The development of
glomerulonephritis causes glomerular injury and renal dysfunction and is thought to increase
renin release, thus activating the renin-angiotensin system (RAS). The aims of this study were to demonstrate activation of the intrarenal RAS and determine the effects of direct
renin inhibition (DRI) on the progression of
glomerulonephritis. Rats were treated with anti-Thy1.1 antibody with or without DRI,
aliskiren (30 mg/kg/d). In the glomerulonephritic rats,
protein, microalbumin excretion levels, urinary
angiotensinogen excretion, glomerular expansion score and intrarenal
transforming growth factor-β and
plasminogen activator inhibitor-1
mRNA levels were augmented compared with control rats; however,
hypertension was not observed in the glomerulonephritic rats, and
aliskiren treatment did not modify their blood pressure. The increases in urinary
protein (94.7 ± 13.0 mg/d) and microalbumin (7.52 ± 2.6 mg/d) excretion were reduced by
aliskiren (43.6 ± 4.5 mg/d of
protein and 2.57 ± 0.7 mg/d of microalbumin). Furthermore, the progression of glomerular expansion and elevation of intrarenal
transforming growth factor-β and
plasminogen activator inhibitor-1 levels were prevented by
aliskiren. Importantly,
aliskiren suppressed the augmentation of urinary
angiotensinogen levels, the increased
angiotensinogen expression in the kidneys and the increases in Ang II levels in renal medulla induced by the anti-Thy1.1 antibody. These results suggest that DRI with
aliskiren prevents intrarenal RAS activation leading to mitigation of the development of
glomerulonephritis. In addition, the renoprotective effects of DRI on
glomerulonephritis occur in a blood pressure-independent manner. Accordingly, treatment with
aliskiren may be an effective approach to treat
glomerulonephritis and other intrarenal RAS-associated
kidney diseases.