Phosphate binders affect vitamin K concentration by undesired binding, an in vitro study

Area of Science:

• Nephrology
• Biochemistry
• Pharmacology

Background:

• Vascular calcification is a significant cause of mortality in end-stage renal disease (ESRD).
• Phosphate binders manage hyperphosphatemia but their effect on vascular calcification is debated.
• Vitamin K2 (menaquinone-7) deficiency exacerbates vascular calcification by reducing matrix Gla protein (MGP) activation.

Purpose of the Study:

• To investigate whether common phosphate binders bind vitamin K2 (menaquinone-7) in vitro.
• To determine if phosphate influences the binding affinity of binders to vitamin K2.
• To assess the potential impact of phosphate binders on vitamin K2 bioavailability.

Main Methods:

• In vitro experiment assessing vitamin K2 (menaquinone-7) binding to five different phosphate binders.
• Vitamin K2 was incubated with binders in media with or without phosphate at pH 6.
• Vitamin K2 levels were analyzed by HPLC after 5.5 hours; experiments were performed in triplicate.

Main Results:

• Sucroferric-oxyhydroxide and sevelamer carbonate showed no significant vitamin K2 binding.
• Calcium acetate/magnesium carbonate strongly bound vitamin K2, with or without phosphate.
• Lanthanum carbonate and calcium carbonate exhibited significant vitamin K2 binding, influenced by the presence of phosphate.

Conclusions:

• Sucroferric-oxyhydroxide and sevelamer carbonate were the only binders that did not bind vitamin K2 in vitro.
• Phosphate significantly affects vitamin K2 binding by certain binders.
• Phosphate binders have the potential to limit vitamin K2 bioavailability, impacting vascular calcification in ESRD patients.