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Urinary neutrophil gelatinase-associated lipocalin rules out nephrotoxic acute kidney injury in children

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Abstract

Background

Nephrotoxic medication exposure is a common cause of acute kidney injury (AKI) in hospitalized children. A key component of the NINJA quality improvement initiative is systematic daily serum creatinine assessment in non-critically ill children exposed to ≥ 3 nephrotoxic medications on 1 day, or intravenous aminoglycoside or vancomycin for ≥ 3 days. Daily venipuncture is invasive and associated with disposable and personnel healthcare costs. Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a marker of renal tubular injury associated with certain nephrotoxic medications. We investigated whether uNGAL is a reliable screening tool for AKI in NINJA and could decrease the need for daily venipuncture.

Methods

This two-center prospective study enrolled 113 children who met NINJA criteria from May 2018 through March 2019. Daily urine samples were obtained for up to the first 7 days of qualifying exposure and 2 days after exposure ended. Our primary outcome was severe AKI (KDIGO stage 2 or 3 AKI). Maximum uNGAL was highest concentration on the day of, or 3 days prior to, severe AKI. The highest uNGAL level from all assessment days was used for patients who did not develop AKI or severe AKI.

Results

Urine NGAL thresholds of 150 and 300 ng/ml demonstrated excellent specificity (92.4 and 97.1% respectively) and negative predictive values (93.3 and 92.8% respectively) for ruling out severe AKI.

Conclusions

We suggest that uNGAL could be used to supplant some of the daily serum creatinine venipunctures in NINJA. The most optimal combination of serum creatinine and uNGAL assessment requires further study.

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Funding

This project was funded by a grant from BioPorto Diagnostics.

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Authors and Affiliations

  1. Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue MLC 7022, Cincinnati, Ohio, 45229, USA

    Stuart L. Goldstein, Kelli A. Krallman, Alexandra Schmerge, Lynn Dill, Bradley Gerhardt, Praneeta Chodaparavu, Abigail Radomsky, Cassie Kirby & David J. Askenazi

  2. Children’s of Alabama, AL, Birmingham, USA

    Lynn Dill & David J. Askenazi

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  1. Stuart L. Goldstein
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  2. Kelli A. Krallman
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  3. Alexandra Schmerge
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  4. Lynn Dill
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  5. Bradley Gerhardt
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  6. Praneeta Chodaparavu
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  7. Abigail Radomsky
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  8. Cassie Kirby
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  9. David J. Askenazi
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Correspondence to Stuart L. Goldstein.

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Conflict of interest

SLG serves as a paid consultant for BioPorto Diagnostics and receives other research grant funding from BioPorto. DA serves as a paid consultant for BioPorto Diagnostics.

Cincinnati Children’s Hospital receives royalties from BioPorto Diagnostics from licensing patent rights related to The NGAL Test™.

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BioPorto Diagnostics had no role in the study design, the conduct of the study, data analysis, or preparation of this manuscript.

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Goldstein, S.L., Krallman, K.A., Schmerge, A. et al. Urinary neutrophil gelatinase-associated lipocalin rules out nephrotoxic acute kidney injury in children. Pediatr Nephrol 36, 1915–1921 (2021). https://doi.org/10.1007/s00467-020-04898-5

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  • DOI: https://doi.org/10.1007/s00467-020-04898-5

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