FGF23: From academic nephrology to personalized patients' care.

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. All of these findings have caused a revolution on our previous knowledge about mineral homeostasis and currently, we are facing a new scenario in the clinical management of CKD, where FGF23 emerges simultaneously as an early biomarker of phosphate retention but also as a therapeutic target. In this review, we describe the disturbances of FGF23 in the CKD and we focus on how the maintenance of circulating FGF23 into a supraphysiological adaptive range from the initial stages of CKD and the control of "unlimited hyperphosphatonism" generated by the resistance to FGF23 action at end stages should emerge as new treatment paradigms in CKD-MBD. The recent development of an automated FGF23 assay, already validated for clinical use, should be the starting point to individualize all our knowledge from epidemiological studies and will allow us to use it properly for the patient's personalized care. Then, now we are in the momentum to assess the discriminating thresholds to distinguish the physiological adaptive FGF23 elevation related to each CKD stage from the exaggerated increase that would be interpreted as a poor regulatory compensation that will requires the adoption of therapeutic intervention.