The evaluation of novel mixed metal hydroxy-carbonates as phosphate binders: an in-vivo study in the rat

Abstract

A number of novel phosphate binders based on mixed metal hydroxide structures incorporating Fe and Ca, or Fe and Mg (classified as CT, Crosfield test compounds), were compared with the established phosphate binders Mg(OH)2, Al(OH)3, CaCO3 and a commercial hydrotalcite (Al- and Mg-based) using a rat model. The changes in urine and soluble faecal phosphate were used to evaluate efficacy of phosphate binding. The binders were mixed into a standard rat maintenance food at a concentration of 1% (w/w). Four rats were used for each binder study group and fed over 7 days. Urine and faeces were collected (in a metabolic cage) over the last 24-h study period and the phosphate content measured. The urinary phosphate was significantly reduced (P < 0.001) with CTFeCa (72+/-44 microm), CTFeMg (13+/-4 microm), CT100 (26+/-11 microm), and Mg(OH)2 (65+/-53 microm), compared with control (766+/-188 microm), Al(OH)3 (1,256+/-279 microm), and CaCO3 (857+/-25 microm). The soluble phosphate content of the faeces was significantly reduced (P < 0.05) by up to 60 % with CTFeCa, CTFeMg and Mg(OH)2, and up to 40% with CT100 and Al(OH)3, compared with 30% in controls and 10% with CaCO3. The new mixed metal hydroxy-carbonate compounds based on FeCa or FeMg are effective phosphate binders in-vivo and warrant further testing in patients.

Different Mg to Fe Ratios in the Mixed Metal MgFe Hydroxy-Carbonate Compounds and the Effect on Phosphate Binding Compared With Established Phosphate Binders

“…Their use as phosphate binders was first reported in this laboratory. We have previously shown that MMHs based on CaFe and MgFe can bind phosphate in solution 40,41. In the present study, we have investigated further the effect of different Mg 2+ :Fe 3+ ratios and preparations, such as aging and drying, on their phosphate binding performances in order to optimize the product.…”

Synthesis of Mg-Fe-Cl hydrotalcite-like nanoplatelets as an oral phosphate binder: evaluations of phosphorus intercalation activity and cellular cytotoxicity

“…On account of this unique characteristic of HTln, several investigations have reported that HTln can probably be used as an oral phosphate binder456. Phosphorus control is a primary goal in the care of patients with end-stage renal disease (ESRD)7.…”

Phosphate binders: New products and challenges

“…In an in vitro study by Rankin et al, it was found that iron‐containing and magnesium‐containing compounds had a higher phosphorus‐binding capacity than iron‐containing and calcium‐containing compounds, which in turn had a higher phosphorus binding capacity than either magnesium hydroxide or calcium carbonate. Furthermore, they demonstrated that in rats there was little absorption of either iron or magnesium from these compounds and hence did not result in changes in iron studies or hypermagnesemia 57 . Given that iron‐containing and magnesium‐containing compounds had the highest phosphorus‐binding capacity, subsequent studies compared the phosphate‐binding capacity of different Mg to Fe ratios in MMH with other phosphate binders.…”

“…Furthermore, they demonstrated that in rats there was little absorption of either iron or magnesium from these compounds and hence did not result in changes in iron studies or hypermagnesemia. 57 Given that iron-containing and magnesium-containing compounds had the highest phosphorus-binding capacity, subsequent studies compared the phosphate-binding capacity of different Mg to Fe ratios in MMH with other phosphate binders. They found that 4:1 and 2:1 ratios of MgFe had a greater percent phosphate bound than the conventional phosphate binders and had a much lower amount of magnesium released a magnesium hydroxide.…”