Four-Hour Hemoperfusion with Stepwise Blood Flow Rates for Toxin Clearance and Safety in Hemodialysis Patients: A Randomized Controlled Trial

Optimal hemoperfusion (HP) parameters combined with hemodialysis (HD) for removing middle-molecule and protein-bound toxins remain undefined. This prospective randomized controlled trial investigated the effects of extending HP duration and increasing blood flow rate. Eighty-eight maintenance hemodialysis patients were randomized to 2-h or 4-h HP with 4-h HD at 220 mL/min (Phase 1). After a 2-week washout, patients received 4-h HP+HD at 180, 220, or 260 mL/min (Phase 2). Analysis of covariance (ANCOVA) adjusted for baseline imbalances, and linear trend tests evaluated dose-response effects. In Phase 1, the 4-h regimen achieved significantly superior adjusted β2-microglobulin clearance (65.11% ± 4.73% vs. 45.93% ± 4.71%; Adjusted P < 0.001) and reduced loss of hemoglobin and albumin (both P < 0.01). In Phase 2, a significant linear dose-response relationship was observed for all toxins (P for trend < 0.001). A flow rate of 260 mL/min achieved optimal reduction ratios for small molecules and hs-CRP (43.12%). Restricted cubic spline analysis suggested that apparent negative hs-CRP reduction ratios may reflect hemoconcentration-related artifacts (Model P = 0.049). All regimens maintained hemodynamic stability with mean systolic pressure drops of 4.7 ± 24.3 mmHg and 4.2 ± 22.9 mmHg in Phases 1 and 2, respectively. Adverse events were low (0-3.45%) and mild. In conclusion, a 4-h HP session combined with HD, particularly at 260 mL/min, enhances the removal of middle molecules, protein-bound toxins, and inflammatory markers without apparent hemodynamic instability in this single-session study, providing evidence for optimizing operational parameters.