Adiponectin and Cardiovascular Disease in the CKiD Children

CKiD 儿童的脂联素与心血管疾病

• 批准号: 7315923
• 负责人: MARK M. MITSNEFES
• 金额: $ 26.25万
• 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/7315923
• 关键词: Accounting; Adipose tissue; Adult; Advisory Committees; Age; Ancillary Study; Anemia due to Chronic Disorder; Anti-Inflammatory Agents; Anti-inflammatory; Appendix; 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; Clinical; Cognitive; Complex; Condition; 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; 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; Personal Satisfaction; Physiological; Plasma; Population; Prevalence; Prevention; Principal Investigator; Procedures; Prospective Studies; Proteins; Protocols documentation; Publishing; Race; Rate; 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; caN protocol; cardiovascular disorder risk; cohort; cost; cytokine; design; expectation; glucose metabolism; human disease; improved; in vivo; indexing; innovation; insulin sensitivity; interest; intima media; mortality; neurodevelopment; novel; outcome forecast; programs; prospective; protective effect; repository; research to practice; resistin; sex; tool; ventricular hypertrophy; 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）： 脂联素是参与调节脂质和葡萄糖代谢的调节的脂肪组织的产物。与其他脂肪因子相反，脂联素赋予了针对动脉粥样硬化的保护作用。低血清脂联素与成年人的心血管结局较差有关。与绝大多数人类疾病的脂联素血浆浓度降低不同，慢性肾脏疾病（CKD）中脂联素的血浆水平超出了生理水平。这些升高的循环脂联素水平如何与CKD患者经常发现的胰岛素抵抗，血脂异常和炎症相互作用。我们建议调查脂联素与轻度至中度肾功能不全儿童儿童中慢性肾脏疾病（CKID）研究的儿童的CV风险和CV结局的关联，这是一项正在进行的NIH资助，多中心，前瞻性观察性研究。目的1：估计血清脂联素及其高分子体重（HMW）和低分子重量（LMW）的水平，并描述按年龄，性别，种族和肾脏不足程度来描述脂联素水平。目的2：研究脂联素水平在并发水平以及其他脂肪细胞（瘦素，抵抗素），胰岛素抵抗和炎症的随后变化上的关联。目的3：研究脂联素及其对同时状态的分数以及CKID队列中CV结构和功能的随后变化的关联。 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.对这些CV结果的评估是CKID研究的一部分。 AIM 4：分析脂联素基因（ACDC）序列变体中的CKID儿童低血清脂联素水平的序列变体。我们的期望是，这项研究的结果将建立脂联素或其亚裂缝作为CKD患者早期CV结果的独立预测指标。脂联素与其他简历危险因素结合使用，将提供进一步的工具，以开发“ CVD面板”，未来的研究人员和临床医生可以将其用作CKD年轻患者的诊断和治疗方法的基础。