Local delivery of a direct renin inhibitor into the kidney ameliorates progression of experimental glomerulonephritis
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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.
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.
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.
This study revealed that renally delivered aliskiren has a renoprotective effect on potentially progressive glomerulosclerosis.
KeywordsProgressive glomerulosclerosis Direct renin inhibitor Local drug delivery Local renin–angiotensin system Renoprotection
This study was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology, Japan (B: no. 15390266, C: no. 12671032, JSPS; 15/03138, to T.O., and a grant-in-aid for young scientists B: no. 17790548 to J.M.) as well as grants from Novartis Pharmaceuticals and Nippon Shinyaku Co., Ltd.
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