Evaluation of anticoagulant effect of nafamostat mesilate in continuous renal replacement therapy with oXiris filter for sepsis-related acute kidney injury_West China Medical Journal

Authors：

ZHU Qianying ^1,2 ,  ZHANG Ling ¹ , YANG Yingying ¹ , FU Ping ¹ , FAN Qing ¹ , WANG Fang ¹ , LIN Li ¹ , TANG Xue ¹

1. Department of Nephrology and Institute of Kidney Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Nephrology, Ya’an No.2 People’s Hospital, Ya’an, Sichuan 625000, P. R. China;

Corresponding?author：

ZHANG Ling, Email: zhanglinglzy@163.com

Keywords：

Nafamostat mesilate; sepsis; acute renal injury; oXiris filter; continuous renal replacement therapy

DOI：

10.7507/1002-0179.202307003

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Objective To evaluate the efficacy and safety of nafamostat mesylate as an in vitro anticoagulant in continuous renal replacement therapy (CRRT) using oXiris filters for patients with sepsis-associated acute kidney injury (SA-AKI). Methods SA-AKI patients at high risk of bleeding who received oXiris filter-CRRT at West China Hospital of Sichuan University between November 2021 and January 2023 were included in the study. Patients who received nafamostat mesylate as an anticoagulant were categorized into the nafamostat group, while patients who did not receive any anticoagulant during the same period were categorized into the control group. A comparative analysis was conducted between the two groups regarding general conditions, the lifespan of the first filter in CRRT, the number and percentage of cases with the first filter lasting 24, 48, and 72 h, activated clotting time (ACT) before and during treatment (both pre-filter and post-filter), laboratory test results before and after treatment, incidence of adverse reactions during treatment, and clinical outcomes of the patients. The mean ± standard deviation was used for normal distribution, and the median (lower quartile, upper quartile) was used for non-normal distribution. Results A total of 118 patients were included in the study, with 90 in the control group and 28 in the nafamostat group. There was no statistically significant difference in the general conditions or pre-treatment laboratory test indicators between the two groups (P>0.05). Kaplan-Meier survival analysis showed that the lifespan of the first filter was longer in the nafamostat group compared to the control group (hazard ratio=0.524, P=0.001). The percentage of patients whose first filter lasted 24 h was higher in the nafamostat group than that in the control group (60.7% vs. 25.7%, P=0.001); however, there was no statistically significant difference between the two groups for the first filter lasting 48 h or 72 h (P>0.05). During CRRT treatment, the mean post-filter ACT was longer in the nafamostat group than that in the control group [(216.7±43.2) vs. (181.6±35.5) s, P<0.001], and the mean post-filter ACT was longer than the pre-filter ACT in the nafamostat group [(216.7±43.2) vs. (183.3±37.7) s, P=0.005]. After the treatment, the international normalized ratio [1.5 (1.1, 1.8) vs. 1.7 (1.4, 2.4)], interleukin-6 levels [(235.5±80.9) vs. (500.5±112.7) pg/mL] were lower, and platelet count [48.0 (31.8, 73.0)×10⁹/L vs. 29.0 (11.0, 61.8)×10⁹/L] was higher in the nafamostat group compared to the control group (P<0.05). There was no statistically significant difference in other laboratory test indicators (P>0.05). The clinical outcomes of the patients did not show statistically significant difference between the two groups (P>0.05). Conclusion Nafamostat mesilate may be an effective and safe anticoagulant in SA-AKI patients at high risk of bleeding underwent oXiris filter-CRRT, and its in vitro anticoagulant effect is better than that without anticoagulant.

Citation： ZHU Qianying, ZHANG Ling, YANG Yingying, FU Ping, FAN Qing, WANG Fang, LIN Li, TANG Xue. Evaluation of anticoagulant effect of nafamostat mesilate in continuous renal replacement therapy with oXiris filter for sepsis-related acute kidney injury. West China Medical Journal, 2024, 39(7): 1082-1087. doi: 10.7507/1002-0179.202307003 Copy

