Adiponectin and Cardiovascular Disease in the CKiD Children

CKiD 儿童的脂联素与心血管疾病

• 批准号: 7766717
• 负责人: MARK M. MITSNEFES
• 金额: $ 0.15万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7766717
• 关键词: Accounting; Adipose tissue; Adult; Advisory Committees; Age; Ancillary Study; Anemia due to Chronic Disorder; Anti-Inflammatory Agents; Anti-inflammatory; Atherosclerosis; Behavior; Biological; Biological Markers; Blood Vessels; Cardiac; Cardiomyopathies; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Cause of Death; Cells; Cessation of life; Child; Childhood; Chronic Kidney Failure; Cognitive; Complex; DNA; DNA Sequence; Deterioration; Development; Diabetes Mellitus; Diagnosis; Dyslipidemias; Echocardiography; End stage renal failure; Enrollment; Epidemic; Epidemiologic Studies; Evaluation; Evolution; Foundations; Functional disorder; Funding; Future; Gene Mutation; Genes; Goals; Growth; Heart Diseases; Hyperparathyroidism; Hypertension; Inflammation; Insulin Resistance; Interleukin-6; Investigation; Kidney; Kidney Failure; Left Ventricular Hypertrophy; Leptin; Letters; Lipids; Masks; Measurement; Measures; Molecular Weight; Morbidity - disease rate; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Observational Study; Outcome; Patients; Peripheral Vascular Diseases; Physiological; Plasma; Population; Prevalence; Prevention; Principal Investigator; Procedures; Prospective Studies; Proteins; Protocols documentation; Publishing; Race; Regulation; Relative (related person); Renal function; Research; Research Infrastructure; Research Personnel; Resolution; Risk; Risk Factors; Role; Serum; Staging; Structure; Therapeutic Intervention; Thick; Time; Ultrasonography; Universities; Variant; Very low density lipoprotein cholesterol; adipokines; adiponectin; aged; arterial stiffness; base; cardiovascular disorder risk; clinical practice; cohort; cost; cytokine; design; expectation; glucose metabolism; human disease; improved; in vivo; indexing; inflammatory marker; innovation; insulin sensitivity; interest; intima media; longitudinal design; mortality; neurodevelopment; novel; outcome forecast; programs; prospective; protective effect; repository; resistin; sex; tool; treatment strategy; young adult

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.

描述（由申请人提供）： 脂联素是脂肪组织的产物，参与脂质和葡萄糖代谢的调节。与其他脂肪因子相比，脂联素具有对抗动脉粥样硬化的保护作用。低血清脂联素与成人较差的心血管结局相关。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（慢性肾病患者常见的病症）相互作用，目前尚不清楚。我们建议调查参加儿童慢性肾病 (CKiD) 研究的轻度至中度肾功能不全儿童的脂联素与 CV 风险和 CV 结局的关联，CKiD 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) 部分的水平，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 2：研究脂联素水平与其他脂肪素（瘦素、抵抗素）、胰岛素抵抗和炎症的并发水平和随后变化的关系。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随后变化的关系。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，例如左心室肥厚（LVH）和左心室功能障碍，以及动脉粥样硬化的早期标志物，例如颈动脉内膜中层厚度增加（cIMT）、颈动脉粥样硬化。壁硬度和主动脉顺应性。对这些 CV 结果的评估是 CKiD 研究的一部分。目标 4：分析血清脂联素水平低的 CKiD 儿童亚队列中的脂联素基因 (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。与其他心血管危险因素结合使用，脂联素将为开发“CVD 组合”提供进一步的工具，未来的研究人员和临床医生可以使用该组合作为年轻 CKD 患者 CVD 诊断和治疗方法的基础。