新生儿重度窒息后急性肾损伤尿细胞周期停滞标志物的临床研究  

The clinical analysis of urinary cell cycle arrest biomarkers in neonatal acute kidney injury after severe asphyxia

作　　者：颜崇兵[1] 马俐 张潇月 张红专 孙婧婧[1] 沈云琳[1] YAN Chongbing;MA Li;ZHANG Xiaoyue;ZHANG Hongzhuan;SUN Jingjing;SHEN Yunlin(Department of Neonatology,Shanghai Children’s Hospital,Shanghai Jiao Tong University,Shanghai 200062,China)

机构地区：[1]上海市儿童医院上海交通大学附属儿童医院新生儿科,上海200062

出　　处：《临床儿科杂志》2021年第12期886-890,共5页Journal of Clinical Pediatrics

基　　金：上海申康医院发展中心第二批临研培育项目(No.SHDC12018X28);上海市儿童医院临床研究培育专项(No.2018YLY002)。

摘　　要：目的探讨尿细胞周期停滞标志物金属蛋白酶组织抑制剂-2(TIMP-2)和胰岛素样生长因子结合蛋白-7(IGFBP7)在新生儿重度窒息后急性肾损伤(AKI)中的动态变化以及临床价值。方法纳入2019年1月至2020年6月生后6小时内住院的重度窒息新生儿共51例。根据全球改善肾脏病预后委员会(KDIGO)新生儿AKI诊断标准分为AKI组和非AKI组。动态观察两组新生儿入院当时、生后24 h、48 h和1周尿细胞周期停滞相关生物标志物TIMP-2和IGFBP7水平和血清肌酐的动态变化。采用受试者工作特征(ROC)曲线分析尿液IGFBP7×TIMP-2诊断窒息新生儿发生AKI的临床意义。结果51例重度窒息新生儿,男26例、女25例,平均胎龄(38.34±1.71)周,出生体质量(3130.6±460.2)g。其中AKI组9例,非AKI组42例,AKI发生率为17.65%。与非AKI组相比,AKI组新生儿入院时、生后24 h尿液中TIMP-2浓度明显增高,入院时尿IGFBP7浓度增高,差异均有统计学意义(P<0.05)。AKI组新生儿入院时、生后24 h尿IGFBP7×TIMP-2较非AKI组明显增高,差异有统计学意义(P<0.05)。采用ROC曲线分析重度窒息新生儿入院时、生后24 h尿液IGFBP7×TIMP-2对AKI的诊断价值,其AUC分别为0.905(95%CI:0.820~0.990)和0.729(95%CI:0.482~0.977)。结论尿液细胞周期停滞标志物IGFBP7×TIMP-2在重度窒息新生儿生后早期可明显增高,可能有助于早期识别AKI的发生,其能否作为一种新型早期诊断AKI的生物标志物,尚需进一步验证。Objective To investigate the dynamic change and clinical value of urinary cell cycle arrest biomarkers,tissue inhibitor of metalloproteinases-2(TIMP-2)and insulin-like growth factor-binding protein 7(IGFBP7),in neonatal acute kidney injury(AKI)patients after severe asphyxia.Methods A total of 51 neonates with severe asphyxia who were hospitalized within 6 hours after birth from January 2019 to June 2020 were included.They were divided into AKI group and non-AKI group based on the diagnostic criteria of neonatal AKI enacted by kidney disease improving global outcome(KDIGO).Dynamic changes of levels of urinary cell cycle arrest biomarkers(TIMP-2 and IGFBP7)and serum creatinine were observed at the time of admission,24 h,48h and 1 week after birth.The receiver operating characteristic(ROC)curve was used to analyze the clinical significance of urine IGFBP7×TIMP-2 in the diagnosis of AKI in neonates with asphyxia.Results The mean gestational age was(38.34±1.71)weeks,and the birth weight was(3130.6±460.2)g.There were 9 neonates in AKI group and 42 neonates in non-AKI group,and the incidence of AKI was 17.65%.Compared with the non-AKI group,urine TIMP-2 concentration in the AKI group was significantly increased at admission and 24h after birth,and urine IGFBP7 concentration was increased at admission,and the differences were statistically significant(P<0.05).Urine IGFBP7×TIMP-2 in AKI group was significantly higher than that in non-AKI group at admission and 24 h after birth,and the difference was statistically significant(P<0.05).ROC curve was used to analyze the diagnostic value of urine IGFBP7×TIMP-2 for AKI in neonates with severe asphyxia at admission and 24 h after birth,and its AUC was 0.905(95%CI:0.820~0.990)and 0.729(95%CI:0.482~0.977),respectively.Conclusions Urine cell cycle arrest marker IGFBP7×TIMP-2 was significantly increased in the early postnatal period of severe asphyxia neonates,which may contribute to the early identification of AKI.Whether it can be used as a novel biomarker for early diagnosi

关 键 词：细胞周期 急性肾损伤 重度窒息 新生儿 生物学标志物 

分 类 号：R722.1[医药卫生—儿科]