# Kidney Injury Urine Biomarker Normal Ranges in Children

## TL;DR

This study establishes age- and sex-dependent normal ranges for kidney injury biomarkers in children's urine to improve early detection of kidney disease.

## Contribution

The study introduces continuous pediatric reference percentiles for urinary biomarkers using LMS modeling, tailored for children aged 0.1 to 18 years.

## Key findings

- Urinary biomarker levels were highest in infancy and declined with age.
- NGAL, DKK3, and MCP-1 showed sex-based differences in their urinary concentrations.
- LMS-based percentiles enable standardized z-score calculations for clinical interpretation.

## Abstract

Traditional biomarkers, serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria, used to diagnose kidney disease have limitations in sensitivity and specificity. Urinary biomarkers that are highly sensitive to kidney injury, such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), dickkopf-3 (DKK3), chitinase 3-like 1 (CHI3L1), monocyte chemoattractant protein-1 (MCP-1), procollagen type III amino-terminal propeptide (PIIINP), and epidermal growth factor (EGF), have become available for adults. The goal of our study was to develop lambda-mu-sigma (LMS)-based continuous pediatric reference values for these urinary biomarkers.

A total of 304 children aged 0.1 to 18 years (161 boys) were enrolled in the Hannover reference values for pediatrics (HARP) study. Urinary biomarkers were assessed by enzyme-linked immunosorbent assay (ELISA) and indexed to urinary creatinine levels. LMS-based continuous reference percentiles were generated using the RefCurv software.

LMS-based percentiles were established for urinary KIM-1, NGAL, DKK3, CHI3L1, MCP1, PIIINP, and EGF to creatinine ratios which were all found to be age dependent. The urinary NGAL, DKK3, and MCP-1 to creatinine ratios were also associated with sex. Urinary KIM-1, DKK3, CHI3L1, MCP1, PIIINP, and EGF to creatinine ratios were highest during infancy, followed by a continuous decline until the age of 18 years. The urinary NGAL to creatinine ratio was generally higher in girls and showed 2 peaks, one in infancy and the other at the age of 18.

All urinary biomarkers of kidney health measured were age-, and in part, sex-dependent. The LMS-based continuous pediatric reference percentiles allow calculation of standardized patient z-scores to facilitate test result interpretation in children.