Noninvasive Quantification of Renal Oxygen Utilization in Early Kidney Disease

早期肾脏疾病中肾氧利用的无创定量

• 批准号: 10551188
• 负责人: Rajiv Deshpande
• 金额: $ 2.61万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10551188
• 关键词: Address; Adult; Affect; Agreement; Albumins; Albuminuria; Animal Model; Biological Markers; Blood; Blood Flow Velocity; Brain; Calibration; Cardiovascular Diseases; Cardiovascular system; Cerebrovascular Circulation; Cerebrum; Chronic Kidney Failure; Clinical; Clinical Markers; Creatinine; Data; Development; Diabetes Mellitus; Diabetic Nephropathy; Diagnosis; Dialysis procedure; Disease; Disease Progression; Diuretics; Early Diagnosis; Early Intervention; Equation; Functional disorder; Future; Glomerular Filtration Rate; Health; Histology; Hyperglycemia; Hypoxia; Internal jugular vein structure; Intervention; Ionizing radiation; Kidney; Kidney Diseases; Label; Light; Literature; Magnetic Resonance Imaging; Measurement; Measures; Medical; Mentors; Methods; Monitor; Morphologic artifacts; Motion; Non-Insulin-Dependent Diabetes Mellitus; Oral; Organ; Outcome; Oxygen; Oxygen saturation measurement; Pathway interactions; Patients; Performance; Phase; Physiologic pulse; Physiological; Play; Positron-Emission Tomography; Prediabetes syndrome; Predisposition; Prevalence; Protons; Public Health; Pulse Oximetry; Relaxation; Renal Tissue; Renal function; Reporting; Research; Risk Factors; Role; Sampling; Scanning; Serum; Signal Transduction; Site; Superior sagittal sinus; Technology; Testing; Tissues; Transplantation Surgery; Urine; Venous; Water; Work; Workload; blood flow measurement; cardiovascular risk factor; demographics; design; diabetic; diabetic patient; experimental study; human subject; imaging modality; kidney dysfunction; kidney imaging; metabolic rate; motion sensitivity; performance tests; radiotracer; renal damage; renal hypoxia; response; tissue oxygenation

Project Summary/Abstract (30 lines): Chronic kidney disease (CKD) is characterized by a progressive loss of kidney function and is a major risk factor for adverse cardiovascular outcomes. It is estimated that CKD affects 15% of US adults. Current measures of kidney function rely on equations to calculate an estimated glomerular filtration rate (eGFR), require multiple blood and urine samples, or detect dysfunction after irreversible damage may already have occurred. These limitations highlight an unmet need for a better biomarker that can detect kidney dysfunction earlier. Renal metabolic rate of oxygen (MRO2) is a suitable metric because it directly represents renal function and workload. Moreover, renal MRO2 has been found to increase during the early stages of diabetic kidney disease. MRO2 can be quantified with magnetic resonance imaging oximetry, including susceptometry-based oximetry (SBO) or T2- based oximetry (T2O). However, SBO is not appropriate for kidney imaging because of restrictions on vessel orientation and lack of adjacent tissue for reference phase measurement. T2O is the preferred option, but current T2-based methods only measure venous oxygen saturation (SvO2) and require a separate measurement of blood flow velocity to quantify MRO2. The proposed research introduces a noninvasive T2-based oximetry method to quantify whole-organ renal MRO2 by simultaneously measuring SvO2 and blood flow velocity in an interleaved manner, thereby overcoming the limitations of other T2-based methods. The central hypothesis of the proposed research is that renal MRO2 has the potential to serve as a direct, quantitative marker of kidney function and enable earlier detection of diabetic CKD. To fulfill this objective and test the central hypothesis, the following specific aims will be pursued: (1A) Develop the MRI oximetry pulse sequence and test in phantoms to assess accuracy of measured parameters. (1B) Implement the pulse sequence to quantify SvO2 in the superior sagittal sinus of the brain and whole-brain cerebral MRO2. Initial studies will quantify whole-brain MRO2 because of minimal physiologic and voluntary motion, and availability of established data to compare with. (2A) Design and implement the pulse sequence for kidney imaging to quantify renal MRO2, and test the performance of the method with an oral diuretic. (2B) Quantify renal MRO2 and calculate eGFR in prediabetic and diabetic patients to evaluate the hypothesis that renal MRO2 can serve as an early marker of kidney dysfunction. The proposed research to quantify renal MRO2 introduces a method to noninvasively quantify renal MRO2 with potential applications as an accurate marker of early-stage kidney disease and for monitoring response to intervention.

项目摘要/摘要（30 行）： 慢性肾病 (CKD) 的特点是肾功能逐渐丧失，是一个主要危险因素 不良心血管结局。据估计，15% 的美国成年人患有 CKD。目前的措施 肾功能依靠方程来计算估计的肾小球滤过率 (eGFR)，需要多个 血液和尿液样本，或在可能已经发生不可逆转的损害后检测功能障碍。这些 局限性凸显了对可以更早检测肾功能障碍的更好生物标志物的需求尚未得到满足。肾 氧代谢率 (MRO2) 是一个合适的指标，因为它直接代表肾功能和工作负荷。 此外，已发现肾脏 MRO2 在糖尿病肾病的早期阶段会增加。 MRO2可以 通过磁共振成像血氧测定法进行量化，包括基于电纳测定法的血氧测定法 (SBO) 或 T2- 基于血氧测定法 (T2O)。然而，由于血管的限制，SBO 不适合肾脏成像 方向和缺乏用于参考相位测量的邻近组织。 T2O 是首选，但目前 基于 T2 的方法仅测量静脉血氧饱和度 (SvO2)，并且需要单独测量 血流速度来量化 MRO2。拟议的研究引入了一种基于 T2 的无创血氧测定法 通过同时测量 SvO2 和血流速度来量化全器官肾 MRO2 的方法 交错方式，从而克服了其他基于T2的方法的局限性。中心假设为 拟议的研究表明，肾脏 MRO2 有潜力作为肾脏的直接定量标记物 功能并能够及早发现糖尿病 CKD。为了实现这一目标并检验中心假设， 将追求以下具体目标： (1A) 开发 MRI 血氧饱和度脉冲序列并在体模中进行测试，以 评估测量参数的准确性。 (1B) 实施脉冲序列以量化上级中的 SvO2 大脑矢状窦和全脑大脑 MRO2。初步研究将量化全脑 MRO2，因为 最小的生理和随意运动，以及可供比较的既定数据的可用性。 (2A) 设计 并实施肾脏成像的脉冲序列来量化肾脏MRO2，并测试性能 用口服利尿剂的方法。 (2B) 量化糖尿病前期和糖尿病患者的肾脏 MRO2 并计算 eGFR 评估肾脏 MRO2 可作为肾功能障碍早期标志物的假设。拟议的 量化肾脏 MRO2 的研究引入了一种无创量化肾脏 MRO2 的方法，具有潜力 应用作为早期肾脏疾病的准确标记和监测干预反应。