Adiponectin and Cardiovascular Disease in the CKiD Children

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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.