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Pediatric reference ranges for acute kidney injury biomarkers

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Abstract

Background

Novel urinary biomarkers are useful for the prediction of acute kidney injury (AKI). Most promising are the urine markers NGAL, IL-18, KIM-1, and LFABP. Each of these has shown considerable promise diagnosing AKI earlier than serum creatinine (Scr) using disease controls. We set out to determine reference levels of these markers in a healthy pediatric population.

Methods

Urine was collected from 368 healthy children and assayed for NGAL, IL-18, KIM-1, and LFABP using commercially available kits or assay materials. Analysis of biomarkers by linear regression and according to age groups (3–<5 years; 5–<10; 10–<15; 15–<18) was performed to determine if biomarker levels differed with age and gender.

Results

Median values were: NGAL (6.6 ng/ml; IQR 2.8–17), IL-18 (21.6 pg/ml; IQR 13.6–32.9), KIM-1 (410 pg/ml; IQR 226–703), LFABP (3.4 ng/ml; IQR 1.6–6.0). Significant gender differences were found with NGAL and IL-18 and significant age differences were found with all markers. 95th percentile values for each marker varied with age and gender greater than median values.

Conclusions

This is the largest pediatric reference range study for the urinary measurement of NGAL, IL-18, KIM-1, and LFABP and highlights age and gender differences in these markers. This information is essential for rational interpretation of studies and clinical trials utilizing these emerging AKI biomarkers.

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Acknowledgments

This work was funded by NIH P50 DK096418 to MB and PD. This research was supported in part by the Cincinnati Children’s Research Foundation and its Cincinnati Genomic Control Cohort.

Disclosures

PD is a co-inventor on patents submitted for the use of NGAL as a biomarker of kidney injury.

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Authors and Affiliations

  1. Biomarker Laboratory, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, ML 7022, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA

    Michael R. Bennett, Edward Nehus, Christopher Haffner, Qing Ma & Prasad Devarajan

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  1. Michael R. Bennett
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  2. Edward Nehus
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  3. Christopher Haffner
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  4. Qing Ma
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  5. Prasad Devarajan
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Correspondence to Michael R. Bennett.

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Bennett, M.R., Nehus, E., Haffner, C. et al. Pediatric reference ranges for acute kidney injury biomarkers. Pediatr Nephrol 30, 677–685 (2015). https://doi.org/10.1007/s00467-014-2989-y

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  • DOI: https://doi.org/10.1007/s00467-014-2989-y

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