Pathophysiology of advanced glycation end-products in renal failure

Abstract

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.