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Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy

Journal of Perinatology (2024)Cite this article

Subjects

Abstract

Objective

Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin-18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH).

Study Design

Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 h of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined.

Results

In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p = 0.024.) A multivariate model including IL-18 at 24 HOL and 5-min Apgar performed best, with an AUC of 0.84 (SE = 0.07, p = 0.02).

Conclusions

Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request with the exception of any protected health information.

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Funding

Funding

Supported by the Arkansas Children’s Research Institute and Arkansas Biosciences Institute and the Department of Pediatrics, Section of Neonatology at the University of Colorado. The study sponsors did not have any role in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

    Megan J. Turner

  2. Department of Pediatrics, Denver Health Medical Center, Denver, CO, USA

    Megan J. Turner

  3. University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Jennifer A. Rumpel & Sherry Courtney

  4. Arkansas Children’s Research Institute, Little Rock, AR, USA

    Beverly J. Spray

  5. Department of Radiology, University of Colorado School of Medicine, Aurora, CO, USA

    Nicholas Stence & Ilana Neuberger

  6. Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA

    Adam Frymoyer & Valerie Y. Chock

  7. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Katja Gist

Authors
  1. Megan J. Turner
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  4. Nicholas Stence
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  8. Sherry Courtney
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  9. Katja Gist
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Contributions

MT collected primary data, structured the study and the analysis plan, and wrote and edited the manuscript with input from all the other listed authors. JR collected primary data, contributed to the analysis and provided edits and additions to the manuscript. BS designed the statistical analysis plan, completed the data analysis, assisted with the creation of figures and tables and wrote the methods section of the manuscript. NS and IN performed blinded reviews of all neonatal MRIs and scored the MRI studies, and provided manuscript oversight in their content area. AF and VC provided input into the analysis plan and edited the manuscript. SC and KJ provided mentorship specific to data collection for this study for MT and JR and provided edits and additions to the manuscript. No form of payment was given to anyone to produce the manuscript.

Corresponding author

Correspondence to Megan J. Turner.

Ethics declarations

Competing interests

KMG is a consultant for Bioporto Diagnostics. Bioporto Diagnostics did not contribute to study design, and KMG did not receive any compensation for participating in this study. AF is a scientific advisor and holds a financial interest in Halo Biosciences which is unrelated to the current work. None of the other authors have any conflict of interest to declare for this study.

Ethics approval and consent to participate

This study was performed in accordance with the Declaration of Helsinki and approved by the University of Arkansas for Medical Sciences Institutional Review Board (IRB# 206873) and the Colorado Multiple Institutional Review Board (COMIRB #21-4699).

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Turner, M.J., Rumpel, J.A., Spray, B.J. et al. Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy. J Perinatol (2024). https://doi.org/10.1038/s41372-024-01937-z

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  • DOI: https://doi.org/10.1038/s41372-024-01937-z

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