ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: FR-PO1072

Cell-Specific Iron Metabolism in Kidney Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms


  • Campbell, Chantalle A., Weill Cornell Medicine, New York, New York, United States
  • Matthews balcombe, Jade, Weill Cornell Medicine, New York, New York, United States
  • Patino, Edwin, Weill Cornell Medicine, New York, New York, United States
  • Baqai, Kanza, 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
  • Akchurin, Oleh M., Weill Cornell Medicine, New York, New York, United States

Chronic kidney disease (CKD) affects 10-15% of the adult U.S. population. Our recent data indicate that in CKD, most kidney macrophages (KMφ) have pathologically depleted cellular labile iron pool, which induces their pro-fibrotic responses. However, the mechanism of intracellular iron deficiency of KMφ and iron metabolism in other cell types that participate in fibrosis, particularly in tubular epithelial cells (TEC) have not been elucidated in CKD.


We used two models of kidney fibrosis, adenine diet and unilateral ureteral obstruction (UUO). We analyzed expression of iron-related genes (Tfrc: iron importer, transferrin receptor 1 [TfR1], a marker of cellular iron deficiency or overload; Fth1 and Ftl: ferritin heavy and light chains; Slc40a1: iron exporter, ferroportin [FPT]; and Ncoa4, a marker of ferritinophagy) and respective proteins in whole kidney tissue, as well as in sorted KMφ and TEC (isolated using CD11b and CD133 magnetic microbeads). We also analyzed expression of these genes in publicly available single cell/nucleus transcriptomic mouse and human kidney fibrosis datasets.


In contrast to KMφ, Tfrc gene was suppressed in whole kidney tissue and in the proximal TEC of UUO kidneys, suggesting iron excess in some (e.g., proximal tubules) and labile iron deficiency in other (e.g., KMφ) cell types during kidney fibrosis. Interestingly, LIP depletion in KMφ was observed despite suppression of FPT in CD11b-positive KMφ, while both Slc40a1 gene and FPT protein were induced in whole kidney tissue during fibrosis. This suggests that regulation of FPT is independent of systemic hepcidin in most kidney cells (but not in KMφ) during fibrosis. Fth1 and Ftl genes were suppressed while FtH and FtL proteins were induced in whole kidney tissue, KMφ, and in TEC during fibrosis. Taken together with TfR1/Tfrc data, this suggests excessive expression of FtH in KMφ and insufficient in TEC during fibrosis. Cell-specific ferritin dysregulation in kidney fibrosis may owe to disrupted ferritinophagy. Indeed, NCOA4 expression was drastically reduced in KMφ and had only a trend toward reduction in TEC during fibrosis.


Cellular iron status varies among different cell types participating in kidney fibrosis, which likely differentially modulates fibrotic responses of these cells and may inform novel cell-specific therapeutic targets.


  • NIDDK Support