Amyloid, advanced glycation end products, and dialysis related arthropathy.

Dialysis associated arthropathy (DRA) is a syndrome peculiar to long term dialysis patients. It includes large and small joint symptoms, pathological fractures through bony cysts and an axial spondyloarthropathy, and is closely associated with carpal tunnel syndrome. It is characterised by deposition of â2 microglobulin (â2M) as an amyloid protein. This was first linked to the osteoarticular syndrome 12 years ago. Several other forms of bone and joint pathology also occur more frequently in dialysis patients, including secondary hyperparathyroidism, osteoporosis, gout, pseudogout, and aluminium induced bone disease. Prevalence of DRA is closely related to age and years of dialysis treatment. Symptoms develop in some patients within four to five years of treatment and are almost universally present in those who have been treated by haemodialysis for 15 years. The number of patients in this at risk group is steadily increasing; in Australia the proportion of patients with over 10 years exposure to dialysis treatment has remained constant around 6% over the past decade but the total number of patients needing dialysis treatment has doubled and the proportion over 65 years rose from 18% to 35%. Other Western countries face a similar problem. Several active areas of investigation and debate remain. The nature of the â2M deposition has been intensively studied, with recent demonstration of non-enzymatic modification of â2M to form advanced glycation end products (AGEs). The roles of diVerent dialysis membranes and techniques in the production and clearance of â2M and the genesis of DRA continues to be actively investigated, although there have been few major technological advances in this area over the past five years.