Figure 1 Disruption of phosphate homeostasis in chronic kidney disease (CKD) Figure 1 | Disruption of phosphate homeostasis in chronic kidney disease (CKD). a | In healthy individuals phosphate loading from either dietary or endogenous sources induces the expression of fibroblast growth factor 23 (FGF-23), which is mainly bone derived, and parathyroid hormone (PTH), which is secreted by the parathyroid glands. FGF-23 and PTH are both potent phosphaturic hormones that stimulate retrieval of the phosphate channel NaPi-2a from the tubular apical membrane. This retrieval limits phosphate reabsorption. FGF-23 expression is controlled by two endocrine negative feedback loops. The first loop involves vitamin D; FGF-23 inhibits activation and induces catabolism of vitamin D, whereas the active form of vitamin D, 1,25-dihydroxyvitamin D, upregulates FGF-23. 1,25-dihydroxyvitamin D also augments phosphate uptake from the gastrointestinal tract by upregulation of the phosphate transporter NaPi-2b. The second endocrine loop involves PTH, which stimulates FGF-23 secretion, whereas in physiological conditions FGF-23 inhibits PTH. b | In CKD, impaired renal phosphate excretion leads to phosphate retention and increased production of FGF-23, which induces vitamin D deficiency. Moreover, phosphate loading and a lack of vitamin D lead to an increase in PTH levels, which results in a further increase in circulating FGF-23 levels. Vervloet, M. G. et al. (2016) The role of phosphate in kidney disease Nat. Rev. Nephrol. doi:10.1038/nrneph.2016.164