| [ Summary ] |
Dialysis-related amyloidosis (DRA) is a serious complication, seen in long-term hemodialysis patients. DRA is characterized by beta2-microglobulin (beta2-m) amyloid deposits, predomonantly in osteoarticular structures, and by destructive arthropathy.
The pathogenesis of DRA is incompletely understood. The main components involved in amyloid formation are beta2-m (native and modified), amyloid P component, extracellular matrix [glycosaminoglycans, advanced glycation end products (AGE) modified collagen, fibronectin], apolipoprotein E, proteinase inhibitors, calcium, macrophages, synovial fibroblasts and ubiquitin. Proteolytic fragments of beta2-m, Ser 21-Lys 41, may be the essential core. The disulfide bond is important for the stability of fibrils. Accumulating evidence suggests that AGEs are endowed with biological activities that can partly account for macrophage infiltration. beta22-m amyloid arthropathy may result from progressive accumulation of AGEs in long-lived amyloid linked to cellular response. |