Novel Risk Factors for Chronic Kidney Disease

描述（由申请人提供）：本申请是根据项目公告PA-03-091“从临床试验、流行病学研究和数据库获取信息的肾脏疾病辅助研究”撰写的。其目的是确定：(1)炎症生物标志物（高敏c反应蛋白、白细胞介素6、肿瘤坏死因子α受体2）之间的关系；(2)氧化应激生物标志物（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志物（e -选择素、细胞间粘附分子1、血管细胞粘附分子1）；(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年内慢性肾脏疾病（CKD）的发生。本项目是作为海狸大坝研究的辅助研究而设计的。测试该项目的具体目标所需的信息将通过结合存储的实验室测量的新数据和海狸坝研究中已经收集的数据来获得。海狸坝研究是正在进行的以43-86岁人群为基础的研究，从1988年到1990年开始，每隔5年进行一次检查。该设计将是比弗水坝研究中的一个嵌套病例队列研究。我们预计会有269例突发CKD，并将选择1150人作为随机样本。突发CKD将定义为估计GFR<60 mL/min / 1.73 m[2]。估计的GFR将使用肾脏疾病的饮食改变方程来计算。基线冷冻血浆样本将被批量分析炎症、内皮功能障碍和氧化应激的生物标志物。使用计算机辅助程序测量视网膜血管直径。这项研究的数据将为评估炎症、氧化应激、内皮功能障碍、微血管特征与CKD的关系提供一个独特的机会。这些新数据可能为低水平的这些标志物对老龄人群CKD发病率的相对保护价值提供见解。

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.