Vitamin D analogs for secondary hyperparathyroidism: What does the future hold?

Brown, Alex

doi:10.1016/j.jsbmb.2006.12.089

Cited by 23 publications

(25 citation statements)

References 46 publications

(50 reference statements)

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“…32,33 Recent observational studies by Litwin et al, 29 Civilibal et al, 28 and Mitsnefes et al 30 and our own work 3 have shown that a high vitamin D dosage adversely affects cIMT 3,29,30 and calcification. 3,28 Newer vitamin D analogues, such as paricalcitriol and doxercalciferol, are shown to be less calcemic 35,36 but have only a marginal survival advantage over calcitriol, 11,12 and their effects on the vasculature have not as yet been studied.…”

Section: Discussionmentioning

confidence: 99%

A Bimodal Association of Vitamin D Levels and Vascular Disease in Children on Dialysis

Shroff

Egerton

Bridel

et al. 2008

Journal of the American Society of Nephrology

173

118

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In addition to its classical role in calcium-phosphate homeostasis, vitamin D has anti-inflammatory effects that may influence vascular disease. This study examined the impact of vitamin D levels on the vascular phenotype in 61 children who had been on dialysis for Ն3 mo and in 40 age-matched control subjects. All dialysis patients were prescribed daily oral 1-␣ hydroxyvitamin D 3 . 92% of patients were deficient in ,25(OH) 2 D] levels were low in 36% and high in 11% of patients. There was a weak correlation between 1␣-hydroxyvitamin D 3 dosage and 1,25(OH) 2 D levels. Both carotid intima-media thickness and calcification scores showed a U-shaped distribution across 1,25(OH) 2 D levels: patients with both low and high 1,25(OH) 2 D had significantly greater carotid intima-media thickness (P Ͻ 0.0001) and calcification (P ϭ 0.0002) than those with normal levels. Low 1,25(OH) 2 D levels were associated with higher high-sensitivity C-reactive protein (P Ͻ 0.0001). Calcification was most frequently observed in patients with the lowest 1,25(OH) 2 D and the highest highsensitivity C-reactive protein. In contrast, 25(OH)D levels did not correlate with any vascular measure. In conclusion, both low and high 1,25(OH) 2 D levels are associated with adverse morphologic changes in large arteries, and this may be mediated through the effects of 1,25(OH) 2 D on calcium-phosphate homeostasis and inflammation. For optimization of strategies to protect the vasculature of dialysis patients, careful monitoring of 1,25(OH) 2 D levels may be required.

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Section: Discussionmentioning

confidence: 99%

A Bimodal Association of Vitamin D Levels and Vascular Disease in Children on Dialysis

Shroff

Egerton

Bridel

et al. 2008

Journal of the American Society of Nephrology

173

118

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“…Vascular changes in CRI could result from hypertension, volume overload, acidosis, anemia, uremic toxins, and also from disturbed calcium-phosphorus balance and secondary hyperparathyroidism (S-HPT) [2, 5,7,8,9]. S-HPT and its metabolic consequences (high serum phosphate and calcium × phosphate product) are associated with cardiovascular disease and its complications in CRI [10, 11], while S-HPT can also influence the remodeling of the vascular wall [12].…”

Section: Introductionmentioning

confidence: 99%

“…S-HPT can be treated using vitamin D and its analogs that inhibit parathyroid hormone (PTH) gene transcription and parathyroid hyperplasia [8]. Paricalcitol is a less hypercalcemic vitamin D analog with a greater safety margin, and it may even provide survival benefit in CRI patients [8].…”

Section: Introductionmentioning

confidence: 99%

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Paricalcitol Treatment and Arterial Tone in Experimental Renal Insufficiency

Karavalakis

Eräranta

Vehmas

et al. 2008

Nephron Exp Nephrol

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Aim: To examine whether treatment of secondary hyperparathyroidism with paricalcitol provides benefits to arteries in uremic rats. Methods: 5/6-nephrectomized rats were treated (NX+Pari) or not treated (NX) with paricalcitol (200 ng/kg, thrice weekly) for 12 weeks. Aortic histology and isolated segments of the main and 2nd-order mesenteric arterial branches were studied. Results: Creatinine clearance was reduced by 54–61%, plasma phosphate increased 2.1- to 2.5-fold, and blood pressure by 40 mm Hg in both NX groups. PTH increased 13-fold in NX and 5-fold in NX+Pari rats. Calcification in aortic cross-sections increased from 2.1 to 7.1% after paricalcitol. In the large mesenteric artery, vasoconstriction to noradrenaline was reduced in NX+Pari rats. In the large and small arteries, vasorelaxation to acetylcholine was impaired in NX rats and unaffected by paricalcitol. In the small artery, paricalcitol increased nitric oxide synthase inhibition-resistant relaxation to acetylcholine, and maximal relaxation to levcromakalim. The small arteries of NX rats featured increased wall cross-sectional area, while paricalcitol further increased wall thickness and the wall:lumen ratio. Conclusion: Paricalcitol treatment showed both benefits and harmful effects in uremic rats: in the large artery vasoconstriction was reduced but calcification increased, while in the small artery vasorelaxation via potassium channels was moderately improved but hypertrophic remodeling was aggravated.

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“…Osteoblasts express both 25-hydroxylase as well as 1-α hydroxylase enzyme systems and can function as independent 1,25(OH) 2 D-producing cells [ 7 ]. The above calcium and phosphorus mobilizing action is at odds with the known mineralization promoting action of vitamin D. By enhancing the absorption of Ca 2+ and PO 4 3− from the intestine and the renal tubules, vitamin D raises the concentrations of both Ca 2+ and PO 4 3− in the blood and extracellular fluid. This increase in the calcium and phosphorus product results in net bone mineralization.…”

Section: Vitamin D Actions Calcemic Actionsmentioning

confidence: 99%

Vitamin D in Chronic Kidney Disease

Torres¹,

Cozzolino²,

Vervloet³

2016

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Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease (CKD) population. CKD is characterized by dysregulation of vitamin D and mineral metabolism. Secondary hyperparathyroidism and its management puts patients with CKD at increased cardiovascular risk. Emergence of experimental and some clinical data suggesting beneficial effects of vitamin D on proteinuria, blood pressure, inflammation and cardiovascular outcomes has pushed it to the center stage of CKD research. Pediatric data on vitamin D dysregulation and its consequences are still in its infancy. Ongoing prospective studies such as Chronic Kidney disease in Children (CKiD) and the Cardiovascular Comorbidity in Children with CKD (4 C) should help to delineate the evolution of disturbances in mineral metabolism and its adverse effects on growth, CKD progression and cardiovascular outcomes.

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Vitamin D analogs for secondary hyperparathyroidism: What does the future hold?

Cited by 23 publications

References 46 publications

A Bimodal Association of Vitamin D Levels and Vascular Disease in Children on Dialysis

A Bimodal Association of Vitamin D Levels and Vascular Disease in Children on Dialysis

Paricalcitol Treatment and Arterial Tone in Experimental Renal Insufficiency

Vitamin D in Chronic Kidney Disease

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