Segregating the effects of ferric citrate-mediated iron utilization and FGF23 in a mouse model of CKD

Ferric citrate (FC) is an approved therapy for chronic kidney disease (CKD) pa- tients as a phosphate (Pi) binder for dialysis-dependent CKD, and for iron de- ficiency anemia (IDA) in non-dialysis CKD. Elevated Pi and IDA both lead to increased FGF23, however, the roles of iron and FGF23 during CKD remain un- clear. To this end, iron and Pi metabolism were tested in a mouse model of CKD (0.2% adenine) ± 0.5% FC for 6 weeks, with and without osteocyte deletion of Fgf23 (flox-Fgf23/Dmp1-Cre). Intact FGF23 (iFGF23) increased in all CKD mice but was lower in Cre+ mice with or without FC, thus the Dmp1-Cre effectively reduced FGF23. Cre+ mice fed AD- only had higher serum Pi than Cre− pre- and post- diet, and the Cre+ mice had higher BUN regardless of FC treatment. Total serum iron was higher in all mice receiving FC, and liver Tfrc, Bmp6, and hepci- din mRNAs were increased regardless of genotype; liver IL- 6 showed decreased mRNA in FC- fed mice. The renal 1,25-dihydroxyvitamin D (1,25D) anabolic enzyme Cyp27b1 had higher mRNA and the catabolic Cyp24a1 showed lower mRNA in FC- fed mice. Finally, mice with loss of FGF23 had higher bone corti- cal porosity, whereas Raman spectroscopy showed no changes in matrix mineral parameters. Thus, FC- and FGF23-dependent and - independent actions were identified in CKD; loss of FGF23 was associated with higher serum Pi and BUN, demonstrating that FGF23 was protective of mineral metabolism. In contrast, FC maintained serum iron and corrected inflammation mediators, potentially pro- viding ancillary benefit.

Creator

• Liesen, Michael P.
• Agoro, R.
• Swallow, E.
• Noonan, M.
• Ni, P.
• Damrath, J.
• Wallace, J.
• Clinkenbeard, E.
• Allen, M.
• White, K.
• Hum, Julia

Publisher

• The Physiological Society

Language

• English

Identifier

• DOI: https://doi.org/10.14814/phy2.15307

Keyword

• iron
• ferric citrate
• CKD
• klotho
• GF23
• kidney

Date created

• 2022

Related URL

• Available from the library catalog:  https://marianunivindianapolis.on.worldcat.org/oclc/9530318928
• Available from the publisher website:  https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15307

Resource type

• Article

Source

• Physiological Reports (Vol.10, no.11)

Rights statement

• http://rightsstatements.org/vocab/InC/1.0/