Pathogenesis and management of dialysis-related amyloid bone disease

Abstract

Dialysis-related amyloidosis (DRA) is a major complication of chronic renal failure and long-term renal replacement therapy. Beta2-Microglobulin is a major constituent of amyloid fibrils in DRA. Amyloid deposition can present as carpal tunnel syndrome, destructive arthropathy, or subchondral bone erosions and cysts. A definitive diagnosis of DRA can only be made using histological findings, but various analytical imaging methods often support diagnosis. Therapy of an established DRA is limited to symptomatic approaches and surgical removal of amyloid deposits. High-flux biocompatible dialysis membranes can be used to delay DRA development. Recent studies have suggested a pathogenic role for a new modification of beta2-microglobulin in DRA. Increased carbonyl compounds modify proteins, which leads to the augmentation of advanced glycation and lipoxidation end products. Thus, uremia might be a state of carbonyl overload with potentially damaging proteins, leading to a new modification of beta2-microglobulin in amyloid fibrils and development of DRA.