Uremic Toxins and Hemodiafiltration: From Molecular Mechanisms to Clinical Outcomes

Uremic syndrome results from the accumulation of biologically active solutes that contribute to inflammation, oxidative stress, endothelial dysfunction, cardiovascular disease, anemia, CKD-mineral and bone disorder, and protein-energy wasting in patients with end-stage kidney disease. While conventional hemodialysis efficiently removes small water-soluble compounds, clearance of middle molecules and protein-bound uremic toxins remains limited. Post-dilution hemodiafiltration (HDF) combines diffusion and convection to enhance removal across a broader molecular-weight spectrum. This review summarizes the mechanisms of uremic toxin accumulation, the biologic and clinical relevance of major retained solutes, and current evidence supporting improved toxin removal with HDF. Randomized trials, meta-analyses, and observational studies have associated HDF with reduced inflammatory burden, improved hemodynamic tolerance, and favorable clinical outcomes, supporting its role as an advanced strategy for targeting the broader spectrum of uremic toxicity.