Distinct roles of ferric carboxymaltose and ferric derisomaltose on phosphate homeostasis in iron deficiency anemia

Abstract

Intravenous (IV) iron-carbohydrate nanoparticles like ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) are used to treat iron deficiency anemia (IDA); however, they differ in their side-effects (e.g., hypophosphatemia). We compared the effects of FCM and FDI in a newly generated mouse model of IDA and determine their efficacy in resolving IDA and effects on mineral homeostasis. Eight-week-old female C57Bl/6J mice were fed an iron-deficient diet for 5 weeks followed by IV bleeding (0.7 % of body weight) for 3 consecutive days to establish IDA. On day 1 and 7 after induction of IDA, mice were injected with vehicle, FCM or FDI (both 20 mg kg^-1). On day 14, blood, urine and tissues were collected. Compared to baseline, all mice developed microcytic hypochromic anemia. FCM and FDI treatment resolved IDA, reversed thrombocytosis, and prevented the development splenomegaly and cardiomegaly observed in vehicle-treated anemic mice. Plasma iron increased to a greater extent with FCM versus FDI. Plasma iron showed an inverse relationship with intact fibroblast growth factor 23 (iFGF23) and C-terminal FGF23 (cFGF23). The ratio of iFGF23:cFGF23 increased in all groups but for different reasons: vehicle (iFGF23↑, cFGF23↔); FCM and FDI (iFGF23↔, cFGF23↓). The ratio was ∼1.8-fold greater in FDI versus FCM at the end of the experimental period. Only FCM caused hypophosphatemia, despite the abundance of the renal Na⁺-P_i cotransporter 2a being similarly lower (∼30 % versus vehicle) with FDI. Our results demonstrate that while FCM and FDI are equally effective at resolving IDA, hypophosphatemia is not solely caused by renal mechanisms.