The control of hyperphosphatemia in renal failure: between vascular calcification and inflammation.

preventing increases in calcium-phosphate product, secondary hyperparathyroidism and ultimately VC. CKD patients develop extensive medial calcification, which contributes to higher cardiovascular morbidity and mortality [2] . In addition to elderly age, male gender, inflammation, mineral metabolism abnormalities and diabetes, new potential factors are emerging which help to better understand the pathogenesis of VC in CKD. In the last decade, both new molecular and cellular mechanisms have been investigated in the pathophysiology of secondary hyperparathyroidism and VC in CKD [3–5] . Accordingly, different bone-related proteins are now certified for their capacity of promoting or inhibiting the process of extraskeletal calcification [6, 7] . The pathogenesis of phosphate-induced VC has been investigated in depth [8] , and different in vitro studies have demonstrated that high phosphate concentration in growth media causes VC by a specific activation of the core-binding factor 1 (Cbfa1), an osteoblast-specific gene that regulates the expression of several bone morphogenic proteins [9] . In CKD, the expression of these proteins was also caused by serum from uremic patients with normal serum phosphate [10] . Interestingly, an increased expression of both Cbfa1 and osteopontin has been shown in calcified arteries from CKD patients [11] . Clearly, these data suggest that VC is an active process. The cellular formation of a In this issue of Blood Purification, I read with interest the article by Hauser et al. [1] on the effects of the aluminumand calcium-free phosphate binder sevelamer carbonate on reducing the levels of tumor necrosis factor and endotoxin in an experimental model of uremia. The authors’ results support one of the potential mechanisms involved in vascular calcification (VC): the role of phosphate in regulating arterial mineralization, in a manner ‘similar’ to bone formation. I have really found the manuscript of interest, and I would like to discuss why these results may be important from the clinical point of view, with special attention to chronic kidney disease (CKD) patients. Accelerated atherosclerosis and VC play a central role in the pathogenesis of cardiovascular disease in CKD patients. Mineral metabolism disorders and increased serum calcium-phosphate product have recently been investigated as inducing factors in cardiovascular calcification [2] . In fact, cardiovascular disease in renal failure appears greatly associated with alterations of bone metabolism. Recently, the treatment of hyperphosphatemia in CKD patients changed from either calciumor aluminum-based phosphate binders to new calciumand aluminum-free phosphate binders, such as sevelamer carbonate and lanthanum carbonate. Therefore, control of serum phosphate in CKD patients becomes crucial in Published online: September 21, 2010