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 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.

scholarly journals Hypocalcemic cardiomyopathy after parathyroidectomy in a patient with uremia: A case report and literature review

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052094211
Author(s):  
Wei Zhang ◽  
Feng Xue ◽  
Quandong Bu ◽  
Xuemei Liu
Keyword(s):  
Heart Failure ◽  
Case Report ◽  
Secondary Hyperparathyroidism ◽  
Calcium Supplementation ◽  
Severe Heart Failure ◽  
Cardiac Complications ◽  
Refractory Heart Failure ◽  
First Case ◽  
Insight Into

Hypocalcemia is a rare, but reversible, cause of dilated cardiomyopathy. Although cardiomyopathy may cause severe heart failure, calcium supplementation can reverse heart failure. We report here a patient with uremia and secondary hyperparathyroidism, who was complicated by persistent hypocalcemia and refractory heart failure. The cardiac failure was refractory to treatment with digitalis and diuretics, but dramatically responded to calcium therapy and restoration of normocalcemia. As a result, the patient was eventually diagnosed with hypocalcemic cardiomyopathy. To the best of our knowledge, this is the first case of this disease to be reported in a patient with uremia. Findings from our case may help clinicians to better understand hypocalcemic cardiomyopathy. Our case might also provide new insight into long-term cardiac complications and prognoses of patients undergoing parathyroidectomy due to secondary hyperparathyroidism.

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.

Lithium-associated hyperparathyroidism

2020 ◽  
Vol 81 (11) ◽  
pp. 1-9
Author(s):  
Simon Mifsud ◽  
Kyle Cilia ◽  
Emma L Mifsud ◽  
Mark Gruppetta
Keyword(s):  
Glycogen Synthase ◽  
Early Recognition ◽  
Bipolar Disorders ◽  
Lithium Therapy ◽  
Acute Effects ◽  
Recurrent Depression ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Acute And Chronic Effects

Lithium is a mood stabiliser widely used in the treatment and prophylaxis of mania, bipolar disorders and recurrent depression. Treatment with lithium can give rise to various endocrine and metabolic abnormalities, including thyroid dysfunction, nephrogenic diabetes insipidus and hypercalcaemia. Lithium may induce hypercalcaemia through both acute and chronic effects. The initial acute effects are potentially reversible and occur as a result of lithium's action on the calcium-sensing receptor pathway and glycogen synthase kinase 3, giving rise to a biochemical picture similar to that seen in familial hypocalciuric hypercalcaemia. In the long term, chronic lithium therapy leads to permanent changes within the parathyroid glands by either unmasking hyperparathyroidism in patients with a subclinical parathyroid adenoma or possibly by initiating multiglandular hyperparathyroidism. The latter biochemical picture is identical to that of primary hyperparathyroidism. Lithium-associated hyperparathyroidism, especially in patients on chronic lithium therapy, is associated with increased morbidity. Hence, regular monitoring of calcium levels in patients on lithium therapy is of paramount importance as early recognition of lithium-associated hyperparathyroidism can improve outcomes. This review focuses on the definition, pathophysiology, presentation, investigations and management of lithium-associated hyperparathyroidism.

scholarly journals Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism

2015 ◽  
Vol 87 (4) ◽  
pp. 846-856 ◽  
Author(s):  
Geert J. Behets ◽  
Goce Spasovski ◽  
Lulu R. Sterling ◽  
William G. Goodman ◽  
David M. Spiegel ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Bone Histomorphometry ◽  
Term Treatment ◽  
Dialysis Patients ◽  
Long Term Treatment ◽  
Before And After

Direct upregulation of parathyroid calcium-sensing receptor and vitamin D receptor by calcimimetics in uremic rats

2009 ◽  
Vol 296 (3) ◽  
pp. F605-F613 ◽  
Author(s):  
Francisco J. Mendoza ◽  
Ignacio Lopez ◽  
Rocio Canalejo ◽  
Yolanda Almaden ◽  
David Martin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Term Treatment ◽  
Parathyroid Cell ◽  
Calcium Sensing Receptor ◽  
Short Term ◽  
Calcium Sensing ◽  
Long Term Treatment ◽  
Acute Increase

To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expression could be separated from their ability to reduce parathyroid cell proliferation, five-sixth nephrectomized (5/6 Nx) rats received vehicle, AMG 641, calcitriol, or AMG 641+calcitriol either daily for 13 days (long-term protocol) or in a single dose (short-term protocol). In the long-term protocol, AMG 641, calcitriol, and their combination significantly reduced the percentage of proliferating parathyroid cells. Proliferation was uncontrolled in the short-term protocol. A significant increase in CaSR mRNA (% vs. β-actin) was detected in rats treated with both calcitriol (1.60 ± 0.30) and AMG 641 (1.66 ± 0.25) for 13 days ( P = 0.01 vs. 5/6 Nx+vehicle, 0.89 ± 0.09); and there was a further increase when both drugs were administered simultaneously (2.46 ± 0.33). In the short-term protocol, only rats receiving AMG 641 alone (2.01 ± 0.33, P < 0.001) showed increased expression of CaSR mRNA, whereas the combination (1.81 ± 0.20) produced no additional benefit. AMG 641 also increased CaSR mRNA expression in vitro. Changes in VDR mRNA paralleled those of CaSR mRNA. In the long-term treatment, both AMG 641 (0.87 ± 0.14) and calcitriol (0.99 ± 0.12) increased VDR mRNA ( P < 0.05 vs. 5/6 Nx+vehicle, 0.49 ± 0.10), and the increase was more accentuated when the drugs were combined (1.49 ± 0.45). In the short-term protocol, only treatment with AMG 641, alone (1.52 ± 0.41) or combined with calcitriol (1.86 ± 0.24), increased VDR mRNA. In conclusion, our results demonstrate an acute increase in CaSR mRNA and VDR mRNA in the parathyroid glands of uremic rats treated with AMG 641, in which cell proliferation was uncontrolled, thus supporting a direct effect of calcimimetics on CaSR and VDR expression by hyperplastic parathyroid cells.

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