New aspects in the pathogenesis of dialysis-related amyloidosis: pathophysiology of advanced glycation end products in renal failure.
It has been demonstrated that 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 hemodialysis patients. However, the molecular pathogenesis of this complication remains unknown. Several lines of evidence suggest that beta 2-microglobulin plays an active role in the development of dialysis-related amyloidosis. It is unlikely that intact beta 2-microglobulin per se contributes to the pathogenesis, because no difference in the plasma levels of intact beta 2-microglobulin has yet been found between hemodialysis patients with and without this complication. Some investigators, therefore, have focused on the modification of this molecule. Recent studies have revealed a new modification of beta 2-microglobulin in amyloid fibrils: advanced glycation end products (AGEs) formed by a nonenzymatic reaction between aldoses and proteins. 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 focuses on the modification of beta 2-microglobulin with AGEs, especially on their structure and pathological role in dialysis-related amyloidosis. Furthermore, the implication of renal failure in the pathophysiology of AGEs is also discussed.
Miyata
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Department of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D006435:Renal Dialysis / Q000009:adverse effects*; D001613:beta 2-Microglobulin / Q000378:metabolism
D017127:Glycation End Products, Advanced; D001613:beta 2-Microglobulin