THE ROLE OF BETA(2)-MICROGLOBULIN IN THE OCCURRENCE AND PROGRESSION OF DIALYSIS AMYLOIDOSIS

Ten years ago, dialysis arthropathy and the carpal tunnel syndrome hav e been associated for the first time with the previously unknown syndr ome of dialysis amyloidosis, which is mainly made of beta(2)-microgobu lin (beta(2)M-fibrils. The incidence of this syndrome increases steadi ly with age and dialysis duration. Its pathogenesis remains an area of intensive research. It is not yet clear whether there is only one dia lysis arthropathy syndrome, or whether several such syndromes of diffe rent origins coexist. Therefore, a word of caution is of order concern ing terminology. Frequently, the terms ''dialysis amyloidosis'', dialy sis arthropathy'' and ''carpal tunnel syndrome'' are used for the same syndrome in dialysis patients, as if they were simply interchangeable . However, at present anon-invasive method is not available allowing t o assess incipient amyloid deposits in vivo. Other forms of arthropath y may be associated, at least in theory, with similar or even identica l clinical and X-ray manifestations. in absence of identifiable beta(2 )M amiloid fibrils. Furthermore it remains yet unclear whether ill pat ients with beta(2)M-amyloidosis the position of amyloid comes fu st an d the arthropathy is secondary, or whether other, still unknown mechan isms effect changes of articular tissues first and amyloid fibrils are deposited theron secondarily. We prefer at present e term ''dialysis amyloidosis of the beta(2)M type''. Concerning pathogenesis, a retenti on of beta(2)M due to chronic renal failure has initially been incrimi nated as a major factor. In more recent years, however, several pieces of evidence have been provided in favor of the hypothesis that other factors play a more important role, such as an increase in the local o r systemic production of inflammatory mediators and the generation of modified beta(2)M, in particular via terminal glycation and oxidation end-products. The latter could also directly exert negative effects on bone and joint structures. Finally, factors related to the dialysis t echnique appear to play a role in beta(2)M amyloid formation as well. Prospective-studies with various dialysis strategies should allow to p rovide a definitive answer to this question in the future.