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Assessment of Kidney Function in Mouse Models of Glomerular Disease
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In vivo expression of VCAM1 precedes nephron loss following kidney tubular necrosis

Anders M Kristensen1, Luca Bordoni1,2, Marie B Nielsen3,4

  • 1Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Science Advances
|October 22, 2025
PubMed

Insights

Vascular cell adhesion molecule 1 (VCAM1) in kidney tubules signals impending nephron loss and dysfunction. This early indicator, identified in mice and human biopsies, precedes kidney fibrosis and offers a potential biomarker for adverse outcomes.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biomarker Discovery

Background:

  • Nephron loss drives chronic kidney disease progression, but repair mechanisms are unclear.
  • Fibrosis is implicated in kidney damage, yet antifibrotic therapies have proven ineffective.
  • Understanding early events in tubule injury is crucial for predicting kidney function decline.

Purpose of the Study:

  • To investigate the role of tubular vascular cell adhesion molecule 1 (VCAM1) in kidney injury and repair.
  • To identify early indicators of nephron loss and long-term kidney dysfunction.
  • To evaluate VCAM1 as a potential biomarker for adverse outcomes in kidney disease.

Main Methods:

  • Serial intravital microscopy in transgenic mice to track tubulointerstitial remodeling over 3 weeks.
  • Analysis of tubular VCAM1 expression in relation to nephron loss, fibrosis, and kidney dysfunction.
  • Correlation of tubular VCAM1 expression with early and 12-month graft function in human kidney transplant biopsies.

Main Results:

  • Tubular VCAM1 expression was found to precede nephron loss, fibrosis, and kidney dysfunction.
  • VCAM1 was rapidly induced in injured tubules, preceding atrophy and fibroblast recruitment.
  • Fibroblasts were confined to injury sites, without causing secondary damage to uninjured tubules.
  • In human biopsies, tubular VCAM1 expression negatively correlated with early and 12-month graft function.

Conclusions:

  • Tubular VCAM1 expression serves as an early indicator of tubular fate and subsequent nephron loss.
  • VCAM1 is a potential biomarker for predicting adverse outcomes in kidney disease.
  • These findings highlight VCAM1's role in the early stages of kidney injury and dysfunction.

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