UNRESOLVED ISSUES IN DIALYSIS: Dialysis‐Related Amyloidosis: Late Finding or Hidden Epidemic?

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Abstract
Dialysis‐related amyloidosis is a complication of end‐stage renal disease (ESRD) that results from retention of β2‐microglobulin (β2M) and its deposition as amyloid fibrils into osteoarticular tissue. The clinical manifestations usually develop after several years of dialysis dependence and include carpal tunnel syndrome, destructive arthropathy, and bone cysts and fractures. High‐flux membranes, daily dialysis, and hemofiltration all would be expected to delay the onset of dialysis‐related amyloidosis because, to varying degrees, each increases the clearance of β2M from the plasma. Thus what is currently a late complication of ESRD might become an even later complication as dialysis practices change. The significance of histologically evident but clinically silent β2M amyloid, detectable not only in osteoarticular tissue but also in blood vessels, is unclear. Accumulating evidence that amyloidogenic proteins have direct and specific effects on cell processes irrespective of the extent of amyloid deposition raises the possibility that early, clinically silent β2M amyloid deposits have unrecognized importance.