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Prediction of urinary dickkopf-3 for AKI, sepsis-associated AKI, and PICU mortality in children

Pediatric Research volume 93, pages 1651–1658 (2023)Cite this article

Abstract

Background

Preoperative urinary dickkopf-3 (DKK3) is proposed as an early biomarker for the prediction of acute kidney injury (AKI) in patients undergoing cardiac surgery. We explored the clinical utility of urinary DKK3 for the early predictive value for AKI, sepsis-associated AKI (SA-AKI), and pediatric intensive care unit (PICU) mortality in critically ill children.

Methods

Urine samples were collected during the first 24 h after admission for measurement of DKK3. AKI diagnosis was based on serum creatinine and urine output using the KDIGO criteria. SA-AKI was defined as AKI that occurred in children who met the sepsis criteria in accordance with the surviving sepsis campaign international guidelines for children.

Results

Of the 420 children, 73 developed AKI, including 24 with SA-AKI, and 30 died during the PICU stay. The urinary DKK3 level was significantly associated with AKI, SA-AKI, and PICU mortality, even after adjustment for confounders. The area under the receiver operating characteristic curve of urinary DKK3 for the discrimination of AKI, SA-AKI, and PICU mortality was 0.70, 0.80, and 0.78, respectively.

Conclusion

Urinary DKK3 was independently associated with an increased risk for AKI, SA-AKI, and PICU mortality and may be predictive of the aforementioned issues in critically ill children.

Impact

  • Urinary dickkopf-3 (DKK3) has been identified as a preoperative biomarker for the prediction of acute kidney injury (AKI) following cardiac surgery or coronary angiography in adult patients. However, little is known about the clinical utility of urinary DKK3 in pediatric cohorts.

  • This study demonstrated that urinary DKK3 is capable of early predicting AKI and pediatric intensive care unit (PICU) mortality and discriminating sepsis-associated AKI (SA-AKI) from other types of AKI.

  • Urinary DKK3 may be an early biomarker for predicting AKI, SA-AKI, and PICU mortality in critically ill children.

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Fig. 1: Comparison of uDKK3/Cr among critical children with different clinical outcomes.
Fig. 2: Forest plot of the association between uDKK3/Cr and AKI, severe AKI, sepsis, SA-AKI, and PICU mortality in logistic regression analyses.
Fig. 3: Receiver operating characteristic curves for the abilities of the PRISIM III score and uDKK3/Cr to predict clinical outcomes.
Fig. 4: Risk of clinical outcomes according to quartiles of uDKK3/Cr.

Data availability

The data analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81971432), Jiangsu Province Science and Technology Support Program (BE2020660), and Key Talent of Women’s and Children’s Health of Jiangsu Province (FRC201738). The funders had no role in study design, data collection, preparation of the manuscript, and decision to publish.

Author information

Author notes

  1. These authors contributed equally: Junlong Hu, Yueying Zhou.

Authors and Affiliations

  1. Department of Nephrology and Immunology, Children’s Hospital of Soochow University, Suzhou, Jiangsu Province, China

    Junlong Hu, Yueying Zhou, Hui Huang, Yuxian Kuai, Xiaozhong Li & Yanhong Li

  2. Pediatric Intensive Care Unit, Children’s Hospital of Soochow University, Suzhou, Jiangsu Province, China

    Jiao Chen & Zhenjiang Bai

  3. Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, Jiangsu Province, China

    Yanhong Li

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Contributions

J.H. performed the data analysis and drafted the manuscript. Y.Z. performed the experiments. H.H. and Y.K. participated in the data analysis and interpretation. J.C. and Z.B. participated in collecting the data and samples. X.L. coordinated and supervised data collection and carried out the initial interpretation of data. Y.L. had primary responsibility for study design, performing the experiments, data analysis, interpretation of data, and writing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yanhong Li.

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This study was approved by the Institutional Review Board of the Children’s Hospital of Soochow University and performed in accordance with the Declaration of Helsinki. Informed consent was obtained from each participating individual’s guardian.

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Hu, J., Zhou, Y., Huang, H. et al. Prediction of urinary dickkopf-3 for AKI, sepsis-associated AKI, and PICU mortality in children. Pediatr Res 93, 1651–1658 (2023). https://doi.org/10.1038/s41390-022-02269-4

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