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https://www.readbyqxmd.com/read/29780355/therapeutic-interference-with-vascular-calcification-lessons-from-klotho-hypomorphic-mice-and-beyond
#1
REVIEW
Florian Lang, Christina Leibrock, Lisann Pelzl, Meinrad Gawaz, Burkert Pieske, Ioana Alesutan, Jakob Voelkl
Medial vascular calcification, a major pathophysiological process associated with cardiovascular disease and mortality, involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). In chronic kidney disease (CKD), osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification is mainly driven by hyperphosphatemia, resulting from impaired elimination of phosphate by the diseased kidneys. Hyperphosphatemia with subsequent vascular calcification is a hallmark of klotho-hypomorphic mice, which are characterized by rapid development of multiple age-related disorders and early death...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29775762/aortic-vascular-calcification-is-inversely-associated-with-the-trabecular-bone-score-in-patients-receiving-dialysis
#2
Jasna Aleksova, Samantha Kurniawan, Mirna Vucak-Dzumhur, Peter Kerr, Peter R Ebeling, Frances Milat, Grahame J Elder
INTRODUCTION: Progressive chronic kidney disease (CKD) confers a marked increase in risk for vascular calcification, cardiovascular disease, fracture and mortality, with likely contributing factors including dysregulated bone metabolism and mineral homeostasis. In general population studies, increased vascular calcification is directly related to mortality and inversely related to bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). In patients with CKD, abnormalities in turnover, mineralization and bone volume, reduce the ability of DXA to predict fracture...
May 15, 2018: Bone
https://www.readbyqxmd.com/read/29764395/longitudinal-changes-in-bone-and-mineral-metabolism-after-cessation-of-cinacalcet-in-dialysis-patients-with-secondary-hyperparathyroidism
#3
Irene Ruderman, Edward R Smith, Nigel D Toussaint, Tim D Hewitson, Stephen G Holt
BACKGROUND: The calcimimetic agent cinacalcet is effective for the management of secondary hyperparathyroidism (SHPT) in dialysis patients. Changes to reimbursement of cinacalcet in Australia provided an opportunity to assess effects of medication cessation on biochemical and clinical outcomes in dialysis patients, including changes to novel biomarkers such as calciprotein particles (CPP). CPP are nanoparticles of mineral and protein in the circulation associated with increased vascular calcification in patients with chronic kidney disease...
May 15, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29763365/effect-of-cross-linked-chitosan-iron-iii-on-vascular-calcification-in-uremic-rats
#4
Barbara Bruna Abreu de Castro, Wander Barros do Carmo, Paulo Giovani de Albuquerque Suassuna, Moises Carminatti, Julia Bianchi Brito, Wagner Vasques Dominguez, Ivone Braga de Oliveira, Vanda Jorgetti, Melani Ribeiro Custodio, Helady Sanders-Pinheiro
Cross-linked chitosan iron (III) is a chitin-derived polymer with a chelating effect on phosphorus, but it is untested in vascular calcification. We evaluated this compound's ability to reduce hyperphosphatemia and its effect on vascular calcification in uremic rats using an adenine-based, phosphorus-rich diet for seven weeks. We used a control group to characterize the uremia. Uremic rats were divided according the treatment into chronic kidney disease, CKD-Ch-Fe(III)CL (CKD-Ch), CKD-calcium carbonate, or CKD-sevelamer groups...
May 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29753400/updates-on-the-mechanisms-and-the-care-of-cardiovascular-calcification-in-chronic-kidney-disease
#5
REVIEW
Lucie Hénaut, Jean-Marc Chillon, Saïd Kamel, Ziad A Massy
In chronic kidney disease (CKD), the progressive decrease in renal function leads to disturbances of mineral metabolism that generally cause secondary hyperparathyroidism. The increase in serum parathyroid hormone is associated with reduced serum calcium and calcitriol levels and/or increased serum fibroblast growth factor-23 and phosphate levels. The resulting CKD-associated disorder of mineral and bone metabolism is associated with various other metabolic dysregulations such as acidosis, malnutrition, inflammation, and accumulation of uremic toxins...
