title: Increased urinary excretion of angiotensinogen is associated with risk of chronic kidney disease.
abstract: BACKGROUND
  The effect of intrarenal renin-angiotensin system (RAS) activity on risk of chronic kidney disease (CKD) has not been well studied in human subjects.
  
  
  METHODS
  We investigated the association between urinary angiotensinogen, a reliable biomarker of intrarenal RAS activity, and risk of CKD in 201 patients and 201 controls. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) or presence of albuminuria ( ≥ 30 mg/24 h).
  
  
  RESULTS
  Compared to controls, median urinary angiotensinogen excretion (45.4 versus 7.4 μg/24 h, P < 0.0001) and angiotensinogen-to-creatinine ratio (26.3 versus 4.4 μg/g, P < 0.0001) were significantly higher in patients with CKD. Log-transformed urinary angiotensinogen excretion and angiotensinogen-to-creatinine ratio were inversely correlated with eGFR (r = -0.59 and -0.57, both P < 0.0001) and positively correlated with log-transformed urinary albumin excretion (r = 0.89 and 0.87, both P < 0.0001). After adjusting for multiple covariables, including the use of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, diuretics and statins, the odds ratios (95% confidence interval) for CKD comparing the highest tertile to the lowest two tertiles of urinary angiotensinogen excretion and angiotensinogen-to-creatinine ratio were 6.70 (3.43, 13.1; P < 0.0001) and 6.45 (3.34, 12.4; P < 0.0001), respectively.
  
  
  CONCLUSIONS
  These data indicate the intrarenal RAS may play an important role in the etiology of CKD, and urinary angiotensinogen may be a useful clinical biomarker for the identification of patients at a high risk for CKD.
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Mills
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Lotuce Lee
authors.initials: LL
authors.lastname: Hamm
authors.forename: Arnold Brent
authors.initials: AB
authors.lastname: Alper
authors.forename: Islam Enver
authors.initials: IE
authors.lastname: Khan
authors.forename: Mahfuz
authors.initials: M
authors.lastname: Rahman
authors.forename: Luis Gabriel
authors.initials: LG
authors.lastname: Navar
authors.forename: Yanxi
authors.initials: Y
authors.lastname: Liu
authors.forename: Grace M
authors.initials: GM
authors.lastname: Browne
authors.forename: Vecihi
authors.initials: V
authors.lastname: Batuman
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000209:etiology / Q000652:urine; D000808:Angiotensinogen / Q000097:blood / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000503:physiopathology / Q000652:urine*; D012084:Renin-Angiotensin System / Q000502:physiology; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D000808:Angiotensinogen; D003404:Creatinine