Comparison of Pre-dilution and Post-dilution Methods on Cytokine Clearance Using Polymethylmethacrylate (PMMA) Membrane Hemofilters in Continuous Hemodiafiltration

In Japan, the post-dilution method is preferred to maintain the dialysis efficiency of low molecular weight substances in continuous hemodiafiltration (CHDF). In contrast, the pre-dilution method is preferable to ensure a stable filter lifetime, especially for membranes with cytokine absorptive characteristics that are at high risk of membrane coagulation. However, the impact of the dilution method on the removal performance of adsorptive membranes for cytokines remains unclear. This study aimed to investigate the effect of different dilution methods on the adsorption clearance of cytokine on polymethylmethacrylate (PMMA) membranes by in vitro experiments. Bovine albumin, interleukin (IL)-6, and creatinine were added to phosphate-buffered saline to achieve final concentrations of 3.5 g/dL, 1000 pg/mL, and 10 mg/dL, respectively. The test solution was passed through the 1.8 m² PMMA membrane hemofilter at a flow rate of 100 mL/min in a single-pass system. The dialysate/filtration flow rates used were 2.5/2.5, 5.0/5.0, and 7.5/7.5 mL/min for each pre- and post-dilution method. Samples were collected seven times from pre- and post-hemofilter every minute, 10 min after the start of CHDF. Samples were frozen and stored, and the concentration of IL-6 was measured by enzyme-linked immunosorbent assay (ELISA), and clearance was calculated. Creatinine clearance increased with an increasing flow rate in pre- and post-dilution, while IL-6 clearance was less affected by flow rate. IL-6 clearance was 35.5 mL/min (32.1-39.6) for pre-dilution and 37.1 mL/min (33.8-41.1) for post-dilution in the 2.5/2.5 setting, and 34.2 mL/min (28.8-36.2) for pre-dilution and 32.4 mL/min (32.4-37.4) for post-dilution in the 5.0/5.0 setting. The dilution methods showed no significant differences. Moreover, in the 7.5/7.5 setting, clearance was 29.5 mL/min (27.7-37.2) for pre-dilution and 39.9 mL/min (37.8-41.5) for post-dilution (P<0.001); however, all clearance values were higher than theoretical values expected from filtration removal. In conclusion, the cytokine removal characteristics of the PMMA membrane hemofilter were not largely affected by the dilution method, and IL-6 clearance could be fully demonstrated even in the pre-dilution method.