Regression of parathyroid gland swelling by treatment with cinacalcet

Terawaki, Hiroyuki; Nakano, Hirofumi; Takeguchi, Fumihiro; Hasegawa, Toshio; Nakayama, Masaaki; Okazaki, Masao; Hosoya, Tatsuo

doi:10.1093/ndt/gfn579

Cited by 14 publications

(14 citation statements)

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“…In support of this finding, another case of parathyroid size regression in response to cinacalcet treatment has been recently reported [17]. Although these observations are promising, they need to be confirmed by studies in larger numbers of patients.…”

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confidence: 67%

Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Komaba

Fukagawa

2008

Nephrology Dialysis Transplantation

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Secondary hyperparathyroidism is one of the most common and serious complications of chronic kidney disease (CKD). The main factors responsible for excessive synthesis and secretion of parathyroid hormone (PTH) include phosphate retention, hypocalcaemia and calcitriol deficiency resulting from decreased kidney function [1,2]. Sustained hypersecretion of PTH is associated with an increase in the parathyroid gland size, initially leading to diffuse parathyroid hyperplasia. Subsequently, some cells in the parathyroid glands proliferate in a monoclonal growth pattern, and the enlarged glands exhibit an advanced type of nodular hyperplasia [3]. In the course of parathyroid hyperplasia, both calcium-sensing receptors (CaSR) and vitamin D receptors (VDR) are progressively down-regulated [4,5], which results in diminished responsiveness of parathyroid glands with nodular hyperplasia to active vitamin D treatment.Conversely, whether regression of parathyroid hyperplasia can occur has remained a matter of discussion. Regression of parathyroid hyperplasia has been reported in rare cases of spontaneous infarction of the glands [6,7]. In addition, enhanced apoptosis of parathyroid cells has been observed in diffuse hyperplasia after kidney transplantation, suggesting the possibility of regression in the long term [8].In the past, the capacity of calcitriol therapy to induce regression of parathyroid hyperplasia had been a matter of debate. In a study of oral calcitriol pulse therapy, given to chronic haemodialysis patients, we observed a significant decrease in the mean ± SD volume of parathyroid glands (from 0.87 ± 0.32 to 0.51 ± 0.23 cm 3 ) after 12 weeks of treatment, with a concomitant significant reduction in intact PTH levels [9]. In contrast, Quarles et al. failed to observe a decrease in the parathyroid gland size after 36 weeks of intermittent intravenous or oral calcitriol treatments [10]; the mean ± SD gland volume was 1.9 ± 0.6 and 2.1 ± Correspondence and offprint requests to:

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confidence: 67%

Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Komaba

Fukagawa

2008

Nephrology Dialysis Transplantation

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“…Preclinical studies have shown that cinacalcet prevents parathyroid cell proliferation and reduces gland weight in an animal model of sHPT [5/6 nephrectomized rats (5/6 Nx)] [23], consistent with studies using the calcimimetic R-568 [24, 25]. Clinically, patients treated with cinacalcet have been shown to exhibit reduced parathyroid glandular volume as visualized by ultrasound [26] and regression of parathyroid gland swelling [27]. Komaba and Fukagawa [28] subsequently reported that cinacalcet effectively decreases serum PTH and reduces parathyroid gland volume in patients with moderate to severe sHPT [29].…”

Section: Introductionmentioning

confidence: 74%

Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD

Miller

Davis

Shatzen

et al. 2011

Nephrology Dialysis Transplantation

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Background.Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar®/Mimpara®); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT.Methods.We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT.Results.Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet-mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium.Conclusions.The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH.

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“…Along with the decreases in intact PTH serum levels in the present study, we showed that there were significant decreases in the total parathyroid gland volume. There are two prior studies in which the volumes of parathyroid glands were shown to be decreased after cinacalcet treatment [17,18]. Terawaki et al [17 ]demonstrated that 50 mg of cinacalcet reduced the volume of all 4 parathyroid glands in 6 months in a hemodialysis patient with secondary hyperparathyroidism.…”

Section: Discussionmentioning

confidence: 99%

“…There are two prior studies in which the volumes of parathyroid glands were shown to be decreased after cinacalcet treatment [17,18]. Terawaki et al [17 ]demonstrated that 50 mg of cinacalcet reduced the volume of all 4 parathyroid glands in 6 months in a hemodialysis patient with secondary hyperparathyroidism. Meola et al [18 ]also showed that cinacalcet reduced the volumes of parathyroid glands in 9 patients in 24–30 months.…”

Section: Discussionmentioning

confidence: 99%

“…These studies suggest that cinacalcet could possibly reduce the size of swollen parathyroid glands in patients with secondary hyperparathyroidism. There are a few recent reports in which the regression of the parathyroid glands was induced by cinacalcet treatment in dialysis patients with secondary hyperparathyroidism; however, these studies examined only a small number of dialysis patients [17,18]. In the present study, we examined whether the total parathyroid gland volumes were reduced after cinacalcet treatment in a larger number of hemodialysis patients with secondary hyperparathyroidism than in previous reports.…”

Section: Introductionmentioning

confidence: 86%

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Decreases in Parathyroid Gland Volume after Cinacalcet Treatment in Hemodialysis Patients with Secondary Hyperparathyroidism

Ichii

Ishimura²,

Okuno³

et al. 2010

Nephron Clin Pract

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Background/Aim: Cinacalcet, an allosteric modulator of the calcium-sensing receptor, effectively reduces serum parathyroid hormone (PTH). It was examined whether a regression of parathyroid glands in hemodialysis patients with secondary hyperparathyroidism was induced by cinacalcet treatment. Methods: Ultrasonography of the parathyroid glands was performed to examine the changes in the parathyroid gland volumes after cinacalcet treatment in 58 patients. Results: After cinacalcet treatment, serum calcium, phosphate, alkaline phosphatase, and intact PTH significantly decreased (p < 0.0001). The total volumes of the parathyroid glands were significantly decreased 6 months after cinacalcet treatment (942 ± 747 vs. 708 ± 550 mm³, p < 0.0005). There was a significant positive correlation between the parathyroid gland volumes at the start of cinacalcet treatment and the volume reduction in parathyroid glands (r = 0.716, p < 0.0001). Of the 58 patients, the total parathyroid gland volume was decreased in 42 patients and increased in 16 although the doses of cinacalcet, phosphate binders or vitamin D were not significantly different. In both groups, the intact PTH serum levels were significantly decreased after cinacalcet treatment. Conclusion: Cinacalcet treatment in patients with secondary hyperparathyroidism significantly reduced the total parathyroid gland volume in a short 6-month period. This study suggests that cinacalcet treatment may postpone parathyroidectomy and/or reduce cases.

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Regression of parathyroid gland swelling by treatment with cinacalcet

Cited by 14 publications

References 4 publications

Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD

Decreases in Parathyroid Gland Volume after Cinacalcet Treatment in Hemodialysis Patients with Secondary Hyperparathyroidism

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