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

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.