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This version published online on October 5, 2004
Endocrine Reviews, doi:10.1210/er.2003-0018
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From hyperglycemia to diabetic kidney disease: The role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines

Bieke F. Schrijvers, An S. De Vriese, and Allan Flyvbjerg*

Medical Department M, Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark Renal Unit, Department of Internal Medicine, Gent University Hospital, Gent, Belgium doi: 10.1210/er.2003-0018

* To whom correspondence should be addressed. E-mail: allan.flyvbjerg{at}dadlnet.dk,.

At present, diabetic kidney disease affects about 15-25% of type 1 and 30-40% of type 2 diabetic patients. Several decades of extensive research has elucidated various pathways to be implicated in the development of diabetic kidney disease. This review focuses on the metabolic factors beyond blood glucose that are involved in the pathogenesis of diabetic kidney disease, i.e. advanced glycation end-products (AGEs) and the aldose reductase (AR) system. Further, the contribution of hemodynamic factors, the renin-angiotensin system (RAS), the endothelin (ET) system and the nitric oxide (NO) system as well as the prominent role of the intracellular signaling molecule protein kinase C (PKC) are discussed. Finally, the respective roles of transforming growth factor {beta} (TGF-{beta}), GH (GH) and insulin-like growth factors (IGFs), vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are covered. The complex interplay between these different pathways will be highlighted. A brief introduction to each system and description of its expression in the normal kidney is followed by in vitro, experimental and clinical evidence addressing the role of the system in diabetic kidney disease. Finally, well-known and potential therapeutic strategies targeting each system are discussed, ending up with an overall conclusion.
Key words: advanced glycation end products • aldose reductase • vasoactive hormones • protein kinase C • cytokines • growth factors • diabetic nephropathy




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