Pharmacological and clinical properties of calcimimetics: Calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism

Nagano, Nobuo

doi:10.1016/j.pharmthera.2005.06.019

Cited by 117 publications

(80 citation statements)

References 199 publications

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“…Calcimimetic agents activate the CaSRs, thereby potentiating the effects of ambient extracellular calcium on parathyroid cell function. 18 This, in effect, reengages a negative feedback loop and suppresses PTH secretion. Calcimimetics also upregulate CaSR-and vitamin D-receptor expression and, in animal models, reduce parathyroid gland hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Calciphylaxis presenting in early chronic kidney disease with mixed hyperparathyroidism

Brucculeri¹,

Haydon²

2011

IJNRD

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Calciphylaxis is a disabling and life-threatening complication that primarily affects patients who are dialysis dependent. Reports have grown in the literature of cases occurring in those who have advanced chronic kidney disease (pre-end-stage renal disease) or in the setting of transplantation. There are also a few reports of cases occurring in those without any form of chronic kidney disease but with primary hyperparathyroidism. This disease entity is characterized by calcification, intimal hypertrophy, and thrombosis of small vessels that result in necrotizing, nonhealing ulcers -many of which are life threatening. Although several strategies aimed at treating and preventing this affliction have been reported in the literature, the outcome for most patients with calciphylaxis remains quite poor. We describe a patient with comparatively early stage-3 chronic kidney disease who developed calciphylaxis in the setting of both primary and secondary hyperparathyroidism. Predictably, after subtotal parathyroidectomy, her wounds did not completely heal and her biochemical markers of hyperparathyroidism did not completely normalize until her underlying secondary hyperparathyroidism was treated medically. It was only after initiating cinacalcet that the patient experienced complete wound healing and resolution of her calciphylaxis. It also supports other authors' findings that cinacalcet may be an important adjunct in the treatment of calciphylaxis. Keywords: calciphylaxis, chronic kidney disease, cinacalcet, parathyroidectomy Case reportA 66-year-old Caucasian woman with a medical history significant for chronic kidney disease (CKD) stage 3, hypertension, and morbid obesity was followed regularly at our nephrology and hypertension clinic. She was being treated aggressively for her hypertension, proteinuria, hyperuricemia, and secondary hyperparathyroidism (SHPT). Her baseline creatinine fluctuated between 1.5 mg/dL and 2.0 mg/dL, and eGFR (6 variable Modification of Diet in Renal Disease) between 24 and 34 mL/min/1.73 m 2 . Her home medications included paricalcitol, gemfibrozil, febuxostat, pantoprazole, furosemide, lisinopril, latanoprost ophthalmic, and ferrous sulfate. Our patient had never taken warfarin, vitamin D, or any oral phosphate binders. In 2009, her intact parathyroid hormone (PTH) levels were noted to be rising despite her receiving oral paricalcitol 1 mcg daily. The dose was eventually adjusted up to 2 mcg daily without controlling her PTH which climbed as high as 216 pg/mL. Her calcium levels climbed from 9.0 to 10.4 mg/dL but never higher. Her serum phosphorous levels ranged from 2.9 to 3.7 mg/dL before, during, and after subsequent treatment. Most importantly, the Ca 2+ × PO 4 2-solubility product was never greater than 33.7. In August 2010, she presented with painful eruptions and ulcerations along the medial aspects of her thighs Dovepress submit your manuscript | www.dovepress.com

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Section: Discussionmentioning

confidence: 99%

Calciphylaxis presenting in early chronic kidney disease with mixed hyperparathyroidism

Brucculeri¹,

Haydon²

2011

IJNRD

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“…Cinacalcet is a calcimimetic that activates the calcium sensing receptor (CaSR) present on parathyroid cells, C-cells of the thyroid, and renal distal tubular cells. Activation of the CaSR reduces PTH secretion and increases calcitonin release, whereas activation of the renal tubular cell CaSR reduces renal calcium resorption independently of changes in PTH 19 . Cinacalcet has been used successfully to treat PHPT in non-pregnant women 15 ' 16 .…”

Section: Discussionmentioning

confidence: 99%

Cinacalcet for Hyperparathyroidism in Pregnancy and Puerperium

Horjus¹,

Groot²,

Telting³

et al. 2009

Journal of Pediatric Endocrinology and Metabolism

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The efficacy and safety of various modes of medical treatment for primary hyperparathyroidism (PHPT) in pregnancy is largely unknown. This report describes two cases of PHPT in pregnancy that were temporarily treated with the calcimimetic cinacalcet. The first case was diagnosed in the 31 st week of pregnancy. The patient was asymptomatic and had an albumin-corrected total calcium level (Ca cor r) of 3.24 mmol/1. As serum calcium was only mildly elevated it was decided to postpone surgery to the postpartum period. Cinacalcet was started immediately after delivery to prevent a postpartum surge in serum calcium. The second patient presented with hypertension and symptomatic hypercalcemia (Ca corr 3.96 mmol/1) in the 32" week of pregnancy. Surgery was postponed because of suspected pheochromocytoma. Treatment with a combination of cinacalcet and calcitonin reduced serum Ca corr to 3.0 mmol/1. This report describes the monitoring of mother and child, and explores the pros and cons of the use of calcimimetics during pregnancy and puerperium.

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“…If allosteric sites have diverged through evolution at a greater rate than orthosteric sites, this is likely to be reflected in greater differences between allosteric sites in species homologs and, therefore, to make translation from initial pharmacological studies on a heterologously expressed human GPCR to animal models of disease even more problematic. Despite these issues, two allosteric regulators, cinacalcet as a PAM at the Ca 2ϩ sensing receptor (Nagano, 2006;Brä uner-Osborne et al, 2007) and maraviroc as a NAM at the chemokine CCR5 receptor (Dorr et al, 2005;Biswas et al, 2007), are now clinically approved medicines.…”

Section: A Allosterism At G Protein-coupled Receptorsmentioning

confidence: 99%

Allostery at G Protein-Coupled Receptor Homo- and Heteromers: Uncharted Pharmacological Landscapes

2010

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Pharmacological and clinical properties of calcimimetics: Calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism

Cited by 117 publications

References 199 publications

Calciphylaxis presenting in early chronic kidney disease with mixed hyperparathyroidism

Calciphylaxis presenting in early chronic kidney disease with mixed hyperparathyroidism

Cinacalcet for Hyperparathyroidism in Pregnancy and Puerperium

Allostery at G Protein-Coupled Receptor Homo- and Heteromers: Uncharted Pharmacological Landscapes

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