P1397LONG-TERM EFFICACY AND SAFETY OF ETELCALCETIDE IN HEMODIALYSIS PATIENTS WITH SEVERE SECONDARY HYPERPARATHYROIDISM

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Carlo Massimetti ◽  
David Micarelli ◽  
Sandro Feriozzi
Keyword(s):  
Vitamin D ◽  
Side Effects ◽  
Secondary Hyperparathyroidism ◽  
Phosphate Binders ◽  
Average Dose ◽  
Efficacy And Safety ◽  
Calcium Salts ◽  
Vitamin D Receptors ◽  
Symptomatic Hypocalcemia ◽  
Gastrointestinal Side Effects

Abstract Background and Aims Currently the therapeutic strategies most frequently used in the treatment of secondary hyperparathyroidism (SHPT) are represented by vitamin D receptors activators (VDRAs) and cinacalcet. However, both drugs have side effects that limit their use. Recently, in the treatment of SHPT has been introduced the etelcalcetide, a second generation calcimimetic given intravenously (i.v.). This new route of administration could improve adherence to therapy and reduce gastrointestinal side effects. The aim of the study was to evaluate the efficacy and safety of the etelcalcetide in hemodialysis (HD) patients with SHPT inadequately controlled with traditional therapy (cinacalcet and/or VDRAs), or who had side effects with cinacalcet, or that were not adherent to cinacalcet therapy. Method For this purpose we have selected 28 HD patients with inadequate control of SHPT (PTH > 500 pg / ml; range 502-2148 pg/ml). Serum albumin-corrected calcium (sCa), phosphate (P), calcium–phosphate product (Ca x P), and PTH were assessed monthly. Baseline 19 patients were taking stable doses of active vitamin D analogs and all patients were taking phosphate binders. Etelcalcetide was administered three times a week after each hemodialysis session. The starting dose was 2.5 or 5.0 mg and then adjusted between 2.5 and 10.0 mg according to sCa and PTH levels. Treatment was temporarily withheld for sCa <7.5 mg/dl, or symptomatic hypocalcemia and was subsequently resumed at a lower dose. The primary endpoint was a PTH reduction > 30% compared to baseline levels. Results At present 12 months have passed since the beginning of etelcalcetide therapy. In most patients PTH levels were reduced immediately after the start of therapy. After 12 months we observed a reduction > 30% in 82% of patients, meanly -54% with a range between – 22% and – 81%. On average PTH levels decreased from 1167±444 to 558±310 pg/ml (P<.001). Serum calcium significantly reduced already after one month of therapy settling on stable levels from the third month onward, sCa decreased from 9.7±0.4 to 9.2±0.5 mg/dl (P<.01). However, the percentage of patients treated with calcium salts rose from 21% at baseline to 44% at F-U, mean dose at F-U 1.8 ± 0.9 g/d, while the percent of patients treated with VDRAs increased from 68% to 91%. Serum phosphate decreased from 6.4±1.4 to 4.6±1.3 mg/dl (P<.001), Ca x P decreased from 60±13 to 42±12 mg2/dl2 (P<.001). The median average dose of etelcalcetide at F-U was 6.2 ± 1.7 mg/HD, with a range of 2.5-10.0 mg/HD. Throughout the study, the only side effect was asymptomatic hypocalcemia that required the use of calcium salts. There were no gastrointestinal adverse effects. Conclusion Our results confirm that in hemodialysis etelcalcetide therapy is effective and safe in the control of SHPT refractory to conventional therapy over a 1-year treatment period.

