Fibroblast growth factor 23 – A review with particular reference to the physiology and pathophysiology of phosphate homeostasis in the cat

Abstract

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone, discovery of which has transformed our understanding of mineral regulation in healthy mammals, including the cat. It is produced by osteoblasts and osteocytes and its prime role is to regulate phosphate entry into extracellular fluid (from bone and via the gut) and its excretion via the kidney. It interacts with other hormones (calcitriol and parathyroid hormone), inhibiting their activation and secretion respectively and so impacts on calcium as well as phosphate homeostasis. Physiological factors regulating its secretion are not well understood, although phosphate ion sensing is likely to be important. Calcium and magnesium ions are also involved and unravelling the control points and integration of the system regulating bone turnover and mineral balance whilst preventing soft tissue (non-osseous) mineralisation is a future research goal. Calciprotein particle size and number likely play an important role in this system but precisely how remains to be determined. Elevated serum FGF23 is the earliest indicator of mineral bone disorder associated with chronic kidney disease in human patients and in cats, enabling reference-range serum phosphorus to be maintained despite reduction in glomerular filtration rate which limits phosphate excretion. FGF23 also predicts CKD progression and survival in cats. The many factors influencing its secretion at different stages of CKD, including relative iron deficiency, anaemia and chronic systemic inflammation, hypomagnesaemia and α-klotho deficiency are discussed in this review, where the data available in cats with naturally occurring CKD is presented alongside that from rodent models and human CKD patients.