1. Осложнения терминальной стадии хронической почечной недостаточности Пушкина А.В. Москва 23 октября 2011 Осенние встречи “ НЕФРО-ЛИГИ ” 2011 Часть II
Active vitamin D and its derivatives reduce the PTH levels, but at the same time they also elevate calcium and phosphorus levels. Increased levels of serum calcium and phosphorus are associated with adverse events such as soft tissue calcification.
Build 1 Allosteric modulators of the CaR (Type II calcimimetics [e.g. cinacalcet]), interact with the membrane-spanning portion of the receptor. 1 Allosteric modulation of the CaR: 2,3 - increases sensitivity of the CaR to calcium - cinacalcet does not activate the CaR in its own right, calcium must be present. Calcimimetics maximize the inhibitory effect of endogenous calcium and, consequently, that of the CaR, which is under-expressed in the parathyroid glands of patients with CKD and SHPT. Administration of a calcimimetic initially leads to a reduction of PTH secretion and then its synthesis (in the presence of calcium). Eventually cell proliferation is also reduced. Calcimimetic therapy shifts the calcium–iPTH curve (and set point) back to the left – restoring calcium sensing. 3 1. Goodman WG et al. Adv Renal Replace Therapy 2002;9:200–8 2. Nemeth EF et al. Proc Natl Acad Sci USA 1998;95:4040–5 3. Nemeth EF. Curr Pharm Des 2002;8:2077–87