The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism

2005 ◽  
Vol 288 (2) ◽  
pp. F253-F264 ◽  
Author(s):  
Mariano Rodriguez ◽  
Edward Nemeth ◽  
David Martin
Keyword(s):  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Positive Impact ◽  
Mineral Metabolism ◽  
Current Treatment ◽  
Phosphate Binders ◽  
Parathyroid Cell ◽  
Calcium Sensing Receptor ◽  
Vitamin D Receptors ◽  
Calcium Sensing

Serum calcium levels are regulated by the action of parathyroid hormone (PTH). Major drivers of PTH hypersecretion and parathyroid cell proliferation are the hypocalcemia and hyperphosphatemia that develop in chronic kidney disease patients with secondary hyperparathyroidism (SHPT) as a result of low calcitriol levels and decreased kidney function. Increased PTH production in response to systemic hypocalcemia is mediated by the calcium-sensing receptor (CaR). Furthermore, as SHPT progresses, reduced expression of CaRs and vitamin D receptors (VDRs) in hyperplastic parathyroid glands may limit the ability of calcium and calcitriol to regulate PTH secretion. Current treatment for SHPT includes the administration of vitamin D sterols and phosphate binders. Treatment with vitamin D is initially effective, but efficacy often wanes with further disease progression. The actions of vitamin D sterols are undermined by reduced expression of VDRs in the parathyroid gland. Furthermore, the calcemic and phosphatemic actions of vitamin D mean that it has the potential to exacerbate abnormal mineral metabolism, resulting in the formation of vascular calcifications. Effective new treatments for SHPT that have a positive impact on mineral metabolism are clearly needed. Recent research shows that drugs that selectively target the CaR, calcimimetics, have the potential to meet these requirements.

Calcium and Vitamin D Supplementation. Myths and Realities with Regard to Cardiovascular Risk

2019 ◽  
Vol 17 (6) ◽  
pp. 610-617 ◽  
Author(s):  
Giovanna Muscogiuri ◽  
Luigi Barrea ◽  
Barbara Altieri ◽  
Carolina Di Somma ◽  
Harjit pal Bhattoa ◽  
...  
Keyword(s):  
Vitamin D ◽  
Side Effects ◽  
Secondary Hyperparathyroidism ◽  
Calcium Supplementation ◽  
Physiological Role ◽  
Bone Diseases ◽  
Current Evidence ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Muscle Health

Vitamin D and calcium are considered crucial for the treatment of bone diseases. Both vitamin D and calcium contribute to bone homeostasis but also preserve muscle health by reducing the risk of falls and fractures. Low vitamin D concentrations result in secondary hyperparathyroidism and contribute to bone loss, although the development of secondary hyperparathyroidism varies, even in patients with severe vitamin D deficiency. Findings from observational studies have shown controversial results regarding the association between bone mineral density and vitamin D/calcium status, thus sparking a debate regarding optimum concentrations of 25-hydroxyvitamin D and calcium for the best possible skeletal health. Although most of the intervention studies reported a positive effect of supplementation with calcium and vitamin D on bone in patients with osteoporosis, this therapeutic approach has been a matter of debate regarding potential side effects on the cardiovascular (CV) system. Thus, the aim of this review is to consider the current evidence on the physiological role of vitamin D and calcium on bone and muscle health. Moreover, we provide an overview on observational and interventional studies that investigate the effect of vitamin D and calcium supplementation on bone health, also taking into account the possible CV side-effects. We also provide molecular insights on the effect of calcium plus vitamin D on the CV system.

Calcimimetics for the Treatment of Secondary Hyperparathyroidism in Peritoneal Dialysis Patients

2008 ◽  
Vol 28 (2_suppl) ◽  
pp. 42-46 ◽  
Author(s):  
Jean Francis ◽  
David B. Simon ◽  
Peter Jeurgensen ◽  
Fredric O. Finkelstein
Keyword(s):  
Vitamin D ◽  
Peritoneal Dialysis ◽  
Secondary Hyperparathyroidism ◽  
Hormone Secretion ◽  
Phosphate Binders ◽  
Serum Phosphate Level ◽  
Dialysis Patients ◽  
Intravenous Vitamin ◽  
Stage Renal Disease ◽  
End Stage

