Abstract: TH-PO246

Iron Deficiency Sensitizes the Kidney to Acute Injuries

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic


  • Wang, Xueqiao, Tongji University, Shanghai, Shanghai, China
  • Shang, Wenjun, Zhengzhou University, Zhengzhou, Henan, China
  • Zheng, Xiaoqing, Tongji University, Shanghai, China
  • Wang, Zhigang, Zhengzhou University, Zhengzhou, Henan, China
  • Zhang, Juanlian, Tongji University, Shanghai, Shanghai, China
  • Zhang, Jushan, Tongji University, Shanghai, Shanghai, China
  • Nie, Jing, Tongji University, Shanghai, Shanghai, China
  • Barasch, Jonathan M., Columbia Presbyterian, New York , New York, United States
  • Qiu, Andong, Tongji University, Shanghai, Shanghai, China

Iron deficiency is the most common micronutrient deficiency in both the developing and developed countries, and it causes defective development of organogenesis in embryos. However, it remains unknown whether iron deficiency impacts acute kidney injuries (AKI) during postnatal life. Here we studied the effects of iron deficiency on AKI in murine models.


Mice were fed either iron deficient (22ppm), moderate iron deficiency (60ppm) or iron-replete (260ppm) diets for 3 weeks, and then subject to cisplatin or rhabdomyolysis AKI. sCR and BUN were analyzed three days after i.p. injection of cisplatin and one day after muscular injection of glycerol. Pro-oxidant and antioxidant , cell death and iron proteins and inflammatory factors were analyzed by Q-PCR, western blot or immunofluorescence and CBA.


We found that iron deficiency markedly exacerbate cisplatin- and rhabdomyolysis-induced AKI when compared with iron-replete condition, and even moderate iron deficiency had similar impacts. Nox4 and inflammatory factors were largely upregulated while catalase was markedly downregulated in the cisplatin-injured kidneys of iron-deficient mice when compared with iron-replete control. Further studies showed that the exacerbation of cisplatin-induced kidney injuries in iron deficient mice could be reversed by Fer-1, a ferroptosis inhibitor, demonstrating that the increased ferroptosis was a major mechanism for the aggravation of AKI. In contrast, Fer-1 failed to rescue the exacerbation of AKI induced by rhabdomyolysis, indicating the existence of a different mechanism for the impacts of iron deficiency on kidney injuries in this model.


Iron deficiency and even moderate iron deficiency markedly exacerbated AKI induced by either cisplatin or rhabdomyolysis, and increased ferroptosis represented a major mechanism of the exacerbation of kidney injuries in iron deficient cisplatin-induced AKI model.


  • Government Support - Non-U.S.