Long-term safety of '4-hour' hemoadsorption combined with hemodialysis (HAHD) in maintenance hemodialysis patients: A multicenter prospective cohort study

Introduction: Current guidelines recommend limiting hemoadsorption (HA) duration to 2 hours during hemodialysis (HD) sessions due to theoretical concerns about adsorbent saturation and clotting risks. This multicenter prospective cohort study evaluated the long-term safety and efficacy of a novel "4Hs" protocol (4-hour HA-HD with blood flow >250 mL/min). Methods: Seventy-eight maintenance HD patients from four centers underwent 26 weeks of 4Hs therapy. Key outcomes included dialysis adequacy (spKt/V, urea reduction ratio [URR]), uremic toxin (UT) clearance (indoxyl sulfate [IS], p-cresyl sulfate [pCS], β2-microglobulin [B2MG]), clotting rates, and adverse events (AEs). Statistical comparisons were made against pre-study conventional HA+HD (2-hour HA) data using paired t-tests and repeated-measures ANOVA. Results: The 4Hs protocol demonstrated non-inferior safety to conventional HA+HD, with comparable clotting rates (1.79% vs. 1.62%, p=0.665) and no significant differences in anemia markers or hypoalbuminemia. Dialysis efficacy improved significantly: spKt/V increased by 0.28 (p=0.012), URR by 1.18% (p=0.003), and UT reduction rates (IS: 56.17% vs. 40.14%, p<0.001; p-CS: 47.39% vs. 35.91%, p<0.001; B2MG: 55.82% vs. 48.41%, p<0.001). Albumin loss remained comparable between protocols (Δ0.5 g/L, p>0.05). Conclusion: Extending HA duration to 4 hours with high-flow hemodynamics (Qb >250 mL/min) is safe and enhances toxin clearance without increasing clotting risks. These findings challenge current SOP limitations on HA duration and support protocol optimization in maintenance HD patients.