FGF23 and hyperinsulinemic hypoglycemia, familial, 4: Current studies have confirmed that dysregulation of the FGF23-Klotho signaling pathway is significantly associated with the occurrence and progression of CKD, and leads to hyperphosphatemia and endothelial dysfunction [38]; in a mouse model of S-Klotho deficiency, the researchers also found evidence of renal impairment due to impaired urinary phosphate excretion [39].