Parathyroid hormone-producing cells exist in adipose tissues surrounding the parathyroid glands in hemodialysis patients with secondary hyperparathyroidism

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.

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Pre-operative Localisation of the Parathyroid Glands in Secondary Hyperparathyroidism: A Retrospective Cohort Study

Scientific Reports ◽

10.1038/s41598-019-51265-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Takahisa Hiramitsu ◽

Toshihide Tomosugi ◽

Manabu Okada ◽

Kenta Futamura ◽

Makoto Tsujita ◽

...

Keyword(s):

Computed Tomography ◽

Cohort Study ◽

Parathyroid Hormone ◽

Secondary Hyperparathyroidism ◽

Retrospective Cohort ◽

Parathyroid Glands ◽

Imaging Modalities ◽

Intact Parathyroid Hormone ◽

Intact Pth ◽

Persistent Hyperparathyroidism

Abstract Complete parathyroidectomy (PTx) is essential during total PTx for secondary hyperparathyroidism (SHPT) to prevent recurrent and persistent hyperparathyroidism. Pre-operative imaging evaluations, including computed tomography (CT), ultrasonography (US), and Tc-99m sestamibi (MIBI) scans, are commonly performed. Between June 2009 and January 2016, 291 patients underwent PTx for SHPT after pre-operative evaluations involving CT, US, and MIBI scans, and the diagnostic accuracies of these imaging modalities for identifying the parathyroid glands were evaluated in 177 patients whose intact parathyroid hormone (PTH) levels were <9 pg/mL after the initial PTx. Additional PTx procedures were performed on 7 of 114 patients whose intact PTH levels were >9 ng/mL after PTx, and the diagnostic validities of the imaging modalities for the remnant parathyroid glands were evaluated. A combination of CT, US, and MIBI scans achieved the highest diagnostic accuracy (75%) for locating bilateral upper and lower parathyroid glands before initial PTx. The accuracies of CT, US, and MIBI scans with respect to locating remnant parathyroid glands before additional PTx were 100%, 28.6%, and 100%, respectively. A combination of CT, US, and MIBI scans is useful for initial PTx for SHPT, and CT and MIBI scans are useful imaging modalities for additional PTx procedures.

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P1425EFFICACY AND SAFETY OF INTRAVENOUS PARICALCITOL TREATMENT IN CHINESE HEMODIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM: A REAL-WORLD DATABASE ANALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1425 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Niansong Wang ◽

Gengru Jiang

Keyword(s):

Parathyroid Hormone ◽

Observational Study ◽

Secondary Hyperparathyroidism ◽

Median Time ◽

Real World ◽

Hemodialysis Patients ◽

Target Range ◽

Total Serum ◽

Weekly Dose

Abstract Background and Aims The aim of this retrospective, real-world data based observational study was to evaluate the efficacy, safety profile of paricalcitol in Chinese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT) under routine clinical practice. Method From the Zemplar Engagement Program (ZEP) database, a total of 668 Chinese hemodialysis patients from 104 dialysis centers between January 2015 and May 2019 were included in the analysis set. Intact parathyroid hormone (iPTH), total serum calcium (Ca), phosphate (P), dosage of intravenous (IV) paricalcitol (Zemplar®) were analyzed and discussed via retrospective analysis of the database during the treatment. The comparison between baseline and end of treatment was made to reveal the fluctuation trend of each biomarker and reflected us with clues of IV paricalcitol’s algorithm in real-world practice. Results Patients were divided into five groups according to the duration of follow-up, which includes Month 0.5-3 (Day 14–90), Month 3-6 (Day 91–180), Month 6-12 (Day 181–360), Month 12-24 (Day 361–720) and Month 24-48 (Day 721–1440). Median iPTH levels decreased from 1183.05 pg/ml at baseline to 676.03 pg/ml at last visit by 30.88% (p < 0.0001). 56.14% of patients had a ≥30% decrease and 29.34% of patients had a ≥50% decrease in iPTH. The proportion of patients achieving the Chinese CKD-MBD Guideline target range (<600 pg/ml) increased from 9.88% at treatment initiation to 40.12% at last observation. Serum Ca levels remained within the normal range throughout the study with only a slight but statistically significant increase in the group of Month 12-24 (P=0.0479). Serum phosphate remained stable in all follow-up groups (P>0.05). Subgroup analyses of 221 patients with hyperphosphatemia at baseline >1.78 mmol/l showed a rapid phosphate reduction from 2.00±0.20 mmol/l to 1.76±0.34mmol/l by 11.64% (P< 0.0001), within the first few weeks, along with the reduction of iPTH. Of all patients, 62.72% experienced a 30% decrease in iPTH within a median time of 16.86 weeks (95% CI, 15.57-17.86), 38.17% experienced a 50% decrease in iPTH within a median time of 21.29 weeks (95% CI, 19.86-23.14). The average weekly dose of paricalcitol was 19.69±8.99ug/week. Total dose of paricalcitol used and baseline iPTH were negatively correlated with the decrease in iPTH. Conclusion This is the first national retrospective real-world observational study since IV paricalcitol is available in China since 2014. It proves that up to 20ug weekly IV paricalcitol treatment is safe and effective in China HD patients with higher iPTH level. Physicians and patients could expect significantly iPTH decrease within 16-21 weeks when IV paricalcitol is initiated. This study also encores the pre-published results of paricalcitol trials and high-quality cohorts, from the real-world perspective. In summary, IV paricalcitol is well tolerated and serves as an effective approach to treat SHPT in Chinese HD patients. Figure.1 Mean iPTH values from baseline to last measurement (pg/ml) Figure.2 iPTH changes compared with baseline stratified by baseline iPTH values (%) Figure.3 Proportion of patients with a >=30% or 50% decrease in parathyroid hormone (%) Figure.4 Changes of iPTH and P from baseline to last measurement in the subgroup of hyperphosphatemia (Mean ± SD); (Hyperphosphatemia, defined as P>1.78 mmol/l)

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