Effective suppression of parathyroid hormone by 1α-hydroxy-vitamin D2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism

Tan, A. U.; Levine, Barton S.; Mazess, Richard B.; Kyllo, Darlene M.; Bishop, Charles; Knutson, Joyce C.; Kleinman, Kenneth S.; Coburn, Jack W.

doi:10.1038/ki.1997.39

Cited by 129 publications

(37 citation statements)

References 26 publications

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“…In addition to PTH, serum Ca and P levels are sensitive to vitamin D treatment (9,10,25,26). The increased serum mineral levels can contribute to hypercalcemia and hyperphosphatemia, both of which have been associated with increased morbidity and mortality in patients who receive dialysis (27).…”

Section: Discussionmentioning

confidence: 99%

Calcimimetic R-568 Decreases Extraosseous Calcifications in Uremic Rats Treated with Calcitriol

López¹,

Aguilera–Tejero²,

Mendoza³

et al. 2006

Journal of the American Society of Nephrology

140

111

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Calcimimetics decrease parathyroid hormone (PTH) levels in uremic patients with secondary hyperparathyroidism without increasing serum calcium (Ca). The aim of this study was to evaluate the effect of calcimimetic R-568 alone or in combination with calcitriol on vascular and other soft tissue calcifications in uremic rats with secondary hyperparathyroidism. Shamoperated and 5/6 nephrectomized Wistar rats were studied. 5/6 Nephrectomized rats were treated with vehicle, calcitriol (80 ng/kg every other day), R-568 (1.5 and 3 mg/kg per d), and both calcitriol and R-568 1.5 mg/kg, as above. Rats were killed after 14 or 56 d of treatment. Blood was drawn for biochemical measurements. Aortic, heart, kidney, lung, and stomach tissue samples were processed for histopathology and measurement of tissue Ca and phosphorus content. PTH concentrations were significantly reduced by all treatments. Treatment with calcitriol induced significant vascular calcification (aortic Ca increased to 4.2 ؎ 1.2 mg/g at day 14 and to 11.4 ؎ 0.7 mg/g at day 56; P < 0.05 versus vehicle). Treatment with R-568 did not induce vascular calcification. Concurrent administration of R-568 with calcitriol reduced the aortic Ca (1.9 ؎ 0.2 mg/g at day 14 and 7.5 ؎ 1.4 mg/g at day 56) in relation to calcitriol alone. Soft tissue calcifications mirrored aortic mineralizations. Survival was significantly (P < 0.001) reduced in calcitriol-treated rats, and mortality was attenuated (P ‫؍‬ 0.01) by concurrent treatment with R-568. In uremic rats, R-568 reduces elevated PTH levels without inducing vascular calcification, prevents calcitriol-induced vascular calcification, and decreases mortality.

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Section: Discussionmentioning

confidence: 99%

Calcimimetic R-568 Decreases Extraosseous Calcifications in Uremic Rats Treated with Calcitriol

López¹,

Aguilera–Tejero²,

Mendoza³

et al. 2006

Journal of the American Society of Nephrology

140

111

View full text Add to dashboard Cite

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“…In patients with CKD stages 2 to 5, clinicians have to rely on the use of calcitriol, its analog 1-alpha 25 OH vitamin D (alfacalcidol), or other active vitamin D sterols, either alone or in combination with oral calcium supplements and/or non-calcium containing phosphate binders, to arrest or retard the steady increase in plasma PTH levels associated with the progression of chronic renal failure (51,52). These treatments are equally effective in CKD 5D patients with moderate to severe hyperparathyroidism (53)(54)(55)(56). Although this is the case in the majority of patients, it is not true in all of them, as shown in a recent prospective study from Japan: 120 dialysis patients with secondary hyperparathyroidism were treated de novo with intravenous calcitriol for up to 48 wk.…”

Section: Case In Favor Of Vitamin D or Active Vitamin D Derivatives Amentioning

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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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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“…However, untreated 2°HPT causes significant morbidity, including severe bone deformities and growth retardation in children (12). The availability of effective calcium-free, metal-free phosphate-binding agents, such as sevelamer (13)(14)(15), combined with new active vitamin D sterols, such as doxercalciferol (16,17), has widened the margin of safety for the treatment of 2°HPT. Although these agents can effectively control serum phosphorus and lower parathyroid hormone (PTH) levels, little is known about their effects on the skeletal lesions of 2°HPT.…”

mentioning

confidence: 99%

Sevelamer Controls Parathyroid Hormone–Induced Bone Disease as Efficiently as Calcium Carbonate without Increasing Serum Calcium Levels during Therapy with Active Vitamin D Sterols

Salusky¹,

Goodman²,

Sahney³

et al. 2005

Journal of the American Society of Nephrology

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Little is known about the impact of various phosphate binders on the skeletal lesions of secondary hyperparathyroidism (2°HPT). The effects of calcium carbonate (CaCO 3 ) and sevelamer were compared in pediatric peritoneal dialysis patients with bone biopsy-proven 2°HPT. Twenty-nine patients were randomly assigned to CaCO 3 (n ‫؍‬ 14) or sevelamer (n ‫؍‬ 15), concomitant with either intermittent doses of oral calcitriol or doxercalciferol for 8 mo, when bone biopsies were repeated. Serum phosphorus, calcium, parathyroid hormone (PTH), and alkaline phosphatase were measured monthly. The skeletal lesions of 2°HPT improved with both binders, and bone formation rates reached the normal range in approximately 75% of the patients. Overall, serum phosphorus levels were 5.5 ؎ 0.1 and 5.6 ؎ 0.3 mg/dl (NS) with CaCO 3 and sevelamer, respectively. Serum calcium levels and the Ca ؋ P ion product increased with CaCO 3 ; in contrast, values remained unchanged with sevelamer (9.6 ؎ 01 versus 8.9 ؎ 0.2 mg/dl; P < 0.001, respectively). Hypercalcemic episodes (>10.2 mg/dl) occurred more frequently with CaCO 3 (P < 0.01). Baseline PTH levels were 980 ؎ 112 and 975 ؎ 174 pg/ml (NS); these values decreased to 369 ؎ 92 (P < 0.01) and 562 ؎ 164 pg/ml (P < 0.01) in the CaCO 3 and the sevelamer groups, respectively (NS between groups). Serum alkaline phosphatase levels also diminished in both groups (P < 0.01). Thus, treatment with either CaCO 3 or sevelamer resulted in equivalent control of the biochemical and skeletal lesions of 2°HPT. Sevelamer, however, maintained serum calcium concentrations closer to the lower end of the normal physiologic range, thereby increasing the safety of treatment with active vitamin D sterols.

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Effective suppression of parathyroid hormone by 1α-hydroxy-vitamin D2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism

Cited by 129 publications

References 26 publications

Calcimimetic R-568 Decreases Extraosseous Calcifications in Uremic Rats Treated with Calcitriol

Calcimimetic R-568 Decreases Extraosseous Calcifications in Uremic Rats Treated with Calcitriol

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

Sevelamer Controls Parathyroid Hormone–Induced Bone Disease as Efficiently as Calcium Carbonate without Increasing Serum Calcium Levels during Therapy with Active Vitamin D Sterols

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