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Obesity and Insulin Resistance in Resistant Hypertension: Implications for the Kidney

  • Akhilesh Rao
    Correspondence
    Address correspondence to Akhilesh Rao, MD, Division of Nephrology and Hypertension, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Five Hospital Drive, DC043.00, Columbia, MO 65212.
    Affiliations
    Division of Nephrology and Hypertension, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO; and Harry S. Truman Memorial Veterans Hospital
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  • Vishwam Pandya
    Affiliations
    Division of Nephrology and Hypertension, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO; and Harry S. Truman Memorial Veterans Hospital
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  • Adam Whaley-Connell
    Affiliations
    Division of Nephrology and Hypertension, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO; and Harry S. Truman Memorial Veterans Hospital
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      There is recognition that the obesity epidemic contributes substantially to the increasing incidence of CKD and resistant hypertension (HTN). The mechanisms by which obesity promotes resistance are an area of active interest and intense investigation. It is thought that increases in visceral adiposity lead to a proinflammatory, pro-oxidative milieu that promote resistance to the metabolic actions of insulin. This resistance to insulin at the level of skeletal muscle tissue impairs glucose disposal/utilization through actions on the endothelium that include vascular rarefaction, reductions in vascular relaxation, and vascular remodeling. Insulin resistance derived from increased adipose tissue and obesity has system-wide implications for other tissue beds such as the kidney that affects blood pressure regulation. The additional autocrine and paracrine activities of adipose tissue contribute to inappropriate activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system that promote kidney microvascular remodeling, stiffness, and sodium (Na+) retention that in turn promote HTN and in the CKD patient, resistance. In this review, we will summarize the important mechanisms that link obesity to CKD as they relate to resistant HTN.

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