Extraskeletal problems and amyloid

Abstract

The major clinical manifestations of dialysis-associated Aβ2M amyloidosis are chronic arthralgias, destructive arthropathy and the carpal tunnel syndrome. For dialysis patients who have been maintained on renal replacement therapy for more than 10-15 years, this complication may become a major physical handicap. It may even be life-threatening in some instances due to cervical cord compression. Amyloid deposits in joint areas precede clinical symptoms and signs by several years. Systemic deposits may also occur but their clinical manifestations are infrequent. The diagnosis of dialysis arthropathy associated with β2-microglobulin-associated (Aβ2M) amyloidosis mostly relies on indirect clinical and radiological evidence. Histologic proof is rarely obtained in vivo. The pathogenesis of the disease is complex. It includes reduced elimination of β2M and potentially also as impaired degradation of Aβ2M as well as enhanced production of Aβ2M amyloid fibrils. Non enzymatic modifications of β2M probably play a role, including β2M protein modification with advanced glycation end-products (AGE) and advanced oxidation protein products. Modified β2M, collagen and proteoglycans appear actively involved in the induction of a local inflammatory response and β2M amyloid formation. There is also evidence in favor of treatment-related factors such as the type of hemodialysis membrane and the purity of dialysis water. Hopefully, the translation of our improving knowledge of all the factors involved will lead to a better treatment and eventually to the prevention of this dramatic complication of dialysis.