beta2-microglobulin-derived amyloidosis: an update.
The present review attempts to summarize recent developments in the field of beta2-microglobulin-derived amyloidosis (A(beta2)m amyloidosis) in patients on chronic dialysis therapy. A key factor in the pathogenesis is the uremic retention of the precursor molecule, beta2-microglobulin (beta2m). However, secondary modifications of the molecule such as limited proteolysis, conformational changes, and the formation of advanced glycation end products have also been described. Finally, in order to explain the striking predilection of the disease for synovial and periarticular structures, a role of local predisposing factors within the synovial membrane (for example, of the particular constituents of the extracellular matrix) must also be postulated. With respect to clinical symptomatology, recent data have confirmed that clinically manifest signs of the amyloidosis represent only the tip of the iceberg, since histologically amyloid deposition is much more widespread. Noninvasive diagnosing of the disease has been advanced by technical changes of the beta2m scintigraphy. Finally, there is accumulating evidence that prevention of the disease not only includes the usage of high-flux synthetic membranes for hemodialysis or hemodiafiltration, but that other factors contribute to the clinical manifestations of amyloidosis such as the dialysate composition and its microbacteriological quality. Such factors, which have changed over the last years as part of general improvements in dialysis care, may explain why the prevalence of the amyloidosis appears to decrease.
Floege
J
J
Division of Nephrology, University of Aachen, Aachen, Germany. juergen.Floege@post.rwth-aachen.de
Ketteler
M
M
D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D002349:Carpal Tunnel Syndrome / Q000209:etiology; D017583:Hemodiafiltration / Q000009:adverse effects; D006801:Humans; D010003:Osteoarthritis / Q000209:etiology; D006435:Renal Dialysis / Q000009:adverse effects*; D014511:Uremia / Q000150:complications / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism*
D001613:beta 2-Microglobulin