Kidney Week

Abstract: TH-PO0255

Reversible Iron Chelation and Iron Restriction Attenuate Ferroptosis and Kidney Fibrosis in CKD Mouse Models

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

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

Avery G. Freund

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

Chantalle A. Campbell

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

Hannah Glenn Federman, MS, PhD

• Patino, Edwin, Weill Cornell Medicine, New York, New York, United States

Edwin Patino, MD

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

Heba Elsayed, MS

• Bhatia, Divya, Weill Cornell Medicine, New York, New York, United States

Divya Bhatia, MS, PhD, MPhil

• 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

Emerging evidence suggests that iron dysregulation and ferroptosis contribute to chronic kidney disease (CKD) progression. Prior experimental studies have reported renoprotective effects of iron restriction or classical chelation in certain CKD models; however, these studies largely did not examine ferroptosis. In addition, previously studied classical iron chelators induce broad systemic iron depletion, raising translational concerns for CKD patients who are already vulnerable to iron deficiency and anemia. We therefore sought to determine whether dietary iron restriction or reversible chelation by ciclopirox olamine (CPX-O) attenuate ferroptosis-associated pathways and kidney fibrosis in two contemporary mouse models of CKD.

Methods

Two mouse models of CKD were used: a 0.2% adenine diet (AD, 8-weeks) and unilateral ureteral obstruction (UUO, 7 days). To induce iron restriction, we used a low-iron diet (starting at 3 weeks). CPX-O was administered intraperitoneally, 10 mg/kg/day for 7 days following UUO.

Results

AD-fed mice exhibited increased kidney mRNA expression of ferroptosis markers Acsl4 and Ptgs2 and decreased ferroptosis inhibitor Gpx4. Iron-restricted AD-fed mice displayed improved kidney function, with BUN declining by 54% compared to untreated AD-fed mice. Iron restriction, as expected, exacerbated anemia, although without mortality or visible reduction in motor activity. UUO mice fed with a normal-iron diet exhibited increased kidney iron and ferritin heavy and light chain proteins (FtH/FtL) content. ACSL4 protein expression was increased in UUO kidneys compared to sham. Iron chelation by CPX-O attenuated UUO-mediated kidney fibrosis, with markedly reduced expression of α-SMA and fibronectin compared to vehicle-treated mice. In contrast to iron restriction, CPX-O did not worsen anemia yet reduced kidney FtH, FtL, and ACSL4, reflecting decreased kidney iron stores and attenuation of ferroptosis. CPX-O treatment also reduced BUN.

Conclusion

Iron restriction improved kidney function in CKD mice. CPX-O attenuated ferroptosis and kidney fibrosis, and improved kidney function without causing anemia, supporting reversible iron chelation as a potential therapeutic approach for mitigating disease progression in CKD patients with iron overload.