Secondary hyperparathyroidism is a common complication in patients with end-stage renal disease. It has been associated with increased cardiovascular events and mortality. Traditional therapy has been based on vitamin D analogs and phosphate binders; but these therapies often do not control secondary hyperparathyroidism, particularly in peritoneal dialysis patients for whom phosphate clearances are limited and intravenous vitamin D is impractical. Cinacalcet, a calcimimetic, suppresses parathormone secretion by interacting with the calcium-sensing receptor on the surface of parathyroid gland cells. The resulting suppression of parathyroid hormone secretion produces a reduction in serum phosphate level and CaxPO4 product. The present paper reviews the efficacy of cinacalcet in the management of secondary hyperparathyroidism in peritoneal dialysis patients.

Albendazole: a review of anthelmintic efficacy and safety in humans

Parasitology ◽  
2000 ◽  
Vol 121 (S1) ◽  
pp. S113-S132 ◽  
Author(s):  
J. HORTON
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Strongyloides Stercoralis ◽  
Efficacy And Safety ◽  
Adverse Experiences ◽  
Ancylostoma Duodenale ◽  
Gastrointestinal Side Effects ◽  
Spectrum Activity ◽  
Cure Rates ◽  
General Community

This comprehensive review briefly describes the history and pharmacology of albendazole as an anthelminthic drug and presents detailed summaries of the efficacy and safety of albendazole's use as an anthelminthic in humans. Cure rates and % egg reduction rates are presented from studies published through March 1998 both for the recommended single dose of 400mg for hookworm (separately for Necator americanus and Ancylostoma duodenale when possible), Ascaris lumbricoides, Trichuris trichiura, and Enterobius vermicularis and, in separate tables, for doses other than a single dose of 400mg. Overall cure rates are also presented separately for studies involving only children 2–15 years. Similar tables are also provided for the recommended dose of 400mg per day for 3 days in Strongyloides stercoralis, Taenia spp. and Hymenolepis nana infections and separately for other dose regimens. The remarkable safety record involving more than several hundred million patient exposures over a 20 year period is also documented, both with data on adverse experiences occurring in clinical trials and with those in the published literature and/or spontaneously reported to the company. The incidence of side effects reported in the published literature is very low, with only gastrointestinal side effects occurring with an overall frequency of just >1%. Albendazole's unique broad-spectrum activity is exemplified in the overall cure rates calculated from studies employing the recommended doses for hookworm (78% in 68 studies: 92% for A. duodenale in 23 studies and 75% for N. americanus in 30 studies), A. lumbricoides (95% in 64 studies), T. trichiura (48% in 57 studies), E. vermicularis (98% in 27 studies), S. stercoralis (62% in 19 studies), H. nana (68% in 11 studies), and Taenia spp. (85% in 7 studies). The facts that albendazole is safe and easy to administer, both in treatment of individuals and in treatment of whole communities where it has been given by paramedical and nonmedical personnel, have enabled its use to improve general community health, including the improved nutrition and development of children.

scholarly journals Challenges in differential diagnosis between primary and secondary forms of hyperparathyroidism

2017 ◽  
Vol 14 (3) ◽  
pp. 48-53
Author(s):  
Natalia G. Mokrysheva ◽  
Anna K. Eremkina ◽  
Svetlana S. Mirnaya ◽  
Elena V. Kovaleva
Keyword(s):  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Clinical Laboratory ◽  
Hypovitaminosis D ◽  
Parathyroid Glands ◽  
Vitamin D Receptors ◽  
Calcium Sensing ◽  
Calcium Exchange ◽  
Excessive Secretion

