At present it is not certain if these untoward effects associated with elevations in FGF23 are due to direct effects of FGF23 on FGFR/α-Klotho complexes in the kidney, off “target effects” of high levels of FGF23 to directly activate FGFRs in the absence of α-Kotho in the heart [22], or represent epiphenomena caused by effects of CKD to increase FGF23 levels. Here, KL is linked to chronic kidney disease.