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Related Experiment Video

Updated: Oct 10, 2025

Assessment of Kidney Function in Mouse Models of Glomerular Disease
09:16

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Identification of VEGF Signaling Inhibition-Induced Glomerular Injury in Rats through Site-Specific Urinary

Yi Yang1, Kenneth Kowalkowski1, Rita Ciurlionis1

  • 1Global Pharmaceutical Research and Development, AbbVie, 1 North Waukegan Road, North Chicago, IL 60064, USA.

International Journal of Molecular Sciences
|December 10, 2021
PubMed
Summary

Vascular Endothelial Growth Factor (VEGF) inhibitors can cause kidney damage. Urinary albumin and β2-microglobulin are sensitive biomarkers for detecting VEGF inhibition-induced glomerular injury in rats.

Keywords:
glomerular injuryurinary biomarkersvascular endothelial growth factor

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Area of Science:

  • Nephrology
  • Oncology
  • Pharmacology

Background:

  • Cancer therapies targeting the vascular endothelial growth factor (VEGF) signaling pathway are crucial for tumor growth inhibition.
  • VEGF pathway inhibition can paradoxically lead to renal damage by affecting the glomerular ultrafiltration apparatus.

Purpose of the Study:

  • To identify sensitive urinary biomarkers for detecting early glomerular changes induced by VEGF receptor (VEGFR) inhibition.
  • To correlate biomarker changes with microscopic and ultrastructural renal alterations in a rat model.

Main Methods:

  • Male Sprague-Dawley rats were treated with an experimental VEGFR inhibitor (ABT-123) for seven days.
  • Glomeruli were isolated using laser capture microdissection for gene expression analysis.
  • Urinary biomarkers, including albumin and β2-microglobulin, were measured and correlated with ultrastructural glomerular changes.

Main Results:

  • ABT-123 induced characteristic ultrastructural glomerular changes, including podocyte foot process fusion and endothelial fenestration loss.
  • These subtle changes were not detectable by light microscopy or standard clinical chemistry.
  • Urinary albumin showed a 44-fold increase by Day 3, and urinary β2-microglobulin levels also rose significantly.

Conclusions:

  • Urinary albumin and β2-microglobulin are sensitive early biomarkers of VEGF inhibition-induced glomerular injury.
  • Standard urinalysis and clinical chemistry assays are insufficient for detecting these specific renal changes.
  • Monitoring these urinary biomarkers can provide valuable diagnostic insight for patients undergoing VEGF-targeted cancer therapies.