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.

项目总结/文摘