Evaluation of <i>in vitro</i> anticoagulation with nafamostat mesilate in continuous renal replacement therapy in patients with sepsis complicated with acute kidney injury_West China Medical Journal

Authors：

ZHU Qianying ^1,2 , CHENG Lixin ¹ , HUANG Lan ³ , FAN Qing ¹ , HE Xuanchen ¹ , WANG Fang ¹ , CHEN Fang ¹ , YANG Yingying ¹ ,  ZHANG Ling ¹ , FU Ping ¹

1. Department of Nephrology and Kidney Research Institute, 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;
3. Department of General Practice, No.5 People’s Hospital Affiliated to Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611130, P. R. China;

Corresponding?author：

ZHANG Ling, Email: zhanglinglzy@163.com

Keywords：

Nafamostat mesilate; sepsis; acute kidney injury; continuous renal replacement therapy; anticoagulation

DOI：

10.7507/1002-0179.202206024

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Objective To evaluate the efficacy and safety of in vitro anticoagulation with nafamostat mesilate in continuous renal replacement therapy (CRRT) in patients with sepsis complicated with acute kidney injury (AKI). Methods The study subjects were sepsis patients with AKI who underwent CRRT in West China Hospital of Sichuan University and were at high risk of bleeding. CRRT patients who received in vitro anticoagulation with nafamostat mesilate between July 2021 and January 2022 were included in the nafamostat group. The medical records of CRRT patients who did not use anticoagulants between January 2020 and December 2020 were retrospectively collected as a control group. The general situation, the lifespan of the first CRRT filter, the number of filters used within 72 hours of treatment, laboratory tests before and after treatment, and the occurrence of adverse reactions during treatment of the two groups of patients were analyzed. Results There were 42 patients in the control group and 21 patients in the nafamostat group. There was no statistically significant difference in age, gender, body mass index, mean arterial pressure, primary disease, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation Ⅱ score, or pre-treatment laboratory test results between the two groups of patients (P>0.05). Kaplan-Meier survival analysis showed that the lifespan of the first filter was longer in the nafamostat group than in the control group (hazard ratio=0.408, P<0.05). The number of filters used by the control group patients after 72 hours of treatment was greater than that of the nafamostat group patients (2.1±0.6 vs. 1.3±0.5, P<0.05). After 72 hours of treatment, serum creatinine levels [(99.4±15.7) vs. (127.6±20.5)] μmol/L], urea nitrogen [(4.5±1.9) vs. (6.8±2.3) mmol/L], cystatin C [(1.0±0.2) vs. (1.2±0.2) mg/L], uric acid [(86.5±15.3) vs. (105.3±20.3) μmol/L] in the nafamostat group were lower than those of the control group (P<0.05), and there was no statistically significant difference in the results of other laboratory tests (P>0.05). There was no statistically significant difference in adverse reactions between the two groups of patients (P>0.05). Conclusion For patients with sepsis complicated with AKI who undergo CRRT and are at high risk of bleeding, nafamostat mesilate may be a safe and effective anticoagulant for in vitro anticoagulation.

Citation： ZHU Qianying, CHENG Lixin, HUANG Lan, FAN Qing, HE Xuanchen, WANG Fang, CHEN Fang, YANG Yingying, ZHANG Ling, FU Ping. Evaluation of in vitro anticoagulation with nafamostat mesilate in continuous renal replacement therapy in patients with sepsis complicated with acute kidney injury. West China Medical Journal, 2023, 38(5): 718-723. doi: 10.7507/1002-0179.202206024 Copy

