Kidney Week

Abstract: FR-PO1177

Urinary Tubular Epithelial Cells Reflect Kidney Iron Toxicity in CKD

Session Information

• CKD: Mechanisms, AKI, and Beyond - 2
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Federman, Hannah Glenn, Weill Cornell Medicine, New York, New York, United States

Hannah Glenn Federman, MS, PhD

• Campbell, Chantalle A., Weill Cornell Medicine, New York, New York, United States

Chantalle A. Campbell

• Elsayed, Heba, Weill Cornell Medicine, New York, New York, United States

Heba Elsayed, MS

• Freund, Avery G, Weill Cornell Medicine, New York, New York, United States

Avery G Freund

• Munera, Ana Maria, Weill Cornell Medicine, New York, New York, United States

Ana Maria Munera, MD, MSc

• Vinchi, Francesca, New York Blood Center Inc, New York, New York, United States

Francesca Vinchi, PhD

• Choi, Mary E., Weill Cornell Medicine, New York, New York, United States

Mary E. Choi, MD

• Akchurin, Oleh M., Weill Cornell Medicine, New York, New York, United States

Oleh M. Akchurin, MD, PhD, FASN

Background

Chronic Kidney Disease (CKD) affects 10–15% of the U.S. population, including over 200,000 children. CKD disrupts iron metabolism and causes anemia, but the role of iron in the pathogenesis of chronic kidney injury remains poorly understood, and its potential toxicity, including nephrotoxicity, is a concern. A major barrier has been the lack of tools to study kidney iron at the cellular level non-invasively.

Methods

We used two CKD mouse models (adenine diet and unilateral ureteral obstruction) and collected fresh urine samples from CKD patients and healthy controls, stratified by CKD severity and iron therapy status (n=5-8 per group). TECs (CD45-AQP1+) were analyzed by flow cytometry and cell sorting then assessed for labile iron pool (LIP) using FerroOrange. Lipid peroxidation was measured with BODIPY. Tubular injury was evaluated by KIM1 expression. RNA-seq was performed on sorted LIP^HI vs. LIP^LOW UUO mouse TECs.

Results

In both CKD mouse models, TECs exhibited marked lipid peroxidation, consistent with ferroptosis. Interestingly, tubular LIP was reduced in CKD mice, suggesting a compensatory response to mitigate ferroptotic injury. Tubular Ferritin-H and Ferroportin expression were upregulated, likely contributing to LIP reduction. Iron chelation with CPX-O further lowered tubular LIP and significantly attenuated kidney fibrosis.
LIP^HI TECs exhibited higher expression of KIM-1 and increased lipid peroxidation compared to LIP^LOW TECs. Importantly, this pattern was also observed in mouse and human urinary TECs. Transcriptomic profiling of LIP^HI TECs revealed upregulation of partial epithelial-to-mesenchymal transition (EMT) programs, while metabolic pathways typical of healthy TECs were suppressed.
Among patients with mild to moderate CKD, TEC-LIP was also reduced compared to healthy controls; however, this reduction was absent in patients receiving oral iron therapy or those with advanced CKD.

Conclusion

Reduction of LIP in TECs appears to be part of their adaptive response to chronic injury during CKD and can be assessed non-invasively in exfoliated urinary TECs. This platform may inform future monitoring strategies for iron toxicity in patients with CKD.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20254t1n63hf