Intra-renal Bold MRI: Application to Diabetic Nephropathy

肾内 Bold MRI：在糖尿病肾病中的应用

• 批准号: 7455313
• 负责人: POTTUMARTHI V PRASAD
• 金额: $ 22.42万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7455313
• 关键词: Accounting; Acute; Acute Kidney Failure; Affect; Age; Albumins; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Antioxidants; Arginine; Attention; Biological Availability; Biological Markers; Blood flow; Caring; Chronic; Clinical; Clinical Trials; Condition; Data; Deposition; Detection; Development; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathy; Dietary Supplementation; Disease; Disease Progression; Doctor of Philosophy; Early Diagnosis; Early Intervention; End stage renal failure; Equilibrium; Excretory function; Figs - dietary; Filtration; Functional disorder; Furosemide; Future; Genetic; Grant; Human; Hyperglycemia; Hypertension; Hypoxia; Incidence; Individual; Injury; Insulin-Dependent Diabetes Mellitus; Inulin; Invasive; Kidney; Kidney Diseases; Laboratories; Lead; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Metabolic Control; Methods; Microalbuminuria; Microelectrodes; Mind; Modeling; Monitor; Motivation; National Institute of Diabetes and Digestive and Kidney Diseases; Nitric Oxide; Nitric Oxide Synthase; None or Not Applicable; Organ; Outcome; Oxidative Stress; Oxygen Consumption; Patients; Pattern; Perfusion; Phase; Physiological; Pilot Projects; Play; Predictive Value; Predisposition; Prevention strategy; Preventive; Principal Investigator; Procedures; Process; Production; Prostaglandin Production; Prostaglandins; Proteinuria; Radio; Range; Rattus; Reactive Oxygen Species; Recruitment Activity; Renal function; Reporting; Reproducibility; Research Personnel; Risk; Risk Factors; Risk Marker; Role; Screening procedure; Signal Transduction; Sodium; Staging; Standards of Weights and Measures; Streptozocin; Superoxides; Supplementation; Surrogate Markers; System; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Tocopherols; Translations; Week; base; blood oxygen level dependent; cell growth; concept; cost; day; design; diabetic; diabetic rat; experience; follow-up; glomerular filtration; glycemic control; hemodynamics; human subject; insight; interest; kidney cortex; kidney medulla; normotensive; novel; novel therapeutics; pre-clinical; prevent; programs; racial and ethnic; renal hypoxia; research study; response; tissue oxygenation; type I diabetic

DESCRIPTION (provided by applicant): Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in the U.S., accounting for approximately 45% of new cases with costs projected to reach $12 billion each year by 2010. Current state-of-care only involves control of hyperglycemia until microalbuminuria develops which could take any where between 5 to 12 years after detection of hyperglycemia. While a clear understanding of the pathophysiology of diabetic nephropathy is not yet complete, significant progress has been made over the last decade or so and novel concepts are being put forward. Renal hypoxia which has been accepted widely to play a major role in ischemic nephropathy is attracting increasing interest in diabetes. There are at least two major reasons for development of chronic renal hypoxia in diabetes: one is due to hyperfiltration resulting in increased oxygen consumption to support enhanced sodium reabsorption, and the other due to oxidative stress which ultimately causes reduced nitric oxide availability. In order to better understand the origins and degree of hypoxia and develop methods to reverse it, there is a need for non-invasive technique to measure/monitor intra-renal oxygenation both in animal models and in humans. Blood oxygenation level dependent (BOLD) MRI technique as applied to intra-renal oxygenation has been shown to be sensitive and efficacious in evaluating renal hypoxia both in rat and human kidneys. Currently there is no other known technique that can be used to monitor renal hypoxia in human kidneys. Further, it has been established that in combination with suitable pharmacological maneuver, BOLD MRI facilitates demonstration of compromised endogenous protective mechanisms such as prostglandins and nitric oxide. Based on this background, this proposal extends the present findings in healthy and hypertensive kidneys using BOLD MRI to evaluate intra-renal oxygenation in diabetes. Using a diabetic rat kidney model, BOLD MRI and GFR measurements will be validated against invasive microprobe and inulin clearance measurements. Also for the first time the technique will be extended to human subjects at different stages of disease progression. Pilot data will also be obtained to follow longitudinal progression. Successful outcome will mean that we will have a non-invasive means to monitor intra-renal oxygenation to follow longitudinal changes during disease progression in diabetic nephropathy, and novel treatments during pre-clinical and clinical trials.

描述（由申请人提供）：糖尿病性肾病是美国终末期肾脏疾病（ESRD）的最常见原因，约占新病例的45％，预计到2010年，每年的成本预计到2010年每年达到120亿美元。目前的现有护理仅涉及高血糖的控制涉及高血糖的控制，直到有没有在5到12年之间才能受到5至12年的影响。尽管对糖尿病性肾病的病理生理学有清晰的了解尚未完整，但在过去十年左右的时间里取得了重大进展，并提出了新的概念。广泛接受以在缺血性肾病中发挥主要作用的肾脏缺氧引起了人们对糖尿病的兴趣的增加。糖尿病中慢性肾脏缺氧的发展至少有两个主要原因：一种是由于过滤导致氧气消耗增加以支持增强的钠重吸收，而另一个由于氧化应激，最终导致一氮氧化物的可用性降低。为了更好地理解缺氧的起源和程度并开发了扭转它的方法，需要非侵入性技术来测量动物模型和人类中的肾脏内充氧。血液氧合水平依赖性（BOLD）MRI技术应用于肾脏内氧合作用，已显示在评估大鼠和人肾脏中肾脏缺氧方面是敏感和有效的。目前，没有其他已知技术可用于监测人肾脏中的肾脏缺氧。此外，已经确定，与合适的药理操作结合使用，大胆的MRI促进了内源性保护机制（例如前列腺素和一氧化氮）的证明。基于此背景，该提案使用BOLD MRI在健康和高血压肾脏中扩展了目前的发现，以评估糖尿病中的肾脏内氧合。使用糖尿病大鼠肾脏模型，将针对侵入性微探针和无蛋白清除率测量值验证BOLD MRI和GFR测量。同样，在疾病进展的不同阶段，该技术将首次扩展到人类受试者。还将获得遵循纵向进程的试点数据。成功的结果将意味着我们将有一种非侵入性手段来监测肾脏内氧合，以跟踪糖尿病肾病疾病进展过程中纵向变化，以及在临床前和临床试验期间的新治疗方法。