Hyperparathyroidism is a disease characterized by excessive secretion of parathyroid hormone (PTH) in the chief cells of parathyroid glands. There are three types of hyperparathyroidism: primary, secondary, and tertiary depending on the cause of this disease. By the secondary hyperparathyroidism calcium-sensing receptors (CaSR) and vitamin D receptors (VDR) lead to disturbance of phosphorus-calcium exchange and to development of a parathyroid glands hyperplasia. Treatment of secondary hyperparathyroidism with vitamin D showed the efficiency not only in normalization of clinical laboratory indicators but also in involution of changes in parathyroid glands. We represent the clinical case of a patient with secondary hyperparathyroidism caused by hypovitaminosis D, parathyroid hyperplasia more than 1 cm. The long-term oral therapy with active vitamin D led to the positive dynamics of PTH levels, as well as complete reduction of parathyroid lesion.

scholarly journals Which Vitamin D in CKD-MBD? The Time of Burning Questions

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Andrea Galassi ◽  
Antonio Bellasi ◽  
Sara Auricchio ◽  
Sergio Papagni ◽  
Mario Cozzolino
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Myocardial Hypertrophy ◽  
Controlled Trials ◽  
Vitamin D Receptors ◽  
Randomized Controlled ◽  
The Impact ◽  
Nutritional Vitamin

Vitamin D is a common treatment against secondary hyperparathyroidism in renal patients. However, the rationale for the prescription of vitamin D sterols in chronic kidney disease (CKD) is rapidly increasing due to the coexistence of growing expectancies close to unsatisfactory evidences, such as (1) the lack of randomized controlled trials (RCTs) proving the superiority of any vitamin D sterol against placebo on patients centered outcomes, (2) the scanty clinical data on head to head comparisons between the multiple vitamin D sterols currently available, (3) the absence of RCTs confirming the crescent expectations on nutritional vitamin D pleiotropic effects even in CKD patients, (4) the promising effects of vitamin D receptors activators (VDRA) against proteinuria and myocardial hypertrophy in diabetic CKD cohorts, and (5) the conflicting data on the impact on mortality of VDRA versus calcimimetic centered regimens to control CKD-MBD. The present review arguments these issues focusing on the opened questions that nephrologists should consider dealing with the prescription of nutritional vitamin D or VDRA and with the choice of a VDRA versus a calcimimetic based regimen in CKD-MBD patients.

P1420IS THE CHANGE FROM CINACALCET TO ETELCALCETIDE SAFE AND EFFECTIVE IN PATIENTS ON HEMODIALYSIS WITH SECONDARY HYPERPARATHYROIDISM?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Fernando Hadad Arrascue ◽  
Alicia Araque ◽  
Ruth Amair ◽  
Florentina Rosique ◽  
Antonio Perez Perez ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Side Effects ◽  
Secondary Hyperparathyroidism ◽  
Safety Profile ◽  
First Generation ◽  
Progressive Increase ◽  
Chronic Hemodialysis ◽  
High Load ◽  
Calcium And Phosphorus

