Abstract: FR-PO0222
Myeloid Ferritin Heavy Chain Drives Anemia in CKD by Promoting Iron Sequestration
Session Information
- Anemia and Iron Metabolism
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 200 Anemia and Iron Metabolism
Authors
- Campbell, Chantalle A., Weill Cornell Medicine, New York, New York, United States
- Federman, Hannah Glenn, Weill Cornell Medicine, New York, New York, United States
- Elsayed, Heba, Weill Cornell Medicine, New York, New York, United States
- Freund, Avery G, Weill Cornell Medicine, New York, New York, United States
- Baqai, Kanza, Weill Cornell Medicine, New York, New York, United States
- Patiño, Edwin, Weill Cornell Medicine, New York, New York, United States
- Bhatia, Divya, Weill Cornell Medicine, New York, New York, United States
- Choi, Mary E., Weill Cornell Medicine, New York, New York, United States
- Vinchi, Francesca, New York Blood Center Inc, New York, New York, United States
- Akchurin, Oleh M., Weill Cornell Medicine, New York, New York, United States
Background
Anemia is a common CKD complication with prevalence increasing as the disease progresses. Altered iron metabolism, driven in part by hepcidin, is a major contributor. However, emerging evidence suggests additional, hepcidin-independent mechanisms. While serum ferritin is a well-recognized biomarker in CKD, the mechanistic role of ferritin in anemia pathogenesis remains poorly understood.
Methods
CKD was induced in eight-week-old wild-type (WT) and myeloid-specific (LysM-Cre) ferritin heavy chain (Fth1) knockout (KO) male mice using a 0.2% adenine diet (containing 40 ppm iron) for eight weeks. Non-heme iron content was quantified in the bone marrow, spleen, and liver using the ferrozine and bathophenanthroline methods. Ferric iron deposition in the bone marrow and spleen was assessed by Perls’ Prussian blue staining.
Results
WT CKD mice developed anemia and hypoferremia, with elevated serum hepcidin compared to healthy controls. CKD mice also displayed significantly higher iron content in the bone marrow, spleen, and liver. In Fth1 LysM-Cre KO CKD mice, iron content in the bone marrow, spleen, and liver were markedly reduced while serum iron increased relative to WT CKD mice. Hemoglobin rose from 11.6 g/dL in WT CKD to 14.1 g/dL in Fth1 LysM-Cre KO CKD mice (P < 0.0001). Interestingly, serum IL-6 was lower in Fth1 LysM-Cre KO CKD mice compared to the WT CKD. There was a trend toward increased serum hepcidin in Fth1 LysM-Cre KO CKD mice compared to WT CKD mice (P = 0.08).
Conclusion
In the absence of iron therapy, myeloid-specific Fth1 deletion rescued anemia in CKD mice by limiting iron sequestration in tissues. These findings identify myeloid ferritin heavy chain as a mechanistic driver of anemia in CKD and a potential therapeutic target.
Funding
- NIDDK Support