建立用药规范在大剂量甲氨蝶呤相关急性肾损伤防范中的作用

Role of the establishment of protocol in the prevention of high-dose methotrexate induced acute kidney injury

目的 评价自行建立的＂大剂量甲氨蝶呤（HD-MTX）用药规范＂在MTX相关急性肾损伤（AKI）防范中的作用. 方法 收集苏州大学附属第一医院2013年1月至2016年12月接受以HD-MTX为基础方案化疗的恶性血液病患者的病历资料进行回顾性分析,以＂HD-MTX用药规范＂建立前（2013年1月至2014年9月）接受化疗的患者为对照组,该规范实施后（2014年10月至2016年12月）接受化疗的患者为观察组.比较2组患者MTX排泄延迟和AKI的发生情况. 结果 纳入分析的患者共234例.对照组78例,男性50例,女性28例;年龄3~64岁,中位年龄25岁;白血病57例,淋巴瘤21例.观察组156例,男性92例,女性64例;年龄6~64岁,中位年龄26岁;白血病129例,淋巴瘤27例.对照组HD-MTX用药前1 d未给予静脉水化及碱化尿液处理者占比均明显高于观察组[60.1%（47/78）比4.5%（7/156）,80.8%（63/78）比8.3%（13/156）],中位静脉水化量明显低于观察组[0（0~500）ml比1 750 （1 250~2 100）ml],差异均具有统计学意义（X2=91.168,P〈0.001;X2=124.415,P〈0.001;Z=-9.224,P〈0.001）.用药后对照组患者MTX排泄延迟发生率和AKI发生率均明显高于观察组[21.8%（17/78）比12.2%（18/156）,20.5%（16/78）比10.3%（16/156）],差异均有统计学意义（X2=4.300,P=0.038;X2=4.634,P=0.031）.对照组16例AKI患者中Ⅰ、Ⅱ、Ⅲ级肾损伤者分别为6、2、8例,观察组16例AKI患者中Ⅰ、Ⅱ、Ⅲ级肾损伤者分别为11、4、 1例,对照组肾损伤程度重于观察组（Z=-2.286,P=0.022）.结论 自行建立的＂HD-MTX用药规范＂有助于MTX相关AKI的防范,可明显降低MTX排泄延迟和AKI发生率,特别是Ⅲ级肾损伤发生率.

Objective To evaluate the function of ＂high-dose methotrexate （HD-MTX） protocol＂ in the patients with HD-MTX-induced acute kidney injury （AKI）.Methods The medical record data of patients with hematological malignancy received HD-MTX therapy in the First Affiliated Hospital of Soochow University from January 2013 to December 2016 were collected and retrospectively analyzed.The patients who received chemotherapy before the establishment of ＂HD-MTX protocol＂ were enrolled into the control group （between January 2013 to September 2014）, and the patients who received chemotherapy after the establishment of ＂HD-MTX protocol＂ were enrolled into the observation group （between October 2014 to December 2016）.The incidence of delayed MTX elimination and AKI between the 2 groups were compared.Results A total of 234 patients were enrolled in the study.There were 78 patients in the control group including 50 males and 28 females with the age 3 to 64 years and median age 25 years, of them, 57 patients with leukemia and 21 patients with lymphoma.There were 156 patients in the observation group including 92 males and 64 females with the age 6 to 64 years and median age 26 years, of them, 129 patients had leukemia and 27 patients had lymphoma.The percentage of patients with no-prehydration and no-preurine alkalinization in the control group was higher than that in the observation group[60.1% （47/78） vs.4.5% （7/156）, 80.8% （63/78） vs.8.3% （13/156）], and the median volume of intravenous hydration was less than that in the observation group[0 （0-500） ml vs.1 750 （1 250-2 100） ml].The differences between the 2 groups were statistically significant （X2=91.168, P〈0.001;X2=124.415, P〈0.001;Z=-9.224, P〈0.001）.The incidence of delayed MTX elimination and AKI after MTX infusion in the control group was higher than that in the observation group [21.8% （17/78） vs.12.2% （18/156）.20.5% （16/78） vs.10.3% （16/156）].The differences between the 2 groups were statistically significant （X2=4.300, P=0.038;X2=4.634, P=0.031）.In the control group, there were 16 patients with AKI, the patients with grade Ⅰ, grade Ⅱ and grade Ⅲ were 6, 2 and 8 respectively.In the observation group, there were 16 patients with AKI, the patients with grade Ⅰ, grade Ⅱ and grade Ⅲ were 11, 4 and 1 respectively.The degree of kidney injury in the control group was higher than that in the observation group （Z=-2.286, P=0.022）.Conclusion The ＂HD-MTX protocol＂ can significantly decrease the incidence of delayed MTX elimination and AKI, especially the incidence of grade Ⅲ AKI.