CT imaging for the assessment of kidney injury distal to renal artery stenosis

CT 成像评估肾动脉狭窄远端肾损伤

• 批准号: 7143568
• 负责人: Lilach O Lerman
• 金额: $ 30.34万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7143568
• 关键词: antihypercholesterolemic agent; artery stenosis; atherosclerosis; bioimaging /biomedical imaging; chronic renal failure; computed axial tomography; diagnosis design /evaluation; intraluminal angioplasty; kidney disorder; kidney disorder chemotherapy; kidney disorder diagnosis; kidney function; kidney imaging /visualization; nonsurgical revascularization; renal artery; swine

DESCRIPTION (provided by applicant): The impact of vascular disease on morbidity and mortality is on the rise in the Western world. Atherosclerotic renal artery stenosis (ARAS), a common etiology of chronic kidney disease, amplifies deterioration of renal function and attenuates its recovery following intervention. However, the mechanisms leading to these grave outcomes are yet to be identified, partly due to the lack of techniques capable of studying the kidney distal to ARAS, and of suitable experimental models of ARAS. The hypothesis underlying this proposal is that atherosclerosis blunts the recovery of the stenotic ARAS kidney following intervention by impairing renal function and exacerbating oxidative stress, inflammation, and fibrosis, and that high-resolution computed tomography (CT) techniques would be useful to explore and characterize renal injury and response to revascularization. This hypothesis will be tested in a novel pig model of unilateral ARAS that we have developed and characterized, using unique imaging approaches that we have refined to study single-kidney function and structure. Electron beam CT (EBCT) will quantify in vivo, in the stenotic kidney of pigs undergoing percutaneous transluminal renal angioplasty, the reversibility of alterations in renal regional volume, perfusion, GFR, segmental tubular function, and response to challenge. Micro-CT will be subsequently used to assess in situ renal microvascular remodeling, a hallmark of atherosclerosis. The imaging studies will be correlated with in vitro studies of renal redox status, inflammation, and fibrosis. Furthermore, the impact of preexisting renal injury on the response to revascularization will be explored by superimposing ARAS on tubulointerstitial injury or glomerulosclerosis. The effect of attenuation of renal injury will be studied using chronic supplementation of statins, drugs that decrease oxidative stress, inflammation, and fibrosis, and might improve renal outcomes before as well as after intervention. Moreover, renal alterations will be correlated with renal recovery, and potential predictors of interventional success will be determined. The proposed studies may greatly advance our understanding of the pathogenesis of renal injury in ARAS, and assist in development of imaging strategies to detect injury markers and identify predictors of renal viability. Thus, these studies may contribute towards management of patients with renovascular disease.

描述（由申请人提供）：西方世界的血管疾病对发病率和死亡率的影响正在上升。动脉粥样硬化肾动脉狭窄（ARAS）是一种慢性肾脏疾病的常见病因，会放大肾功能的恶化，并在干预后减弱其恢复。但是，导致这些严重结果的机制尚未确定，部分原因是缺乏能够研究ARA远端的肾脏的技术以及适当的ARA实验模型。该提议的基本假设是，干预后，动脉粥样硬化钝化了狭窄的阿拉斯肾脏的恢复，这会损害肾脏功能并加剧氧化应激，炎症和纤维化，以及高分辨率计算机层析成像（CT）技术将有助于探索和表征对肾上腺肾脏造成的肾小管损伤和表征。该假设将在我们已经开发和表征的单方面ARA的新型猪模型中进行测试，并使用我们精炼的独特成像方法研究了单kidney功能和结构。电子束CT（EBCT）将在体内量化，在经皮易感肾血管成形术的狭窄肾脏中，肾脏区域体积，灌注，GFR，节段管函数的改变的可逆性以及对挑战的反应。随后将使用Micro-CT来评估原位肾脏微血管重塑，这是动脉粥样硬化的标志。成像研究将与肾脏氧化还原状况，炎症和纤维化的体外研究相关。此外，将肾脏损伤对血运重建的反应的影响将通过叠加Aras对肾小管间隙损伤或肾小球硬化症的影响进行探索。将使用他汀类药物的慢性补充，减少氧化应激，炎症和纤维化的药物来研究肾损伤的衰减作用，并可能在干预之前和干预后改善肾脏结局。此外，肾脏改变将与肾脏恢复相关，并将确定介入成功的潜在预测指标。拟议的研究可能会大大提高我们对ARA肾脏损伤发病机理的理解，并有助于制定成像策略以检测损伤标志物并确定肾脏生存能力的预测指标。因此，这些研究可能有助于治疗肾血管疾病患者。