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Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia.

De Schutter TM, Behets GJ, Geryl H, Peter ME, Steppan S, Gundlach K, Passlick-Deetjen J, D'Haese PC, Neven E - Kidney Int. (2013)

Bottom Line: The aortic calcium content was significantly reduced by CaMg but not by sevelamer.The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups.Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

ABSTRACT
Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification.

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Related in: MedlinePlus

Study setup. CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; Sev750, 750 mg/kg sevelamer.
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fig1: Study setup. CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; Sev750, 750 mg/kg sevelamer.

Mentions: Rats were fed a 0.75% adenine/2.5% protein diet to induce renal failure. After 1 week, treatment with phosphate binders or vehicle was started until the time of killing at week 6 (Figure 1). There was limited mortality: one animal from each treatment group died 1 day before the planned day of killing. No statistically significant differences between groups were seen for body weight and water and food consumption (data not shown).


Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia.

De Schutter TM, Behets GJ, Geryl H, Peter ME, Steppan S, Gundlach K, Passlick-Deetjen J, D'Haese PC, Neven E - Kidney Int. (2013)

Study setup. CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; Sev750, 750 mg/kg sevelamer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3674404&req=5

fig1: Study setup. CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; Sev750, 750 mg/kg sevelamer.
Mentions: Rats were fed a 0.75% adenine/2.5% protein diet to induce renal failure. After 1 week, treatment with phosphate binders or vehicle was started until the time of killing at week 6 (Figure 1). There was limited mortality: one animal from each treatment group died 1 day before the planned day of killing. No statistically significant differences between groups were seen for body weight and water and food consumption (data not shown).

Bottom Line: The aortic calcium content was significantly reduced by CaMg but not by sevelamer.The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups.Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

ABSTRACT
Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification.

Show MeSH
Related in: MedlinePlus