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Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children
Stephen J McWilliam1, Daniel J Antoine, Venkata Sabbisetti
1Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, Merseyside, UK. d.antoine@liv.ac.uk.
Insights
This study establishes reference intervals for kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in healthy children. Findings reveal demographic variations and diurnal patterns for these acute kidney injury biomarkers.
Area of Science:
- Pediatric Nephrology
- Biomarker Discovery
- Clinical Chemistry
Background:
- Acute kidney injury (AKI) diagnosis in children lacks established reference ranges for novel biomarkers.
- Kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) show promise as urinary AKI indicators.
Purpose of the Study:
- To determine reference intervals for urinary KIM-1 and NGAL in healthy pediatric populations.
- To compare biomarker levels across different demographics and analytical platforms.
Main Methods:
- Urinary KIM-1 and NGAL levels were measured in pediatric cohorts from the UK and USA.
- Meso Scale Discovery (MSD) and Luminex platforms were utilized for biomarker quantification.
Main Results:
- Reference intervals were established for KIM-1 and NGAL, stratified by sex and ethnicity.
- Higher NGAL concentrations were observed in females compared to males.
- Lower KIM-1 concentrations were found in African-Americans versus Caucasians, with diurnal variation noted.
Conclusions:
- This study provides the first reference intervals for urinary KIM-1 and NGAL in healthy children across UK and US populations.
- The findings highlight the importance of considering demographic factors and diurnal variation when interpreting these biomarkers.
- Validation across two analytical methods supports the reliability of the established reference ranges.
Aim:
The aim of this study was to establish reference intervals in healthy children for two novel urinary biomarkers of acute kidney injury, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL).
Materials & Methods:
Urinary biomarkers were determined in samples from children in the UK (n = 120) and the USA (n = 171) using both Meso Scale Discovery (MSD) and Luminex-based analytical approaches.
Results:
95% reference intervals for each biomarker in each cohort are presented and stratified by sex or ethnicity where necessary, and age-related variability is explored using quantile regression. We identified consistently higher NGAL concentrations in females than males (p < 0.0001), and lower KIM-1 concentrations in African-Americans than Caucasians (p = 0.02). KIM-1 demonstrated diurnal variation, with higher concentrations in the morning (p < 0.001).
Conclusion:
This is the first report of reference intervals for KIM-1 and NGAL using two analytical methods in a healthy pediatric population in both UK and US-based populations.
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