In patients with renal impairment, levels of both 25(OH)D and 1,25(OH)2D are reduced as CKD progresses, with active vitamin D reduced not only due to impaired synthesis in the kidney, but also as a result of the down-regulation of 1-α-hydroxylase by serum FGF-23, which becomes elevated in response to an increased phosphate balance. The gene discussed is FGF23; the disease is chronic kidney disease.