F Gejyo

Significant amounts of glycosaminoglycans (GAGs) were found in amyloid fibril preparations. Using two-dimensional electrophoresis to fractionate GAG mixtures, we quantified and identified for the first time the GAGs of the fibrils from carpal synovium of patients with amyloid associated with chronic hemodialysis. The total GAG content was small, but the GAG distribution (high relative content of chondroitin sulfate and hyaluronic acid and lack of the other GAGs) was unique, unlike that for the other amyloid fibril preparations. The amyloid-rich heart, liver, and spleen tissues, as well as the fibrils isolated from these tissues of patients with systemic forms (primary amyloid and secondary amyloid) of amyloid disease, were also analyzed for GAGs. Fibrils from heart tissue of a patient with primary amyloidosis, now examined for the first time, contained four major GAGs (chondroitin sulfate, dermatan sulfate, hyaluronic acid, and heparan sulfate).

Dialysis-related amyloidosis (DRA) is a common complication associated with long-term haemodialysis therapy. The elimination of beta2-microglobulin (beta2m), the major constituent of the amyloid fibrils in DRA, from circulation has been expected to bring some clinical benefit. Recently, a direct haemoperfusion method using selective beta2m absorption column to eliminate circulating beta2m has been introduced into clinical practice. According to a recently performed, prospective, multicentre study, joint pain, stiffness and daily activities were significantly improved in patients with established DRA after the introduction of selective beta2m absorption therapy. Meanwhile, although osteoarticular lesions progressed in the control group, there was no significant progression in the selective beta2m absorption therapy group. The absorptive affinity of the column for beta2m is not quite specific and therefore some other unknown uraemic toxins might be removed also. However, the improvement of joint pain and the ability to undertake daily activities showed reversed correlations against plasma beta2m clearance. Symptoms associated with the increased amount of extracorporeal circulation and increased economical burden are areas of concern for this therapy. In conclusion, selective beta2m absorption therapy was suggested to have the potential to ameliorate established DRA symptoms and simultaneously prevent its local development. The mechanism by which DRA symptoms are ameliorated remains obscure.