ENDOTHELIAL DYSFUNCTION, ADIPOCYTOKINES, INFLAMATION AND CHRONIC KIDNEY DISEASE

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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) has become an important public health challenge in the US. 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 experiments. 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. To achieve this goal, we are conducting a case-control study to compare endothelial function, adipocytokines and inflammation between cases with CKD and controls without 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.