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Abstract: SA-OR035

Enteral Ferric Citrate Absorption Is Dependent on Ferroportin

Session Information

Category: Anemia and Iron Metabolism

  • 201 Anemia and Iron Metabolism: Basic

Authors

  • Hanudel, Mark R., UCLA, Los Angeles, California, United States
  • Gabayan, Victoria Rivka, UCLA, Los Angeles, California, United States
  • Qiao, Bo, UCLA, Los Angeles, California, United States
  • Chua, Kristine, UCLA, Los Angeles, California, United States
  • Nemeth, Elizabeta, UCLA, Los Angeles, California, United States
  • Ganz, Tomas, UCLA, Los Angeles, California, United States
Background

Ferric citrate (FC) is approved as an iron replacement product in CKD non-dialysis patients with iron deficiency anemia. FC-delivered iron is enterally absorbed, but the specific mechanisms involved have not been specifically evaluated. The absorption of dietary iron and conventional supplements requires duodenal ferroportin (FPN). To assess whether or not enteral FC absorption is dependent on FPN, we evaluated the effects of FC in a tamoxifen-inducible, enterocyte-specific FPN knockout (KO) murine model (Villin-Cre-ERT2, FPNflox/flox).

Methods

We assessed three groups: uninduced mice, induced mice (FPN KO), and induced mice (FPN KO) supplemented with 1% FC. Mice were injected with vehicle (uninduced group) or tamoxifen (induced groups) at ~7 weeks of age, then terminally assessed 7-8 weeks later. The treated induced mice had their diets supplemented with 1% FC for ~19 days pre-euthanasia.

Results

The FPN KO was effective, as 6 weeks after tamoxifen injection, the induced mice had ~4000 fold lower duodenal FPN mRNA expression than uninduced mice and undetectable FPN protein on the duodenal tissue Western blot.

Confirming that 1% FC prevents anemia, uninduced mice placed on iron-deficient 4 ppm diets for 7 weeks (n=5) became anemic, but uninduced mice placed on iron deficient 4 ppm diets for 4 weeks, then supplemented with 1% FC for 3 weeks (n=6), were rescued from anemia (mean (SD) terminal hemoglobin of 13.8 (0.7) vs. 7.6 (0.8) g/dL, p<0.001).

FPN KO mice on iron-sufficient 50 ppm diets developed anemia whether or not they were supplemented with 1% FC. The FPN KO groups had higher duodenal intracellular iron staining, lower liver iron concentration, lower hemoglobin, lower mean corpuscular volume, and higher red cell distribution width vs. the uninduced group (Figure 1). There were no differences between the untreated and 1% FC-treated FPN KO groups.

Conclusion

The 1% FC diet does not rescue iron deficiency anemia caused by enterocyte FPN KO. Enteral FC absorption is dependent on conventional enterocyte iron transport by FPN.

Funding

  • Commercial Support