Diabetic nephropathy: where hemodynamics meets metabolism

Forbes, J. M., Fukami, K. and Cooper, M. E. (2007) Diabetic nephropathy: where hemodynamics meets metabolism. Experimental and Clinical Endocrinology and Diabetes, 115 2: 69-84. doi:10.1055/s-2007-949721

Author Forbes, J. M.
Fukami, K.
Cooper, M. E.
Title Diabetic nephropathy: where hemodynamics meets metabolism
Journal name Experimental and Clinical Endocrinology and Diabetes   Check publisher's open access policy
ISSN 0947-7349
Publication date 2007
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1055/s-2007-949721
Open Access Status Not yet assessed
Volume 115
Issue 2
Start page 69
End page 84
Total pages 16
Place of publication Stuttgart, Germany
Publisher Johann Ambrosius Barth Verlag in Medizinverlage Heidelberg GmbH & Co. KG
Language eng
Abstract Diabetic nephropathy (DN), the most common cause of end stage renal disease in developed nations, is thought to result from interactions between metabolic and haemodynamic factors. Specific metabolically driven, glucose dependent pathways are activated within diabetic renal tissues. These pathways induce oxidative stress, polyol pathway flux, hexosamine flux and accumulation of advanced glycated end-products (AGEs). Haemodynamic factors are also implicated in the pathogenesis of DN and include elevations of systemic and intraglomerular pressure and activation of various vasoactive hormone pathways including the renin-angiotensin aldosterone system (RAAS), endothelin and urotensin. These altered hemodynamics act independently and in concert with metabolic pathways, to activate intracellular second messengers such as protein kinase C (PKC) and MAP kinase (MAPK), nuclear transcription factors such as nuclear factor-κB (NF-κB) and various growth factors such as the prosclerotic cytokines, transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and the angiogenic, permeability enhancing growth factor, vascular endothelial growth factor, VEGF. Ultimately these molecular mechanisms lead to increased renal albumin permeability, and extracellular matrix accumulation, which results in increasing proteinuria, glomerulosclerosis and tubulointerstitial fibrosis. In the past, the treatment of diabetic nephropathy has focused on control of hyperglycemia and the interruption of the RAAS with certain antihypertensive agents. Newer novel targets, some of which are linked to glucose dependent pathways, appear to be a major focus of new therapies directed against the development and progression of renal damage as a result of diabetes. It is likely that resolution of diabetic nephropathy will require synergistic therapies to target multiple mediators of this disease.
Keyword Advanced glycated end products
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 84 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 100 times in Scopus Article | Citations
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