10 An additional application has been the use of a protein leaky membrane to treat myeloma kidney with good success.11 Flux, in relation to dialysers, can mean two things. It may relate to the passage of larger molecules – with β2 microglobulin (MW 11 800) commonly used as the marker molecule given its likely

importance in the pathogenesis of DRA. Thus high-flux membranes will allow the passage of β2 microglobulin, whereas low-flux membranes will not. However, flux may also relate to the Kuf of the membrane. Kuf is the ultrafiltration coefficient of the membrane – the rate at which water crosses the membrane at a given trans-membrane pressure. Under the conditions of normal dialysis, there exists a trans-membrane pressure – high-flux membranes allow a greater volume of water to cross the dialysis membrane BMN 673 ic50 per unit time at a given pressure. Low-flux membranes typically have Kuf values below 10 mL/min per mmHg, whereas

high-flux membranes most commonly have values above Trametinib 20. The widespread usage of high-flux membranes was in part responsible for the universal application of ultrafiltration monitors to dialysis machines, as these monitors are a mandatory requirement when using these membranes, otherwise the very large obligatory ultrafiltration loss would volume deplete the patient. The benefits of high-flux membranes are said to lie in several domains. The improved biocompatibility is less likely to cause intra-dialytic symptoms such as hypotension, nausea and headaches; however, supportive data are lacking.12 It is also proposed that the high-flux membranes improve cardiovascular stability, especially during dialysis itself. This may relate to the improved biocompatibility with less induction of cardiovascularly active agents, such as the cytokines and to the potential removal of similar agents (e.g. IL-1 and TNF would both be potentially removed by high-flux membranes).13

However, some claim that this cardiovascular stability relates more to improved temperature balance during dialysis because of greater shifts between blood and dialysate.14 PAK5 Furthermore, the clearance of β2 microglobulin probably reduces the likelihood of the development of DRA – observational data would support this although there are no randomized trials to firmly establish this, although several large observational trials are supportive.15 Certainly, the incidence of DRA seems to have diminished markedly in the last 10–15 years. The reduction in DRA may also relate to the reduced cytokine induction, as cytokines such as IL-1 and TNF are involved in this process. Early observational data suggested that high-flux dialysis was associated with improved survival. For example, Woods reported on the experience in Singapore with conversion of a cohort of patients to high-flux dialysis – with demonstration of a reduction in the mortality rate compared with historical controls.