Despite the recommendation that circulating levels of 25(OH)D above 23 ng/ml may effectively attenuate CKD progression (10), it is imperative to recognize that levels above 35 ng/ml may be necessary to suppress PTH with cholecalciferol supplementation in more advanced CKD, as angiotensin II-driven increases in ADAM17/TGFα signaling may cause renal resistance to calcitriol actions through VDR reductions, as demonstrated in hyperplastic parathyroid glands. The gene discussed is VDR; the disease is chronic kidney disease.