镜进行测量，并确定检测到的自动调节是否被消除或 服用呋塞米后可减少。最后，我们将研究使用静息态 MRI 来测量 在自发性高血压大鼠模型的肾病发展过程中，自身调节能力下降。 如果成功，这项工作将提供一种非侵入性工具来更全面地理解机制和 开发预测标记来研究遗传模型，指导新疗法，为同种异体移植提供信息， 并监测肾脏健康。