Abstract Background and Aims Vitamin D analogues stimulate the absorption of calcium and phosphorus, while calcimimetics reduce parathyroid hormone (PTH) without calcium and phosphorus elevation, which reduces the risk of vascular calcification. However, the biggest problem of first-generation calcimimetics is the lack of adherence due to abandonment or non-compliance due to side effects and the high load of tablets taken by our patients. Method A prospective and exploratory 24-week study, which included 54 adult patients on chronic hemodialysis (3 times per week) with secondary hyperparathyroidism (PTH >=150 pg/ml). Thirty-three patients were converted from cinacalcet to etelcalcetide, due to the lack of adherence to cinacalcet treatment and the inability to increase the dose due to the side effects of cinacalcet. The remaining 21 patients started etelcalcetide without previously taking cinacalcet. The dose of etelcalcetide was done according to the baseline PTH value. PTH >150 and <=300 pg/ml, started with 5 mg of etelcalcetide per week, PTH >300 and <=500 pg/ml with 7,5 mg/week, PTH > 500 and <= 800 pg /ml with 10 mg/week, PTH >800 pg/ml with 15mg/week. Results In the first four weeks, calcium decreased significantly, but subsequently remained stable for the rest of the study. From the baseline to the 24-week, serum calcium 8.85 ± 0.85 vs. 8.43 ± 0.83 mg/dl (p <0.05), serum phosphorus 4.64 ± 1.46 vs. 4.51 ± 2.2 mg/dl (p> 0.05). PTH decreased significantly at the end of the study (718.4 ± 450 vs. 391.3 ± 232.7 pg/ml, p =0.03). PTH was reduced by 42% in the group that changed cinacalcet to etelcalcetide, and 50% in the group that did not take calciomimetics before the study. At the beginning of the study, 61.1% of our sample also maintained paricalcitol as a treatment for secondary hyperparathyroidism. At the end of week 24, 51.8% maintained paricalcitol but with a significant reduction of 36.8% of the dose of paricalcitol (3.22 ± 3.78 mg/week), without significant changes in the dose of etelcalcetide at the end of the study (9.5 ± 1.3 mg/week) . No symptomatic hypocalcaemia was recorded throughout the study. At week 12, the dose of etelcalcetide was reduced in 11% of patients and 7% at the end of week 24 due asymptomatic hypocalcemia. Conclusion Etelcalcetide showed a significant reduction in PTH with the optimization of therapeutic compliance. In our population, the use of paricalcitol was reduced by 30% due to a progressive increase in the dose of etelcalcetide, keeping calcium levels stable and safe. Asymptomatic hypocalcemia was the most observed side effect, but it is claimed that etelcalcetide has an even better safety profile than cinacalcet, with respect to digestive side effects. It is advisable to use Etelcalcetide by individualizing the dose in each patient, depending on their levels of PTH and calcium.

scholarly journals The impact of cinacalcet in the mineral metabolism markers of patients on dialysis with severe secondary hyperparathyroidism

2019 ◽  
Vol 41 (3) ◽  
pp. 336-344
Author(s):  
Sérgio Gardano Elias Bucharles ◽  
Fellype Carvalho Barreto ◽  
Miguel Carlos Riella
Keyword(s):  
Vitamin D ◽  
Peritoneal Dialysis ◽  
Secondary Hyperparathyroidism ◽  
Mineral Metabolism ◽  
Phosphate Binders ◽  
Dialysis Patients ◽  
Active Vitamin ◽  
Ipth Level ◽  
Active Vitamin D ◽  
The Impact

Abstract Introduction: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. Methods: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. Results: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. Conclusion: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.

Secondary Hyperparathyroidism in End-Stage Renal Disease: No Longer a Matter for Surgeons?

2016 ◽  
Vol 42 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Mario Cozzolino ◽  
Francesca Elli ◽  
Stefano Carugo ◽  
Paola Ciceri
Keyword(s):  
Vitamin D ◽  
Renal Disease ◽  
Secondary Hyperparathyroidism ◽  
End Stage Renal Disease ◽  
Fibroblast Growth Factor 23 ◽  
Phosphate Binders ◽  
High Turnover ◽  
Skeletal Resistance ◽  
Stage Renal Disease ◽  
End Stage

Hyperphosphatemia, hypocalcemia and vitamin D deficiency are the main factors involved in the pathogenesis of secondary hyperparathyroidism (SHPT). Moreover, the skeletal resistance to parathyroid hormone is not only a high-turnover bone accompanying SHPT, but may also play a crucial role in the onset of low-turnover bone disease in uremia. However, a growing body of evidence suggests that other hormones play a key role in this disease, such as fibroblast growth factor 23, Klotho and sclerostin. SHPT causes both bone-associated and non-skeletal consequences, including cardiovascular calcifications. Furthermore, vitamin D and calcium (Ca)-containing phosphate binders may increase Ca load. Anyway, the rate of parathyroidectomy in end-stage renal disease has greatly decreased during the last decade. Is there any room left for surgeons?

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