甲磺酸萘莫司他在脓毒症相关急性肾损伤oXiris滤器连续性肾脏替代治疗中的抗凝效果评价

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

目的评估甲磺酸萘莫司他体外抗凝在脓毒症相关急性肾损伤(sepsis-associated acute kidney injury,SA-AKI)患者使用oXiris滤器连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)中的有效性和安全性。方法纳入2021年11月-2023年1月四川大学华西医院接受oXiris滤器-CRRT的伴有高出血风险的SA-AKI患者为研究对象,将应用甲磺酸萘莫司他体外抗凝治疗的患者作为萘莫司他组,同期不使用抗凝剂的患者作为对照组。对比分析两组患者一般情况,CRRT的第1个滤器寿命,第1个滤器使用时间达24、48、72 h例数及百分比情况,治疗前及治疗过程中滤器前和滤器后的活化凝血时间(activated clotting time,ACT),治疗前后实验室检查指标,治疗期间发生不良反应的情况及患者的临床结局。正态分布计量资料采用均数±标准差表示,非正态分布计量资料采用中位数(下四分位数,上四分位)表示。结果共纳入118例患者,其中对照组90例,萘莫司他组28例。两组患者一般情况、治疗前实验室检查指标差异均无统计学意义(P>0.05)。Kaplan-Meier生存分析显示,萘莫司他组第1个滤器寿命长于对照组(风险比=0.524,P=0.001)。萘莫司他组第1个滤器使用时间达24 h百分比高于对照组(60.7%vs.25.7%,P=0.001);第1个滤器治疗时长达48 h及72 h的百分比,两组差异无统计学意义(P>0.05)。CRRT治疗过程中,萘莫司他组滤器后平均ACT长于对照组[(216.7±43.2)vs.(181.6±35.5)s,P<0.001],滤器后平均ACT长于滤器前ACT[(216.7±43.2)vs.(183.3±37.7)s,P=0.005]。治疗结束后,萘莫司他组国际标准化比值[1.5(1.1,1.8)vs.1.7(1.4,2.4)]、白细胞介素-6[(235.5±80.9)vs.(500.5±112.7)pg/mL]低于对照组(P<0.05),血小板计数[48.0(31.8,73.0)×10^(9)/L vs.29.0(11.0,61.8)×10^(9)/L]高于对照组(P=0.041),其余实验室检查指标两组差异无统计学意义(P>0.05)。两组患者临床结局差异无统计学意义(P>0.05)。结论甲磺酸萘莫司他应用于oXiris滤器-CRRT伴有高出血风险的SA-AKI患者,体外抗凝效果优于无抗凝剂模式,其可能是一种有效且安全的抗凝药物。

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 prefilter 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.ResultsA 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)×10^(9)/L vs.29.0(11.0,61.8)×10^(9)/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.