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

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

  • J Nephrol. 2018 Apr;31(2):287-296. doi: 10.1007/s40620-018-0471-9.
Joan Perelló 1 2 M Gómez 3 M D Ferrer 4 5 N Y Rodríguez 3 C Salcedo 4 J M Buades 6 M M Pérez 4 J V Torregrosa 3 E Martín 7 F Maduell 3
Affiliations

Affiliations

  • 1 Research and Development Department, Laboratoris Sanifit SL., 07121, Palma de Mallorca, Spain. [email protected].
  • 2 Laboratory of Renal Lithiasis Research, IUNICS, University of the Balearic Islands, 07122, Palma, Spain. [email protected].
  • 3 Nephrology and Renal Transplantation, Hospital Clínic, Barcelona, Spain.
  • 4 Research and Development Department, Laboratoris Sanifit SL., 07121, Palma de Mallorca, Spain.
  • 5 Departament de Biologia Fonamental i Ciències de la Salut, University of the Balearic Islands, 07122, Palma, Spain.
  • 6 Nephrology Service, Hospital Son Llàtzer, Palma de Mallorca, Spain.
  • 7 Kinrel, Madrid, Spain.
Abstract

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.

Keywords

Cardiovascular calcification; End-stage renal disease; Hemodialysis; Phytate.

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