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BMC Nephrol
BMC Nephrol
BMC Nephrology
1471-2369
BioMed Central London

3745
10.1186/s12882-024-03745-1
Matters Arising
How do filter types of renal replacement therapy affect survival in critically ill patients? Concerns about adsorption of nafamostat mesylate on AN69 membranes
Qian Yiqi 1
Wu Wei 1
Wang Minmin 2
Wei Yifan 2
Zhong Ming zhong.ming@zs-hospital.sh.cn

1
1 grid.8547.e 0000 0001 0125 2443 Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180, Fenglin Rd, 200032 Shanghai, China
2 grid.418232.e 0000 0001 0296 1954 Baxter Healthcare Corporation, Deerfield, IL US
20 9 2024
20 9 2024
2024
25 31431 5 2024
4 9 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
We are writing to you in response to the article published in BMC Nephrology titled “Dose of nafamostat mesylate during continuous kidney replacement therapy in critically ill patients: a two-centre observational study”. The study provided valuable information on the use of nafamostat mesylate (NM) during continuous renal replacement therapy (CRRT) in critically ill patients. We noticed in this study that a higher dose of NM resulted in a decrease in ICU and hospital mortality. However, the underlying mechanism behind this phenomenon remains unclear. We believe exploring this further is warranted.

Keywords

Continuous renal replacement therapy
Nafamostat mesylate
Filter membrane
Adsorption
issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcDear Editor,

We are writing to you in response to the article published in BMC Nephrology titled “Dose of nafamostat mesylate during continuous kidney replacement therapy in critically ill patients: a two-centre observational study“ [1]. The study provided valuable information on the use of nafamostat mesylate (NM) during continuous renal replacement therapy (CRRT) in critically ill patients. We noticed in this study that a higher dose of NM resulted in a decrease in ICU and hospital mortality. However, the underlying mechanism behind this phenomenon remains unclear. We believe exploring this further is warranted.

Many in vitro experiments have shown that various filter membrane materials exhibit different levels of adsorption effect on NM. The acrylonitrile and methallyl sulfonate copolymer (AN) 69 membrane demonstrates a higher adsorption capacity for NM compared to other filter types including polysulfone (PS) membrane, polymethyl methacrylate (PMMA) membrane, cellulose triacetate (CTA) membrane, and polyester-polymer alloy (PEPA) membrane [2, 3].

A retrospective in vivo study [4] evaluated the NM adsorption capacity of various filter materials by monitoring the NM concentration and activated coagulation time (ACT) at the outlet of the filter. The results showed that although the dose of NM in the AN69ST group was higher than that in the non-AN69ST group (median dose of NM: 29 mg/h vs. 12 mg/h, P < 0.001), the former group had lower ACT than the latter (ACT median: 159 s vs. 199 s, P < 0.001), indicating that the AN69 membranes have a stronger adsorption capacity for NM. Therefore, when using the AN69 series filter membranes, higher dose of NM is required to achieve the anticoagulation effect during CRRT.

AN69 membranes have drawn much attention in the intensive care field due to the ability to adsorb cytokines and endotoxins. The use of AN69ST membranes showed potential benefits in septic patients with CRRT, as several studies have suggested AN69ST membranes might be associated with better clinical outcomes. A retrospective study in Japan [5] showed that in-hospital mortality was 50.0% in the AN69ST group and 54.0% in the non-AN69ST group, respectively. Adjusted odds ratio (OR) of AN69ST membrane for in-hospital mortality was 0.65 (95% CI 0.45–0.93). The use of the AN69ST membrane was also independently associated with shorter ICU length of stay (LOS).

The adsorption effect of NM on AN69 membrane may lead to higher dose of NM in clinical practice. Though the filter was taken as a variable for the adjustment of confounding factors (eTable 2), there were other factors closely related to filter types that may also influence the interpretation of the results, including the indication for choosing different filters which may underlie the discrepancy in disease severity, and the anticoagulant doses prescribed for those situations or for different filters types. We consider it important to know whether there is a difference in baseline characteristics, laboratory data, NM doses and clinical outcomes in AN69ST group comparing with other filter types that have no significant adsorption effect of NM. Also, it would be beneficial to provide more details about the analysis process with consideration of confounding factors to further explain the results and clarify whether the beneficial effect of high dose NM on prognosis was attributed to the anticoagulant or the advantage of using AN69 membranes.

We look forward to hearing from you. Thank you for your time and effort.

Yours sincerely,

Ming Zhong

Acknowledgements

Not applicable.

Author contributions

MZ conceptualized the idea. YQ and YW drafted the manuscript. MW and WW provided critical feedback and input to the manuscript. All authors contributed to and approved the final manuscript.

Funding

Not applicable.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

MZ is involved in a clinical research with Baxter Healthcare Corporation. This article is not supported by any company or funding. No other author has reported a potential conflict of interest relevant to this article.

Abbreviations

NM Nafamostat mesylate

CRRT Continuous renal replacement therapy

AN Acrylonitrile and methallyl sulfonate copolymer

PS Polysulfone

PMMA Polymethyl methacrylate

CTA Cellulose triacetate

PEPA Polyester-polymer alloy

LOS Length of stay

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

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