1.	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.
2.	Ma S, Evans RG, Iguchi N, et al. Sepsis-induced acute kidney injury: a disease of the microcirculation. Microcirculation, 2019, 26(2): e12483.
3.	Poston JT, Koyner JL. Sepsis associated acute kidney injury. BMJ, 2019, 364: k4891.
4.	馮長福, 周森, 邢柏. 可溶性 CD73 聯合 SOFA 評分對膿毒癥相關急性腎損傷患者 28 d 死亡風險的預測價值. 中國急救醫學, 2022, 42(1): 13-18.
5.	覃英鐠, 劉煥皓. 枸櫞酸抗凝劑用于血液凈化的臨床研究進展. 藥物評價研究, 2018, 41(5): 929-933.
6.	Legrand M, Tolwani A. Anticoagulation strategies in continuous renal replacement therapy. Semin Dial, 2021, 34(6): 416-422.
7.	Pschowski R, Briegel S, Von Haehling S, et al. Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure. Anaesth Intensive Care, 2015, 43(6): 764-770.
8.	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.
9.	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.
10.	Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med, 2021, 49(11): e1063-e1143.
11.	Kidney Disease:Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl, 2012, 2(1): 1-138.
12.	Karkar A, Ronco C. Prescription of CRRT: a pathway to optimize therapy. Ann Intensive Care, 2020, 10(1): 32.
13.	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.
14.	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.
15.	Thompson A, Li F, Gross AK. Considerations for medication management and anticoagulation during continuous renal replacement therapy. AACN Adv Crit Care, 2017, 28(1): 51-63.
16.	Annich GM, Zaulan O, Neufeld M, et al. Thromboprophylaxis in extracorporeal circuits: current pharmacological strategies and future directions. Am J Cardiovasc Drugs, 2017, 17(6): 425-439.
17.	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.
18.	Lin T, Song L, Huang R, et al. Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies. BMC Nephrol, 2019, 20(1): 472.
19.	Wen M, Küchle C, Steubl D, et al. A novel citrate-based protocol versus heparin anticoagulation for sustained low-efficiency dialysis in the ICU: safety, efficacy, and cost. BMC Nephrol, 2018, 19(1): 79.
20.	Bianchi NA, Altarelli M, Eckert P, et al. Complications of regional citrate anticoagulation for continuous renal replacement therapy: an observational study. Blood Purif, 2020, 49(5): 567-575.
21.	Ng CJH, Poh CB, Koduri S, et al. Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy. Clin Exp Nephrol, 2021, 25(9): 963-969.
22.	楊曉波, 王金柱, 劉明晨, 等. 枸櫞酸鈉在膿毒癥伴高危出血因素患者行連續性腎臟替代治療中的應用效果分析. 護理與康復, 2018, 17(9): 10-14.
23.	Li L, Bai M, Yu Y, et al. Regional citrate anticoagulation vs no-anticoagulation for CRRT in hyperlactatemia patients with increased bleeding risk: a retrospective cohort study. Semin Dial, 2020: 8.
24.	Choi JY, Kang YJ, Jang HM, et al. Nafamostat mesilate as an anticoagulant during continuous renal replacement therapy in patients with high bleeding risk: a randomized clinical trial. Medicine (Baltimore), 2015, 94(52): e2392.
25.	Makino S, Egi M, Kita H, et al. Comparison of nafamostat mesilate and unfractionated heparin as anticoagulants during continuous renal replacement therapy. Int J Artif Organs, 2016, 39(1): 16-21.

1. 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.
2. Ma S, Evans RG, Iguchi N, et al. Sepsis-induced acute kidney injury: a disease of the microcirculation. Microcirculation, 2019, 26(2): e12483.
3. Poston JT, Koyner JL. Sepsis associated acute kidney injury. BMJ, 2019, 364: k4891.
4. 馮長福, 周森, 邢柏. 可溶性 CD73 聯合 SOFA 評分對膿毒癥相關急性腎損傷患者 28 d 死亡風險的預測價值. 中國急救醫學, 2022, 42(1): 13-18.
5. 覃英鐠, 劉煥皓. 枸櫞酸抗凝劑用于血液凈化的臨床研究進展. 藥物評價研究, 2018, 41(5): 929-933.
6. Legrand M, Tolwani A. Anticoagulation strategies in continuous renal replacement therapy. Semin Dial, 2021, 34(6): 416-422.
7. Pschowski R, Briegel S, Von Haehling S, et al. Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure. Anaesth Intensive Care, 2015, 43(6): 764-770.
8. 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.
9. 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.
10. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med, 2021, 49(11): e1063-e1143.
11. Kidney Disease:Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl, 2012, 2(1): 1-138.
12. Karkar A, Ronco C. Prescription of CRRT: a pathway to optimize therapy. Ann Intensive Care, 2020, 10(1): 32.
13. 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.
14. 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.
15. Thompson A, Li F, Gross AK. Considerations for medication management and anticoagulation during continuous renal replacement therapy. AACN Adv Crit Care, 2017, 28(1): 51-63.
16. Annich GM, Zaulan O, Neufeld M, et al. Thromboprophylaxis in extracorporeal circuits: current pharmacological strategies and future directions. Am J Cardiovasc Drugs, 2017, 17(6): 425-439.
17. 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.
18. Lin T, Song L, Huang R, et al. Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies. BMC Nephrol, 2019, 20(1): 472.
19. Wen M, Küchle C, Steubl D, et al. A novel citrate-based protocol versus heparin anticoagulation for sustained low-efficiency dialysis in the ICU: safety, efficacy, and cost. BMC Nephrol, 2018, 19(1): 79.
20. Bianchi NA, Altarelli M, Eckert P, et al. Complications of regional citrate anticoagulation for continuous renal replacement therapy: an observational study. Blood Purif, 2020, 49(5): 567-575.
21. Ng CJH, Poh CB, Koduri S, et al. Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy. Clin Exp Nephrol, 2021, 25(9): 963-969.
22. 楊曉波, 王金柱, 劉明晨, 等. 枸櫞酸鈉在膿毒癥伴高危出血因素患者行連續性腎臟替代治療中的應用效果分析. 護理與康復, 2018, 17(9): 10-14.
23. Li L, Bai M, Yu Y, et al. Regional citrate anticoagulation vs no-anticoagulation for CRRT in hyperlactatemia patients with increased bleeding risk: a retrospective cohort study. Semin Dial, 2020: 8.
24. Choi JY, Kang YJ, Jang HM, et al. Nafamostat mesilate as an anticoagulant during continuous renal replacement therapy in patients with high bleeding risk: a randomized clinical trial. Medicine (Baltimore), 2015, 94(52): e2392.
25. Makino S, Egi M, Kita H, et al. Comparison of nafamostat mesilate and unfractionated heparin as anticoagulants during continuous renal replacement therapy. Int J Artif Organs, 2016, 39(1): 16-21.

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