Hyperparathyroidism In Stage Research Articles

The cost-effectiveness of extended-release calcifediol versus paricalcitol for the treatment of secondary hyperparathyroidism in stage 3–4 CKD

Aims: Patients with chronic kidney disease (CKD) not on dialysis frequently have vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT), which are associated with an increased risk of cardiovascular (CV) disease, fracture, CKD progression, and death. This study estimated the cost-effectiveness of extended-release calcifediol (ERC) vs paricalcitol for the treatment of patients with CKD stages 3–4 that have SHPT and VDI.Materials and methods: An economic analysis of SHPT treatments among a hypothetical cohort of 1,000 patients with CKD Stage 3 and 4 with SHPT and VDI was developed to estimate differences in the rates and costs of CV events, fractures, CKD stage progression, and mortality in patients treated with ERC and paricalcitol. A Markov model was developed with 1-year cycles and a 5-year time horizon from a US Medicare payer perspective with costs valued in 2017 US dollars.Results: The outcomes of the model were rates of clinical events, total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Across a 1,000-person cohort, ERC was the dominant (less costly, more effective) treatment strategy when compared with paricalcitol. Treatment with ERC resulted in cost savings of $14.8 M (95% CI = –$10.0 M–$45.2 M) and an incremental gain of 340 QALYs (95% CI = 200–496) compared to treatment with paricalcitol.Limitations: Bridging biochemical levels to clinical outcomes may not represent real-world risk of the clinical events modeled. Future real-world outcomes of patients treated with ERC and paricalcitol may be used to evaluate the model results.Conclusions: This model demonstrated favorable short- and long-term clinical benefits associated with the use of ERC in patients with CKD Stage 3 and 4 with SHPT and VDI, suggesting ERC may be cost-effective from the Medicare perspective compared to paricalcitol.

Secondary hyperparathyroidism in patient with type 2 diabetes and stages 3–4 chronic kidney disease

Secondary hyperparathyroidism is an early complication of chronic kidney disease, with increasing severity as the glomerular filtration rate decreases and characterized by a progressive increase in parathyroid hormone and growth of the parathyroid glands. It is generally accepted that a deficiency in active form of vitamin D or calcitriol levels seems to play a relevant role in its development and progression of secondary hyperparathyroidism. A reduction in plasma calcitriol levels occurs early in renal disease. Major renal guidelines recommend use of vitamin D for secondary hyperparathyroidism in chronic kidney disease. In the treatment vitamin D receptor activation inhibit glandular hyperplasia; reduce parathyroid hormone levels impact on bone turnover and mineral density. Treatment with calcitriol can occasionally result in hypercalcemia and hyperphosphatemia in renal patients due promotes intestinal calcium and phosphorus absorption. This limits its suitability for the treatment. But next generation vitamin-D analogs such as paricalcitol have lower intestinal absorption of calcium, phosphorous and significantly lowers renin levels, albuminuria and blood pressure.
 In this article, we present the case of a Caucasian male with type 2 diabetes and secondary hyperparathyroidism in stages 34 chronic kidney disease. Our case study shows that in treating for secondary hyperparathyroidisms selective vitamin D receptor activation with paricalcitol reduction of levels parathyroid hormone, albuminuria, offering low chance hypercalcemia, hyperphosphatemia and other side effects.

Extended-release calcifediol for secondary hyperparathyroidism in stage 3-4 chronic kidney disease

