KL and hyperinsulinemic hypoglycemia, familial, 4: However a large prospective cohort study and basic research are still in urgent needs to consolidate our conclusions and verify the following: (a) a detailed mechanism that kidney how to maintain α-Klotho homeostasis; (b) FGF-23 upregulation, α-Klotho deficiency, which occurs first; (c) whether replacement therapy (exogenous and endogenous) is safe and clinically effective.