Specific deletion of Klotho in distal tubules has also been reported to inhibit the increase in renal Pi excretion in response to FGF23 (89), which suggests that Klotho deficiency limits its regulation of FGF23 production and that hyperphosphataemia, which usually become evident in CKD stage 3, remains the principal regulator of FGF23 secretion in CKD (90). This evidence concerns the gene FGF23 and chronic kidney disease.