ABSTRACTIntroduction: Extended-release calcifediol (ERC) 30 µg capsules were recently approved as Rayaldee® by the United States Food and Drug Administration (FDA) for the treatment of secondary hyperparathyroidism (SHPT) in adults with stage 3–4 (not 5) chronic kidney disease (CKD) and vitamin D insufficiency (serum total 25-hydroxyvitamin D < 30 ng/mL). Calcifediol is 25-hydroxyvitamin D3, a prohormone of calcitriol (1,25-dihydroxyvitamin D3), the endogenous active vitamin D hormone. ERC capsules have a lipophilic fill which gradually releases calcifediol, corrects vitamin D insufficiency and increases serum calcitriol and thereby suppresses production of parathyroid hormone (PTH) in CKD patients without perturbing normal vitamin D and mineral metabolism.Areas covered: This review focuses on the chemical, pharmacokinetic, pharmacodynamic and clinical profiles of ERC and describes the product’s utility relative to other current treatment options for SHPT.Expert commentary: Randomized clinical trials (RCTs) have demonstrated that nutritional vitamin D is ineffective for treating SHPT whereas vitamin D receptor activators can correct elevated PTH but with increased risk of hypercalcemia and hyperphosphatemia. ERC offers healthcare professionals a new treatment option that has been demonstrated in RCTs to be safe and effective for controlling SHPT without meaningfully increasing serum concentrations of calcium or phosphorus.

Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease

Background/Aims: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. Methods: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. Results: ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. Conclusion: Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD.

Vitamin D and Stage 5 Chronic Kidney Disease: A New Paradigm?

Vitamin D receptor agonists (VDRA) are currently recommended for the treatment of secondary hyperparathyroidism in stage 5 CKD. They are considered to be contraindicated in the presence of low or normal (for a dialysis patient) levels of PTH due to the risk of developing adynamic bone disease, with consequent vascular calcification. However, these recommendations are increasingly at odds with the epidemiological evidence, which consistently shows a large survival advantage for patients treated with low-dose VDRAs, regardless of plasma calcium, phosphate, or PTH. A large number of pleiotropic effects of vitamin D have been described, including inhibition of renin activity, anti-inflammation, and suppression of vascular calcification stimulators and stimulation of vascular calcification inhibitors present in the uremic milieu. Laboratory studies suggest that a normal cellular vitamin D level is necessary for normal cardiomyocyte and vascular smooth muscle function. While pharmacological doses of VDRA can be harmful, the present evidence suggests that the level of 1,25-dihydroxycholecalciferol should also be more physiological in stage 5 CKD, and that widespread use of low-dose VDRA would be beneficial. A randomized controlled trial to test this hypothesis is warranted.

Cinacalcet should be used to treat secondary hyperparathyroidism in stage 3–4 chronic kidney disease

This, the second of two opposing Viewpoints, presents the case for the use of cinacalcet for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease who are not receiving dialysis. The authors assert that cinacalcet effectively reduces serum parathyroid hormone level in this setting, and that any adverse effects of the drug on calcium or phosphorus levels can be managed by monitoring and treating patients accordingly.

Cinacalcet should not be used to treat secondary hyperparathyroidism in stage 3–4 chronic kidney disease

In the first of two opposing Viewpoints, Daniel W Coyne questions the use of cinacalcet to treat secondary hyperparathyroidism in non-dialysis-dependent patients with chronic kidney disease. He highlights the absence of FDA approval and the lack of published data for cinacalcet in this setting. Cinacalcet does not, he argues, address a universal pathophysiologic feature of secondary hyperparathyroidism; in addition, it has considerable adverse effects.

Effect of Depot Oral Cholecalciferol Treatment on Secondary Hyperparathyroidism in Stage 3 and Stage 4 Chronic Kidney Diseases Patients

