(A) Increased phosphate (Pi), iron deficiency (ID) and iron deficiency anemia (IDA) increase transcription of Fgf23 resulting in increased production of intact FGF23 (iFGF23). Phosphate increases stabilization of iFGF23 and minimizes its cleavage, while ID and IDA increase FGF23 cleavage. (B) In consequence, in animals and patients without impaired kidney function, increased phosphate levels trigger an increase in total FGF23, assessed by cFGF23, and iFGF23 levels. In contrast, iron deficiency and anemia lead to an increase in cFGF23 but only mild elevations of iFGF23. In CKD, where FGF23 cleavage is reduced, hyperphosphatemia, iron deficiency and anemia increased circulating levels of both total cFGF23 and iFGF23. Administration of ferric citrate (FC), which decreases intestinal phosphate absorption, increases circulating iron and corrects anemia, results in reductions of both total and intact FGF23.