**3.1 Removal of ß2-microglobulin (B2M)**

ß2-microglobulin is a 99 amino acid protein produced by all nucleated cells with the exception of red blood cells, it has a molecular weight of 11.8 k Daltons. It plays an important role in the immune system; it is involved in the defense against bacterial and viral infections as well as in the prevention of cancerous cells [16]. B2M accumulation in dialysis can lead to its aggregation into amyloid fibers that deposit in joint spaces causing a dialysis-related amyloidosis, resulting in carpal tunnel syndrome, arthropathy, and organ deposition of amyloid proteins [17]. It can also cause inflammation and immune dysfunction. B2M accretion has been associated with a decrease in residual kidney function [18] and an increased risk of all-cause, cardiovascular and infectious deaths [19–20]. Serum B2M remains positively associated with mortality, in a study of 23,976 patients, conducted by the Dialysis Outcomes and Practice Patterns Study (DOPPS) over a period of 10 years [17].

Convective techniques, including HDF and HF dialysis, provide better removal of middle molecules. In addition, several randomized controlled studies suggest that HF dialyzers are more effective in removing B2M than low flux membranes. Regarding HDx, studies have shown that HDx with MCO membranes results in a greater reduction ratio of a broad range of molecules, including B2M compared to HF membranes [8, 20–23]. There are several factors that can affect the clearance of B2M [8], in the study conducted by Lim [24], the reduction ratio achieved was slightly lower, and the B2M clearance was not significantly different, which was probably due to a low blood flow rate. B2M levels were found to be more important than initial levels even after one year of HDX.

Another factor that may influence the inability to remove the B2M is the rebound phenomenon, probably secondary to resistance due to a massive transfer between different body compartments that limits the clearance of B2M [25], leading sometimes to an increase in B2M levels even with MCO membranes [26].
