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Nephrology Dialysis Transplantation
Year: 2009  |  Volume: 24  |  Issue: 6  |  Page No.: 1790 - 1799

Adequate phosphate binding with lanthanum carbonate attenuates arterial calcification in chronic renal failure rats

E Neven, G Dams, A Postnov, B Chen, N De Clerck, M. E De Broe, P. C D`Haese and V. Persy    

Abstract:

Background. Hyperphosphataemia is a risk factor for arterial calcification contributing to the high cardiovascular mortality in patients with chronic kidney disease. Calcium-based phosphate binders can induce hypercalcaemia and are associated with progression of vascular calcification. Therefore, the effect of lanthanum carbonate, a non-calcium phosphate binder, on the development of vascular calcification was investigated in uraemic rats.

Methods. Chronic renal failure (CRF) was induced by feeding rats an adenine-enriched diet for 4 weeks. After 2 weeks, 1% or 2% lanthanum carbonate was added to the diet for 6 weeks. Calcification in the aorta, carotid and femoral arteries was evaluated histomorphometrically, biochemically and by ex vivo micro-CT. Chondro-/osteogenic conversion of vascular smooth muscle cells was also analysed in the rat aorta.

Results. Treatment with 1% lanthanum carbonate (1% La) did not reduce vascular calcification, but in the 2% lanthanum carbonate (2% La) group vascular calcium content and area% Von Kossa positivity were decreased compared with control CRF rats. The aortic calcified volume measured with ex vivo micro-CT was significantly reduced in rats treated with 2% La. Although calcification was inhibited by treatment with 2% La, the chondrocyte transcription factor sox-9 was abundantly expressed in the aorta.

Conclusion. Treatment of CRF rats with 2% La reduces the development of vascular calcification by adequate phosphate binding resulting in a decreased supply of phosphate as a substrate for vascular calcification.

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