The calcimimetic R-568 retards uremia-enhanced vascular calcification and atherosclerosis in apolipoprotein E deficient (apoE−/−) mice

Ivanovski, Ognen; Nikolov, Igor; Joki, Nobuhiko; Caudrillier, Axelle; Phan, Olivier; Mentaverri, Romuald; Maizel, Julien; Hamada, Y.; Nguyen–Khoa, Thao; Fukagawa, Masafumi; Kamel, Saı̈d; Lacour, Bernard; Drüeke, Tilman B.; Massy, Ziad A.

doi:10.1016/j.atherosclerosis.2008.10.043

Cited by 103 publications

(79 citation statements)

References 35 publications

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“…In experimental animals, calcimimetics attenuated or even halted the progression of osteitis fibrosa (24). They also have been shown to reduce the progression of arterial calcification or prevent their appearance in uremic rats (25,26) and mice (22).…”

Section: Development Of Calcimimetics and Calcilyticsmentioning

confidence: 99%

“…Thus, the use of calcimimetics led to a decrease in PTH synthesis and PTH release (17); modulated the regulation of genes involved in these processes, including upregulation of CaR (18) and VDR (19); reduced parathyroid cell proliferation (20); attenuated progression of parathyroid hyperplasia (21,22); and enhanced parathyroid cell apoptosis (23). In experimental animals, calcimimetics attenuated or even halted the progression of osteitis fibrosa (24).…”

Section: Development Of Calcimimetics and Calcilyticsmentioning

confidence: 99%

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Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

Drüeke¹,

Ritz²

2009

Clinical Journal of the American Society of Nephrology

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The discovery of the calcium-sensing receptor (CaR) 15 yr ago was rapidly followed by the development of drugs modulating its activity, the so-called calcimimetics (increasing the CaR signal) and calcilytics (decreasing the CaR signal). The indication for calcimimetics is treatment of primary and secondary hyperparathyroidism, whereas calcilytics have potential for treatment of osteoporosis. A large number of clinical studies has shown that cinacalcet, the only presently available calcimimetic, effectively reduces serum parathyroid hormone in dialysis patients with secondary hyperparathyroidism. In contrast to the effect of active vitamin D derivatives, it simultaneously decreases serum calcium and phosphorus. Experimental studies showed a concomitant decrease in parathyroid hyperplasia. In the treatment of secondary hyperparathyroidism of dialysis patients, important questions remain unresolved, for example, whether there are reasons to prefer calcimimetics to active vitamin D derivatives and whether combined administration offers advantages compared with calcimimetics or active vitamin D given in isolation. For lowering parathyroid hormone, available evidence from recent studies suggests that combination therapy should be preferred to single drug treatment because of less side-effects and greater efficacy in controlling parathyroid overfunction. Future randomized controlled trial must answer whether calcimimetics impact on cardiovascular events or survival and whether in this respect there are differences between vitamin D sterols and calcimimetics.

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Section: Development Of Calcimimetics and Calcilyticsmentioning

confidence: 99%

Section: Development Of Calcimimetics and Calcilyticsmentioning

confidence: 99%

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

Drüeke¹,

Ritz²

2009

Clinical Journal of the American Society of Nephrology

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“…Cinacalcet hydrochloride (also known as Sensipar) was approved in 2004 by the FDA for treating severe secondary hyperparathyroidism in stage 5 kidney disease (13) as well as parathyroid cancer (145). Studies in experimental animals have suggested that administration of a calcimimetic in uremic animals reduces some of the long-term complications of this condition, including progression of renal impairment, atherosclerosis (74), and, in combination with vitamin D treatment, mortality (140). Studies are currently in progress in humans assessing the efficacy of the drug in decreasing cardiovascular disease and mortality.…”

Section: Casr-based Therapeutics: Renal Implicationsmentioning

confidence: 99%

Physiology and pathophysiology of the calcium-sensing receptor in the kidney

Riccardi

Brown

2010

American Journal of Physiology-Renal Physiology

298

239

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“…In addition, calcimimetic-induced upregulation of the calcium-sensing receptor in vascular smooth muscle and endothelial cells may attenuate the progression of vascular calcification (8)(9)(10). In patients receiving hemodialysis, cinacalcet may slow the progression of vascular and cardiac-valve calcification (11).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis

Parfrey¹,

Drüeke²,

Correa‐Rotter³

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

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The calcimimetic R-568 retards uremia-enhanced vascular calcification and atherosclerosis in apolipoprotein E deficient (apoE−/−) mice

Cited by 103 publications

References 35 publications

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

Physiology and pathophysiology of the calcium-sensing receptor in the kidney

The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis

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