By the time patients require dialysis replacement therapy, nearly all chronic kidney diseases (CKD) patients are affected with uremic bone diseases. High-turnover osteodystrophy can be prevented; patients with CKD should be monitored for imbalances in calcidiol (25 OH vitamin D), calcium, and phosphate homeostasis. We aimed to determine the effect of a monthly oral 300,000 IU vitamin D3 (cholecalciferol) supplementation on the uremic bone diseases (UBD) markers such as iPTH and alkaline phosphatase in CKD patients. Among a total of 70 patients under treatment in the nephrology unit, 40 predialysis CKD patients (mean age of 49 ± 14, male/female 20/20) were included the study. The patients were randomly divided into two groups. Treatment group included 20 patients (mean age of 51 ± 14, male/female 9/11), and the control group comprised 20 patients (mean age of 47 ± 14, male/female 9/11). Treatment group patients were given a single dose of Devit3 ampoule (300,000 U cholecalciferol) per month orally way. Patients in the control group did not take any vitamin D for a month. The level of calcidiol was lower than normal range in two groups. After a month, treatment group patient's calcidiol increased statistically significant (6.8 ± 3.5 to 17.8 ± 21.4 ng/mL, p < 0.001). After a month, iPTH level decreased in the treatment group statistically significantly (368 ± 274 to 279 ± 179 pg/ml, p < 0.001). At the 30th day of the treatment, in 9/20 of the treatment group patients (45%), the iPTH value decreased at least 30% (p < 0.001). We suggest that oral depot cholecalciferol treatment causes a statistically significant decrease of serum iPTH level but does not cause a statistically significant change in Ca, P, ratio of Ca × P, or urinary calcium creatinine rate in UBD predialysis CKD. This treatment can be used safely for the predialysis CKD patients, along with the cautious control of serum calcium and phosphor.

Paricalcitol Capsule for the Treatment of Secondary Hyperparathyroidism in Stages 3 and 4 CKD

The safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 5. The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD. Three randomized, placebo-controlled, phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT. Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2 (0.25 and 1.00 mL/s/1.73 m2), an average of 2 consecutive intact parathyroid hormone (iPTH) levels greater than 150 pg/mL (ng/L), 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL (2.00 and 2.50 mmol/L), and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less (< or = 1.68 mmol/L). Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks. Dosing was based on serum iPTH, calcium, and phosphorus levels. The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30% from baseline. Two hundred twenty patients participated (n = 107, paricalcitol; n = 113, placebo). At least 2 consecutive decreases in iPTH levels of 30% or greater from baseline occurred in 91% of paricalcitol versus 13% of placebo patients (P < 0.001). Incidences of hypercalcemia, hyperphosphatemia, and elevated calcium-phosphorus product levels were not significantly different between groups. Similarly, no significant differences in urinary calcium and phosphorus excretion or deterioration in kidney function were detected in patients administered paricalcitol compared with placebo. Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels, phosphorus balance, and kidney function in patients with stages 3 and 4 CKD.

Cinacalcet HCl: A novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease

Cinacalcet HCl: A novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease. Background Chronic kidney disease (CKD) alters the regulation of calcium and phosphate homeostasis, leading to secondary hyperparathyroidism, metabolic bone disease, soft tissue calcifications, and other metabolic derangements that have a significant impact on morbidity and mortality. The parathyroid gland is the central organ responsible for regulating these adaptive responses. Suppression of parathyroid hormone (PTH) secretion, hypertrophy, and hyperplasia are a major goal of treatment of CKD. Methods Current literature was reviewed and combined with the author's experience to address a number of issues regarding the optimal treatment of secondary hyperparathyroidism in hemodialysis patients. Results The calcium sensing receptor (CASR) is the most important factor regulating parathyroid gland function, and allosteric modulators of CASR, called calcimimetics, provide a novel drug therapy to suppress PTH secretion. The current use of active vitamin D analogues to suppress PTH is often limited by hypercalcemia and hyperphosphatemia. Clinical trials of cinacalcet HCl, the first calcimimetic to be approved for treatment of secondary hyperparathyroidism in CKD, have demonstrated suppression of circulating PTH levels without increments in the calcium-phosphorus (Ca × P) product, making it easier to achieve the stringent management guidelines proposed for subjects with CKD by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI™). Conclusion The management of disordered calcium and phosphate homeostasis in CKD patients is evolving based on our knowledge of the major importance of the calcium sensing receptor (CASR) in controlling parathyroid gland function and the potent actions of calcimimetics to target CASR. The purpose of this presentation is to provide an overview of the role of the CASR in regulation of parathyroid gland function, to examine the mechanisms whereby calcimimetics target the CASR, and to review the clinical trials that support the use of cinacalcet HCl for the treatment of secondary hyperparathyroidism in stage 5 chronic kidney disease (CKD).