Pathogenesis of dialysis-related amyloidosis.
Beta 2-microglobulin has been demonstrated to be a major constituent of amyloid fibrils in dialysis-related amyloidosis. However, the molecular pathogenesis of this complication remains unknown. Several lines of evidence suggest that beta 2-microglobulin is not an innocent bystander, but plays an active role in the development of dialysis-related amyloidosis. The evidence remains inconclusive, however, as to whether it is intact or modified beta 2-microglobulin which is amyloidogenic and contributes to bone and joint destruction. Recent biochemical and immunohistological studies have revealed a new modification of beta 2-microglobulin in amyloid fibrils, the advanced glycation end products formed nonenzymatically between aldoses and proteins. Further study has suggested that the interaction of advanced glycation end product-modified beta 2-microglobulin with monocytes/macrophages gives a plausible, albeit incomplete, explanation for the mechanism of bone and joint destruction in dialysis-related amyloidosis. This review focuses on new aspects of the pathogenesis of dialysis-related amyloidosis.
Miyata
T
T
Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Maeda
K
K
D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007596:Joints / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D006435:Renal Dialysis / Q000009:adverse effects*; D001613:beta 2-Microglobulin / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D017127:Glycation End Products, Advanced; D001613:beta 2-Microglobulin