Cytokine Removal during Continuous Renal Replacement Therapy: An Ex Vivo Comparison of Convection and Diffusion

Abstract

Background and objectives It is unknown whether cytokine adsorption to the membrane during continuous renal replacement therapy is affected by the technique. Such knowledge might affect the choice of technique in vivo. Accordingly, we conducted an ex vivo study to test whether continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodialysis (CVVHD) affect cytokine adsorption differently. Setting Laboratory attached to the Intensive Care Unit of a tertiary hospital Design Six healthy human volunteers donated blood, which was incubated with endotoxin. Control blood was left at room temperature, and treatment blood was recirculated for eight hours through closed circuits using polyacrylonitrile membranes (AN69). The effect of CVVH and CVVHD on cytokine removal from the circuits was compared. Measurements The concentrations of interleukins (IL)-1ß, 6, 8, 10 and TNF were measured in the control samples, pre-and post-filter and in the effluent at baseline and hourly thereafter. The clearances by adsorption, and filtration were calculated. Results Control cytokine concentrations remained the same or increased slightly. Adsorption was the major mechanism of removal for all cytokines with the exception of IL-1ß, but the effect was short-lived. Peak adsorption generally occurred at baseline before the start of CVVH and CVVHD, with clearances ranging from 43.7ml/min (for IL-8) to 7.6ml/min (for IL-10). The time-weighted average total clearances during CVVH were 23.3, 4.3, 3.8, –2.0, and 15ml/min for IL-8, IL-1ß, TNF, IL-6, and IL-10 respectively. The corresponding clearances during CVVHD were 19.0, 10.7, 2.7, 2.4, and 0.3ml/min. IL-10 clearances were greater during CVVH than CVVHD (p=0.03). Non adsorptive CVVH clearance of IL-1ß was greater than CVVHD clearance, but this advantage was outweighed by an increased tendency of the membrane to release IL-1ß into the circuit during HF. Conclusions The technique of solute removal had only a minor effect on the magnitude of cytokine adsorption, and neither technique had the advantage for all the measured cytokines.