title: Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity.
abstract: Phosphate homeostasis is coordinated and regulated by complex cross-organ talk through delicate hormonal networks. Parathyroid hormone (PTH), secreted in response to low serum calcium, has an important role in maintaining phosphate homeostasis by influencing renal synthesis of 1,25-dihydroxyvitamin D, thereby increasing intestinal phosphate absorption. Moreover, PTH can increase phosphate efflux from bone and contribute to renal phosphate homeostasis through phosphaturic effects. In addition, PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), which is able to inhibit renal tubular phosphate reabsorption, thereby increasing urinary phosphate excretion. FGF23 can also fine-tune vitamin D homeostasis by suppressing renal expression of 1-alpha hydroxylase (1α(OH)ase). This review briefly discusses how FGF23, by forming a bone-kidney axis, regulates phosphate homeostasis, and how its dysregulation can lead to phosphate toxicity that induces widespread tissue injury. We also provide evidence to explain how phosphate toxicity related to dietary phosphorus overload may facilitate incidence of noncommunicable diseases including kidney disease, cardiovascular disease, cancers and skeletal disorders.
authors.affiliation: Department of Hospitality Management and Dietetics, College of Human Ecology, Kansas State University , Manhattan, KS, USA.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Brown
authors.affiliation: Department of Applied Oral Sciences, Forsyth Institute , Cambridge, MA, USA ; Division of Research & Development, VPS Healthcare , Abu Dhabi, UAE.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Razzaque