Interaction between Vitamin D and calcimimetics in chronic kidney disease

For many years vitamin D has been the only available drug to suppress parathyroid hormone (PTH) hypersecretion in patients with renal insufficiency. This effect is accomplished directly through activation of the vitamin D receptor (VDR) on parathyroid cells. However, vitamin D also stimulates intestinal absorption of calcium and phosphate, thus often resulting in hypercalcemia and hyperphosphatemia, both undesirable in renal patients. For this reason vitamin D analogs with less calcemic effects have been developed, with some improvement of this problematic effect. The discovery of calcium sensing receptor (CaSR) and the subsequent production of drugs capable of stimulating it, has allowed the introduction of calcimimetics as an alternative therapy to vitamin D. Cinacalcet, the first to be available for clinical uses, has been successfully employed to reduce serum PTH levels in patients with end stage renal disease. At variance with vitamin D, calcimimetics, while decreasing PTH, also decrease serum levels of calcium and phosphate. The effect on serum calcium is of such entity that symptomatic hypocalcemia may occur. As a consequence, vitamin D is frequently associated and instead of becoming an alternative, cinacalcet is mostly prescribed together with vitamin D. Importantly, we have clear experimental evidence that vitamin D administration increases the expression of CaSR on target cells and that, reciprocally, calcimimetics increase VDR expression. This interaction allows presuming potential clinical advantages to control secondary hyperparathyroidism. Further, since both VDR and CaSR are expressed also in tissues not involved with mineral metabolism, other still unpredicted clinical effects are possible.