Urinary angiotensinogen reflects the activity of intrarenal renin-angiotensin system in patients with IgA nephropathy.
BACKGROUND
A potential contribution of local activation of the renin-angiotensin system (RAS) to the pathogenesis of renal injury has been indicated by evidence for blood pressure-independent renoprotective effects of angiotensin II (AngII) receptor blockers (ARBs). The present study was performed to test the hypothesis that urinary angiotensinogen provides a specific index of intrarenal RAS status in patients with immunoglobulin A (IgA) nephropathy.


METHODS
This paper is a survey of urine specimens from three groups: healthy volunteers, patients with IgA nephropathy and patients with minor glomerular abnormality (MGA). Patients with hypertension, diabetes, reduced glomerular filtration rate and/or who were under any medication were excluded from this study. Urinary angiotensinogen levels were measured by a sandwich enzyme-linked immunosorbent assay system.


RESULTS
Urinary angiotensinogen levels were not different between healthy volunteers and patients with MGA. However, urinary angiotensinogen levels, renal tissue angiotensinogen expression and AngII immunoreactivity were significantly higher in patients with IgA nephropathy than in patients with MGA. Baseline urinary angiotensinogen levels were positively correlated with renal angiotensinogen gene expression and AngII immunoreactivity but not with plasma renin activity or the urinary protein excretion rate. In patients with IgA nephropathy, treatment with an ARB, valsartan (40 mg/day), significantly increased renal plasma flow and decreased filtration fraction, which were associated with reductions in urinary angiotensinogen levels.


CONCLUSIONS
These data indicate that urinary angiotensinogen is a powerful tool for determining intrarenal RAS status and associated renal derangement in patients with IgA nephropathy.
Nishiyama
Akira
A
Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan. akira@kms.ac.jp
Konishi
Yoshio
Y
Ohashi
Naro
N
Morikawa
Takashi
T
Urushihara
Maki
M
Maeda
Isseki
I
Hamada
Masahiro
M
Kishida
Masatsugu
M
Hitomi
Hirofumi
H
Shirahashi
Nobuo
N
Kobori
Hiroyuki
H
Imanishi
Masahito
M
D000808:Angiotensinogen / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D001794:Blood Pressure; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000503:physiopathology* / Q000652:urine*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000502:physiology*
D015415:Biomarkers; D000808:Angiotensinogen; D003404:Creatinine