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Refining the Composition and Significance of Human Kidney Intratubular Casts Using Spatial Protein Imaging.

Azuma Nanamatsu1, Angela R Sabo1, Daria Barwinska1

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|January 28, 2026
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Summary
This summary is machine-generated.

Prominin-1 (PROM1) is a novel major component of kidney intratubular casts, indicating tubular injury. Urinary PROM1 may serve as a potential biomarker for acute kidney injury (AKI).

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Area of Science:

  • Nephrology
  • Renal Pathology
  • Biomarker Discovery

Background:

  • Kidney intratubular casts are common in distal nephron segments and associated with kidney disease.
  • The composition and pathological significance of these casts remain understudied.

Purpose of the Study:

  • To investigate the protein composition of kidney intratubular casts.
  • To determine the association between cast composition and tubular injury.
  • To explore the potential of urinary Prominin-1 (PROM1) as an acute kidney injury (AKI) biomarker.

Main Methods:

  • Utilized Hematoxylin and Eosin (H&E) staining and Co-detection by indexing (CODEX) multiplexed spatial protein imaging on human kidney biopsies.
  • Analyzed intratubular casts from the Kidney Precision Medicine Project (KPMP).
  • Performed immunoblotting for urinary PROM1 and assessed publicly available urinary proteomics data.

Main Results:

  • Identified PROM1 and insulin-like growth factor binding protein 7 (IGFBP7) as major cast constituents, alongside uromodulin (UMOD).
  • Observed a significant loss of sodium-chloride cotransporter (NCC) and aquaporin-2 (AQP2) expression in tubules with casts, correlating with cast protein content.
  • Found elevated urinary PROM1 levels in patients with AKI compared to healthy controls, with intra-cast PROM1 strongly associated with tubular injury (OR 26.7).

Conclusions:

  • Prominin-1 (PROM1), an epithelial cell dedifferentiation and injury marker, is a novel major component of kidney intratubular casts.
  • Cast protein composition varies with disease state and is linked to distal nephron tubular injury.
  • Urinary PROM1 shows potential as a valuable biomarker for detecting acute kidney injury (AKI).