title: Urinary angiotensinogen as a marker of intrarenal angiotensin II activity associated with deterioration of renal function in patients with chronic kidney disease.
abstract: 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.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, Japan. ytatsuo@hama-med.ac.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Fukasawa
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujigaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000808:Angiotensinogen / Q000097:blood / Q000652:urine*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D024042:Collagen Type I; D000808:Angiotensinogen; D000804:Angiotensin II; D019808:Losartan