Adsorption Removal of Protein-Bound Uremic Toxins: Material Strategies, Dissociation Mechanisms, and Clinical Challenges

Chronic kidney disease (CKD) is a highly prevalent condition that is associated with an increased burden of cardiovascular diseases and mortality. Between 7% and 12% of the general population are affected by CKD. In patients with end-stage renal disease (ESRD), the most severe form of CKD, large amounts of uremic toxins are retained in the blood due to impaired kidney function, leading to uremic symptoms and functional as well as biochemical alterations. Currently, extracorporeal blood purification techniques, including hemodialysis, hemofiltration, hemodiafiltration, and hemoperfusion, are widely used to remove small- to medium-sized uremic toxins, maintain homeostasis, and sustain the lives of ESRD patients. However, the available blood purification methods do not efficiently eliminate protein-bound uremic toxins (PBUTs), such as indoxyl sulfate (IS), hippuric acid (HA), p-cresyl sulfate (PCS), and indole-3-acetate (IAA), due to their strong affinity for albumin. The accumulation of PBUTs unfortunately contributes to kidney fibrosis, oxidative stress, cardiovascular events, and poor long-term survival. Therefore, the development of novel blood purification techniques to improve PBUT elimination is of considerable clinical significance. In this review, we first discuss the limitations of current blood purification modalities of PBUT removal and then summarize recent advances in hemoperfusion adsorbents, adsorptive hemodialysis membranes, and dialysate regeneration systems with enhanced PBUT clearance. Finally, we discuss potential challenges and future research directions in this field, with the aim of providing opportunities for more personalized and targeted blood purification therapies for ESRD patients.