May 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29742957/abnormalities-of-vascular-histology-and-collagen-fiber-configuration-in-patients-with-advanced-chronic-kidney-disease
#6
Michael Allon, Silvio H Litovsky, Jason Chieh Sheng Tey, Chad A Sundberg, Yingying Zhang, Zhen Chen, Yun Fang, Alfred K Cheung, Yan-Ting Shiu
INTRODUCTION: Several histologic features have been identified in the upper-extremity arteries and veins of patients with advanced chronic kidney disease, which may affect arteriovenous fistula maturation. However, it is unclear whether these chronic kidney disease vascular features are abnormal. METHODS: We obtained upper-extremity arterial and venous specimens from 125 advanced chronic kidney disease patients undergoing arteriovenous fistula creation and from 15 control subjects...
May 1, 2018: Journal of Vascular Access
https://www.readbyqxmd.com/read/29733462/current-and-potential-therapeutic-strategies-for-the-management-of-vascular-calcification-in-patients-with-chronic-kidney-disease-including-those-on-dialysis
#7
REVIEW
Irene Ruderman, Stephen G Holt, Tim D Hewitson, Edward R Smith, Nigel D Toussaint
Patients with CKD have accelerated vascular stiffening contributing significantly to excess cardiovascular morbidity and mortality. Much of the arterial stiffening is thought to involve vascular calcification (VC), but the pathogenesis of this phenomenon is complex, resulting from a disruption of the balance between promoters and inhibitors of calcification in a uremic milieu, along with derangements in calcium and phosphate metabolic pathways. Management of traditional cardiovascular risk factors to reduce VC may be influential but has not been shown to significantly improve mortality...
May 7, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29716795/metformin-prevents-the-development-of-severe-chronic-kidney-disease-and-its-associated-mineral-and-bone-disorder
#8
Ellen Neven, Benjamin Vervaet, Kerstin Brand, Ulrike Gottwald-Hostalek, Britt Opdebeeck, Annelies De Maré, Anja Verhulst, Jean-Daniel Lalau, Said Kamel, Marc E De Broe, Patrick C D'Haese
Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular calcification and renal osteodystrophy, an entity called 'CKD-Mineral and Bone Disorder' (CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable effects on progressive, severe CKD and concomitant mineral metabolism disturbances. Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with 200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe, stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these rats which led to arterial calcification and high bone turnover disease...
April 28, 2018: Kidney International
https://www.readbyqxmd.com/read/29701175/sclerostin-is-not-associated-with-cardiovascular-event-or-fracture-in-kidney-transplantation-candidates
#9
Hanne Skou Jørgensen, Simon Winther, Laust Dupont, Morten Bøttcher, Lars Rejnmark, Ellen-Margrethe Hauge, My Svensson, Per Ivarsen
BACKGROUND: Sclerostin, a bone-derived protein, has been linked to cardiovascular calcifications in chronic kidney disease (CKD). The aim of this study was to investigate the associations between sclerostin and mineral and bone disorder in CKD, specifically whether sclerostin levels could predict cardiovascular event, fracture, or all-cause mortality. MATERIALS AND METHODS: Kidney transplantation candidates (n = 157) underwent computed tomography scans of the chest, abdomen, and pelvis...
April 27, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29689558/fibulin-3-attenuates-phosphate-induced-vascular-smooth-muscle-cell-calcification-by-inhibition-of-oxidative-stress
#10
Trang T D Luong, Nadeshda Schelski, Beate Boehme, Manousos Makridakis, Antonia Vlahou, Florian Lang, Burkert Pieske, Ioana Alesutan, Jakob Voelkl
BACKGROUND/AIMS: Fibulin-3, an extracellular matrix glycoprotein, inhibits vascular oxidative stress and remodeling in hypertension. Oxidative stress is prevalent in chronic kidney disease (CKD) patients and is an important mediator of osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells (VSMCs) during hyperphosphatemia. Therefore, the present study explored the effects of Fibulin-3 on phosphate-induced vascular calcification. METHODS: Experiments were performed in primary human aortic smooth muscle cells (HAoSMCs) treated with control or with phosphate without or with additional treatment with recombinant human Fibulin-3 protein or with hydrogen peroxide as an exogenous source of oxidative stress...
