Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies.
Glycation is the process whereby sugars bind to the free amine residues of proteins. These newly formed modified molecular species are known as 'advanced glycation end-products', or AGEs. AGE toxicity may occur through at least three mechanisms: interaction with the receptor for AGEs (RAGE); tissue deposition; and in situ glycation. AGEs trigger proinflammatory, profibrotic and procoagulant cellular responses that are capable of damaging tissues, often targeting particular organs. In diabetic patients, the conditions needed to promote AGE formation are all present, and are further accentuated by accompanying renal failure. The aim of this review is to outline the involvement of AGEs in the various forms of renal pathology associated with diabetic and non-diabetic nephropathies. AGEs are present in all renal compartments in diabetic patients, including the vessels, glomeruli, tubules and interstitium. Many cell types may be activated-specifically, endothelial, tubular and mesangial cells, and podocytes. AGEs play a major role in the accumulation of extracellular matrix, as occurs in diabetic glomerulosclerosis, and are also involved in most diabetic (renovascular, microangiopathic and glomerular) and non-diabetic renal injury associated with progressive glomerulosclerosis and ageing.
Daroux
M
M
Vascular Aging Biology, Research Division, Lille Medical School, 1 place de Verdun, Lille, France.
Prévost
G
G
Maillard-Lefebvre
H
H
Gaxatte
C
C
D'Agati
V D
VD
Schmidt
A M
AM
Boulanger
E
E
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D050527:Mesangial Cells / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D051437:Renal Insufficiency / Q000378:metabolism
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic