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A risk-stratified assessment of biomarker-based acute kidney injury phenotypes in children

Abstract

Background

The functional acute kidney injury (AKI) diagnostic tests serum creatinine (SCr) and urine output are imprecise and make management challenging. Combining tubular injury biomarkers with functional markers reveal AKI phenotypes that may facilitate personalized care. However, when and in whom to obtain injury biomarkers remains unclear.

Methods

This was a prospective, observational study of patients admitted to a pediatric intensive care unit (PICU). Using the Renal Angina Index (RAI), subjects were screened for the presence (RAI+) or absence (RAI−) of renal angina 12 h post-admission and assigned an AKI phenotype using urinary NGAL (NGAL+: ≥150 ng/ml) and SCr (SCr+: ≥KDIGO Stage 1). Outcomes for each AKI phenotype were assessed and compared by RAI status.

Results

In all, 200/247 (81%) subjects were RAI+. RAI+ subjects who were NGAL+ had higher risk of Day 3 AKI, renal replacement therapy use, and mortality and fewer ventilator- and PICU-free days, compared to NGAL−, irrespective of Day 0 SCr. Similar findings were not demonstrated in RAI− subjects, though NGAL+/SCr+ was associated with fewer ventilator- and PICU-free days compared to NGAL−/SCr+.

Conclusions

NGAL- and SCr-based AKI phenotypes provide improved prognostic information in children with renal angina (RAI+) and/or with SCr elevation. These populations may be appropriate for targeted biomarker testing.

Impact

  • New consensus recommendations encourage the integration of kidney tubular injury biomarkers such as urinary NGAL with serum creatinine for diagnosis and staging of acute kidney injury; however, no structured testing framework exists guiding when to test and in whom.

  • Urinary NGAL- and serum creatinine-based acute kidney injury phenotypes increase diagnostic precision in critically ill children experiencing renal angina (RAI+) or serum creatinine-defined acute kidney injury.

  • These data provide preliminary evidence for a proposed framework for directed urinary NGAL assessment in the pediatric intensive care unit.

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Fig. 1: Functional and tubular injury biomarker-based acute kidney injury (AKI) phenotypes.
Fig. 2: CONSORT flow chart of the included patients.

Data availability

The dataset generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank Lin Fei, PhD, for statistical assistance during the design and analysis of this study, and the Center for Acute Care Nephrology research staff for their work on the TAKING FOCUS 2 study.

Funding

R.S.C., K.K., and S.L.G. receive support from the National Institute of Diabetes and Digestive and Kidney (NIDDK) Diseases grant (P50 DK 096418-06). N.L.S. receives support from the National Center for Advancing Translational Sciences of the National Institutes of Health (institutional CT2 grant, 2UL1TR001425-05A1).

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Contributions

N.L.S. conceptualized and designed the project, acquired the data, analyzed and interpreted the data, drafted and revised and manuscript for important intellectual content, and approved the final version to be published. K.K. acquired the data, drafted and revised and manuscript for important intellectual content, and approved the final version to be published. R.S.C. conceptualized and designed the project, drafted and revised and manuscript for important intellectual content, and approved the final version to be published. S.L.G. conceptualized and designed the project, analyzed and interpreted the data, drafted and revised and manuscript for important intellectual content, and approved the final version to be published.

Corresponding author

Correspondence to Natalja L. Stanski.

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Competing interests

S.L.G. receives consulting fees from BioPorto Diagnostics, Inc. and Cincinnati Children’s Hospital Medical Center and receives grant funding from BioPorto Diagnostics, Inc. separate from this project. BioPorto, Inc. had no input into the conduct of this study.

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This study was conducted with a waiver of informed consent.

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Stanski, N.L., Krallman, K.A., Chima, R.S. et al. A risk-stratified assessment of biomarker-based acute kidney injury phenotypes in children. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-02233-2

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