Sevelamer and the bone-vascular axis in chronic kidney disease: bone turnover, inflammation, and calcification...

Hyperphosphatemia is a central characteristic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Phosphorus excess is an independent cardiovascular risk factor for morbidity and mortality in patients with advanced CKD. Over the past 40 years, hyperphosphatemia has been a central therapeutic issue in advanced CKD. Mainstays of hyperphosphatemia treatment are reduction of dietary phosphorus, use of phosphate binders, and optimized phosphorus removal via dialysis. Currently, several phosphate binders are approved for use (aluminum, calcium, lanthanum, sevelamer); all share a common functionality in that they bind phosphorus and reduce the amount absorbed in the gastrointestinal lumen. Over the last decade, nephrologists have debated the relative tolerability and efficacy of these agents, especially the potential for vascular calcification and cardiovascular risk reduction. Recent research has focused on the question of whether a metal-free, calcium-free, and non-absorbed binder, such as sevelamer, offers advantages over other binder types. Most notable may be the potential benefit of reducing calcium load. In addition, sevelamer has several additional pleiotropic effects that may extend its basic indication, some of which may help attenuate vascular calcification. These include effects on bone turnover and the link between abnormal vascular processes and bone metabolism (the so-called 'bone-vascular axis'), as well as lipid metabolism, and systemic inflammatory mediators such as fetuin-A. We review the evidence for these pleiotropic effects, and suggest these may help in some way to improve the substantial disease burden in the CKD-MBD population.