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Twenty years have passed since the identification of klotho and the fibroblast growth factor 23 (FGF23), the regulatory binomial of phosphate homeostasis. Being kidney the main source of klotho as well as a target organ in the phosphate regulation, most studies involving klotho and FGF23 had a «nephrocentric» focus. Considering that circulating FGF23 can reach exaggerated levels at the end stage of chronic kidney disease (CKD), the bias of this approach allowed to recognize the harmful «off target» klotho-independent effect of FGF23. A

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