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


CONCLUSIONS
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.
Neven
Ellen
E
Department of Pathophysiology, University of Antwerp, Antwerp, Belgium.
Dams
Geert
G
Postnov
Andrei
A
Chen
Bing
B
De Clerck
Nora
N
De Broe
Marc E
ME
D'Haese
Patrick C
PC
Persy
Veerle
V
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020219:Chondrogenesis / Q000187:drug effects; D054559:Hyperphosphatemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007811:Lanthanum / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D010710:Phosphates; C119467:lanthanum carbonate; D007811:Lanthanum