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Evaluation of acute kidney injury by urinary tissue inhibitor metalloproteinases-2 and insulin-like growth factor-binding protein 7 after pediatric cardiac surgery

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Abstract

Background

With adult patients, the measurement of [TIMP-2]*[IGFBP7] can predict the risk of moderate to severe AKI within 12 h of testing. In pediatrics, however, the performance of [TIMP-2]*[IGFBP7] as a predictor of AKI was less studied and yet to be widely utilized in clinical practice. This study was conducted to validate the utility of [TIMP-2]*[IGFBP7] as an earlier biomarker for AKI prediction in Chinese infants and small children.

Methods

We measured urinary [TIMP-2]*[IGFBP7] using NEPHROCHECK® at eight perioperative time points in 230 patients undergoing complex cardiac surgery and evaluated the performance of [TIMP-2]*[IGFBP7] for predicting severe AKI within 72 h of surgery.

Results

A total of 50 (22%) of 230 developed AKI stages 2–3 within 72 h after CPB initiation. In the AKI stage 2–3 patients, two patterns of serum creatinine (SCr) elevations were observed. The patients with only a transient increase in SCr within 24 h (< 24 h, early AKI 2–3) did not experience a worse outcome than patients in AKI stage 0–1. AKI stage 2–3 patients with SCr elevation after 24 h (24–72 h, late AKI 2–3), as well as AKI dialysis patients (together designated severe AKI), did experience worse outcomes. Compared to AKI stages 0–1, significant elevations of [TIMP-2]*[IGFBP7] values were observed in severe AKI patients at hours T2, T4, T12, and T24 following CPB initiation. The AUC for predicting severe AKI with [TIMP-2]*[IGFBP7] at T2 (AUC = 0.76) and maximum T2/T24 (AUC = 0.80) are higher than other time points. The addition of the NEPHROCHECK® test to the postoperative parameters improved the risk assessment of severe AKI.

Conclusions

Multiple AKI phenotypes (early versus late AKI) were identified after pediatric complex cardiac surgery according to SCr-based AKI definition. Urinary [TIMP-2]*[IGFBP7] predicts late severe AKI (but not early AKI) as early as 2 h following CPB initiation.

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Data availability

All datasets underlying the manuscript results are available upon request to the corresponding author (XZM).

Abbreviations

AKI:

Acute kidney injury

CPB:

Cardiopulmonary bypass

SCr:

Serum creatinine

KDIGO:

Kidney Disease Improving Global Outcomes

TIMP-2:

Tissue inhibitor metalloproteinases-2

IGFBP7:

Insulin-like growth factor-binding protein 7

RACHS:

Risk adjusted classification for congenital heart surgery

RACHS-1:

Risk adjustment for congenital heart surgery score version 1

IQR:

Inter-quantile range

ROC:

Receiver operating curve

AUC:

Area under curve

CI:

Confidence intervals

MVIS:

Maximal vasoactive inotrope scores

CSA-AKI:

Cardiac surgery-associated acute kidney injury

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Acknowledgements

Zhuoming Xu, Wei Wang, and Ji Liang are co-corresponding authors for this study. We would like to thank the patients and their parents for their support and participation in this study. This work was supported by the Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics (20dz2260900).

Funding

This work was supported by the Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics (20dz2260900).

Author information

Author notes

  1. Yue Tao, Fabienne Heskia, Mingjie Zhang, Rong Qin, Bin Kang and Luoquan Chen contributed equally to this work

Authors and Affiliations

  1. Shanghai Children’s Medical Center–bioMérieux Laboratory, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Yue Tao, Bin Kang, Luoquan Chen, Fei Wu, Xi Mo & Ji Liang

  2. The Laboratory of Pediatric Infectious Diseases, Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Yue Tao & Xi Mo

  3. Global Medical Affairs Department, bioMérieux SA, Marcy l’Etoile, France

    Fabienne Heskia & Rong Qin

  4. Department of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Mingjie Zhang, Jihong Huang, Huiwen Chen, Wei Wang & Zhuoming Xu

  5. bioMérieux (Shanghai) Company Limited, Shanghai, China

    Bin Kang, Luoquan Chen, Fei Wu & Ji Liang

  6. Open Innovation & Partnerships Department, bioMérieux SA, Marcy l’Etoile, France

    Karen Brengel-Pesce

Authors
  1. Yue Tao
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Contributions

Y Tao, F Heskia, JH Huang, J Liang, W Wang, and ZM Xu designed the study. R Qin, Y Tao, MJ Zhang, LQ Chen, and F Wu collected patient data and samples. LQ Chen and F Wu performed NEPHROCHECK® tests. B Kang, Y Tao, F Heskia, HW Chen, J Liang, and ZM Xu analyzed the data. Y Tao, F Heskia, MJ Zhang, K Brengel-Pesce, X Mo, J Liang, W Wang, and ZM Xu discussed the results and performed additional analyses. The first draft of the manuscript was written by Y Tao, F Heskia, B Kang, LQ Chen, J Liang, and ZM Xu, and all authors commented on previous versions of the manuscript. ZM Xu, W Wang, and J Liang take responsibility for the content of the manuscript and the accuracy of the reported data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhuoming Xu.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Institutional Review Board and the Ethics Committee of Shanghai Children’s Medical Center (SCMCIRB-K2019009). Written informed consent was obtained from all participating patients and/or their parents. Clinical Trial Registry Number: NCT03963284.

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Not applicable.

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The authors declare no competing interests.

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Tao, Y., Heskia, F., Zhang, M. et al. Evaluation of acute kidney injury by urinary tissue inhibitor metalloproteinases-2 and insulin-like growth factor-binding protein 7 after pediatric cardiac surgery. Pediatr Nephrol 37, 2743–2753 (2022). https://doi.org/10.1007/s00467-022-05477-6

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