Adsorption of Nafamostat Mesilate by Hemodialysis Membranes

Inagaki, Oshi; Nishian, Yoshihiko; Iwaki, Ryotaro; Nakagawa, Kiyohiko; Takamitsu, Yoshihiro; Fujita, Yukihisa

doi:10.1111/j.1525-1594.1992.tb00551.x

Cited by 24 publications

(21 citation statements)

References 14 publications

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“…The reason why the adsorption rate of arbekacin onto AN69 was high is likely to be the formation of ionic bonds between the positively charged arbekacin with the negatively charged AN69 membrane. This result is consistent with findings from a previous study on the influence of charge of low molecular weight proteins on adsorption onto hemodialysis membranes [14] and a study showing that positively charged nafamostat mesilate adsorbed onto AN69 membrane [9], which indicates that adsorption onto hemodialysis membranes depends on the charge of adsorbed substances. In our in vitro adsorption experiment using a minimodule, we found that when polysulfone was used, the circulating arbekacin concentration (i.e., the concentration that reflects adsorption) barely changed at all over 240 min and the arbekacin concentration in the ultrafiltrate was the same as the circulating arbekacin concentration, which indicates that arbekacin mostly permeated through polysulfone without being adsorbed.…”

Section: Discussionsupporting

confidence: 92%

“…Therefore, it is believed that removal of arbekacin by hemodialysis must be taken into account when determining dosages for patients on hemodialysis [5,6]. Although adsorption onto hemodialysis membranes has been reported as a mechanism of drug removal by dialysis [8][9][10], there have been very few studies Dialysate flow rate (mL/min) 500 500 500…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, low molecular weight proteins such as β 2 microglobulin are removed by adsorption onto some hemodialysis membranes [7]. Adsorption of drugs such as the aminoglycoside antibiotic amikacin onto certain hemodialysis membranes has also been reported [8][9][10], so adsorption onto hemodialysis membranes is one mechanism of drug removal. In a previous in vitro experiment that we conducted, we found that arbekacin is adsorbed onto sulfonated polyacrylonitrile (AN69), a type of hemodialysis membrane [11].…”

Section: Introductionmentioning

confidence: 99%

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Interaction of arbekacin with dialysis membrane

et al. 2016

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Background: The interaction between arbekacin and the hemodialysis membrane is unclear. The aim of this study was to evaluate the adsorption of arbekacin (ABK) onto hemodialysis membranes and to establish a simpler system for evaluating the adsorption properties of the drug. Methods: First, small cut pieces of polysulfone or sulfonated polyacrylonitrile (AN69) hollow fiber membranes were stirred in a solution of ABK for the qualitative assessment. Then, we designed the experimental system that was approximately 1/100 of the actual size using a small dialyzer "mini-module" of our original design for the polysulfone or AN69. We circulated ABK solution in this system for the quantitative assessment. Finally, we administered ABK in subjects undergoing hemodialysis as a clinical trial to evaluate the adsorption of ABK onto polysulfone or AN69. Results: In the qualitative assessment, the rates of ABK adsorption onto polysulfone and AN69 were 6.2 ± 2.9 and 49.8 ± 1.8 %, respectively. In the quantitative assessment, although there was almost no change in the circulating ABK concentration with the use of polysulfone, there was about 68 % decrease in the circulating ABK concentration with the use of AN69. In the clinical trial, clearance by the dialyzer using AN69 was high at 10 min after starting dialysis, despite the sieving coefficient being 0. However, reduction of ABK clearance was observed with time; the removal rate of ABK at the completion of the dialysis using polysulfone or AN69 was about 67 %, with no difference between the two membranes. The main limitation of this study was the small sample size in the clinical trial. Conclusions: These findings suggest that ABK is adsorbed onto AN69. Furthermore, the present adsorption experiment with a mini-module was considered useful as an evaluation system because it was easy to handle, using less solvent and drugs compared with a previous report, and it reflected the results of the clinical trial.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interaction of arbekacin with dialysis membrane

et al. 2016

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“…As a consequence, the anti-thrombogenicity of the AN69ST membrane exceeds that of the native AN69 membrane and anticoagulant-free hemodialysis using AN69ST membrane has been reported [40,41]. On the other hand, as the sulfonyl groups on the AN69 membrane adsorb nafamostate mesilate, this anticoagulant is not compatible enough with the AN69/ AN69ST membrane [42]. Appropriate priming is most important and unfractionated heparin or low molecular weight heparin is recommended if possible.…”

Section: Pmma Hemofiltermentioning

confidence: 99%

Cytokine-adsorbing hemofilter: old but new modality for septic acute kidney injury

Hattori

Oda

2016

Ren Replace Ther

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While evidence supporting the hypothesis that blood purification improve outcome in septic acute kidney injury (AKI) has not been established, many physicians hope to improve outcome in septic AKI by blood purification. Elucidation of the pathophysiology of sepsis has revealed close involvement of humoral mediators, including cytokines, pathogen-associated molecular patterns, and alarmins, in the development of severe sepsis. Removal of substances by blood purification involves three major principles, namely filtration, dialysis (diffusion), and adsorption. Multiple large randomized controlled trials (RCTs) of high-volume hemofiltration (HVHF) for patients with AKI were conducted, but failed to prove the clinical efficacy of HVHF. Blood purification for the removal of mediators through dialysis and filtration using a high cutoff (HCO) membrane hemofilter has not also been established. Furthermore, a HCO membrane hemofilter shares a common problem with HVHF, which is excessive removal of useful substances, such as antimicrobial agents and/or nutrients. Accordingly, continuous hemodiafiltration using cytokine-adsorbing hemofilters (CAH-CHDF) such as polymethylmethacrylate (PMMA) and AN69ST membrane hemofilters has been attracting attention recently. In this review, we report recent findings regarding these old hemofilters with new applications. Although the number of in vitro and in vivo studies conducted to date has been limited, the studies suggest a possibility that these modalities are useful particularly for the treatment of septic shock and septic AKI. CAH-CHDF is expected to be recognized globally as a treatment of septic shock and septic AKI in the near future.

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“…The AN69ST membrane was developed based on the AN69 membrane, which was released in the market in France in 1969. Because the AN69 membrane has a strong negative charge, it poses problems such as induction of bradykinin production [7] and adsorption of pharmacological agents such as NM [8]. Therefore, with the AN69ST membrane, surface treatment has been performed to neutralize the negative charge at the surface of the membrane.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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BackgroundIn 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.MethodsIn 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.ResultsThe 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.ConclusionsThe 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.

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Adsorption of Nafamostat Mesilate by Hemodialysis Membranes

Abstract: The adsorption of the anticoagulant nafamostat mesilate (FUT-175) by five different hemodialysis mem-brane\ was studied in vivo and in vitro. In vivo, FUT-

Cited by 24 publications

References 14 publications

Interaction of arbekacin with dialysis membrane

Interaction of arbekacin with dialysis membrane

Cytokine-adsorbing hemofilter: old but new modality for septic acute kidney injury

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

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