Novel Risk Factors for Chronic Kidney Disease

描述(由申请人提供)：本申请是针对PA-03-091计划公告“肾脏疾病辅助研究获取临床试验、流行病学研究和数据库中的信息”而写的。其目的是确定：(1)炎症的生物标记物(高敏C反应蛋白、白介素6、肿瘤坏死因子-α受体2)；(2)氧化应激的生物标记物(血浆游离F2-异前列腺素、血浆蛋白羰基含量)；(3)内皮功能障碍的生物标记物(E-选择素、细胞间黏附分子1、血管细胞黏附分子1)；以及(4)视网膜微血管直径与估计的肾小球滤过率(GFR)、估计的GFR的15年变化以及15年间慢性肾脏疾病(CKD)的发生发展的关系。该项目被设计为海狸大坝研究的辅助研究。测试该项目具体目标所需的信息将通过将储存的实验室测量的新数据与海狸水坝研究中已经收集的数据结合起来，这是一项正在进行的基于人口的研究，从1988年至1990年开始每隔5年对43-86岁的人进行检查。该设计将是一项嵌套的病例队列研究，在海狸大坝研究中进行。我们预计269例CKD事件，并将随机选择1150人作为样本。事故CKD将被定义为每1.73米的估计GFR&lt；60毫升/分钟[2]。估计的肾小球滤过率将使用修正的肾脏疾病饮食方程来计算。将对基线冰冻血浆样本进行批量分析，以确定炎症、内皮功能障碍和氧化应激的生物标志物。已经使用计算机辅助程序测量了视网膜血管直径。这项研究的数据将为评估炎症、氧化应激、内皮功能障碍、微血管特征和CKD之间的关系提供一个独特的机会。这一新的数据可能为了解低水平的这些标记物对老年人口中CKD发病率的相对保护价值提供洞察力。

DESCRIPTION (provided by applicant): This application is written in response to Program Announcement PA-03-091, "Ancillary Studies of Kidney Disease Accessing Information from Clinical Trials, Epidemiological Studies, and Databases". Its aims are to determine the relation of: (1) biomarkers of inflammation (high sensitivity C-reactive protein, interleukin 6, tumor necrosis factor-alpha Receptor 2); (2) biomarkers of oxidative stress (plasma free F2-isoprostanes, plasma protein carbonyl content); (3) biomarkers of endothelial dysfunction (E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1); and (4) retinal microvascular diameters to estimated glomerular filtration rate (GFR), 15-year change in estimated GFR, and the development of incident chronic kidney disease (CKD) over a 15-year interval. This project is designed as an ancillary study to the Beaver Dam Studies. The information necessary to test the specific aims of the project will be obtained by combining new data from stored laboratory measures and data already collected in the Beaver Dam Studies, ongoing population-based studies of persons 43-86 years who were examined at 5-year intervals beginning in 1988- 1990.. The design will be a nested case-cohort study within the Beaver Dam Studies. We anticipate 269 cases of incident CKD and will select 1150 persons for the random sample. Incident CKD will be defined as an estimated GFR<60 mL/min per 1.73 meter[2]. The estimated GFR will be calculated using the Modification of Diet in Renal Disease equation. Baseline frozen plasma samples will be batch-analyzed for biomarkers of inflammation, endothelial dysfunction, and oxidative stress. Retinal vessel diameters have been measured using a computer-assisted program. Data from this study will provide a unique opportunity to evaluate the relationship of inflammation,, oxidative stress, endothelial dysfunction, microvascular characteristics and CKD. The new data may provide insights into the relative protective value of low levels of these markers on the incidence CKD in an aging population.