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

描述（由申请人提供）：慢性肾脏疾病（CKD）患者人数呈上升趋势。这在一定程度上是由于糖尿病和高血压患者人数的增加。据估计，目前美国有超过1500万人患有中度慢性肾病。但其中只有一小部分会进展，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会进步。确定这一点在患者管理方面具有重要意义。因此，最近人们对开发替代标志物来表征CKD的兴趣越来越大。我们建议测试一种或几种MRI标记物是否有助于识别有进展风险的受试者。在这项研究中，我们将在少数中度CKD患者中评估这些测量。目前提出了三种类型的标志物，一种是简单的肾脏大小测量。第二是描述肾脏的结构组成。纤维化是慢性肾病的后果，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程度。现在人们普遍认为，在患病的情况下，肾脏变得更加缺氧，这实际上可能会导致纤维化的发生。我们率先使用BOLD MRI来评估肾内氧合，并将测试它是否能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。所有建议的方法都不需要任何外源性对比管理。如果项目成功，可能会产生一个或多个标记，用于识别有进展风险的受试者，进而可能对患者管理产生重大影响。此外，这些标志物可用于监测疾病进展和干预措施。这将对药物开发和在动物模型和人类中测试新的干预策略具有重要意义。

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.