Clearance of Protein-Bound Uremic Toxins Using Anion Nanotraps with Record High Uptake

Abstract

Traditional hemodialysis often fails to remove protein-bound uremic toxins (PBUTs) like p-cresyl sulfate (pCS) and indoxyl sulfate (IS) due to their strong binding to human serum albumin, which is linked to adverse cardiovascular outcomes. Herein, a class of cationic polymeric networks, denoted as CPN-X6−CPN-X9, are reported for the efficient removal of PBUTs. The abundant imidazole-based nanotraps in these cationic polymeric networks confer a highly positive charge density, resulting in CPN-X7 achieving a maximum sorption capacity of 1000.8 mg/g for pCS and CPN-X6 offering a maximum sorption capacity of 1028.4 mg/g for IS, surpassing all previously reported sorbents. Furthermore, CPN-X9, which is relatively hydrophobic, exhibits remarkable selectivity in competitive experiments involving large amount of chloride ions and serum albumin, attaining removal rates of up to 74% for pCS and 93% for IS in the recycling in vitro dialysis mode. Meanwhile, CPN-X9 demonstrates excellent recyclability over five cycles, and the cationic polymeric network materials exhibit satisfactory hemocompatibility. The sorption mechanism of the anion exchange process is fully elucidated and verified by density functional theory (DFT) calculations. This study provides valuable insights into enhancing the removal efficiency of PBUTs and presents broad prospects in the field of clinical blood purification.