(731.2) Effects of ferric carboxymaltose on phosphate and calcium homeostasis in a murine model of iron-deficiency anemia

Poster Board Number: E236

Monica Stevens (University of South Florida), Linto Thomas (University of South Florida), Timo Rieg (University of South Florida, James A. Haley VA), Jessica Dominguez Rieg (University of South Florida, James A. Haley VA)

Iron deficiency anemia (IDA) can be caused by heavy uterine bleeding, inflammatory bowel disease, or chronic kidney disease. Ferric carboxymaltose (FCM) is an intravenous form of iron replacement therapy that has been shown clinically to induce severe hypophosphatemia. However, the mechanism by which this occurs is poorly understood. The objective of this study was to develop and characterize a mouse model that would allow investigating the effects of FCM on phosphate (Pi) and calcium (Ca2+) homeostasis. Female C57Bl/6J mice (n=40; 10/group) were randomized to either iron deficient (ID) diet (4 ppm iron) or control diet (48 ppm iron) for 4 weeks followed by intravenous bleeding (0.7% of body weight) 4 and 2 days prior to starting the study. Baseline blood and urine was collected for hematocrit, complete blood count, and serum and urine Pi and Ca2+ levels. Subsequently, mice were treated with a single IV injection of either vehicle (saline) or FCM (20 mg/kg) via retroorbital injection. One week later, terminal blood, urine, feces, liver, and spleen were collected. At baseline, compared with controls, ID mice had lower hematocrit (35±1% vs 39±1%; Plt;0.05) and microcytic hypochromic anemia. After 7 days, FCM-treated ID mice had significantly higher hematocrit compared with vehicle-treated ID mice (43±1% vs 30±1%; Plt;0.05). FCM treatment also significantly increased iron content in liver and spleen in control mice (18±1 vs 6±1 μmol/g and 36±2 vs 27±3 μmol/g, respectively; Plt;0.05) and ID mice (16±1 vs 1±0.1 μmol/g and 21±2 vs 6±1 μmol/g, respectively; Plt;0.05). At baseline, urinary Pi/creatinine ratios were significantly lower in ID mice compared with controls (30±5 vs 58±7 mmol/mmol; Plt;0.05); however, FCM treatment in ID mice did not affect urinary Pi/creatinine ratios after 7 days (31±6 vs 18±5 mmol/mmol; not significant). There were no differences between groups for serum Pi, erythrocyte Pi, or fecal Pi. Under baseline conditions, no differences in plasma Ca2+ or urinary Ca2+/creatinine ratios were observed between groups; however, FCM-treated ID mice had significantly lower plasma Ca2+ levels after 7 days compared with ID mice at baseline (2.3±0.1 vs 2.6±0.1 mmol; Plt;0.05) and lower urinary Ca2+/creatinine ratios (0.1±0.1 vs 1.3±0.2 mmol/mmol; Plt;0.05). We speculate this may be due to increased PTH and FGF23 levels in FCM-treated ID mice. In summary, our study demonstrates for the first time that FCM affects Pi and Ca2+ homeostasis in a murine model of IDA. Further studies are needed to better understand the mechanisms of FCM on mineral homeostasis as well as the driving factors for species differences.

This work was supported by a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant 1R01DK110621 (TR), VA Merit Review Award IBX004968A (TR), American Heart Association Transformational Research Award 19TPA34850116 (TR), NIDDK Diabetic Complications Consortium RRID:SCR_001415 (TR), and grants DK076169 and DK115255 (TR). LT was supported by an American Heart Association Postdoctoral Fellowship (828731). MS was supported by a USF Summer Scholarly Award Experience.