Kidney Week

Abstract: FR-OR058

Redefining the Composition and Significance of Human Renal Intratubular Casts Using Spatial Protein Imaging

Session Information

• Pathology: Novel Mechanisms and Modalities
  November 07, 2025 | Location: Room 371A, Convention Center
  Abstract Time: 05:00 PM - 05:10 PM

Category: Pathology and Lab Medicine

• 1800 Pathology and Lab Medicine

Authors

• Nanamatsu, Azuma, Indiana University School of Medicine, Indianapolis, Indiana, United States

Azuma Nanamatsu, MD, PhD

• Sabo, Angela R., Indiana University School of Medicine, Indianapolis, Indiana, United States

Angela R. Sabo, PhD

• Barwinska, Daria, Indiana University School of Medicine, Indianapolis, Indiana, United States

Daria Barwinska, PhD

• Bowen, William S., Indiana University School of Medicine, Indianapolis, Indiana, United States

William S. Bowen, PhD

• Hata, Jessica Lynn, Indiana University School of Medicine, Indianapolis, Indiana, United States

Jessica Lynn Hata, MD, MS

• Ferkowicz, Michael J., Indiana University School of Medicine, Indianapolis, Indiana, United States

Michael J. Ferkowicz, PhD

• Hato, Takashi, Indiana University School of Medicine, Indianapolis, Indiana, United States

Takashi Hato, MD

• Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States

Michael T. Eadon, MD, FASN

• Dagher, Pierre C., Indiana University School of Medicine, Indianapolis, Indiana, United States

Pierre C. Dagher, MD, FASN

• Rosenberg, Avi Z., Johns Hopkins University, Baltimore, Maryland, United States

Avi Z. Rosenberg, MD, PhD

• El-Achkar, Tarek M., Indiana University School of Medicine, Indianapolis, Indiana, United States

Tarek M. El-Achkar, MD, FASN

Group or Team Name

• For the Kidney Precision Medicine Project (KPMP).

Background

Renal intratubular casts are frequently observed in the distal nephron segments of the kidney and have long been regarded as a sign of renal disease. However, the composition and pathological significance of intratubular casts have remained understudied.

Methods

We leveraged co-detection by indexing (CODEX) multiplex protein imaging and histological staining on human kidney biopsy specimens from the Kidney Precision Medicine Project (KPMP). We identified intratubular casts on Hematoxylin and Eosin (H&E) stained sections and analyzed protein expression profiles within intratubular casts and associated tubules using the CODEX data on the same section. We also conducted immunoblotting of PROM1 in healthy urine and assessed PROM1 expression data from publicly available urinary proteomics datasets of the KPMP consortium.

Results

We analyzed 424 intratubular casts across 33 healthy and diseased individuals. We specifically identified PROM1 (Prominin-1, CD133; positive in 90.1% of casts) and IGFBP7 (35.6%) as novel constituents of casts, alongside the established cast constituent UMOD (86.1%). These components exhibited diverse alterations depending on the disease state. Intratubular casts were predominantly detected in distal nephron segments. Plugging of tubules by intratubular casts was associated with a marked loss of NCC and AQP2 expression in the surrounding tubular epithelium, suggesting that intratubular casts contribute to injury in the distal nephron segments. The loss of these membrane transporters was correlated with protein components within casts, with PROM1 positivity of casts showing the strongest correlation. Urinary PROM1 secretion was confirmed by immunoblotting and was increased in patients with acute kidney injury (AKI) in the proteomics data.

Conclusion

We identified PROM1, a marker associated with tubular injury and altered tubular state, as a novel major constituent of urinary casts. The cast composition was correlated with tubular injury in the distal nephron segments. Our study also suggests that urinary PROM1 may serve as a potential biomarker for AKI.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025bc8q3gdk