In vitro study of dual layer mixed matrix hollow fiber membranes for outside-in filtration of human blood plasma

Abstract

Hemodialysis mainly removes small water-soluble uremic toxins but cannot effectively remove middle molecules and protein-bound uremic toxins. Besides, the therapy is intermittent leading to fluctuating blood values and fluid status which adversely impacts patients' health. Prolonged hemodialysis (with adequate anticoagulation) could improve the removal of toxins and the development of portable and wearable artificial kidneys could offer more flexibility in the dialysis scheme. This would enhance patients' overall health, autonomy, mobility and flexibility, allowing patients to participate in social and economic life. However, the time that patients' blood is exposed to the dialyzer material is longer during prolonged hemodialysis, and blood clots could obstruct the fiber lumen, resulting in a decrease of the effective membrane surface area available for toxin removal. The outside-in filtration (OIF) mode, wherein blood flows through the inter-fiber space instead of through the fiber lumina, has been applied widely in blood oxygenators to prevent fiber clotting, but not in hemodialysis. In this study, we present for the first time the development of a mixed matrix membrane (MMM) for OIF of human blood plasma. This MMM combines diffusion and adsorption and consists of a polymeric membrane matrix with activated carbon (AC) particles on the inside layer, and a polymeric particle-free layer on the outer fiber layer. Our results show that in vitro MMM fibers for OIF demonstrate superior removal of the protein-bound uremic toxins, indoxyl sulfate and hippuric acid, compared to both earlier MMM fibers designed for inside-out filtration mode and commercial high-flux fibers. STATEMENT OF SIGNIFICANCE: Current hemodialysis therapy cannot effectively remove protein-bound toxins. Prolonged hemodialysis could improve toxin removal. However, during prolonged hemodialysis, blood clots could obstruct the fiber lumen, resulting in decreased effective membrane surface area available for toxin removal. We have prepared, for the first time, dual layer mixed matrix hollow fiber membranes (MMM) for outside-in filtration (OIF). The OIF mode wherein blood would flow through the inter-fiber space instead of through the fiber lumina could prevent fiber clotting. Moreover, the MMMs combine diffusion and adsorption to improve (protein-bound) toxin removal. We believe that the new design of our MMM fibers is an important contribution concerning the development of artificial kidney systems and the improvement of the health and well-being of patients with renal failure.

Keywords: Hemodialysis; Mixed matrix membrane; Outside-in filtration; Protein-bound uremic toxins.