April 18, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29689070/fti-277-inhibits-smooth-muscle-cell-calcification-by-up-regulating-pi3k-akt-signaling-and-inhibiting-apoptosis
#11
Arvind Ponnusamy, Smeeta Sinha, Gareth D Hyde, Samantha J Borland, Rebecca F Taylor, Emma Pond, Heather J Eyre, Colette A Inkson, Andrew Gilmore, Nick Ashton, Philip A Kalra, Ann E Canfield
BACKGROUND: Vascular calcification is associated with increased cardiovascular morbidity and mortality in patients with atherosclerosis, diabetes and chronic kidney disease. However, no viable treatments for this condition have been identified. This study aimed to determine whether farnesyl transferase inhibitors (FTIs) can reduce vascular calcification and the mechanism by which this reduction occurs. RESULTS: We demonstrate that FTI-277 significantly inhibits phosphate-induced mineral deposition by vascular smooth muscle cells (VSMC) in vitro, prevents VSMC osteogenic differentiation, and increases mRNA expression of matrix Gla protein (MGP), an inhibitor of mineralization...
2018: PloS One
https://www.readbyqxmd.com/read/29672176/prevalence-and-risk-factors-for-vascular-calcification-in-chinese-patients-receiving-dialysis-baseline-results-from-a-prospective-cohort-study
#12
Zhi-Hong Liu, Xue-Qing Yu, Jun-Wei Yang, Ai-Li Jiang, Bi-Cheng Liu, Chang-Ying Xing, Ji-Zhuang Lou, Mei Wang, Hong Cheng, Jun Liu, Jun-Zhou Fu, Ai-Hua Zhang, Miao Zhang, Qiao-Ling Zhou, Chen Yu, Rong Wang, Li Wang, Yu-Qing Chen, Tian-Jun Guan, Ai Peng, Chen Nan, Chuan-Ming Hao, Xu-Yang Cheng
OBJECTIVE: With limited data available on calcification prevalence in chronic kidney disease (CKD) patients on dialysis, the China Dialysis Calcification Study (CDCS) determined the prevalence of vascular/valvular calcification (VC) and association of risk factors in Chinese patients with prevalent hemodialysis (HD) or peritoneal dialysis (PD). METHODS: CKD patients undergoing HD/PD for ≥6 months were enrolled. Prevalence data for calcification and medical history were documented at baseline...
April 19, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29661746/effects-of-oral-vitamin-d-3-supplementation-in-stage-3-chronic-kidney-disease-subjects-insulin-resistance-syndrome-and-hormonal-disturb-interactions
#13
Amina Tahar, Faiza Zerdoumi, Messaoud Saidani, Lakhdar Griene, Elhadj-Ahmed Koceir
The 1-25-hydroxyvitamine D (1-25OHD) or calcitriol deficiency in chronic kidney disease (CKD) patients was associated with increases vascular calcification risk, nephrons reduction, bone deficit and cardiovascular mortality by atherosclerosis. The objective of this study was to investigate the pleiotropic effects of 200.000 IU (D200 group) every 3 months versus 30.000 IU (D30 group) every month dose vitamin D supplementation in stage 3 CKD patients. A cohort of 132 adult subjects was randomized into 2 groups according to dose vitamin D supplementation in deficient subjects (25OHD <50 nmol/L or <20 ng/mL)...
April 16, 2018: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29622969/relationship-between-serum-osteoprotegerin-and-vascular-calcifications-in-hemodialysis-patients
#14
Tarek Z El Baz, Osama A Khamis, Amal El-Shehaby, Hussein Chahine, Ahmad Alaa Al-Din Ahmed, Mostafa A Alsawasany
Background: Uremia is a vasculopathic process, and both cardiac calcification and vascular calcification seen from the early stages of chronic kidney disease. Osteoprotegerin could play a crucial role in atherosclerotic plaque formation, maturation and calcification. The goal of this study was to determine the relationship of serum osteoprotegerin with vascular calcification in patients with end stage kidney disease who were maintained on regular hemodialysis. Methods: Sixty clinically stable chronic renal failure patients undergoing regular hemodialysis were enrolled in this cross sectional study...
