AN69ST membranes adsorb nafamostat mesylate and affect the management of anticoagulant therapy: a retrospective study

Abstract

Background: In Japan, nafamostat mesylate (NM) is frequently used as an anticoagulant during continuous renal replacement therapy (CRRT). The dialyzer membrane AN69ST has been reported to adsorb NM and affect the management of anticoagulant therapy. However, the adsorbed amount has not yet been quantitatively assessed. Therefore, in this study, we evaluated the pre- and post-hemofilter prolongation of the activated clotting time (ACT) in patients with AN69ST and PS membranes. We also measured the adsorption of NM in three types of CRRT membranes using an experimental model.

Methods: In a study of patients who underwent CRRT using AN69ST or PS membranes in 2015 at the Advanced Emergency and Critical Care Center, Okayama University Hospital, pre- and post-hemofilter ACT measurements were extracted retrospectively, and the difference was calculated. In addition, AN69ST (sepXiris100), PS (HEMOFEEL SHG-1.0), and PMMA membranes (HEMOFEEL CH-1.0N) were used in an in vitro model of a dialysis circuit, and the concentrations of NM were measured in pre- and post-hemofilter membranes and filtrates.

Results: The ACT difference was significantly lower in the group using AN69ST membranes (p < 0.01). In the in vitro model (n = 4) with adsorption and filtration, the post-hemofilter and filtrate concentrations of NM in AN69ST membranes were significantly lower than those in the PS and PMMA membranes (p < 0.01). The NM adsorption clearance of the AN69ST membrane was significantly higher than that of the PS and PMMA membranes.

Conclusions: The AN69ST membrane had higher NM adsorption than the PS and PMMA membranes. This may have resulted in the lower ACT difference in patients undergoing CRRT using the AN69ST membrane than in patients undergoing CRRT using PS or PMMA membranes.

Keywords: AN69ST; Adsorption; Anticoagulant therapy; Continuous renal replacement therapy; Nafamostat mesylate.

Fig. 1

Activating clotting time (ACT) sampling sites

Fig. 2

Diagram of in vitro experimental setup (single pass). The heights of all sites of measurement of the inlet pressure, filtration pressure, and return pressure were aligned with the heights of the sites of connection between the dialyzer and the patient. Adjustments were made to maintain a fixed/constant pressure inside the circuit. During sampling, caution was taken not to apply negative pressure. Extracorporeal ultrafiltration method (ECUM) model

Fig. 3

Comparison of ACT difference. a Pre- and post-filter ACT for the AN69ST (n = 122) and PS (n = 37) hemofilters. b Pre- and post-hemofilter ACT difference. Data represent the mean (SD) of four independent experiments. Asterisk indicates p < 0.01 by Mann-Whitney U test

Fig. 4

Results of the in vitro assay (single pass). AN69ST polyacrylonitrile (surface treated), PS polysulfone, PMMA polymethylmethacrylate, conc. concentration. Study of the adsorbed/filtered amounts of NM (ECUM). Data represent the mean (SD) of four independent experiments. Asterisk indicates Tukey’s post-tests that were used to determine the significant differences between groups

Fig. 5

Nafamostat mesylate (NM) clearance. Data represent the mean (SD of total clearance) of four independent experiments. Asterisk indicates Tukey’s post-tests that were used to determine differences between the groups. The theoretical maximum value of the filtration clearance is shown as a dotted line, and the theoretical maximum value of the adsorption clearance is shown as a gray line. AN69ST polyacrylonitrile (surface treated), PS polysulfone, PMMA polymethylmethacrylate