Fabrication of hollow fiber membranes with different inner diameters for enhanced uremic toxins removal in hemodialysis: Exploring from high-flux to high molecular weight retention onset classes

Abstract

Developing a hemodialysis membrane that sufficiently removes both small-sized toxins and the middle molecule is essential. Protein-bound uremic toxins (PBUTs) are involved in an increased risk of cardiovascular events and mortality; however, their removal pathway has not been explored yet. Herein, this work aimed to fabricate novel hemodialysis membranes under different inner diameters (ID) with approaching two classes: high-flux (M#1, M#2) and high molecular weight retention onset (MWRO) (M#3, M#4). The results showed that membrane with smaller ID (M#1: 218 μm) performed a superior removal of small molecules i.e., urea: 266,394 mg/m2 and creatinine: 11,985 mg/m2. Spinning conditions, such as bore and dope solution flowrate, had a significant impact on pore size distribution, porosity, and dimensions, but not entirely on the membrane structure. These factors are crucial to govern the efficiency of uremic toxin clearance and the level of protein loss/leaking. Consequently, a high MWRO of M#4 at 13,998 Da favored enhanced removal of middle molecules, resulting in lysozyme removal of 5120 mg/m2 and a high sieving coefficient of β2-microglobulin (0.91). A minimized loss (2.46 g/session) and minor leaking (0.08 g/session) of protein were attained in M#4 e.g., MWRO class. Notably, we first explored the removal pathway of protein-bound uremic toxins (PBUTs) with i) Free Form-PBUTs removal by diffusion ii) Free Form-PBUTs removal by adsorption iii) Bovine serum albumin (BSA)-PBUTs conjugate adsorption on a membrane, and iv) Leaking of BSA-PBUTs conjugate to the dialysate. Our high-flux and MWRO membranes removed hippuric acid of 2911 mg/m2; 3476 mg/m2, indoxyl sulfate of 1640 mg/m2; 1452 mg/m2, p-cresol of 3,1469 mg/m2; 3702 mg/m2, respectively. Overall, our study proposes a promising membrane for hemodialysis application that exhibited either higher flux or high molecular weight retention onset compared to commercial membranes. Their properties facilitate an increase in the removal of middle molecules but still retain a minimized loss of protein and minor leakage.