Abstract
Backgroud
Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP-7) and the combination of TIMP-2 and IGFBP-7 ([TIMP-2]•[IGFBP7]) are proposed to be predictive biomarkers for acute kidney injury (AKI). The intention of our study was to determine whether there is any significant predictive value of these biomarkers for the occurrence of AKI and severe AKI in critically ill neonates.
Methods
Urinary samples were serially collected in 237 neonates during neonatal intensive care unit (NICU) stay for measurements of TIMP-2 and IGFBP-7 in this prospective study. AKI diagnosis was based on KDIGO classification without urine output or serum creatinine >1.2 mg/dL.
Results
Twenty neonates developed AKI, including 11 with KDIGO stage 1, defined as mild AKI, and 9 with stages 2 and 3, defined as severe AKI. Urinary IGFBP-7 and [TIMP-2]•[IGFBP7] remained associated with AKI after adjustment for gestational age, gender and illness severity. Urinary [TIMP-2]•[IGFBP7] achieved an AUC of 0.71 (P = 0.034) and displayed a sensitivity of 88.9% and a specificity of 50.9% for discriminating severe AKI at the optimal cut-off value of 0.045.
Conclusion
The combination of TIMP-2 and IGFBP-7 had independent discriminative value for severe AKI in critically ill neonates.
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Acknowledgements
We thank the staff in biochemistry laboratory for technical assistance. This work was supported by grants from the National Natural Science Foundation of China (81370773, 81741054, 81971432), JiangSu province science and technology support Program (Social Development BE2016675), Natural Science Foundation of Jiangsu province (BK20171217), Key talent of women’s and children’s health of JiangSu province (FRC201738), SuZhou clinical key disease diagnosis and treatment technology foundation (LCZX201611), SuZhou science and technology development project (SYS201760). The funders had no role in the study design, data collection, preparation of the manuscript, and decision to publish.
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J.C. participated in data analysis and drafted the manuscript. Y.S. performed the experiments. S.W., X.D. and H.H. participated in collecting the data and samples. X.D. participated in data analysis. Z.B. and X.L. participated in data analysis and interpretation. J.W. participated in the design of the study and coordination. Y.L. had primary responsibility for study design, performing the experiments, data analysis, interpretation of data, and writing of the manuscript. All authors read and approved the final manuscript.
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Chen, J., Sun, Y., Wang, S. et al. The effectiveness of urinary TIMP-2 and IGFBP-7 in predicting acute kidney injury in critically ill neonates. Pediatr Res 87, 1052–1059 (2020). https://doi.org/10.1038/s41390-019-0698-8
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DOI: https://doi.org/10.1038/s41390-019-0698-8
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