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Abstract: FR-PO479

Ferric Carboxymaltose Restores Iron Status and Transiently Increases FGF23 in a Mouse Model of Iron Deficiency

Session Information

Category: Anemia and Iron Metabolism

  • 201 Anemia and Iron Metabolism: Basic

Authors

  • Capella, Maralee, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
  • Gerber, Claire, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
  • Courbon, Guillaume, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
  • Neuburg, Samantha, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
  • Francis, Connor, University of Florida College of Medicine, Gainesville, Florida, United States
  • Dussold, Corey, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
  • Wang, Xueyan, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
  • Qi, Lixin, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
  • Wolf, Myles, Duke University, Durham, North Carolina, United States
  • Martin, Aline, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
  • David, Valentin, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
Background

Iron deficiency stimulates FGF23 transcription and cleavage, resulting in high circulating levels of total FGF23 (tFGF23) due to increased FGF23 fragments but relatively normal levels of biologically active intact FGF23 (iFGF23), and hence no hypophosphatemia. While this suggests that treating iron deficiency will decrease circulating levels of FGF23, recent publications have shown transient asymptomatic hypophosphataemia secondary to iFGF23 increase, in response to certain intravenous iron preparations such as ferric carboxymaltose (FCM).

Methods

We investigated whether treatment with FCM could impact FGF23 production in a mouse model of dietary iron deficiency. To induce iron deficiency, we fed 3 week-old C57BL6 mice an iron deficient diet (ID) for 3 weeks or a diet containing an adequate amount of iron (Ctr). Subsequently, six week old ID mice were treated with a single iv dose of 30mg/Kg FCM or saline vehicle (Veh). We then performed biochemical analyses of urine and serum from mice collected at different time points up to 2 weeks post injection.

Results


Compared to Ctr mice, six-week old ID animals showed evidence of iron deficiency anemia including low serum iron (23±6 vs 53±18 µg/dL), low red blood cells (7.9 ±0.3 vs 8.4±0.3 M/µL), and hemoglobin (10.0±0.2 vs 13.2 ±0.6 g/dL) (p<0.05, ID vs Ctr). FCM treatment rapidly increased serum iron levels 6 hours post-injection (290±21 vs 28±20 µg/dL) and hemoglobin (11.6±0.4 vs. 10.0±0.4 g/dL) after 48 hours (p<0.05, FCM vs Veh).
As shown previously, tFGF23 was increased in ID animals (1013±143 vs 202±14 pg/mL) while iFGF23 was only slightly elevated (132±8 vs 82±5 pg/mL) (p<0.05, ID vs Ctr). FCM administration, led to a transient increase in tFGF23 (2448±269 vs 1343±256 pg/mL) and iFGF23 (193±13 vs 124±8 pg/mL) compared to iron deficient vehicle mice (p<0.05, FCM vs Veh). However, one week after FCM treatment, tFGF23 (378±76 vs 1142±186 pg/mL) and iFGF23 (112±7 vs 163±6 pg/mL) levels were corrected (p<0.05, FCM vs Veh), likely due to partial correction of iron deficiency .

Conclusion

Our data show that FCM administration to iron deficient mice corrects iron deficiency anemia and transiently increases iFGF23. The causes of this increase remain to be elucidated .

Funding

  • NIDDK Support