6 This contributed to dialysis symptoms and intolerance, and in the long term may have contributed to dialysis-related cachexia. They were also only available in Selleckchem Pritelivir low-flux form – they only allowed the passage of small molecules with very few molecules above a molecular weight (MW) of 5000 gaining passage through the membrane. Dialysis-related amyloidosis (DRA) was a problem in longer-term survivors because of the lack of removal of β2 microglobulin, the accumulation of which contributed to amyloid formation.7 The next step was the development of modified cellulosic membranes – membranes based on cellulose but with different
substitutions (cf. copper), especially acetate – as cellulose acetate, diacetate and triacetate. These were less inflammatory to the host and were able to be produced with slightly larger pore sizes, especially the triacetate form. Nevertheless, the problem of bioincompatibility was not eliminated and the search for improved membranes continued. Synthetic’ membranes were the next to appear. These were manufactured membranes that included such compounds as polyamide, polymethylmethacrylate, polysulfone and polyacrylonitrile. These molecules were able to be spun into fibres with pore sizes of various sizes, such
that manufacturers were able to determine MW cut-offs – most allow good clearance of larger molecules, such as β2 microglobulin (‘high-flux’), although can also be produced in ‘low-flux’ format. They also offered excellent ‘biocompatibility’, check details LY2606368 research buy that
is, low levels of induction of inflammatory mediators.8 The downside of the synthetic membranes is that they are thick-walled (see Fig. 1). Although the ‘dialysis’ predominantly occurs at the inner skin of these membranes, the thick wall provides some impedance to dialysis. In contrast, it may provide some benefits in terms of biocompatibility (see below). Another variety of membrane also exists – that of a backbone of a common membrane, for example, cellulose based, but then coated with an additional compound for putative benefit. The most common of these are vitamin E-coated membranes, which have potential benefits in terms of reduced oxidative stress, although the benefits seem relatively minor and no survival benefits have been demonstrated.9 Finally, recent developments include the generation of superflux membranes. As mentioned above, the synthetic membranes can be spun with predetermined pore sizes. Several manufacturers have produced membranes with large pores that allow the passage of larger molecules, especially proteins. These tend to allow the loss of some albumin during dialysis and may have putative benefits in terms of further preventing the development of amyloidosis.