Tissue Oxygenation in Human Renovascular Hypertension

人类肾血管性高血压中的组织氧合

• 批准号: 7700641
• 负责人: Stephen C Textor
• 金额: $ 30.04万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7700641
• 关键词: Accounting; Affect; African American; Age; Angiography; Animals; Antihypertensive Agents; Atherosclerosis; Biological Markers; Biological Preservation; Blood; Blood Pressure; Blood Vessels; Blood flow; Cardiovascular Diseases; Cardiovascular system; Caucasians; Caucasoid Race; Cessation of life; Chronic; Chronic Kidney Failure; Condition; Diabetes Mellitus; Dialysis procedure; Disease; Disease Attributes; End stage renal failure; Ethnic Origin; Event; F2-Isoprostanes; Fibrosis; Functional disorder; Furosemide; Glomerular Filtration Rate; Goals; Health Care Costs; Hemoglobin; Human; Hypertension; Individual; Injury; Intervention; Invasive; Kidney; Kidney Diseases; Magnetic Resonance; Measurement; Measures; Medical; Methodology; Methods; Minor; Morbidity - disease rate; Myocardial Infarction; National Health and Nutrition Examination Survey; Oxidative Stress; Oxygen; Oxygen Consumption; Oxygen measurement, partial pressure, arterial; Pathogenesis; Pathway interactions; Patients; Perfusion; Pharmacotherapy; Physical Dialysis; Population; Principal Investigator; Procedures; Proteinuria; Regional Blood Flow; Regulation; Renal Artery Stenosis; Renal Blood Flow; Renal Replacement Therapy; Renal function; Renin-Angiotensin System; Renovascular Hypertension; Research Personnel; Risk Factors; Role; Signal Transduction; Sodium; Stenosis; Testing; Time; Tissues; Transforming Growth Factor beta; Tubular formation; Vascular Diseases; Venous; Week; base; blood oxygen level dependent; cardiovascular risk factor; cohort; deoxyhemoglobin; detector; disorder risk; fibrogenesis; human disease; injury and repair; interstitial; kidney cortex; kidney vascular structure; mortality; new technology; pressure; programs; renal ischemia; research study; response; tissue oxygenation

Chronic kidney disease (CKD) is increasing in the U.S., particularly in older individuals. More than eight million people in the US have reduced kidney function. Even minor degrees of CKD attributed to hyper- tension and diabetes predict major cardiovascular risks, including death from myocardial infarction. Both conditions are characterized by small vessel disease within the kidney. Atherosclerosis of the larger renal vessels can accelerate hypertension, is superimposed upon small vessel disease and produces renal injury. Renovascular disease both activates oxidative pathways and produces fibrosis. The regulation of these pathways in human disease is poorly understood. BOLD (Blood Oxygen Level Dependent) magnetic resonance (MR) provides a direct, non-invasive measure of deoxygenated hemoglobin. Experimental studies indicate that BOLD MR levels relate directly to regional oxygen tension within kidney cortex and medulla. Our preliminary results indicate that deoxyhemoglobin changes measured by BOLD MR during blockade of sodium reabsorption are related to levels of irreversible kidney dysfunction in atherosclerotic renovascular disease. The overall hypothesis to be examined in these studies is that deoxygenated hemoglobin signals (the basis for BOLD magnetic resonance methodology), which reflect regional kidney ischemia, predict activation of oxidative and fibrogenic pathways in kidneys with atherosclerotic vascular disease. We propose to utilize these methods as a means of elucidating the pathogenesis and guiding therapy in human atherosclerotic renovascular disease. Our specific aims will examine the role of age, ethnicity and large-vessel renovascular disease under conditions that modify kidney oxygen consumption to examine their role in regulating injury pathways: Aim No. 1 will examine the role of small vessel changes related to age and ethnicity to determine medullary and cortical changes in BOLD MR induced by furosemide and their relationship to regional blood flow (measured by multi-detector CT), oxidative pathways and fibrogenic biomarkers. Aim No. 2 will examine serial changes in medullary and cortical BOLD MR induced by furosemide in stenotic and non-stenotic kidneys after changing levels of oxygen consumption with endovascular revascularization. Aim No. 3 will examine serial changes in regional BOLD MR in stenotic and non-stenotic kidneys during systemic blood pressure reduction using antihypertensive therapy without renalrevascularization. These projects will provide a critical extension into humans from the other studies of our program project related to mechanisms of renovascular hypertension and injury (Romero), microvascular injury and repair (Lerman) and pathways of cell signaling in renal fibrogenic responses (Grande).

慢性肾脏疾病（CKD）在美国正在增加，尤其是在老年人中。超过8个