title: Urinary angiotensinogen as a novel biomarker of the intrarenal renin-angiotensin system status in hypertensive patients.
abstract: We reported previously that urinary angiotensinogen (UAGT) levels provide a specific index of the intrarenal renin-angiotensin system (RAS) status in angiotensin II-dependent hypertensive rats. To study this system in humans, we recently developed a human angiotensinogen ELISA. To test the hypothesis that UAGT is increased in hypertensive patients, we recruited 110 adults. Four subjects with estimated glomerular filtration levels <30 mL/min per 1.73 m(2) were excluded because previous studies have already shown that UAGT is highly correlated with estimated glomerular filtration in this stage of chronic kidney disease. Consequently, 106 paired samples of urine and plasma were analyzed from 70 hypertensive patients (39 treated with RAS blockers [angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers; systolic blood pressure: 139+/-3 mm Hg] and 31 not treated with RAS blockers [systolic blood pressure: 151+/-4 mm Hg]) and 36 normotensive subjects (systolic blood pressure: 122+/-2 mm Hg). UAGT, normalized by urinary concentrations of creatinine, were not correlated with race, gender, age, height, body weight, body mass index, fractional excretion of sodium, plasma angiotensinogen levels, or estimated glomerular filtration. However, UAGT/urinary concentration of creatinine was significantly positively correlated with systolic blood pressure, diastolic blood pressure, urinary albumin:creatinine ratio (r=0.5994), and urinary protein:creatinine ratio (r=0.4597). UAGT/urinary concentration of creatinine was significantly greater in hypertensive patients not treated with RAS blockers (25.00+/-4.96 microg/g) compared with normotensive subjects (13.70+/-2.33 microg/g). Importantly, patients treated with RAS blockers exhibited a marked attenuation of this augmentation (13.26+/-2.60 microg/g). These data indicate that UAGT is increased in hypertensive patients, and treatment with RAS blockers suppresses UAGT, suggesting that the efficacy of RAS blockade to reduce the intrarenal RAS activity can be assessed by measurements of UAGT.
authors.affiliation: Department of Medicine, Renal Center of Excellence, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112-2699, USA. hkobori@tulane.edu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: A Brent
authors.initials: AB
authors.lastname: Alper
authors.forename: Rajesh
authors.initials: R
authors.lastname: Shenava
authors.forename: Akemi
authors.initials: A
authors.lastname: Katsurada
authors.forename: Toshie
authors.initials: T
authors.lastname: Saito
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.forename: Maki
authors.initials: M
authors.lastname: Urushihara
authors.forename: Kayoko
authors.initials: K
authors.lastname: Miyata
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Satou
authors.forename: L Lee
authors.initials: LL
authors.lastname: Hamm
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000808:Angiotensinogen / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology* / Q000652:urine; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D015415:Biomarkers; D000808:Angiotensinogen; D003404:Creatinine