Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/9740
A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma
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ISSN: 2045-2322
WOS ID: 000425968800009
Scopus EID: 2-s2.0-85026633228
PMID: 28761091
Embase PUI: L626151092
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2017-07-31Document type
research articleCitation
Ferrer Reynés MD, Perez MM, Canaves MM, Buades-Reine'S JM, Salcedo C, Perello Bestard J. A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma. Sci Rep. 2017 Jul 31;7:68581.Abstract
Cardiovascular calcification (CVC) is a progressive complication of chronic kidney disease and a predictor of CV events and mortality. The use of bionarkers to predict CV risk and activities of potential or current treatment drugs in these patients could have a crucial impact on therapeutic approaches. Our aim was to develop a novel assay for measurement of the rate of calcium phosphate crystallization in human plasma and provide a tool to evaluate the effects of crystallization inhibitors. The efficacy of inhibitors was determined by adding inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to control samples. The assay was additionally validated for SNF472, an experimental formulation of phytate being developed for the treatment of calciphylaxis and CVC in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The method was repeatable and reproducible. The plasma crystallization rate was reduced up to 80% in a concentration-dependent manner following treatment with inhibitors in vitro, among which SNF472 was the most potent. This method appears beneficial in evaluating and discriminating between inhibitory activities of compounds such as polyphosphates on calcium phosphate crystallization, which present a novel therapeutic approach to treat CVC in ESRD patients.
Publisher version
https://dx.doi.org/10.1038/s41598-017-07203-xMeSH
Calcium Chelating AgentsMale
Rats
Animals
Humans
Plasma
Spectrophotometry
Calciphylaxis
Rats, Sprague-Dawley
Calcium Phosphates
Drug Evaluation, Preclinical
DeCS
AnimalesEvaluación Preclínica de Medicamentos
Ratas
Ratas Sprague-Dawley
Humanos
Quelantes del Calcio
Calcifilaxia
Plasma
Fosfatos de Calcio
Masculino
Espectrofotometría
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Instituto de Investigación Sanitaria Islas Baleares - IDISBA > Comunicación científicaHospital Universitario Son Llàtzer - HUSLL > Comunicación científica