1.	Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA, 2016, 315(8): 801-810.
2.	Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med, 2015, 41(8): 1411-1423.
3.	Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA, 2005, 294(7): 813-818.
4.	Liu J, Xie H, Ye Z, et al. Rates, predictors, and mortality of sepsis-associated acute kidney injury: a systematic review and meta-analysis. BMC Nephrol, 2020, 21(1): 318.
5.	Wong ET, Ong V, Remani D, et al. Filter life and safety of heparin-grafted membrane for continuous renal replacement therapy. A randomized controlled trial. Semin Dial, 2021, 34(4): 300-308.
6.	Broman ME, Hansson F, Vincent JL, et al. Endotoxin and cytokine reducing properties of the oXiris membrane in patients with septic shock: a randomized crossover double-blind study. PLoS One, 2019, 14(8): e0220444.
7.	Feng J, Zhang S, Ai T, et al. Effect of CRRT with oXiris filter on hemodynamic instability in surgical septic shock with AKI: a pilot randomized controlled trial. Int J Artif Organs, 2022, 45(10): 801-808.
8.	Pickkers P, Vassiliou T, Liguts V, et al. Sepsis management with a blood purification membrane: European experience. Blood Purif, 2019, 47(Suppl 3): 36-44.
9.	Ma S, Evans RG, Iguchi N, et al. Sepsis-induced acute kidney injury: a disease of the microcirculation. Microcirculation, 2019, 26(2): e12483.
10.	Doi K, Nishida O, Shigematsu T, et al. The Japanese clinical practice guideline for acute kidney injury 2016. Clin Exp Nephrol, 2018, 22(5): 985-1045.
11.	朱倩瑩, 程立新, 黃蘭, 等. 甲磺酸萘莫司他體外抗凝在膿毒癥合并急性腎損傷患者連續性腎臟替代治療中的應用評價. 華西醫學, 2023, 38(5): 718-723.
12.	Zarbock A, Nadim MK, Pickkers P, et al. Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup. Nat Rev Nephrol, 2023, 19(6): 401-417.
13.	Karkar A, Ronco C. Prescription of CRRT: a pathway to optimize therapy. Ann Intensive Care, 2020, 10(1): 32.
14.	Vlaar APJ, Dionne JC, de Bruin S, et al. Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine. Intensive Care Med, 2021, 47(12): 1368-1392.
15.	Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med, 2021, 47(11): 1181-1247.
16.	北村伸哉, 張凌. 甲磺酸萘莫司他在連續性腎臟替代治療中的抗凝應用. 華西醫學, 2018, 33(7): 801-805.
17.	Feng Y, Peng JY, Peng Z. Blood purification in sepsis and systemic inflammation. Curr Opin Crit Care, 2021, 27(6): 582-586.
18.	Zarbock A, Küllmar M, Kindgen-Milles D, et al. Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial. JAMA, 2020, 324(16): 1629-1639.
19.	Pellizzari L, Facchinetti R, Corrà L, et al. Can we reliably predict the level of anticoagulation after enoxaparin injection in elderly patients with renal failure?. Aging Clin Exp Res, 2018, 30(6): 605-608.
20.	中華醫學會腎臟病學分會專家組. 連續性腎臟替代治療的抗凝管理指南. 中華腎臟病雜志, 2022, 38(11): 1016-1024.
21.	李江濤, 王立瑞, 李馨, 等. oXiris 濾器-連續性腎臟替代治療應用甲磺酸萘莫司他抗凝 1 例體會. 中華腎臟病雜志, 2022, 38(8): 731-733.
22.	Hirayama T, Nosaka N, Okawa Y, et al. AN69ST membranes adsorb nafamostat mesylate and affect the management of anticoagulant therapy: a retrospective study. J Intensive Care, 2017, 5: 46.
23.	Romagnoli S, Ricci Z, Ronco C. Renal replacement therapy during septic renal dysfunction//Vincent JL. Annual update in intensive care and emergency medicine. Cham: Springer, 2019: 365-382.
24.	Hellman T, Uusalo P, J?rvisalo MJ. Renal replacement techniques in septic shock. Int J Mol Sci, 2021, 22(19): 10238.
25.	Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp, 2018, 6(1): 12.
26.	李江濤, 王愛麗, 王立瑞, 等. oXiris 濾器在膿毒癥急性腎損傷治療中的應用評價: 病例系列研究. 中華腎臟病雜志, 2021, 37(10): 831-834.
27.	Iba T, Levy JH, Levi M. Viral-induced inflammatory coagulation disorders: preparing for another epidemic. Thromb Haemost, 2022, 122(1): 8-19.
28.	Griffin BR, Jovanovich A, You Z, et al. Effects of baseline thrombocytopenia and platelet decrease following renal replacement therapy initiation in patients with severe acute kidney injury. Crit Care Med, 2019, 47(4): e325-e331.
29.	Zhang L, Yan Tang GK, Liu S, et al. Hemofilter with adsorptive capacities: case report series. Blood Purif, 2019, 47(Suppl 3): 45-50.

