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 Twitter

Kidney Week

Abstract: SA-PO326

Enteral Iron Therapy and Renal Autophagy in Juvenile Mice with Adenine-Induced CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis


  • Akchurin, Oleh M., Weill Cornell Medical College, NEW YORK, New York, United States
  • Patino, Edwin A, Weill Cornell Medical College, NEW YORK, New York, United States
  • Bhatia, Divya, Weill Cornell Medical College, NEW YORK, New York, United States
  • Dalal, Vidhi, NYP Cornell, Cornell, New York, United States
  • Angara, Sureshbabu, Weill Cornell Medicine, New York City, New York, United States
  • Rivella, Stefano, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Choi, Mary E., Weill Cornell Medical College, NEW YORK, New York, United States

Autophagy has been implicated in the pathophysiology of chronic renal injury and fibrosis. Iron therapy is common in patients with chronic kidney disease (CKD) and non-hematologic effects of iron therapy in CKD are of great interest. Iron-induced oxidative stress can damage cellular proteins and organells, which then need to be recycled by autophagy. However, the effect of iron on renal autophagy has not been elucidated.


Autophagy proteins Beclin 1 and LC3b were evaluated by western blot in the whole kidney lysates of juvenile C57Bl/6 male mice fed the following four diets from age 3 to 11 weeks:
(1) physiologic diet,
(2) 0.2% adenine diet (CKD),
(3) 0.5% carbonyl iron diet (iron therapy),
(4) 0.2% adenine + 0.5% carbonyl iron diet.
Mice were euthanized after 8 weeks of experimental diet.
Data were analyzed with ANOVA followed by Tukey post-hoc test.


Adenine-induced CKD, as expected, was characterized by elevated serum hepcidin, low serum iron, and low hemoglobin. Iron therapy normalized serum iron and improved anemia in mice with CKD, while further elevating serum hepcidin. Iron therapy led to elevated non-heme iron content in the kidneys of mice with and without CKD. mRNA expression of iron exporter ferroportin was induced by high iron diet in control mice but not in mice with CKD, while kidney ferroportin protein expression was reduced in CKD, irrespective of iron therapy. Iron therapy led to higher expression of autophagy proteins Beclin 1 and LC3b in the kidneys of mice with CKD, as compared to mice with CKD not treated with iron. In contrast, expression of NCOA4, a marker of ferritinophagy, was reduced in mice with CKD, without significant influence of systemic iron status.


To our knowledge, this is the first study that demonstrated induction of renal autophagy by iron therapy in CKD. This effect was not specific to ferritinophagy, as ferritin cargo receptor NCOA4, which mediates its autophagy, was not induced by iron therapy in this model. In our ongoing experiments, we are evaluating mechanistic relationship between iron-mediated autophagy and renal fibrosis in CKD.


  • NIDDK Support