Diagnosis, pathogenesis, and treatment of dialysis-related amyloidosis

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 mainly involves bone and joint structures, presenting as carpal tunnel syndrome, destructive arthropathy, and subchondral bone erosions and cysts. While a definitive diagnosis of DRA can only be made by histological findings, various imaging techniques often support diagnosis. The molecular pathogenesis of this complication remains unknown. Recent studies, however, have suggested a pathogenic role of a new modification of beta2-microglobulin in amyloid fibrils, i.e. the advanced glycation end products (AGEs). Increased carbonyl compounds derived from autoxidation of both carbohydrates and lipids modify proteins in uremia, leading to augment not only AGE production but also the advanced lipoxidation end product production. Thus, uremia might be a state of carbonyl overload with potentially damaging proteins ('carbonyl stress'). Therapy of DRA is limited to symptomatic approaches and surgical removal of amyloid deposits. High-flux biocompatible dialysis membranes could be used to delay DRA development.