Therapeutic strategies in the treatment of diabetic nephropathy - a translational medicine approach

Imtiaz M. Shah, Simon P. Mackay, G.A. Mckay

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Type 2 Diabetes (T2D) is an important cause of renal dysfunction and the most common cause of end-stage renal disease (ESRD). Diabetic nephropathy is also associated with an increased risk of vascular disease and patient mortality. Aggressive management of hypertension to reduce microalbuminuria, together with tight glycaemic control are important therapeutic strategies for renal and vascular disease prevention in T2D. The main pathophysiological mechanisms associated with diabetic nephropathy result from activation of the renin-angiotensin-aldosterone system (RAAS), protein kinase C pathway, pro-inflammatory cytokines and various growth factors. Angiotensin II and transforming growth factor-beta (TGF-beta) are two important molecular mediators. The production of advanced glycation end-products (AGEs) and increased oxidative stress further exacerbates renal injury. These molecular changes within the renal tissue result in mesangial expansion, increased extracellular matrix deposition and an alteration in podocyte structure and function. Therapeutic targeting of these molecular pathways is an important area of translational research in diabetes. The elucidation of new genetic associations and proteomic biomarkers of diabetic kidney disease will also assist in the identification and treatment of high-risk patients. This review article will discuss both the molecular and clinical aspects of diabetic nephropathy, providing a bench-to-bedside research perspective to potential new therapeutic strategies.
LanguageEnglish
Pages997-1016
Number of pages19
JournalCurrent Medicinal Chemistry
Volume16
Issue number8
DOIs
Publication statusPublished - 1 Mar 2009

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Translational Medical Research
Diabetic Nephropathies
Kidney
Vascular Diseases
Type 2 Diabetes Mellitus
Podocytes
Advanced Glycosylation End Products
Therapeutics
Renin-Angiotensin System
Angiotensin II
Transforming Growth Factor beta
Proteomics
Protein Kinase C
Chronic Kidney Failure
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Oxidative Stress
Biomarkers
Cytokines
Hypertension

Keywords

  • type 2 diabetes
  • diabetic nephropathy
  • hyperglycaemia
  • renin angiotensin aldosterone system
  • inflammatory mediators
  • oxidative stress
  • growth factors
  • translational medicine

Cite this

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Therapeutic strategies in the treatment of diabetic nephropathy - a translational medicine approach. / Shah, Imtiaz M.; Mackay, Simon P.; Mckay, G.A.

In: Current Medicinal Chemistry, Vol. 16, No. 8, 01.03.2009, p. 997-1016.

Research output: Contribution to journalArticle

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