The severity of parathyroid cell growth determines not only the degree of SHPT but also contributes to marked reductions in parathyroid VDR, calcium sensing receptor, FGF receptors, and cell membrane klotho, thus impairing PTH suppression in response to the correction of vitamin D deficiency or to therapeutic interventions with calcitriol or its analogs, oral calcium, or by the progressive elevations in FGF23 that take place in the course of CKD. This evidence concerns the gene CASR and chronic kidney disease.