1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA, 2016, 315(8): 801-810.
2. Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med, 2015, 41(8): 1411-1423.
3. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA, 2005, 294(7): 813-818.
4. Liu J, Xie H, Ye Z, et al. Rates, predictors, and mortality of sepsis-associated acute kidney injury: a systematic review and meta-analysis. BMC Nephrol, 2020, 21(1): 318.
5. Wong ET, Ong V, Remani D, et al. Filter life and safety of heparin-grafted membrane for continuous renal replacement therapy. A randomized controlled trial. Semin Dial, 2021, 34(4): 300-308.
6. Broman ME, Hansson F, Vincent JL, et al. Endotoxin and cytokine reducing properties of the oXiris membrane in patients with septic shock: a randomized crossover double-blind study. PLoS One, 2019, 14(8): e0220444.
7. Feng J, Zhang S, Ai T, et al. Effect of CRRT with oXiris filter on hemodynamic instability in surgical septic shock with AKI: a pilot randomized controlled trial. Int J Artif Organs, 2022, 45(10): 801-808.
8. Pickkers P, Vassiliou T, Liguts V, et al. Sepsis management with a blood purification membrane: European experience. Blood Purif, 2019, 47(Suppl 3): 36-44.
9. Ma S, Evans RG, Iguchi N, et al. Sepsis-induced acute kidney injury: a disease of the microcirculation. Microcirculation, 2019, 26(2): e12483.
10. Doi K, Nishida O, Shigematsu T, et al. The Japanese clinical practice guideline for acute kidney injury 2016. Clin Exp Nephrol, 2018, 22(5): 985-1045.
11. 朱倩瑩, 程立新, 黃蘭, 等. 甲磺酸萘莫司他體外抗凝在膿毒癥合并急性腎損傷患者連續性腎臟替代治療中的應用評價. 華西醫學, 2023, 38(5): 718-723.
12. Zarbock A, Nadim MK, Pickkers P, et al. Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup. Nat Rev Nephrol, 2023, 19(6): 401-417.
13. Karkar A, Ronco C. Prescription of CRRT: a pathway to optimize therapy. Ann Intensive Care, 2020, 10(1): 32.
14. Vlaar APJ, Dionne JC, de Bruin S, et al. Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine. Intensive Care Med, 2021, 47(12): 1368-1392.
15. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med, 2021, 47(11): 1181-1247.
16. 北村伸哉, 張凌. 甲磺酸萘莫司他在連續性腎臟替代治療中的抗凝應用. 華西醫學, 2018, 33(7): 801-805.
17. Feng Y, Peng JY, Peng Z. Blood purification in sepsis and systemic inflammation. Curr Opin Crit Care, 2021, 27(6): 582-586.
18. Zarbock A, Küllmar M, Kindgen-Milles D, et al. Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial. JAMA, 2020, 324(16): 1629-1639.
19. Pellizzari L, Facchinetti R, Corrà L, et al. Can we reliably predict the level of anticoagulation after enoxaparin injection in elderly patients with renal failure?. Aging Clin Exp Res, 2018, 30(6): 605-608.
20. 中華醫學會腎臟病學分會專家組. 連續性腎臟替代治療的抗凝管理指南. 中華腎臟病雜志, 2022, 38(11): 1016-1024.
21. 李江濤, 王立瑞, 李馨, 等. oXiris 濾器-連續性腎臟替代治療應用甲磺酸萘莫司他抗凝 1 例體會. 中華腎臟病雜志, 2022, 38(8): 731-733.
22. Hirayama T, Nosaka N, Okawa Y, et al. AN69ST membranes adsorb nafamostat mesylate and affect the management of anticoagulant therapy: a retrospective study. J Intensive Care, 2017, 5: 46.
23. Romagnoli S, Ricci Z, Ronco C. Renal replacement therapy during septic renal dysfunction//Vincent JL. Annual update in intensive care and emergency medicine. Cham: Springer, 2019: 365-382.
24. Hellman T, Uusalo P, J?rvisalo MJ. Renal replacement techniques in septic shock. Int J Mol Sci, 2021, 22(19): 10238.
25. Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp, 2018, 6(1): 12.
26. 李江濤, 王愛麗, 王立瑞, 等. oXiris 濾器在膿毒癥急性腎損傷治療中的應用評價: 病例系列研究. 中華腎臟病雜志, 2021, 37(10): 831-834.
27. Iba T, Levy JH, Levi M. Viral-induced inflammatory coagulation disorders: preparing for another epidemic. Thromb Haemost, 2022, 122(1): 8-19.
28. Griffin BR, Jovanovich A, You Z, et al. Effects of baseline thrombocytopenia and platelet decrease following renal replacement therapy initiation in patients with severe acute kidney injury. Crit Care Med, 2019, 47(4): e325-e331.
29. Zhang L, Yan Tang GK, Liu S, et al. Hemofilter with adsorptive capacities: case report series. Blood Purif, 2019, 47(Suppl 3): 45-50.

West China Medical Journal

Evaluation of anticoagulant effect of nafamostat mesilate in continuous renal replacement therapy with oXiris filter for sepsis-related acute kidney injury

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