Impact of Cinacalcet and Etelcalcetide on Bone Mineral and Cardiovascular Disease in Dialysis Patients

Bernardor, Julie; Mul, Aurélie De; Bacchetta, Justine; Schmitt, Claus Peter

doi:10.1007/s11914-023-00782-x

Cited by 5 publications

(4 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Still, we observed consistent and distinct changes in serum levels of CPM and CPP, supporting the hypothesis that bone is a significant source of these particles in hemodialysis with bone disease. Given that high CPP levels have been associated with vascular stiffness[ 35 ] and calcification [ 36 , 37 ], and an increased cardiovascular morbidity and mortality in patients with chronic kidney disease [ 12 , 38 ], lowering CPP levels could contribute to improved outcomes of these patients.…”

Section: Discussionmentioning

confidence: 99%

The effect of parathyroid hormone lowering by etelcalcetide therapy on calcification propensity and calciprotein particles in hemodialysis patients

Thiem,

Lenz,

Haller

et al. 2024

Clinical Kidney Journal

View full text Add to dashboard Cite

Background This study investigated whether parathyroid hormone (PTH) lowering with etelcalcetide, and the consequent effects on mineral and bone metabolism, could improve serum calcification propensity (T50 time) and decrease calciprotein particle (CPP) load in hemodialysis patients with secondary hyperparathyroidism. Methods In this single-arm, prospective, dose-escalation proof-of-principle study, hemodialysis patients received etelcalcetide at 2.5 mg/dialysis session with increments of 2.5 mg every four weeks to a maximum dose of 15 mg thrice weekly or until a pre-specified safety endpoint was reached, followed by an eight-week washout phase. Results Out of 36 patients recruited (81% male, 62±13 years), 16 patients completed the study per protocol with a mean maximum tolerated dose of etelcalcetide of 9.5±2.9 mg/dialysis session. With escalating doses of etelcalcetide, PTH and serum calcium levels significantly decreased (p<0.0001). While there was no significant change in T50 times or serum phosphate levels, etelcalcetide did yield significant and consistent reductions in serum levels of endogenous calciprotein monomers [-35.4 (-44.4 to -26.5)%, p<0.0001], primary [-22.4 (-34.5 to -10.3)%, p<0.01] and secondary CPP [-29.1 (-45.7 to -12.4)%, p<0.01], an effect that was reversed after therapy withdrawal. Serum levels of osteoclastic markers significantly decreased with escalating doses of etelcalcetide, while levels of the osteoblastic marker remained stable. Conclusions Lowering of PTH with etelcalcetide did not result in statistically significant changes in T50. In contrast, homogenous reductions in serum levels of calciprotein monomers, primary and secondary CPP were observed.

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of parathyroid hormone lowering by etelcalcetide therapy on calcification propensity and calciprotein particles in hemodialysis patients

Thiem,

Lenz,

Haller

et al. 2024

Clinical Kidney Journal

View full text Add to dashboard Cite

show abstract

“…The associated healthcare costs and consequences for patients are considerable, contributing to remarkably high levels of morbidity and mortality. The potential synergistic effects of these treatments on bone health need, however, further exploration, with considerations made for underlying mechanisms [25,26].…”

Section: Discussionmentioning

confidence: 99%

Fragility Fractures in End-Stage Chronic Kidney Disease (CKD) Population: Patient-Related and CKD-Related Factor Analysis—A Single-Center Experience

