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Urinary Angiotensinogen as a Marker of Intrarenal Angiotensin II Activity Associated with Deterioration of Renal Function in Patients with Chronic Kidney Disease

Tatsuo Yamamoto^*, Tsutomu Nakagawa, Hiroyuki Suzuki^*, Naro Ohashi^*, Hirotaka Fukasawa^*, Yoshihide Fujigaki^*, Akihiko Kato, Yukio Nakamura, Fumiaki Suzuki and Akira Hishida^*

^* First Department of Medicine and Division of Blood Purification, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka; and Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan

Address correspondence to: Dr. Tatsuo Yamamoto, First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. Phone: +81-53-435-2261; Fax: +81-53-434-9447; ytatsuo{at}hama-med.ac.jp

Received for publication June 3, 2006. Accepted for publication February 12, 2007.

In chronic kidney disease (CKD), enhanced intrarenal angiotensin II (AngII) is involved in deterioration of renal function, but it is difficult to measure it. For assessment of the potential of urinary angiotensinogen as a marker of intrarenal AngII activity, the correlation of plasma and urinary renin-angiotensin system components, including angiotensinogen, with deterioration of renal function was investigated in 80 patients who had CKD and were not treated with AngII blocking agents. Changes that were induced by 14 d of losartan treatment (25 mg/d) were also measured in 28 patients. Angiotensinogen was measured by RIA of AngI after incubation with renin. Urinary angiotensinogen levels were greater in patients with low estimated GFR and elevated urinary protein and type IV collagen and correlated with renal AngII and type I collagen immunostaining intensities. The risk for deterioration of renal function (i.e., estimated GFR decline of >2.5 ml/min per yr) during a mean follow-up period of 23 mo (maximum 43 mo) was associated with urinary angiotensinogen of >3.0 nmol AngI equivalent per 1 g of urinary creatinine (AngI Eq/g Cre) at enrollment (hazard ratio 3.52). The event-free survival for deterioration of renal function was better in patients with urinary angiotensinogen <3.0 nmol AngI Eq/g Cre than those >3.0 nmol AngI Eq/g Cre. Losartan reduced urinary and plasma angiotensinogen, urinary protein and type IV collagen, and systolic BP, despite concomitant increases in plasma renin and AngII. These data suggest that urinary angiotensinogen is a potentially suitable marker of intrarenal AngII activity associated with increased risk for deterioration of renal function in patients with CKD.

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				N. Ohashi, T. Yamamoto, Y. Huang, T. Misaki, H. Fukasawa, H. Suzuki, A. Togawa, S. Suzuki, Y. Fujigaki, T. Nakagawa, et al. Intrarenal RAS activity and urinary angiotensinogen excretion in anti-thymocyte serum nephritis rats Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1512 - F1518. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673