Urinary Angiotensinogen as a Novel Biomarker of Intrarenal Renin-Angiotensin System in Chronic Kidney Disease.

Abstract

An activated intrarenal reninangiotensin system (RAS) plays a crucial role in the pathogenesis of hypertension and chronic kidney diseases (CKD). Angiotensinogen (AGT) is the only known substrate for renin, which is the rate-limiting enzyme of the RAS. Because the levels of AGT are close to the Michaelis-Menten constant for renin, AGT levels can also control the RAS activity, and upregulation of AGT may lead to elevated angiotensin peptide levels and increases in blood pressure. Recent studies on experimental animal models have documented the involvement of AGT in the intrarenal RAS activation and development of hypertension. Enhanced intrarenal AGT mRNA and/or protein levels occur in experimental models of hypertension and kidney diseases supporting important roles in the development and progression of hypertension and kidney diseases. Urinary excretion rates of AGT provide a specific index of intrarenal RAS status in angiotensin II-infused rats. Also, a direct quantitative method was recently developed to measure urinary AGT using human AGT ELISA. These data prompted us to measure urinary AGT in patients with hypertension and CKD, and investigate correlations with clinical parameters. This brief review will address the potential of urinary AGT as a novel biomarker of the intrarenal RAS status in hypertension and CKD.