Adiponectin and Cardiovascular Disease in the CKiD Children

描述（由申请人提供）： 脂联素是脂肪组织的产物，参与调节脂质和葡萄糖代谢。与其他脂肪因子相比，脂联素具有抗动脉粥样硬化的保护作用。低血清脂联素与成人心血管预后不良相关。与绝大多数人类疾病中脂联素血浆浓度降低不同，慢性肾病（CKD）中脂联素的血浆水平升高超过生理水平。这些升高的循环脂联素水平如何与胰岛素抵抗、血脂异常和炎症（CKD患者常见的疾病）相互作用尚不清楚。我们建议在参加儿童慢性肾脏病（CKiD）研究的轻度至中度肾功能不全儿童中研究脂联素与CV风险和CV结局的相关性，该研究是一项正在进行的NIH资助的多中心前瞻性观察性研究。目标1：估计CKiD队列中血清脂联素及其高分子量（HMW）和低分子量（LMW）组分的水平，并按年龄、性别、种族和肾功能不全程度描述脂联素水平。目标二：研究脂联素水平与其他脂肪细胞素（瘦素，Leptin）、胰岛素抵抗和炎症的同时水平和随后变化的相关性。目标3：研究脂联素及其组分与CKiD队列中CV结构和功能的并发状态和后续变化的相关性。将进行超声心动图和颈动脉超声检查，以评估是否存在心肌病的早期标志物，如左心室肥大（LVH）和LV功能障碍，以及动脉粥样硬化的早期标志物，如颈动脉内膜中层厚度（cIMT）增加、颈动脉壁僵硬度和主动脉顺应性。这些CV结局的评价是CKiD研究的一部分。目的4：分析低血清脂联素水平的CKiD儿童的脂联素基因（ACDC）序列变异。我们的期望是，这项研究的结果将确立脂联素或其亚组分作为CKD患者早期CV结局发展的独立预测因子。脂联素与其他心血管风险因素结合使用，将为开发“CVD面板”提供进一步的工具，未来的研究人员和临床医生可将其用作年轻CKD患者CVD诊断和治疗方法的基础。

DESCRIPTION (provided by applicant): Adiponectin is a product of adipose tissue involved in the regulation of lipid and glucose metabolism. In contrast to other adipokines, adiponectin confers a protective effect against atherosclerosis. Low serum adiponectin is associated with worse cardiovascular outcomes in adults. Unlike in the vast majority of human diseases where adiponectin plasma concentration is decreased, the plasma level of adiponectin in chronic kidney disease (CKD) is increased beyond the physiological levels. How these elevated circulatory adiponectin levels interact with insulin resistance, dyslipidemia and inflammation, conditions frequently found in patients with CKD, is not clearly understood. We propose to investigate the associations of adiponectin with CV risks and CV outcomes in children with mild to moderate renal insufficiency enrolled in the Chronic Kidney Disease in Children (CKiD) study, an ongoing NIH-funded, multicenter, prospective observational study. Aim 1: to estimate levels of serum adiponectin and its high-molecular-weight (HMW) and low-molecular weight (LMW) fractions in the CKiD cohort and describe adiponectin levels by age, sex, race, and degree of renal insufficiency. Aim 2: to investigate the association of adiponectin levels on the concurrent levels and subsequent changes in other adipocynes (leptin, resistin), insulin resistance and inflammation. Aim 3: to investigate the association of adiponectin and its fractions on the concurrent status and subsequent changes in CV structure and function in the CKiD cohort. Echocardiography and carotid artery ultrasound will be performed to assess the presence of early markers of cardiomyopathy, such as left ventricular hypertrophy (LVH) and LV dysfunction and early markers of atherosclerosis, such as increased carotid artery intima-media thickness (cIMT), carotid arterial wall stiffness and aortic compliance. Evaluation of these CV outcomes is a part of the CKiD study. Aim 4: Analyze adiponectin gene (ACDC) sequence variants in a sub-cohort of the CKiD children with low serum adiponectin levels. Our expectations are that the results of this study will establish adiponectin or its sub-fractions as an independent predictor for the development of early CV outcomes in CKD patients. Used in combination with other CV risk factors, adiponectin will provide further tools in developing a 'CVD Panel' that can be used by future researchers and clinicians as a foundation for diagnosis and treatment approaches to CVD in young patients with CKD.