Abstract: 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.

Key words: cell cycle; acute kidney injury; severe asphyxia; neonate; biomarke