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 (B.F.S., A.F.), Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, DK-8000 Aarhus, Denmark; and Renal Unit (B.F.S., A.S.D.V.), Department of Internal Medicine, Gent University Hospital, B-9000 Gent, Belgium
Correspondence: Address all correspondence and requests for reprints to: Allan Flyvbjerg, M.D., D.M.Sc., Medical Department M/Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. 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. Severaldecades of extensive research has elucidated various pathwaysto be implicated in the development of diabetic kidney disease.This review focuses on the metabolic factors beyond blood glucosethat are involved in the pathogenesis of diabetic kidney disease,i.e., advanced glycation end-products and the aldose reductasesystem. Furthermore, the contribution of hemodynamic factors,the renin-angiotensin system, the endothelin system, and thenitric oxide system, as well as the prominent role of the intracellularsignaling molecule protein kinase C are discussed. Finally,the respective roles of TGF-ß, GH and IGFs, vascularendothelial growth factor, and platelet-derived growth factorare covered. The complex interplay between these different pathwayswill be highlighted. A brief introduction to each system anddescription of its expression in the normal kidney is followedby in vitro, experimental, and clinical evidence addressingthe role of the system in diabetic kidney disease. Finally,well-known and potential therapeutic strategies targeting eachsystem are discussed, ending with an overall conclusion.
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