Longitudinal changes in the intra-renal oxygenation by BOLD MRI in patients with

描述（由申请人提供）：受慢性肾脏疾病（CKD）影响的人数正在增加。部分原因是糖尿病和高血压患者人数不断增加。目前，据估计，在美国有超过1500万人患有中度CKD。但只有一小部分会进展并最终需要移植或透析服务。目前，还没有一个好的方法来确定谁将取得进展的主题。确定这一点在患者管理方面具有重要意义。因此，最近人们越来越关注开发替代标记物来表征CKD。我们建议测试是否一个或几个MRI标记物将是有用的，在确定受试者的进展风险。在本研究中，我们将在少数中度CKD受试者中评价这些测量结果。三种类型的标志物被提出，一种是简单的肾脏大小测量。第二是表征肾脏的结构组成。纤维化是CKD的后果，并且已知是疾病进展的关键决定因素。我们将使用表观扩散系数测量来评估纤维化的程度。现在人们也普遍认为，肾脏在疾病条件下变得更加缺氧，这实际上可能会推动纤维化发展的过程。我们率先使用BOLD MRI来评估肾内氧合，并将测试它是否可以识别有进展风险的受试者。我们还将测试动脉自旋标记法来评估相对肾灌注。所有提出的方法不需要任何外源性造影剂的管理。如果该项目成功，可能会产生一种或多种用于识别有进展风险的受试者的标志物，进而可能对患者管理产生重大影响。此外，这些标志物可能有助于监测疾病进展和干预措施。这对于药物开发和在动物模型和人类中测试新的干预策略都具有重要意义。 公共卫生相关性：目前，据估计，美国有超过1500万人患有中度慢性肾病，但其中只有一小部分会进展并最终需要移植或透析服务。目前，还没有一个好的方法来确定谁将取得进展的主题。本研究旨在测试一种或多种MRI标记物是否可用于识别有进展风险的受试者。这将对我们了解疾病和评估新干预措施的能力产生重大影响。

DESCRIPTION (provided by applicant): The number of people affected by chronic kidney disease (CKD) is on the rise. This is partly attributed to the increasing number of diabetics and hypetensives. Currently it is estimated that over 15 million people have moderate CKD in the US. But only a fraction of these will progress and ultimately require transplantaion or dialysis services. Currently, there is not a good way of identifying subjects who will progress. Determining this has important implications in terms of patient management. So, there has recently been an increased interest in developing alternate markers to characterize CKD. We propose to test whether one or several MRI markers would be useful in identifying subjects at risk of progression. In this study, we will evaluate these measurements in a small number of subjects with moderate CKD. Three types of markers are being proposed, one is simple kidney size measurement. The second is to characterize the structural makeup of the kidney. Fibrosis is a consequence of CKD and is known to be a key determinant for the disease progression. We will use apparent diffusion coefficient measurement to evaluate the degree of fibrosis. It is also now becoming well accepted that kidneys become more hypoxic under diseased conditions and this actually may drive the processes responsible for development of fibrosis. We have pioneered in the use of BOLD MRI to evaluate intrarenal oxygenation and will test if it can identify subjects at risk of progression. We will also test arterial spin labeling method to evaluae relative renal perfusion. All the proposed methods do not require any exogenous contrast administration. If the project is successful, it may lead to one or more markers for identifying subjects at risk of progression and in turn may have a significant impact on patient management. Also, these markers could be useful in monitoring disease progression and interventions. This would be significant for drug development and testing novel interventional strategies both in animal models and in humans. PUBLIC HEALTH RELEVANCE: Currently it is estimated that over 15 million people in the US have moderate level of chronic kidney disease, but only a fraction of these will progress and ultimately require transplantaion or dialysis services. Currently, there is not a good way of identifying subjects who will progress. This study is designed to test whether one or several MRI markers would be useful in identifying subjects at risk of progression. This will have significant impact on our understanding of the disease and the ability to evaluate novel interventions.