Pathophysiology of advanced glycation end-products in renal failure.
beta 2-Microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis, a serious complication leading to bone and joint destruction in long-term haemodialysis patients. However, the molecular pathogenesis of this complication remains unknown. Intact beta 2-microglobulin per se seems an unlikely contributor to the pathogenesis, because no difference in the plasma levels of intact beta 2-microglobulin has yet been found between haemodialysis patients with and without this complication. Some investigators have therefore focused on the modification of this molecule. Recent studies have revealed a new modification of beta 2-microglobulin in amyloid fibrils-the advanced glycation end-products (AGEs) formed by a non-enzymatic reaction between sugar aldose and protein. Further studies have suggested that the interaction of AGE-modified beta 2-microglobulin with monocyte/macrophage and osteoclast/osteoblast gives a plausible albeit partial explanation for the mechanism of bone and joint destruction in dialysis-related amyloidosis. This article discusses the pathophysiology of AGEs in renal failure and the modification of beta 2-microglobulin with AGEs, especially focusing on their structure and pathological role in dialysis-related amyloidosis.
Miyata
T
T
Department of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
Iida
Y
Y
Horie
K
K
Cai
Z
Z
Sugiyama
S
S
Maeda
K
K
D000682:Amyloid / Q000502:physiology; D000686:Amyloidosis / Q000209:etiology / Q000503:physiopathology; D001862:Bone Resorption / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology* / Q000628:therapy; D015416:Maillard Reaction; D006435:Renal Dialysis / Q000009:adverse effects; D001613:beta 2-Microglobulin / Q000502:physiology
D000682:Amyloid; D017127:Glycation End Products, Advanced; D001613:beta 2-Microglobulin