Abstract: Protein-bound uremic toxins (PBUT), such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS), exhibit strong binding to albumin and are therefore poorly removed by conventional hemodialysis. Their progressive accumulation in patients with chronic kidney disease (CKD), especially those with end-stage kidney disease (ESKD), has been recognized as a key contributor to adverse clinical outcomes. This review summarizes current advances in understanding the metabolism, clearance mechanisms, and biological effects of PBUT, with particular focus on their roles in multisystem injury and emerging therapeutic strategies. Recent evidence demonstrates that IS and PCS trigger oxidative stress, inflammation, endothelial dysfunction, and profibrotic signaling, thereby accelerating cardiovascular complications, renal function decline, cognitive impairment, and immune dysregulation in dialysis patients. Due to their high protein-binding affinity, traditional diffusion-based dialysis provides limited clearance. Novel approaches-including adsorption materials, high-performance dialysis membranes, modulation of gut microbiota, and pharmacological or dietary interventions-have shown potential to enhance PBUT elimination. A comprehensive understanding of PBUT kinetics and pathogenic pathways is essential for improving detoxification efficiency and clinical management. Integrating innovative clearance technologies with conventional dialysis modalities may help reduce toxin burden and improve prognosis and quality of life in dialysis patients.

Key words: protein-bound uremic toxins, p-cresyl sulfate, indoxyl sulfate, hemodialysis, pathophysiological mechanisms, treatment progress