Cinacalcet Reduces the Set Point of the PTH-Calcium Curve

Abstract

The calcimimetic cinacalcet increases the sensitivity of the parathyroid calcium-sensing receptor to calcium and therefore should produce a decrease in the set point of the parathyroid hormone (PTH)-calcium curve. For investigation of this hypothesis, nine long-term hemodialysis patients with secondary hyperparathyroidism were given cinacalcet for 2 mo, the dosage was titrated per a protocol based on intact PTH and plasma calcium concentrations. Dialysis against low-and high-calcium (0.75 and 1.75 mM) dialysate was used to generate curves describing the relationship between PTH and calcium. Compared with precinacalcet levels, cinacalcet significantly reduced mean serum calcium, intact PTH and whole PTH (wPTH; all P Ͻ 0.001). The set points for PTH-calcium curves were significantly reduced, and both maximum and minimum levels of PTH (intact and whole) were significantly decreased. The calciummediated inhibition of PTH secretion was more marked after cinacalcet treatment. In addition, cinacalcet shifted the inverse sigmoidal curve of wPTH/non-wPTH ratio versus calcium to the left (i.e., less calcium was required to reduce the wPTH/non-wPTH ratio). In conclusion, cinacalcet increases the sensitivity of the parathyroids to calcium, causing a marked reduction in the set point of the PTH-calcium curve, in hemodialysis patients with secondary hyperparathyroidism.

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

“…Importantly, in ESRD patients cinacalcet effectively controls secondary hyperparathyroidism over prolonged time periods, up to at least 3 yr (43). Of note, the pathologic rightward shift of the Ca2ϩ-PTH curve seen in many dialysis patients with secondary hyperparathyroidism can be reversed by cinacalcet treatment (44,45).…”

Open label study to assess the safety and efficacy of cinacalcet in refractory hyperparathyroidism with chronic renal failure

“…It plays a central role in the pathogenesis of secondary hyperparathyroidism in CKD patients and consequent is an attractive therapeutic target. 26 The term calcimimetic has been coined for those compounds that can modulate the activity of calcium receptor. 26 Type II calcimimetics are organic compounds that bind to regions within the membrane spanning domain of CaR and have the potential to increase the sensitivity of CaR to calcium, lowering the threshold of receptor activation by calcium.…”

Vitamin D and the Calcium-Sensing Receptor

“…High Ca 2þ o suppresses PTH secretion [26], PTH gene expression [47], and parathyroid cellular proliferation [5], and stimulates PTH degradation [48]. Like the CaSR, the VDR also suppresses PTH secretion [49], PTH gene expression [50], and parathyroid cellular proliferation [51e53].…”