Urinary angiotensinogen excretion is associated with blood pressure in obese young adults

Abstract

Intrarenal RAS has been suggested to be involved in the pathogenesis of hypertension. It was recently reported that urinary angiotensinogen excretion levels are associated with intrarenal RAS. However, few markers predicting intrarenal RAS have been investigated in obese young subjects. The present study evaluated the association between blood pressure and intrarenal RAS activity, inflammation and oxidative stress in obese young adults. Urinary angiotensinogen excretion and urinary monocyte chemotactic protein (MCP)-1, and urinary thiobarbituric acid reaction substance (TBARS) as markers of intrarenal RAS activity, inflammation, and oxidative stress, respectively, were determined from morning urine of 111 young male adults. Participants were divided into two groups based on the body mass index (BMI). Natural log-transformed urinary angiotensinogen excretion level was significantly associated with blood pressure, MCP-1 excretion, and TBARS excretion elevation in the obese group (BMI ≥25 kg/m(2)). Multivariable analyses showed that every 1 standard deviation increase in natural-log transformed urinary angiotensinogen and MCP-1 excretion, but not TBARS excretion level was associated with elevated blood pressure in the obese group. These results indicate that urinary angiotensinogen and MCP-1 excretion were associated with blood pressure elevation in this population of obese young adults. It suggested that inappropriate RAS activity and inflammation precedes hypertension in obese young subjects and urinary angiotensinogen could be a screening maker for hypertension in young obese subjects.

Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children

“…In this study, we further extended this result and clarified that it is observed regardless of the obesity index considered: classes of BMI or tertiles of WHtR or percent body fat mass. Although contrary to our initial hypothesis this result in obese but otherwise healthy children is in accordance with that of the only two studies concerning obesity and intrarenal RAAS, which reported similar U-AGT between obese and nonobese adults [7,18]. In contrast, animal models of obesity show an imbalance of renal RAAS components.…”

“…The rise in U-AGT precedes the onset of microalbuminuria, suggesting that U-AGT might be an early marker of nephropathy [15]. Interestingly, excessive activation of the adipose RAAS seems to be crucial for establishment and progression of kidney disease [13,17] but only two small sample studies have been performed in the setting of human obesity [7,18]. In both studies, no difference was found in U-AGT between obese adults and nonobese controls.…”

Independent regulation of renin–angiotensin–aldosterone system in the kidney

“…Then, inappropriate production of Ang II may further stimulate local expression of angiotensinogen and associated Ang II generation in the kidney. Such vicious cycle of intrarenal RAAS activation is suggested to be a critical factor for the progression of diabetic nephropathy [ 52 , 53 ]. Studies have also shown that treatment with ARBs significantly decreases both angiotensinogen expression and Ang II levels in the kidney [ 6 , 10 , 12 , 54 , 55 ].…”

Urinary Angiotensinogen Displays Sexual Dimorphism in Non-Diabetic Humans and Mice with Overweight

“…Obesity is associated with proteinuria and loss of nephron function which exacerbates hypertension [ 26 ]. In the kidneys, the activation of the RAS has also been associated with the augmentation of uAGT, increased SBP, and the development of CKD [ 27 , 28 ]. In the present study, despite the significant increase in BMI, we did not detect changes in SBP or albuminuria in OW and control lean human subjects, which is consistent with a non-diabetic phenotype.…”