INVITED REVIEW Augmented intrarenal and urinary angiotensinogen in hypertension and chronic kidney disease

Abstract Activated intrarenal renin–angiotensin system plays a cardinal role in the pathogenesis of hypertension and chronic kidney disease. Angiotensinogen is the only known substrate for renin, which is the rate-limiting enzyme of the renin–angiotensin system. Because the levels of angiotensinogen are close to the Michaelis–Menten constant values for renin, angiotensinogen levels as well as renin levels can control the renin–angiotensin system activity, and thus, upregulation of angiotensinogen leads to an in-crease in the angiotensin II levels and ultimately increases blood pressure. Recent studies using experimental animal models have documented the involvement of angiotensino-gen in the intrarenal renin–angiotensin system activation and development of hypertension. Enhanced intrarenal angiotensinogen mRNA and/or protein levels were observed in experimental models of hypertension and chronic kidney disease, supporting the important roles of angiotensinogen in the development and the progression of hypertension and chronic kidney disease. Urinary excretion rates of angioten-sinogen provide a specific index of the intrarenal renin– angiotensin system status in angiotensin II-infused rats. Also, a direct quantitative method has been developed re-cently to measure urinary angiotensinogen using human angiotensinogen enzyme-linked immunosorbent assay. These data prompted us to measure urinary angiotensinogen in patients with hypertension and chronic kidney disease, and investigate correlations with clinical parameters. This short article will focus on the role of the augmented intra-renal angiotensinogen in the pathophysiology of hyperten-sion and chronic kidney disease. In addition, the potential of urinary angiotensinogen as a novel biomarker of the intra-renal renin–angiotensin system status in hypertension and chronic kidney disease will be also discussed