Abstract
BackgroundCardiovascular 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.MethodsDialyzability 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.ResultsPhytate 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.ConclusionPhytate 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.
Highlights
Chronic kidney disease (CKD) is a serious condition associated with significant morbidity, premature mortality and decreased quality of life [1]
A longer experiment was performed with SNF472 at a final concentration of 30 mg/l subjected to dialysis for a total of 4 h (Fig. 2G)
The development and acceleration of Cardiovascular calcification (CVC) is especially enhanced in patients undergoing dialysis, in which pyrophosphate seems to be lost through the dialysis system [10, 41]
Summary
Chronic kidney disease (CKD) is a serious condition associated with significant morbidity, premature mortality and decreased quality of life [1]. OL-HDF has demonstrated that it can deliver the most efficient removal treatment over a wide range of molecular weight (MW) uremic toxins [4] as well as improve survival [5] and quality of life. 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. 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. As SNF472 is infused during the whole dialysis session, the low clearance would not affect the drug’s systemic exposure
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