Physiological regulation of phosphate homeostasis

Phosphate homeostasis is dependent on the interaction and coordination of four main organ systems: thyroid/parathyroids, gastrointestinal tract, bone and kidneys, and three key hormonal regulators, 1,25-hydroxyvitamin D3, parathyroid hormone and FGF23 with its co- factor klotho. Phosphorus is a critical nutritional element for normal cellular function, but in excess can be toxic to tissues, particularly the vasculature. As phosphate, it also has an important interaction and inter-dependence with calcium and calcium homeostasis sharing some of the same controlling hormones, although this is not covered in our article. We have chosen to provide a current overview of phosphate homeostasis only, focusing on the role of two major organ systems, the gastrointestinal tract and kidneys, and their contribution to the control of phosphate balance. We describe in some detail the mechanisms of intestinal and renal phosphate transport, and compare and contrast their regulation. We also consider a significant example of phosphate imbalance, with phosphate retention, which is chronic kidney disease; why consequent hyperphosphatemia is important, and some of the newer means of managing it.