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Kidney Injury Urine Biomarker Normal Ranges in Children

Hannah Weber1, Katharina Schermuly1, Anna Tschirner1

  • 1Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany.

Kidney International Reports
|March 11, 2026
PubMed

Insights

New pediatric reference values for urinary kidney injury biomarkers like KIM-1 and NGAL have been established. These age- and sex-dependent values improve the interpretation of kidney health in children.

Area of Science:

  • Pediatric Nephrology
  • Biomarker Discovery
  • Clinical Chemistry

Background:

  • Traditional kidney disease biomarkers (e.g., eGFR, albuminuria) have limitations in sensitivity and specificity.
  • Novel urinary biomarkers (KIM-1, NGAL, DKK3, CHI3L1, MCP-1, PIIINP, EGF) show promise for detecting kidney injury in adults.
  • Lack of established pediatric reference values hinders the clinical use of these sensitive urinary biomarkers in children.

Purpose of the Study:

  • To develop lambda-mu-sigma (LMS)-based continuous pediatric reference values for sensitive urinary kidney injury biomarkers.
  • To establish age- and sex-specific reference ranges for urinary KIM-1, NGAL, DKK3, CHI3L1, MCP-1, PIIINP, and EGF in children.
  • To facilitate standardized interpretation of kidney biomarker test results in pediatric populations.

Main Methods:

  • The Hannover reference values for pediatrics (HARP) study enrolled 304 children aged 0.1 to 18 years.
  • Urinary biomarkers were quantified using enzyme-linked immunosorbent assay (ELISA) and normalized to urinary creatinine.
  • LMS-based continuous reference percentiles were generated using RefCurv software.

Main Results:

  • LMS-based percentiles were established for urinary KIM-1, NGAL, DKK3, CHI3L1, MCP1, PIIINP, and EGF to creatinine ratios, all demonstrating age dependency.
  • Urinary NGAL, DKK3, and MCP-1 to creatinine ratios were also associated with sex.
  • Most urinary biomarker to creatinine ratios peaked in infancy and declined by age 18, with NGAL showing a secondary peak at age 18, particularly in girls.

Conclusions:

  • All measured urinary biomarkers of kidney health exhibited age-dependency and, in part, sex-dependency.
  • The developed LMS-based continuous pediatric reference percentiles enable standardized patient z-score calculation.
  • These reference values are crucial for accurate and reliable interpretation of kidney biomarker test results in children.
Abstract

Keywords:
CHI3L1DKK3EGFKIM-1MCP-1PIIINP

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