Markers of Renal Damage in Renovascular Hypertension

肾血管性高血压中肾损伤的标志物

• 批准号: 7327505
• 负责人: Juan C Romero
• 金额: $ 28.78万
• 依托单位: MAYO CLINIC ROCHESTER
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7327505
• 关键词: Angioplasty; Angiotensin II; Angiotensin Receptor; Angiotensins; Animals; Antihypertensive Agents; Antioxidants; Atrophic; Bladder; Blood; Blood Circulation; Blood Pressure; Blood Vessels; Blood capillaries; Blood flow; Catheterization; Clinical; Collagen; Condition; Consumption; Contralateral; Deposition; Development; Diagnosis; Disease regression; Distal; Elevation; Excretory function; Exhibits; Fibrosis; Financial compensation; Furosemide; Glomerular Filtration Rate; Henle' s loop; Hydralazine; Hyperplasia; Hypertension; Hypertrophy; Impairment; Individual; Inflammation; Kidney; Lead; Lesion; Liquid substance; Losartan; Magnetic Resonance Imaging; Measures; Medial; Medical; Metabolic; Microcirculation; Na(+)-K(+)-Exchanging ATPase; Nephrectomy; Nephrons; Operative Surgical Procedures; Outcome; Oxidative Stress; Oxygen; Oxygen Consumption; Perfusion; Principal Investigator; Procedures; Production; Pyelonephritis; Reaction; Recovery; Recovery of Function; Relative (related person); Renal Circulation; Renal clearance function; Renal function; Renal tubule structure; Renin; Renovascular Hypertension; Research Personnel; Reserpine; Residual state; Resolution; Series; Severities; Sodium; Staging; Stenosis; Techniques; Testing; Thinking; Tissues; Transforming Growth Factor beta; Tubular formation; Uncertainty; Ureter; Urine; Vasodilator Agents; arteriole; artery occlusion; deoxyhemoglobin; diagnosis evaluation; falls; fluid flow; follow-up; functional decline; glomerulosclerosis; hemodynamics; improved; interstitial; novel; pressure; programs; renal artery; renal ischemia; research study; response; tempol

For years the diagnosis, .evaluation of renal function and the treatment of renovascular hypertension has been the subject of intense debate. Most of these uncertainties are due to the lack of important information about the changes in intrarenal hemodynamics, glomerular filtration rate and proximal and distal tubular function in the stenotic kidney (ST-KD) as well as in the contralateral kidney (CONT-KD). Renal clearances are not useful in these conditions because of mixture of urine in the bladder whereas independent catheterization of ureters (split renal function) lead to pyelonephritis. In this proposal we intend to answer these questions by using a novel three-dimensional tomographer with high temporal resolution that measures accurately individual kidney blood flow (including cortical and medullary flow), proximal loop of Henle and distal tubular fluid flow and fluid reabsorption. Actual renal ischemia is measured in each kidney by estimating with magnetic resonance imaging (MRI), blood (capillary) oxygen (O2) levels of deoxyhemoglobin (BOLD technique). In the kidney O2 consumption is determined by sodium (Na) reabsorption in distal tubules by Na, K ATPase. Its inhibition with furosemide suppress O2 consumption (FSOC) and decrease blood levels of deoxyhemoglobin. The proposal contains three specific aims. In the first, the hypothesis to be tested is that the degree of arterial obstruction will determine a) the stage of functional deficit in the ST-KD; b) the degree of increase in blood pressure; and c) the functional compensation reaction (hypertrophy) of the CONT-KD. These different responses will correlate with either increases (CONT-KD) or decreases (ST-KD) of Na delivery and O2 consumption in distal nephrons. The second specific aim tests the hypothesis that the efficacy of PTRA to restore renal function is determined by a) the degree of atrophy and functional decline in the ST-KD; b) the amount of ST-KD function that has been transferred to CONT-KD; c) the degree of hypertension; and d) the inability of furosemide to induce O2 suppression. This study will define the conditions under which PTRA is successful in recovering renal function in both the ST- and CONT-KD. Finally, the third specific aims, tests the hypothesis that normalization of hypertension by medical treatment significantly aggravates the function of the ST-KD but may be beneficial to recover CONT-KD function. The conditions under which the CONT-KD may benefit from medical treatment are related to the possible reversal of vascular hyperplasia in preglomerular arterioles and that residual circulation is sufficient to meet the metabolic demands of tubular hypertrophy. It is also assumes that anti-hypertensives that suppress the production of angiotensin II or oxidative stress will be more effective in reversal of renal function to normal than non-specific vasodilators. Elucidation of all these issues will have enormous clinical repercussion in the diagnosis, follow up, and treatment of renovascular hypertension.

多年来，诊断，肾功能评估和肾血管高血压的治疗已有 是激烈辩论的主题。这些不确定性大多数是由于缺乏重要信息 关于肾内血流动力学，肾小球滤过率以及近端和远端管状的变化 在狭窄肾脏（ST-KD）以及对侧肾脏（续）中的功能。肾脏清理 由于膀胱中的尿液混合而在这些条件下没有用 输尿管的导管（肾功能分裂）导致肾盂肾炎。在此提案中，我们打算回答 这些问题通过使用具有高时间分辨率的新颖的三维三维层造影师 准确地衡量单个肾脏血流（包括皮质和髓质流），近端环 Henle和远端管状流体流量和流体吸收。实际肾脏缺血是在每个肾脏中测量的 通过磁共振成像（MRI），血液（毛细血管）氧（O2）水平估计 脱氧血红蛋白（粗体技术）。在肾脏中，消耗是通过钠（NA）确定的 Na，K ATPase在远端小管中的重吸收。它用速尿抑制抑制O2消耗 （FSOC）并降低脱氧血红蛋白的血液水平。该提案包含三个具体目标。在 首先，要检验的假设是动脉阻塞的程度将决定a） ST-KD的功能不足； b）血压的增加程度； c）功能 续KD的补偿反应（肥大）。这些不同的响应将与任何一个相关 远端肾脏中Na递送和O2消耗的增加（cont-kd）或减少（st-kd）。这 第二个特定目的检验了PTRA恢复肾功能的疗效的假设由 a）ST-KD的萎缩程度和功能下降； b）已有的ST-KD功能的量 转移到cont-kd； c）高血压程度； d）速尿无法诱导O2 抑制。这项研究将定义PTRA成功恢复肾脏的条件 在st-kd和cont-kd中的功能。最后，第三个特定目的是检验的假设 通过治疗使高血压归一化可显着加剧ST-KD的功能，但 可能有益于恢复cont-kd函数。 CONT-KD可能受益的条件 从医疗治疗中可能与肿瘤前血管增生的可能逆转有关 小动脉和残留循环足以满足管状肥大的代谢需求。这是 还假设抑制血管紧张素II或氧化应激产生的抗高血压是 比非特异性血管扩张剂更有效地将肾功能逆转为正常。阐明所有这些 问题将在诊断，随访和治疗中具有巨大的临床影响 高血压。