αKlotho levels start to decline in CKD stage 2 and precede the elevation of FGF23, PTH, and serum phosphate.105 Low levels of circulating αKlotho are associated with increased cardiovascular events and mortality in patients with CKD/ESRD.106, 107, 108, 109 It is, therefore, conceivable that some of the adverse physiological effects that have been attributed to increased FGF23 may be either caused by, or compounded by, lower αKlotho (Figure 2). This evidence concerns the gene FGF23 and chronic kidney disease.