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2018 ; 31
(2
): 287-296
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SNF472, a novel inhibitor of vascular calcification, could be administered during
hemodialysis to attain potentially therapeutic phytate levels
#MMPMID29350348
Perelló J
; Gómez M
; Ferrer MD
; Rodríguez NY
; Salcedo C
; Buades JM
; Pérez MM
; Torregrosa JV
; Martín E
; Maduell F
J Nephrol
2018[Apr]; 31
(2
): 287-296
PMID29350348
show ga
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.
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