Dialysis related amyloidosis: Pathogenetic aspects and therapeutic considerations

Beyond renal transplantation and the provision of symptomatic relief, approaches to treat dialysis-related amyloidosis (DRA), an important long-term complication in patients on regular dialysis, must be based on the knowledge of the underlying pathogenetic process. Retention of beta(2)-microglobulin (beta(2)m) is the prerequisite; biochemical alterations of beta(2)m increasing its amyloidogenicity, and local predisposing tissue factors together with age appear to be relevant. A growing body of evidence points toward the importance of pro-inflammatory effects of dialysis (blood-membrane interactions, pyrogen-related priming of cytokine-producing mononuclear cells) in the development of DRA. Advanced glycation endproduct formation (AGE-beta(2)m) may represent a central element in the pathogenesis of DRA. For non-transplant therapy of DRA, the main goals must be the optimization of beta(2)m removal (high-flux haemodialysis, haemofiltration, especially pre-dilution haemofiltration) and reduction of pro-inflammatory effects of dialysis (use of noncomplement activating biocompatible membranes, pyrogen free dialysate). At least patients at high risk for DRA should be treated according to these guidelines.