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Cardinal Role of the Intrarenal Renin-Angiotensin System in the Pathogenesis of Diabetic Nephropathy
  1. Hiroyuki Kobori, MD, PhD, FJSIM, FAHA, FASN, FJSH, FJSN, FACP*,
  2. Masumi Kamiyama, PhD*,
  3. Lisa M. Harrison-Bernard, PhD,
  4. L. Gabriel Navar, PhD*
  1. From the *Department of Physiology, and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, and †Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA.
  1. Received September 7, 2012, and in revised form October 21, 2012.
  2. Accepted for publication October 22, 2012.
  3. Reprints: Hiroyuki Kobori, MD, PhD, FJSIM, FAHA, FASN, FJSH, FJSN, FACP, Departments of Medicine and of Physiology, Director of the Molecular Core in Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, 1430 Tulane Ave, #SL39/M720, New Orleans, LA 70112. E-mail: hkobori{at}
  4. Drs Kobori and Kamiyama contributed equally to this work.
  5. The authors’ laboratories are supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072408); National Center for Research Resources (P20RR017659); National Heart, Lung, and Blood Institute (R01HL026371); and by the American Heart Association Grant-in-Aid (GRNT2250875 and GRNT3020018). Supported in part by a grant from the National Center for Research Resources (R13 RR023236).


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.

Key Words
  • diabetic nephropathy
  • renin-angiotensin system
  • angiotensinogen
  • kidney

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