Urinary Angiotensinogen Accurately Reflects Intrarenal Renin-Angiotensin System Activity

Abstract

Background: We recently reported that immunoreactivity of intrarenal angiotensinogen (AGT) is significantly increased in IgA nephropathy patients. Meanwhile, we have developed direct enzyme-linked immunosorbent assays to measure plasma and urinary AGT (UAGT) in humans. This study was performed to test the hypothesis that UAGT levels are increased in chronic glomerulonephritis patients. Methods: We analyzed 100 urine samples from 70 chronic glomerulonephritis patients (26 from IgA nephropathy, 24 from purpura nephritis, 8 from lupus nephritis, 7 from focal segmental glomerulosclerosis, and 5 from non-IgA mesangial proliferative glomerulonephritis) and 30 normal control subjects. Results: UAGT–creatinine ratio (UAGT/UCre) was correlated positively with diastolic blood pressure (p = 0.0326), urinary albumin–creatinine ratio (p < 0.0001), urinary protein–creatinine ratio (p < 0.0001) and urinary occult blood (p = 0.0094). UAGT/UCre was significantly increased in chronic glomerulonephritis patients not treated with renin-angiotensin system (RAS) blockers compared with control subjects (p < 0.0001). Importantly, glomerulonephritis patients treated with RAS blockers had a marked attenuation of this augmentation (p = 0.0021). Conclusion: These data indicate that UAGT are increased in chronic glomerulonephritis patients and treatment with RAS blockers suppressed UAGT. The efficacy of RAS blockade to reduce the intrarenal RAS activity can be confirmed by measurement of UAGT in chronic glomerulonephritis patients.