Comparative effects of treatment with ferric carboxymaltose versus ferric derisomaltose in a murine model of iron-deficiency anemia

Abstract

Intravenous (IV) iron preparations like ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) are used to treat iron deficiency anemia (IDA) due to heavy uterine bleeding, inflammatory bowel disease, and chronic kidney disease. These preparations greatly differ in terms of their side-effect profiles (e.g, hypophosphatemia). However, studies that directly compare FCM and FDI are limited. The objective of this study was to compare the effects of FCM and FDI in a mouse model of IDA and investigate changes in blood parameters and mineral homeostasis. Female C57Bl/6J mice were fed iron-deficient diet for 5 weeks followed by IV bleeding (0.7% of body weight [b.w.]) for 3 consecutive days. On day 0 (last day of bleeding), baseline blood and urine were analyzed for hematocrit, CBC, P i and Ca 2+ . Mice were randomized to vehicle (saline, 2 μl/g b.w.; n=16), FCM (20 mg/kg; n=12), or FDI (20 mg/kg; n=12) treatment via retroorbital injection on day 0 and 7. On day 14, terminal blood, urine, spleen, and heart were collected. At baseline, compared with pre-bleeding, all mice had low hematocrit (22±1 vs 48±0.3%; P<0.05) and microcytic hypochromic anemia. After 14 days, mice treated with FCM and FDI had higher hematocrit compared with vehicle (47±0.4 and 46±0.3 vs 25±1%; P<0.05). WBC were similar on day 14 compared with day 0 for mice treated with FCM (8±1 vs 7±1 x10 9 /L; NS) or FDI (7±1 vs 7±1 x10 9 /L; NS); however, WBC were decreased in vehicle-treated mice (4±1 vs 6±1 x10 9 /L; P<0.05). Thrombocytes were increased in vehicle-treated mice on day 14 compared with day 0 (1405±55 vs 795±23 x10 9 /L; P<0.05); while there was no change in thrombocytes in mice treated with FDI (706±16 vs 831±29 x10 9 /L; NS), they were decreased in FCM-treated mice (583±41 vs 771±30 x10 9 /L; P<0.05). Both FCM and FDI prevented splenomegaly that was seen in vehicle-treated mice (88±3 and 87±20 vs 263±40 mg; P<0.05). Similarly, FCM and FDI prevented greater heart weight that was seen in vehicle-treated mice (0.43±0.01 and 0.45±0.01 vs 0.48±0.01 g/b.w. %; P<0.05). After 14 days, mice treated with FCM and FDI had lower plasma P i compared with vehicle (1.9±0.1 and 2.1±0.1 vs 2.4±0.1 mmol; P<0.05); although FCM-treated mice showed greater hypophosphatemia compared with FDI ( P<0.05). There were no differences between groups for urinary P i . Plasma Ca 2+ was similar between groups on day 14; but compared with day 0, it was higher in vehicle (2.7±0.1 vs 2.5±0.1 mmol; P<0.05) and FCM-treated mice (2.8±0.1 vs 2.5±0.1 mmol; P<0.05). Urinary Ca 2+ /creatinine was higher in mice treated with vehicle compared with day 0 (0.4±0.04 vs 0.1±0.01 mmol/mmol; P<0.05) but was lower with FCM (0.09±0.03 vs 0.14±0.04 mmol/mmol; P<0.05) and FDI (0.08±0.01 vs 0.3±0.06 mmol/mmol; P<0.05). In summary, our study shows that both iron preparations have similar effects on blood parameters, but mice were more hypophosphatemic when treated with FCM vs FDI. We speculate this may be due to variations in PTH and FGF23 levels. This work was supported by 1R01DK110621, VA Merit Award IBX004968A, NIDDK Diabetic Complications Consortium RRID:SCR_001415, DK076169 and DK115255 (all to TR). LT was supported by an AHA Postdoctoral Fellowship (828731). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.