Haemodialysis-associated beta 2M amyloidosis: current controversies

Beta 2M amyloidosis is a major complication of long-term haemodialysis. Beta 2M, the precursor molecule of amyloid fibrils, accumulates in renal failure because of diminished renal excretion. Whether, in addition, a minor increase of synthesis occurs in dialysed patients is still controversial. Beta 2M amyloidosis differs from most other forms of amyloid by its preferential osteoarticular location. This points to some peculiar role of the microenvironment in the synovial space, which is currently poorly defined. A finding which remains so far unexplained is the more delayed appearance of beta 2M amyloidosis in patients dialysed with polyacrylonitrile membranes. In principle, however, beta 2M amyloidosis is seen with all dialysis modalities and possibly even before maintenance dialysis. Differences between treatment modalities relate either to removal of beta 2M or some aspect of bioincompatibility, e.g. proteolytic processing. Finally, the exact chemical nature of amyloid fibrils, i.e. whether they constitute native beta 2M molecules or processed molecules, is currently controversial.