ENDOTHELIAL DYSFUNCTION, ADIPOCYTOKINES, INFLAMATION AND CHRONIC KIDNEY DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 慢性肾脏病（CKD）是美国一项重要的公共卫生挑战。CKD是终末期肾病（ESRD）、心血管疾病（CVD）和过早死亡的主要风险因素。了解CKD的新风险因素可能为早期干预提供有效方法，以降低CKD相关的发病率和死亡率。在小型临床研究和动物实验中，内皮功能障碍、脂肪细胞因子和炎症与ESRD和CVD相关。然而，其在CKD病因学中的作用尚未确定。 本研究的总体目标是检测内皮功能障碍、脂肪细胞因子和炎症对CKD风险的影响。 拟议研究的具体目标是：（1）检查内皮功能障碍的生物标志物之间的关联，（血浆不对称二甲基精氨酸、内皮素-1、细胞间粘附分子-1、血管细胞粘附分子1、E-选择素、L-精氨酸和NO2/NO3（NOx）水平，和NO2/NO3（NOx）的尿排泄）以及使用高分辨率超声通过肱动脉反应性评估的内皮功能和CKD的风险;（2）研究脂肪细胞因子与（瘦素、瘦素和脂联素）与CKD风险的关系;（3）检查炎症与CKD风险之间的关系。（C-反应蛋白、白细胞介素-6和肿瘤坏死因子-a）与CKD风险的关系;以及（4）检测内皮功能障碍的生化标志物与使用高分辨率超声通过肱动脉反应性评估的内皮功能之间的相关性。 这项研究具有重要的临床和公共卫生意义。了解CKD患者的内皮功能障碍、脂肪细胞因子和炎症的性质将为制定定制的干预策略提供见解，包括正常化内皮功能障碍、靶向脂肪细胞因子和炎症，以预防和治疗CKD和相关CVD。此外，如果获得资助，拟议的研究将提供重要的初步数据，以进行前瞻性队列研究，以检查内皮功能障碍，脂肪细胞因子和炎症与CKD和相关CVD进展的纵向关联。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic kidney disease (CKD) is an important public health challenge in the United States . CKD is a major risk factor for end-stage renal disease (ESRD), cardiovascular disease (CVD), and premature death. Understanding novel risk factors for CKD may provide effective approaches for early intervention in order to reduce the morbidity and mortality related to CKD. Endothelial dysfunction, adipocytokines and inflammation have been associated with ESRD and CVD in small clinical studies and animal experiements. However their role in the etiology of CKD has not been established. The overall objectives of this proposed study are to examine the effects of endothelial dysfunction, adipocytokines, and inflammation on the risk of CKD. The specific aims of the proposed study are: (1) to examine the association between biomarkers of endothelial dysfunction (plasma levels of asymmetric dimethylarginine, endothelin-1, intercellular adhesion molecule-1, vascular cell adhesion molecule 1, E-selectin, L-arginine and NO2/NO3 (NOx), and urinary excretion of NO2/NO3 (NOx)) as well as endothelial function assessed by brachial artery reactivity using high-resolution ultrasound and risk of CKD; (2) to examine the association between adipocytokines (leptin, resistin, and adiponectin) and risk of CKD; (3) to examine the association between inflammation (C-reactive protein, interleukin-6, and tumor necrosis factor-a) and risk of CKD; and (4) to examine the correlation between biochemical markers of endothelial dysfunction and endothelial function assessed by brachial artery reactivity using high-resolution ultrasound. This study has important clinical and public health implications. Understanding the nature of endothelial dysfunction, adipocytokines and inflammation in patients with CKD will provide insight into developing tailored intervention strategies including normalizing endothelial dysfunction, targeting adipocytokines and inflammation for the prevention and treatment of CKD and related CVD. In addition, the proposed study, if funded, will provide important preliminary data to conduct a prospective cohort study to examine the longitudinal association of endothelial dysfunction, adipocytokines and inflammation with the progression of CKD and related CVD.