Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4

Coburn, Jack W.; Maung, Hla M.; Elangovan, Logan; Germain, Michael J.; Lindberg, Jill S.; Sprague, Stuart M.; Williams, Mark E.; Bishop, Charles

doi:10.1053/j.ajkd.2004.01.012

Cited by 152 publications

(124 citation statements)

References 35 publications

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“…Nevertheless, calcitriol did significantly decrease PTH (20%-30%), and bone histology tended to improve (15,16). In a placebo-controlled trial in stages 3-4 CKD, doxercalciferol significantly suppressed PTH 46% with minimal hypercalcemia (defined as .10.7 mg/dl) and a slight increase in hypercalciuria (20). A double-blind placebo-controlled trial of paricalcitol suppressed PTH 42%, with hypercalcemia (defined as .10.5 mg/dl) occurring in 2% of patients without an increase in urinary calcium (14).…”

Section: Discussionmentioning

confidence: 94%

“…Thus, most patients with CKD require VDRA therapy to control hyperparathyroidism. The available VDRAs (calcitriol and paricalcitol) and the prohormone VDRAs (doxercalciferol and alfacalcidol) suppress PTH in a dose-dependent fashion independent of the CKD stage (14,15,20,21). Studies of calcitriol in the late 1980s enrolled few patients and were designed to increase serum calcium and not specifically to suppress PTH.…”

Section: Discussionmentioning

confidence: 99%

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A Randomized Multicenter Trial of Paricalcitol versus Calcitriol for Secondary Hyperparathyroidism in Stages 3–4 CKD

Coyne

Goldberg

Faber

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Calcitriol is used to treat secondary hyperparathyroidism in patients with CKD. Paricalcitol is less calcemic and phosphatemic in preclinical studies and in some trials in dialysis patients, but head-to-head comparisons in nondialysis patients are lacking. A large meta-analysis of trials concluded that these agents did not consistently reduce parathyroid hormone (PTH) and increased the risk of hypercalcemia and hyperphosphatemia. Therefore, the objective of this multicenter trial was to compare the rate of hypercalcemia between calcitriol and paricalcitol, while suppressing PTH 40%-60%.Design, setting, participants, & measurements Patients with stages 3-4 CKD (n=110) with a PTH level .120 pg/ml were recruited and randomized to 0.25 mg/d of calcitriol or 1 mg/d of paricalcitol between April 2009 and July 2011. Subsequent dose adjustments were by protocol to achieve 40%-60% PTH suppression below baseline. The primary endpoint was the rate of confirmed hypercalcemia of .10.5 mg/dl between groups.Results Forty-five patients in each group completed the 24 weeks of treatment. Both agents suppressed PTH effectively (252% with paricalcitol and 246% with calcitriol; P=0.17), although the paricalcitol group reached a 40% reduction in PTH sooner at a median 8 weeks (interquartile range [IQR], 4, 12) versus 12 weeks (IQR,8,18; P=0.02) and had a lower pill burden of 240 (IQR, 180, 298) versus 292 (IQR, 231, 405; P=0.01). Confirmed hypercalcemia was very low in both groups (three with paricalcitol and one with calcitriol) and was not significantly different (P=0.36). Both groups had small increases in calcium and phosphorus levels (0.3-0.4 mg/dl in each electrolyte) and significant decreases in alkaline phosphatase, a marker of high bone turnover, with no significant differences between groups.Conclusions These results show that both calcitriol and paricalcitol achieved sustained PTH and alkaline phosphatase suppression in stages 3-4 CKD, with small effects on serum calcium and phosphorus and a low incidence of hypercalcemia.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

A Randomized Multicenter Trial of Paricalcitol versus Calcitriol for Secondary Hyperparathyroidism in Stages 3–4 CKD

Coyne

Goldberg

Faber

et al. 2014

Clinical Journal of the American Society of Nephrology

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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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“…Treatment with calcitriol has been associated with improvements in markers of bone metabolism in peritoneal dialysis patients [99] and haemodialysis patients undergoing PTX [100], as well as increases in BMD in haemodialysis patients [101] and CKD patients not on dialysis [102]. Additional studies with vitamin D and doxercalciferol have demonstrated significant positive effects on markers of bone metabolism, including increases in cancellous bone areas in non-dialysed patients with CRI [103], and decreases in serum C-telopeptide and N-telopeptide and bone-specific alkaline phosphatase levels in subjects with stages 3 and 4 CKD [103,104].…”

Section: Bone Diseasementioning

confidence: 99%

Mineral metabolism disturbances in patients with chronic kidney disease

Kestenbaum

Belozeroff

2007

Eur J Clin Investigation

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Background Kidney disease, especially chronic kidney disease (CKD), is a worldwide public health problem with serious adverse health consequences for affected individuals. Secondary hyperparathyroidism, a disorder characterized by elevated serum parathyroid hormone levels, and alteration of calcium and phosphorus homeostasis are common metabolic complications of CKD that may impact cardiovascular health. Materials and methodsHere, we systematically review published reports from recent observational studies and clinical trials that examine markers of altered mineral metabolism and clinical outcomes in patients with CKD.

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Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4

Cited by 152 publications

References 35 publications

A Randomized Multicenter Trial of Paricalcitol versus Calcitriol for Secondary Hyperparathyroidism in Stages 3–4 CKD

A Randomized Multicenter Trial of Paricalcitol versus Calcitriol for Secondary Hyperparathyroidism in Stages 3–4 CKD

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

Mineral metabolism disturbances in patients with chronic kidney disease

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