June 2017: The Egyptian heart journal: (EHJ): official bulletin of the Egyptian Society of Cardiology
https://www.readbyqxmd.com/read/29619868/fibroblast-growth-factor-23-is-a-strong-predictor-of-insulin-resistance-among-chronic-kidney-disease-patients
#15
Ahmed Fayed, Mahmoud M El Nokeety, Ahmed A Heikal, Dina O Abdulazim, Mervat M Naguib, Usama A A Sharaf El Din
Insulin resistance (IR) is very common among chronic kidney disease (CKD) patients. Disturbance in mineral and bone metabolism (MBD) seems to play a role in the pathogenesis of insulin resistance. Fibroblast growth factor-23 (FGF23) is evolving as the most important link between MBD and many pathologic sequences of CKD. The aim was to evaluate IR in pre-dialysis CKD patients looking for a possible association to mineral metabolism among CKD patients. A total of 100 stage 3-5 CKD patients were selected beside 20 normal control subjects...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29603070/high-calcium-phosphate-and-calcitriol-supplementation-leads-to-an-osteocyte-like-phenotype-in-calcified-vessels-and-bone-mineralisation-defect-in-uremic-rats
#16
Sarah-Kim Bisson, Roth-Visal Ung, Sylvain Picard, Danika Valade, Mohsen Agharazii, Richard Larivière, Fabrice Mac-Way
A link between vascular calcification and bone anomalies has been suggested in chronic kidney disease (CKD) patients with low bone turnover disease. We investigated the vascular expression of osteocyte markers in relation to bone microarchitecture and mineralization defects in a model of low bone turnover CKD rats with vascular calcification. CKD with vascular calcification was induced by 5/6 nephrectomy followed by high calcium and phosphate diet, and vitamin D supplementation (Ca/P/VitD). CKD + Ca/P/VitD group (n = 12) was compared to CKD + normal diet (n = 12), control + normal diet (n = 8) and control + Ca/P/VitD supplementation (n = 8)...
March 30, 2018: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/29584693/is-matrix-gla-protein-associated-with-vascular-calcification-a-systematic-review
#17
REVIEW
Hilary Barrett, Mary O'Keeffe, Eamon Kavanagh, Michael Walsh, Eibhlís M O'Connor
Specific patient cohorts are at increased risk of vascular calcification. Functional matrix-gla protein (MGP), a tissue-derived vitamin K dependent protein, is reported to be an important inhibitor of vascular calcification and may have clinical potential to modify the progression of vascular calcification through regulation of functional MGP fractions. This systematic review examines twenty-eight studies which assess the relationship between circulating protein expressions of MGP species and vascular calcification in different arterial beds...
March 27, 2018: Nutrients
https://www.readbyqxmd.com/read/29580636/pyrophosphate-deficiency-in-vascular-calcification
#18
REVIEW
Ricardo Villa-Bellosta, W Charles O'Neill
Pathologic cardiovascular calcification is associated with a number of conditions and is a common complication of chronic kidney disease. Because ambient calcium and phosphate levels together with properties of the vascular matrix favor calcification even under normal conditions, endogenous inhibitors such as pyrophosphate play a key role in prevention. Genetic diseases and animal models have elucidated the metabolism of extracellular pyrophosphate and demonstrated the importance of pyrophosphate deficiency in vascular calcification...
March 24, 2018: Kidney International
https://www.readbyqxmd.com/read/29566379/apabetalone-mediated-epigenetic-modulation-is-associated-with-favorable-kidney-function-and-alkaline-phosphatase-profile-in-patients-with-chronic-kidney-disease
#19
Ewelina Kulikowski, Christopher Halliday, Jan Johansson, Mike Sweeney, Kenneth Lebioda, Norman Wong, Mathias Haarhaus, Vincent Brandenburg, Srinivasan Beddhu, Marcello Tonelli, Carmine Zoccali, Kamyar Kalantar-Zadeh
BACKGROUND/AIMS: The association between serum alkaline phosphatase (ALP) with adverse cardiovascular outcomes, in Chronic Kidney Disease (CKD) patients has previously been reported and may be a result of increased vascular calcification and inflammation. Here we report, for the first time, the effects of pharmacologic epigenetic modulation on levels of ALP and kidney function via a novel oral small molecule BET inhibitor, apabetalone, in CKD patients. METHODS: A post-hoc analysis evaluated patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1...
March 16, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29563538/ucma-grp-inhibits-phosphate-induced-vascular-smooth-muscle-cell-calcification-via-smad-dependent-bmp-signalling
#20
Brecht A Willems, Malgorzata Furmanik, Marjolein M J Caron, Martijn L L Chatrou, Dennis H M Kusters, Tim J M Welting, Michael Stock, Marta S Rafael, Carla S B Viegas, Dina C Simes, Cees Vermeer, Chris P M Reutelingsperger, Leon J Schurgers
Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification...
March 21, 2018: Scientific Reports
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