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Horm Metab Res 2005; 37: 26-34
DOI: 10.1055/s-2005-861360
Review
© Georg Thieme Verlag KG Stuttgart · New York

AGE-RAGE and AGE Cross-link Interaction: Important Players in the Pathogenesis of Diabetic Kidney Disease

L.  J.  N.  Jensen1 , J.  Østergaard1 , A.  Flyvbjerg1
  • 1 The Medical Research Laboratories, Clinical Institute and the Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark
Further Information

Publication History

Received 6 December 2004

Accepted after Revision 27 January 2005

Publication Date:
25 May 2005 (online)

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Abstract

At present, diabetic kidney disease affects about 15 - 25 % of all type 1 diabetic patients and 20 - 40 % of all patients with type 2 diabetes. The mechanisms underlying the development of diabetic kidney disease are extremely complex and not yet fully understood. Among the many potential pathogenic mechanisms responsible for the progression in diabetic kidney disease, the involvement of metabolic factors beyond blood glucose (such as advanced glycation end products (AGEs)) has been suggested. This review will present the emerging evidence in support of a significant role of AGE formation in the development of diabetic kidney disease. AGEs mediate their effects through two main pathways - through a receptor-independent AGE cross-link formation pathway and through a receptor-dependent pathway where AGEs bind to specific cell surface associated receptors, the receptor for AGE (RAGE) being the most well-characterised so far. First, we will describe the AGE-RAGE system, including its localisation in the normal kidney, and then move on to discuss in vitro and in vivo studies (that is, experimental and clinical data) in support of a pathogenic role of AGE-RAGE and AGE cross-link interaction in the development of diabetic kidney disease. Finally, the effects of known and potential inhibitors of AGE-RAGE and AGE cross-link systems in diabetic kidney disease will be examined.

Key words

Diabetic nephropathy - TGF-β - CTGF - VEGF - PDGF - IGF-I - PKC - ROS - NF-κB - Aminoguanidine - Pyridoxamine - OPB-9195 - LR-90 - 2,3 diaminophenazine - Cross-link breakers - ALT-711 - ALT-946 - PTB - sRAGE - RAGE Antibody

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Allan Flyvbjerg, M. D., D.M.Sc

The Medical Research Laboratories · Clinical Institute · Medical Department M (Diabetes and Endocrinology) · Aarhus University Hospital

Nørrebrogade 44 · DK-8000 Aarhus C · Denmark

Phone: +45 89 49 21 61

Fax: +45 86 56 00 87

Email: allan.flyvbjerg@dadlnet.dk