Cardinal Role of the Intrarenal Renin-Angiotensin System in the Pathogenesis of Diabetic Nephropathy

Diabetes mellitus is one of the most prevalent diseases and is associated with increased incidence of structural and functional derangements in the kidneys, eventually leading to end-stage renal disease in a significant fraction of afflicted individuals. The renoprotective effects of renin-angiotens...

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Bibliographic Details
Published in:Journal of investigative medicine 2013-02, Vol.61 (2), p.256-264
Main Authors: Kobori, Hiroyuki, Kamiyama, Masumi, Harrison-Bernard, Lisa M., Navar, L. Gabriel
Format: Article
Language:English
Subjects:
Angiotensinogen - physiology
Animals
Biomarkers - metabolism
Cytokines
Diabetes
Diabetic Nephropathies - etiology
Diabetic Nephropathies - metabolism
Disease Models, Animal
Enzymes
Humans
Kidney Cortex - enzymology
Kidney Cortex - pathology
Kidneys
Localization
Mice
Minors
Mortality
Pathogenesis
Peptidyl-Dipeptidase A - metabolism
Proteins
Ratios
Rats
Renin - physiology
Renin-Angiotensin System - physiology
Rodents
Studies
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Summary:Diabetes mellitus is one of the most prevalent diseases and is associated with increased incidence of structural and functional derangements in the kidneys, eventually leading to end-stage renal disease in a significant fraction of afflicted individuals. The renoprotective effects of renin-angiotensin system (RAS) blockade have been established; however, the mechanistic pathways have not been fully elucidated. In this review article, the cardinal role of an activated RAS in the pathogenesis of diabetic nephropathy (DN) is discussed with a focus on 4 themes: (1) introduction to RAS cascade, (2) intrarenal RAS in diabetes, (3) clinical outcomes of RAS blockade in DN, and (4) potential of urinary angiotensinogen as an early biomarker of intrarenal RAS status in DN. This review article provides a mechanistic rational supporting the hypothesis that an activated intrarenal RAS contributes to the pathogenesis of DN and that urinary angiotensinogen levels provide an index of intrarenal RAS activity.
ISSN:1081-5589
1708-8267
DOI:10.2310/JIM.0b013e31827c28bb