scholarly journals Decreased expression of calcium-sensing receptor and parafibromin in secondary hyperparathyroidism with an abnormal whole PTH/intact PTH ratio

2013 ◽  
Vol 6 (4) ◽  
pp. 429-432 ◽  
Author(s):  
Shunsuke Yamada ◽  
Masanori Tokumoto ◽  
Masatomo Taniguchi ◽  
Hidehisa Kitada ◽  
Kazuhiko Tsuruya ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Calcium Sensing Receptor ◽  
Intact Pth ◽  
Calcium Sensing ◽  
Whole Pth

scholarly journals The impact of CASR A990G polymorphism in response to cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jaruwan Ngamkam ◽  
Somratai Vadcharavivad ◽  
Nutthada Areepium ◽  
Titinun Auamnoy ◽  
Kullaya Takkavatakarn ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Hemodialysis Patients ◽  
Serum Phosphate ◽  
Clinical Factors ◽  
Calcium Sensing Receptor ◽  
Intact Pth ◽  
Baseline Serum ◽  
Calcium Sensing ◽  
The Impact ◽  
Pth Level

AbstractThe objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT.

scholarly journals Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism

2005 ◽  
Vol 153 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Takehisa Kawata ◽  
Yasuo Imanishi ◽  
Keisuke Kobayashi ◽  
Takao Kenko ◽  
Michihito Wada ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Secondary Hyperparathyroidism ◽  
Murine Model ◽  
Hormone Secretion ◽  
Suppressive Effect ◽  
Receptor Expression ◽  
Parathyroid Glands ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet’s effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93–99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.

scholarly journals Novel treatment options for secondary hyperparathyroidism in end-stage kidney disease patients on hemodialysis therapy

2017 ◽  
Vol 20 (1) ◽  
pp. 32-38
Author(s):  
Liudmila Y. Rozhinskaya ◽  
Zhanna E. Belaya ◽  
Alexander S. Lutsenko
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Bone Structure ◽  
Treatment Options ◽  
Cardiovascular Complications ◽  
Calcium Sensing Receptor ◽  
Blood Calcium ◽  
Calcium Sensing ◽  
Focus On Results ◽  
End Stage ◽  
Fgf 23

Pathogenesis of secondary hyperparathyroidism is based on D-hormone deprivation, leading to bone remodeling impairment, increase in FGF-23, PTH levels, changes in blood calcium and phosphorus levels. Taken together with alteration of calcium-sensing receptor (CaSR) sensitivity, these changes result in alteration of bone structure and cardiovascular complications. CaSR agonists are one of the most important medications for treatment of secondary hyperparathyroidism in dialysis patients. Until recently, there was only one CaSR agonist with proven effectiveness – cinacalcet, which is administered per os, daily. Now, a new drug is registered in US, Europe and Russia – etelcalcetide, which is administered intravenously 3 times a week. In this review we focus on results of clinical trials regarding etelcalcetide effectiveness and possible compliance benefits.

Practical use of parenteral calcimimetics for severe secondary hyperparathyroidism. A case report

2021 ◽  
Vol 2 (3(5)) ◽  
pp. 58-62
Author(s):  
S.E. Khoroshilov ◽  
◽  
S.V. Besedin ◽  
A.V. Nikulin ◽  
◽  
...  
Keyword(s):  
Clinical Trials ◽  
Case Report ◽  
Secondary Hyperparathyroidism ◽  
Cardiovascular Complications ◽  
Treatment Session ◽  
Dialysis Patients ◽  
Calcium Sensing Receptor ◽  
Serum Parathyroid Hormone ◽  
Calcium Sensing

Secondary hyperparathyroidism (SHPT) leads to bone disorders and cardiovascular complications in long-term dialysis patients. SHPT is caused by hyperphosphatemia. Abnormalities of calcium-sensing receptor (CaSR) are associated with the pathogenesis of SHPT. Clinical trials have shown that calcimimetics significantly reduce the risks of parathyroidectomy, bone fracture and cardiovascular hospitalization among long-term dialysis patients with SHPT. Etelcalcetide, a novel calcimimetic compound, acts as a direct CaSR agonist, restores the sensitivity of the CaSR in parathyroid cells, and decreases serum parathyroid hormone without inducing hypercalcemia or hyperphosphatemia. Etelcalcetide's properties allow it to be administered intravenously thrice weekly at the end of a hemodialysis treatment session improving medication adherence.

The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism

2005 ◽  
Vol 288 (2) ◽  
pp. F253-F264 ◽  
Author(s):  
Mariano Rodriguez ◽  
Edward Nemeth ◽  
David Martin
Keyword(s):  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Positive Impact ◽  
Mineral Metabolism ◽  
Current Treatment ◽  
Phosphate Binders ◽  
Parathyroid Cell ◽  
Calcium Sensing Receptor ◽  
Vitamin D Receptors ◽  
Calcium Sensing

Serum calcium levels are regulated by the action of parathyroid hormone (PTH). Major drivers of PTH hypersecretion and parathyroid cell proliferation are the hypocalcemia and hyperphosphatemia that develop in chronic kidney disease patients with secondary hyperparathyroidism (SHPT) as a result of low calcitriol levels and decreased kidney function. Increased PTH production in response to systemic hypocalcemia is mediated by the calcium-sensing receptor (CaR). Furthermore, as SHPT progresses, reduced expression of CaRs and vitamin D receptors (VDRs) in hyperplastic parathyroid glands may limit the ability of calcium and calcitriol to regulate PTH secretion. Current treatment for SHPT includes the administration of vitamin D sterols and phosphate binders. Treatment with vitamin D is initially effective, but efficacy often wanes with further disease progression. The actions of vitamin D sterols are undermined by reduced expression of VDRs in the parathyroid gland. Furthermore, the calcemic and phosphatemic actions of vitamin D mean that it has the potential to exacerbate abnormal mineral metabolism, resulting in the formation of vascular calcifications. Effective new treatments for SHPT that have a positive impact on mineral metabolism are clearly needed. Recent research shows that drugs that selectively target the CaR, calcimimetics, have the potential to meet these requirements.

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