De Mauro,

De Luca,

Marino

et al. 2024

JCM

View full text Add to dashboard Cite

Background: Chronic kidney disease (CKD) stands as a prevalent global health concern, and mineral and bone disease are among the most impactful consequences. A severe complication arising from mineral and bone disease is the occurrence of fragility fractures, which disproportionately affect individuals with CKD compared to the general population. The prevalence of these fractures impacts both survival rates and quality of life. The aims of this study are analyzing and identifying (i) patient-related risk factors and (ii) CKD-related risk factors to contribute to the development of preventive measures for fragility fractures for this population. Methods: A retrospective, single-center observational study was conducted, encompassing patient data from the years 2021 to 2023. Registry data were recorded, including patient-related and CKD-related data. Patients were interviewed about traumatological history, and their answers were recorded. Logistic regression analysis was employed to investigate the association between independent variables and dependent variables. Results: Eighty-four patients, with a mean age of 64.3 ± 15.2 years and a male percentage of 58.3%, were included in this study. Among them, 19.5% exhibited smoking habits. The mean Charlson Comorbidity Index was 3.06 ± 1.21. All patients were diagnosed with end-stage chronic kidney disease, with mean durations of 208 months from the diagnosis and 84.5 months from the beginning of dialysis. The logistic regression analysis, adjusted for age, sex, and CCI, revealed that smoking habits play a significant role as a risk factor for fragility fractures in lower limbs (p: 0.011 *). The incidence of fragility fractures increases directly proportionally to the time since diagnosis (p-value: 0.021 *) and the beginning of dialysis treatment (p-value: 0.001 *). Conclusions: Among patient-related factors, smoking habits seem to significantly affect lower-limb fracture rates (p < 0.05), whereas among CKD-related factors, time since CKD diagnosis and time since the beginning of dialysis treatment are directly related to higher risks of fragility fractures. No relevant correlations emerged in the studied treatments, except for a reduction in proximal femur fracture occurrence when patients underwent a combined treatment of a calcimimetic and a vitamin D analog.

show abstract

“…Данные ЛП снижают количество частиц кальципротеина в сыворотке крови, которые участвуют в патогенезе формирования эндотелиальной дисфункции, атерогенеза и кальцификации сосудов. Клинические исследования на взрослых предполагают умеренное замедление прогрессирования сердечно-сосудистой кальцификации при применении цинакальцета [5]. В результате были сделаны выводы, что аллостерические модуляторы, которые специфически повышают чувствительность кальций-чувствительного рецептора, называемые кальцимиметиками, используемые в сочетании с активными метаболитами витамина D у взрослых пациентов на диализе, приводят к стойкому снижению уровня паратирео-АКТУАЛЬНЫЕ ОБЗОРЫ АКТУАЛЬНЫЕ ОБЗОРЫ идного гормона без повышенного уровня продукта кальция и фосфора.…”

Section: перспективы применения в реальной клинической практикеunclassified

“…В результате были сделаны выводы, что аллостерические модуляторы, которые специфически повышают чувствительность кальций-чувствительного рецептора, называемые кальцимиметиками, используемые в сочетании с активными метаболитами витамина D у взрослых пациентов на диализе, приводят к стойкому снижению уровня паратирео-АКТУАЛЬНЫЕ ОБЗОРЫ АКТУАЛЬНЫЕ ОБЗОРЫ идного гормона без повышенного уровня продукта кальция и фосфора. Если уровень кальция или фосфора в плазме высок при наличии повышенного уровня паратиреоидного гормона, кальцимиметики могут стать ЛП первого выбора [5]. У детей, находящихся на диализе, с персистирующим и тяжёлым гиперпаратиреозом при высоком уровне кальция, несмотря на традиционное лечение, включая активный витамин D, следует рассмотреть назначение цинокальцета, но с осторожностью ввиду недостаточных данных применения ЛП среди педиатрических пациентов [6].…”

Section: перспективы применения в реальной клинической практикеunclassified

Prospects for the use of allosteric drugs in real-world clinical practice

Svechkareva,

Kolbin

2023

MyRWD

View full text Add to dashboard Cite

While the clinical validity of the use of allosteric regulation is known, scientists are working on the discovery of new methods for the development of allosteric drugs that can modulate the functions of enzymes, depending on the desired therapeutic effect, and have a broader safety profile compared with alternative drugs. Allosteric modulators are of increasing interest in medicine, some of which are already used in the clinic and some can potentially be used in real-world clinical practice. This article summarizes the current knowledge about allosteric modulation of receptors and their clinical prospects.

show abstract

Impact of Cinacalcet and Etelcalcetide on Bone Mineral and Cardiovascular Disease in Dialysis Patients

Cited by 5 publications

References 68 publications

The effect of parathyroid hormone lowering by etelcalcetide therapy on calcification propensity and calciprotein particles in hemodialysis patients

The effect of parathyroid hormone lowering by etelcalcetide therapy on calcification propensity and calciprotein particles in hemodialysis patients

Fragility Fractures in End-Stage Chronic Kidney Disease (CKD) Population: Patient-Related and CKD-Related Factor Analysis—A Single-Center Experience

Prospects for the use of allosteric drugs in real-world clinical practice

Contact Info

Product

Resources

About