End-stage renal disease (ESRD) patients rely on renal replacement therapies to survive. Hemodialysis (HD), the most widely applied treatment, is responsible for the removal of excess fluid and uremic toxins (UTs) from blood, particularly those with low molecular weight (MW < 500 Da). The development of high-flux membranes and more efficient treatment modes, such as hemodiafiltration, have resulted in improved removal rates of UTs in the middle molecular weight range. However, the concentrations of protein-bound uremic toxins (PBUTs) remain essentially untouched. Due to the high binding affinity to large proteins, such as albumin, PBUTs form large complexes (MW > 66 kDa) which are not removed during HD and their accumulation has been strongly associated with the increased morbidity and mortality of patients with ESRD. In this review, we describe adsorption- and displacement-based approaches currently being studied to enhance the removal of PBUTs. The development of mixed matrix membranes (MMMs) with selective adsorption properties, infusion of compounds capable of displacing UTs from their binding site on albumin, and competitive binding membranes show promising results, but the road to clinical application is still long, and further investigation is required.

The production of medical devices follows strict guidelines where bio- and hemocompatibility, mechanical strength, and tear resistance are important features. Segmented polyurethanes (PUs) are an important class of polymers that fulfill many of these requirements, thus justifying the investigation of novel derivatives with enhanced properties, such as modulated carbon dioxide and oxygen permeability. In this work, three segmented polyurethane-based membranes, containing blocks of hard segments (HSs) dispersed in a matrix of soft segment (SS) blocks, were prepared by reacting a PU prepolymer (PUR) with tris(hydroxymethyl)aminomethane (TRIS), Congo red (CR) and methyl-β-cyclodextrin (MBCD), rendering PU/TRIS, PU/CR and PU/MBCD membranes. The pure (control) PU membrane exhibited the highest degree of phase segregation between HSs and SSs followed by PU/TRIS and PU/MBCD membranes, and the PU/CR membrane displayed the highest degree of mixing. Pure PU and PU/CR membranes exhibited the highest and lowest values of Young’s modulus, tangent moduli and ultimate tensile strength, respectively, suggesting that the introduction of CR increases molecular mobility, thus reducing stiffness. The CO₂ permeability was highest for the PU/CR membrane, 347 Barrer, and lowest for the pure PU membrane, 278 Barrer, suggesting that a higher degree of mixing between HSs and SSs leads to higher CO₂ permeation rates. The permeability of O₂ was similar for all membranes, but ca. 10-fold lower than the CO₂ permeability.