β₂-microglobulin and renal bone disease

Dialysis-related amyloidosis (DRA) is characterized by amyloid deposition mainly in bone and joint structures, presenting as carpal tunnel syndrome, destructive arthropathy, and subchondral bone erosions and cysts. β₂-microglobulin has been demonstrated to be a major constituent of amyloid fibrils. DRA occurs not only in patients undergoing long-term hemodialysis, but also in patients undergoing continuous ambulatory peritoneal dialysis. The incidence of this complication increases with the duration of dialytic therapy and the age of the patient. While a definitive diagnosis of DRA can be made only by histological findings, various imaging techniques often support diagnosis. The molecular pathogenesis of this complication remains unknown. Recent studies have, however, suggested a pathogenic role of a new modification of β₂-microglobulin in amyloid fibrils - that is, the advanced glycation end-products (AGEs) formed with carbonyl compounds derived from autoxidation of both carbohydrates and lipids ('carbonyl stress'). Therapy for DRA is limited to symptomatic approaches and surgical removal of amyloid deposits. High-flux biocompatible dialysis membranes could be used to delay DRA development.