Obesity, kidney dysfunction and hypertension: mechanistic links

• Published in: Nature reviews. Nephrology Vol. 15; no. 6; pp. 367 - 385
• Main Authors: Hall, John E, do Carmo, Jussara M, da Silva, Alexandre A, Wang, Zhen, Hall, Michael E
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.06.2019
• Subjects: Adipokines - metabolism; Aldosterone - metabolism; Angiotensin II - metabolism; Antihypertensive drugs; Blood pressure; Care and treatment; Chronic illnesses; Chronic kidney failure; Complications and side effects; Corticosteroids; Diagnosis; Dosage and administration; Health aspects; Humans; Hypertension; Hypertension - metabolism; Hypertension - physiopathology; Intermedin; Kidney - innervation; Kidney - metabolism; Kidney Tubules - metabolism; Leptin - metabolism; Measurement; Nervous system; Obesity; Obesity - metabolism; Obesity - physiopathology; Oxidative Stress; Pro-Opiomelanocortin - metabolism; Receptor, Melanocortin, Type 4 - metabolism; Receptors, Mineralocorticoid - metabolism; Renal Reabsorption - physiology; Renin - metabolism; Risk factors; Sodium; Sodium - metabolism; Sympathetic Nervous System - physiopathology; United States
• ISSN: 1759-5061; 1759-507X
• DOI: 10.1038/s41581-019-0145-4

Excessive adiposity raises blood pressure and accounts for 65-75% of primary hypertension, which is a major driver of cardiovascular and kidney diseases. In obesity, abnormal kidney function and associated increases in tubular sodium reabsorption initiate hypertension, which is often mild before the development of target organ injury. Factors that contribute to increased sodium reabsorption in obesity include kidney compression by visceral, perirenal and renal sinus fat; increased renal sympathetic nerve activity (RSNA); increased levels of anti-natriuretic hormones, such as angiotensin II and aldosterone; and adipokines, particularly leptin. The renal and neurohormonal pathways of obesity and hypertension are intertwined. For example, leptin increases RSNA by stimulating the central nervous system proopiomelanocortin-melanocortin 4 receptor pathway, and kidney compression and RSNA contribute to renin-angiotensin-aldosterone system activation. Glucocorticoids and/or oxidative stress may also contribute to mineralocorticoid receptor activation in obesity. Prolonged obesity and progressive renal injury often lead to the development of treatment-resistant hypertension. Patient management therefore often requires multiple antihypertensive drugs and concurrent treatment of dyslipidaemia, insulin resistance, diabetes and inflammation. If more effective strategies for the prevention and control of obesity are not developed, cardiorenal, metabolic and other obesity-associated diseases could overwhelm health-care systems in the future.