Strategies to lower fibroblast growth factor 23 bioactivity

Fibroblast growth factor 23 (FGF23) is a circulating hormone derived from the bone whose release is controlled by many factors and exerts a multitude of systemic actions. There are congenital and acquired disorders of increased and decreased FGF23 levels. In chronic kidney disease (CKD), elevations of FGF23 levels can be 1000-fold above the upper physiological limit. It is still debated whether this high FGF23 in CKD is a biomarker or causally related to morbidity and mortality. Data from human association studies support pathogenicity, while experimental data are less robust. Knowledge of the biology and pathobiology of FGF23 has generated a plethora of means to reduce FGF23 bioactivity at many levels that will be useful for therapeutic translations. This article summarizes these approaches and addresses several critical questions that still need to be answered.