Abstract
BackgroundVascular calcification is a major contributing factor to mortality in end stage renal disease (ESRD). Despite the efficacy of phosphate binders to improve hyperphosphatemia, data on vascular calcification are less clear. There seems to be a difference in attenuation or delay in progression between different binders. In this in vitro experiment we tested whether phosphate binders could limit bioavailability of vitamin K2 by undesired binding. Vitamin K-deficiency limits activation of the vascular tissue mineralization inhibitor matrix γ-carboxyglutamate (Gla) protein (MGP) thereby exacerbating vascular calcification.MethodsIn this experiment vitamin K2 (menaquinone-7; MK-7) binding was assessed by adding 1 mg of vitamin K2 to a medium with pH 6 containing 67 mg phosphate binder with either 7 mg of phosphate or no phosphate. Five different phosphate binders were tested. After five and a half hours vitamin K was analyzed by HPLC. All experiments were performed in triplicate.ResultsSucroferric-oxyhydroxide and sevelamer carbonate did not significantly bind vitamin K2, both in solution only containing vitamin K2 or in combination with phosphate. Calcium acetate/magnesium carbonate binds vitamin K2 strongly both in absence (p = 0.001) and presence of phosphate (p = 0.003). Lanthanum carbonate significantly binds vitamin K2 in solution containing only vitamin K2 (p = 0.005) whereas no significant binding of vitamin K2 was observed in the solution containing vitamin K2 and phosphate (p = 0.462). Calcium carbonate binds vitamin K2 significantly in a solution with vitamin K2 and phosphate (p = 0.009) whereas without phosphate no significant binding of vitamin K2 was observed (p = 0.123).ConclusionsSucroferric-oxyhydroxide and sevelamer carbonate were the only binders of the five binders studied that did not bind vitamin K2 in vitro. The presence or absence of phosphate significantly interferes with vitamin K2 binding so phosphate binders could potentially limit bioavailability vitamin K2.
Highlights
Vascular calcification is a major contributing factor to mortality in end stage renal disease (ESRD)
In the presence of phosphate, K2 binding was attenuated for sevelamer carbonate (SC) and lanthanum carbonatehydrate (LA), but increased for calcium carbonate (CC)
Solutions containing only phosphate with or without a binder only showed negligible vitamin K2 concentration, excluding interference of phosphate or phosphate binders with the vitamin K2 measurement. In this in vitro study we demonstrate that calciumcontaining phosphate binders and lanthanum carbonate bind vitamin K2
Summary
Vascular calcification is a major contributing factor to mortality in end stage renal disease (ESRD). Vitamin K-deficiency limits activation of the vascular tissue mineralization inhibitor matrix γcarboxyglutamate (Gla) protein (MGP) thereby exacerbating vascular calcification. Neradova et al BMC Nephrology (2017) 18:149 progresses despite adequate phosphate concentrations [10] This has been attributed to increasing calcium load from calcium based binders [11], chronic inflammation [12] and other factors such as vitamin K deficiency [13]. We hypothesized that phosphate binders inhibit gastrointestinal uptake of vitamin K2 by undesired binding since the binding of fat soluble vitamins has been described previously [16, 17] If confirmed this could contribute to vitamin K deficiency and as such possibly to the progress of vascular calcification
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