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Local delivery of a direct renin inhibitor into the kidney ameliorates progression of experimental glomerulonephritis.
MedLine Citation:
PMID:  22327564     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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. CONCLUSION: This study revealed that renally delivered aliskiren has a renoprotective effect on potentially progressive glomerulosclerosis.
Authors:
Ayako Sato; Hoglan Piao; Yukiko Nozawa; Tetsuo Morioka; Hiroshi Kawachi; Takashi Oite
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-11
Journal Detail:
Title:  Clinical and experimental nephrology     Volume:  -     ISSN:  1437-7799     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9709923     Medline TA:  Clin Exp Nephrol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Cellular Physiology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
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