Revisiting the Role of Flux in β2-Microglobulin Removal

tion and hemodiafiltration, reduce plasma 2 -microglobulin concentrations, and their use is associated with a lower incidence of treatment-related amyloidosis. Nevertheless it is highly probable that residual renal function is probably the most important determinant of plasma 2 microglobulin levels in hemodialysis patients and removal via this route even with minimal renal function may supersede enhanced convective clearance [6] . Despite this, considerable effort has been placed into the improvement of membrane permeability to 2 -microglobulin over recent years [7] . Additionally the kinetics of 2 microglobulin removal are thought to be generalizable and representative of the kinetic behavior of other middle molecules prompting its use as a general marker for middle molecules by European Best Practice Guidelines for Haemodialysis [8] . In the study by Traut and colleagues [10] , the topic of 2 -microglobulin removal has been revisited and their study has confirmed that patients treated using high-flux polyamide membranes have lower plasma 2 -microglobulin levels compared with patients treated using low-flux cellulose-based membranes. Their observation that, in common with normal controls, significantly higher amounts of 2 -microglobulin were bound to the cells of patients undergoing dialytic treatment with high-flux membranes compared to patients treated with low-flux membranes is of considerable interest. Additionally, Traut and colleagues also noted that more 2 -microglobulin was released from the cells during dialysis with low2 -Microglobulin is the light chain complex of the major histocompatibility complex (MHC) class 1 molecule which is synthesized by all cells that express such molecules. Once shed from the cell surface, 2 -microglobulin disassociates and enters the circulation as a monomer with a molecular weight of 11,815 Da. In normal subjects it is cleared by the human kidney where it is freely filtered and almost fully adsorbed and catabolized by proximal tubular cells. In patients with impaired renal function plasma levels are elevated and removal by dialytic techniques is highly dependent upon convection. 2 -Microglobulin is widely recognized as a key component in the genesis and development of dialysis-associated amyloidosis, a syndrome that is clinically expressed in terms of destructive arthropathies and carpal tunnel syndrome [1] . The mechanisms whereby 2 -microglobulin mediates osteoarticular amyloidosis remain incompletely understood; chemotaxis, activation of monocytes and macrophages with subsequent release of cytokines and metalloproteinases secondary to the modification of 2 -microglobulin by advanced glycation end products are pivotal as is the formation of amyloid fibrils arising from the binding of 2 -microglobulin to collagen [2–4] . Although no firm relationship exists between plasma 2 -microglobulin concentrations and the degree of severity of dialysis-associated amyloidosis [5] , observational studies have demonstrated that the use of high-flux hemodialysis and convective therapies such as hemofiltraPublished online: October 23, 2007