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

Authors:

Joan Perelló M Gómez M D Ferrer N Y Rodríguez C Salcedo J M Buades M M Pérez J V Torregrosa E Martín F Maduell

J Nephrol 2018 04 19;31(2):287-296. Epub 2018 Jan 19.

Nephrology and Renal Transplantation, Hospital Clínic, Barcelona, Spain.

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.

Download full-text PDF	Source
http://dx.doi.org/10.1007/s40620-018-0471-9	DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829128	PMC

April 2018

Publication Analysis

Keyword Occurance

Similar Publications

Effects of SNF472, a Novel Inhibitor of Hydroxyapatite Crystallization in Patients Receiving Hemodialysis - Subgroup Analyses of the CALIPSO Trial.

Authors:

Paolo Raggi Antonio Bellasi Smeeta Sinha Jordi Bover Mariano Rodriguez Markus Ketteler David A Bushinsky Rekha Garg Joan Perelló Alex Gold Glenn M Chertow

Kidney Int Rep 2020 Dec 4;5(12):2178-2182. Epub 2020 Nov 4.

Department of Medicine, Stanford University, Palo Alto, California, USA.

Introduction: Coronary artery calcium (CAC) is highly prevalent and linked with poor outcomes in patients receiving maintenance hemodialysis, and its reduction may improve patient prognosis. SNF472, a selective inhibitor of hydroxyapatite crystallization, slows CAC progression in patients receiving maintenance hemodialysis. In this analysis, we assessed the efficacy of SNF472 in prespecified patient subgroups. Read More

View Article and Full-Text PDF

December 2020

Similar Publications

A novel assay to measure calcification propensity: from laboratory to humans.

Authors:

M Mar Perez Miguel D Ferrer Marta Lazo-Rodriguez Ana Zeralda Canals Elisenda Banon-Maneus Josep M Campistol Stephan Miller Rekha Garg Alex Gold Carolina Salcedo Joan Perelló

Sci Rep 2020 10 16;10(1):17578. Epub 2020 Oct 16.

Sanifit Therapeutics, Parc Bit - Europa Building, 2nd Floor, 07121, Palma de Mallorca, Spain.

Cardiovascular calcification (CVC) contributes to morbidity and mortality in patients undergoing dialysis. We examined the pharmacodynamic effects of SNF472, a calcification inhibitor, on plasma calcium phosphate crystallization using spectrometric measurements, and its correlations with effects on CVC in rats or humans. Rats (N = 38) injected with vitamin D (days 1-3) to induce CVC were infused with saline or SNF472 (days 1-12). Read More

View Article and Full-Text PDF

October 2020

Similar Publications