Diabetic nephropathy

Mechanisms of renal disease progression

Yashpal S. Kanwar, Jun Wada, Lin Sun, Ping Xie, Elisabeth I. Wallner, Sheldon Chen, Sumant Chugh, Farhad R. Danesh

Research output: Contribution to journalArticle

418 Citations (Scopus)

Abstract

Diabetic nephropathy is characterized by excessive amassing of extracellular matrix (ECM) with thickening of glomerular and tubular basement membranes and increased amount of mesangial matrix, which ultimately progress to glomerulosclerosis and tubulo-interstitial fibrosis. In view of this outcome, it would mean that all the kidney cellular elements, i.e., glomerular endothelia, mesangial cells, podocytes, and tubular epithelia, are targets of hyperglycemic injury. Conceivably, high glucose activates various pathways via similar mechanisms in different cell types of the kidney except for minor exceptions that are related to the selective expression of a given molecule in a particular renal compartment. To begin with, there is an obligatory excessive channeling of glucose intermediaries into various metabolic pathways with generation of advanced glycation products (AGEs), activation of protein kinase C (PKC), increased expression of transforming growth factor-β (TGF-β), GTP-binding proteins, and generation of reactive oxygen species (ROS). The ROS seem to be the common denominator in various pathways and are central to the pathogenesis of hyperglycemic injury. In addition, there are marked alterations in intraglomerular hemodynamics, i.e., hyperfiltration, and this along with metabolic derangements adversely compounds the hyperglycemia-induced injury. Here, the information compiled under various subtitles of this article is derived from an enormous amount of data summarized in several excellent literature reviews, and thus their further reading is suggested to gain in-depth knowledge of each of the subject matter.

Original languageEnglish
Pages (from-to)4-11
Number of pages8
JournalExperimental Biology and Medicine
Volume233
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Diabetic Nephropathies
Disease Progression
Reactive Oxygen Species
Kidney
Glucose
Wounds and Injuries
Hemodynamics
Transforming Growth Factors
GTP-Binding Proteins
Protein Kinase C
Podocytes
Glomerular Basement Membrane
Mesangial Cells
Chemical activation
Metabolic Networks and Pathways
Hyperglycemia
Molecules
Endothelium
Extracellular Matrix
Reading

Keywords

  • Advance glycation products
  • GTP binding proteins
  • Hyperglycemia
  • Hypertension
  • Protein kinase C
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kanwar, Y. S., Wada, J., Sun, L., Xie, P., Wallner, E. I., Chen, S., ... Danesh, F. R. (2008). Diabetic nephropathy: Mechanisms of renal disease progression. Experimental Biology and Medicine, 233(1), 4-11. https://doi.org/10.3181/0705-MR-134

Diabetic nephropathy : Mechanisms of renal disease progression. / Kanwar, Yashpal S.; Wada, Jun; Sun, Lin; Xie, Ping; Wallner, Elisabeth I.; Chen, Sheldon; Chugh, Sumant; Danesh, Farhad R.

In: Experimental Biology and Medicine, Vol. 233, No. 1, 01.2008, p. 4-11.

Research output: Contribution to journalArticle

Kanwar, YS, Wada, J, Sun, L, Xie, P, Wallner, EI, Chen, S, Chugh, S & Danesh, FR 2008, 'Diabetic nephropathy: Mechanisms of renal disease progression', Experimental Biology and Medicine, vol. 233, no. 1, pp. 4-11. https://doi.org/10.3181/0705-MR-134
Kanwar, Yashpal S. ; Wada, Jun ; Sun, Lin ; Xie, Ping ; Wallner, Elisabeth I. ; Chen, Sheldon ; Chugh, Sumant ; Danesh, Farhad R. / Diabetic nephropathy : Mechanisms of renal disease progression. In: Experimental Biology and Medicine. 2008 ; Vol. 233, No. 1. pp. 4-11.
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