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GDF-15 and uEGF Independently Associate With CKD Progression in Children

Julia Bartels1, Mansoureh Tabatabaeifar1, Marietta Kirchner2

  • 1Division of Pediatric Nephrology, Medical Faculty Heidelberg, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.

Kidney International Reports
|October 27, 2025
PubMed

Insights

Predicting pediatric chronic kidney disease (CKD) progression is challenging. Higher serum growth differentiation factor 15 (GDF-15) and urinary epidermal growth factor (uEGF) levels indicate increased CKD risk in children.

Area of Science:

  • Pediatric Nephrology
  • Biomarker Discovery
  • Chronic Kidney Disease Research

Background:

  • Predicting chronic kidney disease (CKD) progression in children remains a significant clinical challenge.
  • Previous research identified low urinary epidermal growth factor (uEGF) as a predictor of CKD progression in pediatric patients.
  • The potential of serum growth differentiation factor 15 (GDF-15) as a prognostic biomarker in pediatric CKD requires further investigation.

Purpose of the Study:

  • To investigate serum GDF-15 as a novel biomarker for CKD progression in children.
  • To explore the combined predictive value of GDF-15 and uEGF for pediatric CKD progression.
  • To validate findings in independent pediatric CKD cohorts.

Main Methods:

  • Serum GDF-15 levels were analyzed in 671 children with CKD (ages 6-17) from the 4C study.
  • A composite endpoint included kidney replacement therapy, 50% estimated glomerular filtration rate (eGFR) loss, or eGFR < 10 ml/min/1.73 m².
  • Results were validated in 329 participants from the ESCAPE trial, with an 8-year median follow-up.

Main Results:

  • Elevated serum GDF-15 levels were significantly associated with an increased risk of CKD progression (HR: 1.40; 95% CI: 1.10-1.77).
  • This association remained independent of established risk factors like age, sex, baseline eGFR, proteinuria, and blood pressure.
  • Combining GDF-15 and uEGF improved the predictive model's fit more than either biomarker alone.

Conclusions:

  • Serum GDF-15 and urinary EGF show promise as complementary biomarkers for predicting pediatric CKD progression.
  • These biomarkers may enhance risk stratification for personalized management strategies in pediatric CKD.
  • Future prognostic biomarker panels could incorporate GDF-15 and uEGF for improved clinical utility.
Abstract

Keywords:
CKD progressionchronic kidney diseaseepidermal growth factorgrowth differentiation factor 15pediatric CKD

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