Local delivery of a direct renin inhibitor into the kidney ameliorates progression of experimental glomerulonephritis.
BACKGROUND
Increasing evidence indicates that locally blocking renin-angiotensin system activity exerts a beneficial effect on glomerulonephritis (GN) progression leading to irreversible glomerulosclerosis. This is the first study on the pharmacological effect of the renal delivery of aliskiren, a direct renin inhibitor, in a progressive model of anti-Thy-1 GN.


METHODS
Local blockade of renin activity was accomplished by subrenal capsular implantation of a collagen sponge with aliskiren. The pharmacological effect was evaluated by semiquantitative and quantitative analysis of immunohistological findings and by analysis of glomerular microcirculation using an intravital microscope system.


RESULTS
Quantitative mesangial matrix analysis showed that local treatment with aliskiren significantly suppressed mesangial matrix expansion and ameliorated the glomerular sclerotic index in the progressive model of ATS GN. Immunofluorescent studies revealed that renin expression at the juxtaglomerular region was enhanced in the ATS + aliskiren group, and pathological expressions of α-smooth muscle cell actin and type I collagen in ATS GN were remarkably decreased by local treatment with aliskiren. Furthermore, local delivery of aliskiren significantly improved glomerular blood flow levels.


CONCLUSIONS
This study revealed that renally delivered aliskiren has a renoprotective effect on potentially progressive glomerulosclerosis.
Department of Cellular Physiology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Ayako
A
Sato
Hoglan
H
Piao
Yukiko
Y
Nozawa
Tetsuo
T
Morioka
Hiroshi
H
Kawachi
Takashi
T
Oite
D000199:Actins / Q000378:metabolism; D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D005921:Glomerulonephritis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D015918:Infusion Pumps, Implantable; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000502:physiology; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D000092502:Renin Inhibitors
D000199:Actins; D000577:Amides; D000911:Antibodies, Monoclonal; D024042:Collagen Type I; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren