Limits...
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.

Show MeSH

Related in: MedlinePlus

mRNA expression of the different target genes relative to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in the aorta of rats with chronic renal failure (CRF) compared with rats with normal renal function (NRF). The number of animals for each study group is indicated in the bars of Figure 1. Data are expressed as mean±s.d. bmp-2, bone morphogenic protein 2; CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; cbfa-1 core binding factor-α1; mgp, matrix gla protein; Osx, osterix; Sev, sevelamer; Sev750, sevelamer carbonate 750 mg/kg; sox9, sex determining region Y-box 9; TRPM7, transient receptor potential cation channel, subfamily M, member 7; VC, vascular calcification; VK, von Kossa positivity. *Significant difference versus NRF; °significant difference versus VC of the same group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3674404&req=5

fig5: mRNA expression of the different target genes relative to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in the aorta of rats with chronic renal failure (CRF) compared with rats with normal renal function (NRF). The number of animals for each study group is indicated in the bars of Figure 1. Data are expressed as mean±s.d. bmp-2, bone morphogenic protein 2; CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; cbfa-1 core binding factor-α1; mgp, matrix gla protein; Osx, osterix; Sev, sevelamer; Sev750, sevelamer carbonate 750 mg/kg; sox9, sex determining region Y-box 9; TRPM7, transient receptor potential cation channel, subfamily M, member 7; VC, vascular calcification; VK, von Kossa positivity. *Significant difference versus NRF; °significant difference versus VC of the same group.

Mentions: Figure 5 illustrates the expression of osteochondrogenic genes in the aorta. The expression of bmp-2 (bone morphogenetic protein 2), the chondrocyte-specific transcription factor sox9 (sex determining region Y-box 9), and the calcification inhibitor mgp (matrix gla protein) was significantly increased in CRF rats compared with rats with normal renal function. Interestingly, in CRF animals the expression of bmp-2, sox9, and mgp was clearly associated with the presence of vascular calcification in the aorta. Despite a reduction of calcification, there was no difference in the expression pattern of these genes in the phosphate binder groups compared with vehicle or between the different phosphate binder groups. There was no change in the expression of osx (osterix), cbfa-1 (core binding factor-α1), and the magnesium transporter TRPM7 (transient receptor potential cation channel, subfamily M, member 7) between CRF and normal renal function groups, and there was no difference in the expression of these genes between calcified and noncalcified vessels.


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)

mRNA expression of the different target genes relative to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in the aorta of rats with chronic renal failure (CRF) compared with rats with normal renal function (NRF). The number of animals for each study group is indicated in the bars of Figure 1. Data are expressed as mean±s.d. bmp-2, bone morphogenic protein 2; CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; cbfa-1 core binding factor-α1; mgp, matrix gla protein; Osx, osterix; Sev, sevelamer; Sev750, sevelamer carbonate 750 mg/kg; sox9, sex determining region Y-box 9; TRPM7, transient receptor potential cation channel, subfamily M, member 7; VC, vascular calcification; VK, von Kossa positivity. *Significant difference versus NRF; °significant difference versus VC of the same group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: mRNA expression of the different target genes relative to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in the aorta of rats with chronic renal failure (CRF) compared with rats with normal renal function (NRF). The number of animals for each study group is indicated in the bars of Figure 1. Data are expressed as mean±s.d. bmp-2, bone morphogenic protein 2; CaMg, calcium acetate/magnesium carbonate; CaMg375, CaMg 375 mg/kg; CaMg750, CaMg 750 mg/kg; cbfa-1 core binding factor-α1; mgp, matrix gla protein; Osx, osterix; Sev, sevelamer; Sev750, sevelamer carbonate 750 mg/kg; sox9, sex determining region Y-box 9; TRPM7, transient receptor potential cation channel, subfamily M, member 7; VC, vascular calcification; VK, von Kossa positivity. *Significant difference versus NRF; °significant difference versus VC of the same group.
Mentions: Figure 5 illustrates the expression of osteochondrogenic genes in the aorta. The expression of bmp-2 (bone morphogenetic protein 2), the chondrocyte-specific transcription factor sox9 (sex determining region Y-box 9), and the calcification inhibitor mgp (matrix gla protein) was significantly increased in CRF rats compared with rats with normal renal function. Interestingly, in CRF animals the expression of bmp-2, sox9, and mgp was clearly associated with the presence of vascular calcification in the aorta. Despite a reduction of calcification, there was no difference in the expression pattern of these genes in the phosphate binder groups compared with vehicle or between the different phosphate binder groups. There was no change in the expression of osx (osterix), cbfa-1 (core binding factor-α1), and the magnesium transporter TRPM7 (transient receptor potential cation channel, subfamily M, member 7) between CRF and normal renal function groups, and there was no difference in the expression of these genes between calcified and noncalcified vessels.

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