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  • Editor in Chief: Prof. Giovanni Gambaro
  • Co-Editor: Benedetta Bussolati
  • Current issue: Vol. 26 issue Suppl. 22 , 2013 (November-December)

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Vol. 22 Issue 3 (May-June)

Renin, prorenin and the kidney: a new chapter in an old saga

Renin, prorenin and the kidney: a new chapter in an old saga

J Nephrol 2009; 22(3): 306 - 311

Article Type: THOROUGH CRITICAL APPRAISAL

Authors

Atsuhiro Ichihara, Mariyo Sakoda, Asako Kurauchi-Mito, Yuki Kaneshiro, Hiroshi Itoh

Abstract

The binding of prorenin to the (pro)renin receptor triggers 2 major pathways: a nonproteolytic conformational
change in prorenin to its active form (angiotensin II-dependent pathway) and an intracellular pathway
via the (pro)renin receptor itself (angiotensin II-independent pathway). In diabetic animals, an increased
plasma prorenin level not only causes the generation of angiotensin II via the angiotensin II-dependent
pathway, it also stimulates the (pro)renin receptor’s own intracellular signaling pathway in a manner that
is independent of the generated angiotensin II. Thus, the administration of a “handle” region peptide (HRP),
which acts as a decoy peptide and competitively inhibits the binding of prorenin to the (pro)renin receptor,
has a beneficial effect in the kidneys of diabetic animals with low plasma renin levels. However, the
benefits of HRP are slightly reduced in animal models of essential hypertension with relatively high plasma
renin levels, and these benefits disappear altogether in animal models of hypertension with extremely high
plasma renin levels. Thus, in the kidneys of animal models of diabetes and/or hypertension, both renin
and prorenin competitively bind to the (pro)renin receptor and contribute to the pathophysiology of nephropathy.
Consequently, renin, prorenin and the (pro) renin receptor may be important therapeutic targets
for the prevention and regression of nephropathy in patients with diabetes and/or hypertension.

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Authors

  • Ichihara, Atsuhiro [PubMed] [Google Scholar]
    Departments of Anti-Aging Medicine & Endocrinology, Keio University School of Medicine, Tokyo - Japan
  • Sakoda, Mariyo [PubMed] [Google Scholar]
    Departments of Internal Medicine, Keio University School of Medicine, Tokyo - Japan
  • Kurauchi-Mito, Asako [PubMed] [Google Scholar]
    Departments of Internal Medicine, Keio University School of Medicine, Tokyo - Japan
  • Kaneshiro, Yuki [PubMed] [Google Scholar]
    Departments of Internal Medicine, Keio University School of Medicine, Tokyo - Japan
  • Itoh, Hiroshi [PubMed] [Google Scholar]
    Departments of Internal Medicine, Keio University School of Medicine, Tokyo - Japan

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