In this work we summarizes the steps that allowed the identification of the fibroblast growth factor (FGF) 23/Klotho axis as the principal regulator of phosphate homeostasis, exerting actions on intestine, bone, parathyroid glands, and kidney. We review the not fully understood mechanisms of action of this axis on the regulation of mineral homeostasis and, in addition, we discuss its potential role in the pathophysiology of chronic kidney disease and the associated complications. We also reflect the actual tendency to consider the components of this system as better predictors of the pathological conditions frequently associated to mineral disorders, and review some recent studies linking these components to cardiovascular disease even in population without mineral disorders. Finally, we consider the numerous processes in which Klotho is involved, including anti-ageing and mineral control processes, independently of its functions as obligated-coreceptor for FGF23.
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