Renal Replacement Therapy with High-Cutoff Hemofilters: Impact of Convection and Diffusion on Cytokine Clearances and Protein Status

Background: High-cutoff hemofilters are characterized by an increased effective pore size designed to facilitate the elimination of inflammatory mediators in sepsis. This study compares diffusive versus convective high-cutoff renal replacement therapy (RRT) in terms of cytokine clearance rates and effects on plasma protein levels. Methods: Twenty-four patients with sepsis-induced acute renal failure were studied. A polyflux hemofilter with a cutoff point of approximately 60 kd was used for RRT. Patients were randomly allocated to either continuous venovenous hemofiltration (CVVH) with an ultrafiltration rate of 1 L/h (group 1) or 2.5 L/h (group 2) or continuous venovenous hemodialysis (CVVHD) with a dialysate flow rate of 1 L/h (group 3) or 2.5 L/h (group 4). Interleukin-1 (IL-1) receptor antagonist (IL-1ra), IL-1β, IL-6, tumor necrosis factor-α (TNF-α), and plasma proteins were measured daily. Results: CVVH achieved significantly greater IL-1ra clearance compared with CVVHD (P = 0.0003). No difference was found for IL-6 (P = 0.935). Increasing ultrafiltration volume or dialysate flow led to a highly significant increase in IL-1ra and IL-6 clearance rates (P < 0.00001). Peak clearances were 46 mL/min for IL-1ra and 51 mL/min for IL-6. TNF-α clearance was poor for both RRT modalities. A significant decline in plasma IL-1 ra and IL-6 clearance was observed in patients with high baseline levels. Protein and albumin losses were greatest during the 2.5-L/h hemofiltration mode. Conclusion: High-cutoff RRT is a novel strategy to clear cytokines more effectively. Convection has an advantage over diffusion in the clearance capacity of IL-1ra, but is associated with greater plasma protein losses.