Shedding Light on the Complex Regulation of FGF23

Abstract

Early research has suggested a rather straightforward relation between phosphate exposure, increased serum FGF23 (Fibroblast Growth Factor 23) concentrations and clinical endpoints. Unsurprisingly, however, subsequent studies have revealed a much more complex interplay between autocrine and paracrine factors locally in bone like PHEX and DMP1, concentrations of minerals in particular calcium and phosphate, calciprotein particles, and endocrine systems like parathyroid hormone PTH and the vitamin D system. In addition to these physiological regulators, an expanding list of disease states are shown to influence FGF23 levels, usually increasing it, and as such increase the burden of disease. While some of these physiological or pathological factors, like inflammatory cytokines, may partially confound the association of FGF23 and clinical endpoints, others are in the same causal path, are targetable and hence hold the promise of future treatment options to alleviate FGF23-driven toxicity, for instance in chronic kidney disease, the FGF23-associated disease with the highest prevalence by far. These factors will be reviewed here and their relative importance described, thereby possibly opening potential means for future therapeutic strategies.