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Local delivery of a direct renin inhibitor into the kidney ameliorates progression of experimental glomerulonephritis

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Cellular Physiology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan

    Ayako Sato, Hoglan Piao, Yukiko Nozawa, Tetsuo Morioka & Takashi Oite

  2. Department of Cellular Biology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan

    Hiroshi Kawachi

  3. Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare, 1398 Shimami-cho, Kita-ku, Niigata, 950-3198, Japan

    Takashi Oite

  4. Department of Laboratory Medicine, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan

    Ayako Sato

Authors
  1. Ayako Sato
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  2. Hoglan Piao
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  3. Yukiko Nozawa
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  4. Tetsuo Morioka
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  5. Hiroshi Kawachi
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  6. Takashi Oite
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Correspondence to Takashi Oite.

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Sato, A., Piao, H., Nozawa, Y. et al. Local delivery of a direct renin inhibitor into the kidney ameliorates progression of experimental glomerulonephritis. Clin Exp Nephrol 16, 539–548 (2012). https://doi.org/10.1007/s10157-012-0601-y

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  • DOI: https://doi.org/10.1007/s10157-012-0601-y

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