SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels

Background Cardiovascular calcification (CVC) is a major concern in hemodialysis (HD) and the loss of endogenous modulators of calcification seems involved in the process. Phytate is an endogenous crystallization inhibitor and its low molecular mass and high water solubility make it potentially dial...

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Autores: Perello, Joan, Gomez, M., Ferrer, Miguel D., Rodriguez, N. Y., Salcedo, Carolina, Buades-Fuster, Juan Manuel, Perez, M. M., Torregrosa, José Vicente, Martin, E., Maduell, F.
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/9373
Acceso en línea:https://hdl.handle.net/20.500.13003/9373
Access Level:acceso abierto
Palabra clave:Dialysis Solutions
Vascular Calcification
Hemodiafiltration
Phytic Acid
Creatinine
Calcium
Humans
Renal Dialysis
Calcificación Vascular
Diálisis Renal
Hemodiafiltración
Ácido Fítico
Soluciones para Diálisis
Humanos
Calcio
Creatinina
Cardiovascular calcification
End-stage renal disease
Hemodialysis
Phytate
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spelling SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levelsPerello, JoanGomez, M.Ferrer, Miguel D.Rodriguez, N. Y.Salcedo, CarolinaBuades-Fuster, Juan ManuelPerez, M. M.Torregrosa, José VicenteMartin, E.Maduell, F.Dialysis SolutionsVascular CalcificationHemodiafiltrationPhytic AcidCreatinineCalciumHumansRenal DialysisCalcificación VascularDiálisis RenalHemodiafiltraciónÁcido FíticoSoluciones para DiálisisHumanosCalcioCreatininaCardiovascular calcificationEnd-stage renal diseaseHemodialysisPhytateBackground Cardiovascular calcification (CVC) is a major concern in hemodialysis (HD) and the loss of endogenous modulators of calcification seems involved in the process. Phytate is an endogenous crystallization inhibitor and its low molecular mass and high water solubility make it potentially dialyzable. SNF472 (the hexasodium salt of phytate) is being developed for the treatment of calciphylaxis and CVC in HD patients. We aimed to verify if phytate is lost during dialysis, and evaluate SNF472's behaviour during dialysis. Methods Dialyzability was assessed in vitro using online-hemodiafiltration and high-flux HD systems in blood and saline. SNF472 was infused for 20 min and quantified at different time points. Results Phytate completely dialyzed in 1 h at low concentrations (10 mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions, calcium was slightly chelated during SNF472 infusion but when the system was switched to dialysis mode the calcium in the bath compensated this chelation. Conclusion Phytate dialyses with a low clearance. The administration of SNF472 as an exogenous source of phytate allows to attain supra-physiological levels required for its potential therapeutic properties. As SNF472 is infused during the whole dialysis session, the low clearance would not affect the drug's systemic exposure.Springer Heidelberg20182018-04-0120182018-04-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/9373reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/93732026-06-22T12:44:07Z
dc.title.none.fl_str_mv SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels
title SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels
spellingShingle SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels
Perello, Joan
Dialysis Solutions
Vascular Calcification
Hemodiafiltration
Phytic Acid
Creatinine
Calcium
Humans
Renal Dialysis
Calcificación Vascular
Diálisis Renal
Hemodiafiltración
Ácido Fítico
Soluciones para Diálisis
Humanos
Calcio
Creatinina
Cardiovascular calcification
End-stage renal disease
Hemodialysis
Phytate
title_short SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels
title_full SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels
title_fullStr SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels
title_full_unstemmed SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels
title_sort SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels
dc.creator.none.fl_str_mv Perello, Joan
Gomez, M.
Ferrer, Miguel D.
Rodriguez, N. Y.
Salcedo, Carolina
Buades-Fuster, Juan Manuel
Perez, M. M.
Torregrosa, José Vicente
Martin, E.
Maduell, F.
author Perello, Joan
author_facet Perello, Joan
Gomez, M.
Ferrer, Miguel D.
Rodriguez, N. Y.
Salcedo, Carolina
Buades-Fuster, Juan Manuel
Perez, M. M.
Torregrosa, José Vicente
Martin, E.
Maduell, F.
author_role author
author2 Gomez, M.
Ferrer, Miguel D.
Rodriguez, N. Y.
Salcedo, Carolina
Buades-Fuster, Juan Manuel
Perez, M. M.
Torregrosa, José Vicente
Martin, E.
Maduell, F.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Dialysis Solutions
Vascular Calcification
Hemodiafiltration
Phytic Acid
Creatinine
Calcium
Humans
Renal Dialysis
Calcificación Vascular
Diálisis Renal
Hemodiafiltración
Ácido Fítico
Soluciones para Diálisis
Humanos
Calcio
Creatinina
Cardiovascular calcification
End-stage renal disease
Hemodialysis
Phytate
topic Dialysis Solutions
Vascular Calcification
Hemodiafiltration
Phytic Acid
Creatinine
Calcium
Humans
Renal Dialysis
Calcificación Vascular
Diálisis Renal
Hemodiafiltración
Ácido Fítico
Soluciones para Diálisis
Humanos
Calcio
Creatinina
Cardiovascular calcification
End-stage renal disease
Hemodialysis
Phytate
description Background Cardiovascular calcification (CVC) is a major concern in hemodialysis (HD) and the loss of endogenous modulators of calcification seems involved in the process. Phytate is an endogenous crystallization inhibitor and its low molecular mass and high water solubility make it potentially dialyzable. SNF472 (the hexasodium salt of phytate) is being developed for the treatment of calciphylaxis and CVC in HD patients. We aimed to verify if phytate is lost during dialysis, and evaluate SNF472's behaviour during dialysis. Methods Dialyzability was assessed in vitro using online-hemodiafiltration and high-flux HD systems in blood and saline. SNF472 was infused for 20 min and quantified at different time points. Results Phytate completely dialyzed in 1 h at low concentrations (10 mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions, calcium was slightly chelated during SNF472 infusion but when the system was switched to dialysis mode the calcium in the bath compensated this chelation. Conclusion Phytate dialyses with a low clearance. The administration of SNF472 as an exogenous source of phytate allows to attain supra-physiological levels required for its potential therapeutic properties. As SNF472 is infused during the whole dialysis session, the low clearance would not affect the drug's systemic exposure.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-04-01
2018
2018-04-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/9373
url https://hdl.handle.net/20.500.13003/9373
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Heidelberg
publisher.none.fl_str_mv Springer Heidelberg
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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