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 （IGFBP 7）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IGFBP 7×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（3 130 . 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

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 (IGFBP 7 ), 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 IGFBP 7 ) and serum creatinine were observed at the time of admission, 24 h, 48 h and 1 week after birth. The receiver operating characteristic (ROC) curve was used to analyze the clinical significance of urine IGFBP 7×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 IGFBP 7× 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 24h 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 IGFBP 7×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 diagnosis of AKI needs further validation.