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.

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.

Kidney and haemostasis

2015 ◽  
Vol 35 (01) ◽  
pp. 73-76
Author(s):  
K. Andrassy
Keyword(s):  
Renal Insufficiency ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Cardiovascular Complications ◽  
Water Soluble ◽  
New Oral Anticoagulants ◽  
Waste Products ◽  
End Stage ◽  
Fgf 23

SummaryRenal insufficiency is characterized by thrombocytopathy, caused by the accumulation of water soluble and protein bound waste products of protein metabolism, which are not adequately eliminated by the kidney. The kidneys also excrete drugs and their metabolites, which accumulate if dosages are not adjusted to the renal function and may cause clinically relevant bleeding (i. e. synthetic penicillins, vitamin K antagonists, new oral anticoagulants). Therefore, each patients kidney function (GFR) ought to be evaluated by the KDIGO guidelines. The survival of chronic renal patients is lowered by increasing cardiovascular complications. Particularly frequent is non-valvular atrial fibrillation. The recommended prophylaxis with vitamin K antagonists for renal insufficiency is hampered by increased bleeding as well as by augmented (coronary) vascular and valvular calcification. It is not known yet whether prophylaxis with vitamin K may prevent this complication. Conclusion: Because new oral anticoagulants are equally or even more effective and cause less bleeding, they may be favoured in future and even in end-stage renal failure if more is known about dosing, safety and efficacy. The measurement of serum FGF 23 concentration may be helpful as a marker for their use.

Emerging roles of calcium-sensing receptor in the local regulation of intestinal transport of ions and calcium

2020 ◽  
Author(s):  
Krittikan Chanpaisaeng ◽  
Jarinthorn Teerapornpuntakit ◽  
Kannikar Wongdee ◽  
Narattaphol Charoenphandhu
Keyword(s):  
Transient Receptor Potential ◽  
Calcium Absorption ◽  
Intestinal Transport ◽  
Receptor Potential ◽  
Negative Control ◽  
Paracrine Factor ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Fgf 23 ◽  
Feedback Responses

Whether the intestinal mucosal cells are capable of sensing calcium concentration in the lumen and pericellular interstitium remains enigmatic for decades. Most calcium-regulating organs, such as parathyroid gland, kidney and bone, are capable of using calcium-sensing receptor (CaSR) to detect plasma calcium and trigger appropriate feedback responses to maintain calcium homeostasis. Although both CaSR transcripts and proteins are abundantly expressed in the crypt and villous enterocytes of the small intestine as well as the surface epithelial cells of the large intestine, the studies of CaSR functions have been limited to amino acid sensing and regulation of epithelial fluid secretion. Interestingly, several lines of recent evidence have indicated that the enterocytes use CaSR to monitor luminal and extracellular calcium levels, thereby reducing the activity of transient receptor potential channel, subfamily V, member 6, and inducing paracrine and endocrine feedback responses to restrict calcium absorption. Recent investigations in zebra fish and rodents have also suggested the role of fibroblast growth factor (FGF)-23 as an endocrine and/or paracrine factor participating in the negative control of intestinal calcium transport. In this review article, besides the CaSR-modulated ion transport, we elaborate the possible roles of CaSR and FGF-23 as well as their crosstalk as parts of a negative feedback loop for counterbalancing the seemingly unopposed calciotropic effect of 1,25-dihydroxyvitamin D3 on the intestinal calcium absorption.

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.

Sign in / Sign up

Export Citation Format

Share Document