Sevelamer for hyperphosphataemia in kidney failure: controversy and perspective

Abstract

The term 'chronic kidney disease-mineral and bone disorder' (CKD-MBD), coined in 2006, was introduced in a position statement by the Kidney Disease: Improving Global Outcomes (KDIGO) organization. According to the KDIGO guidelines, CKD-MBD is a systemic disorder and patients with vascular or valvular calcifications should be included in the group with the greatest cardiovascular risk. Therefore, the presence or absence of calcification is a key factor in strategy decisions for such patients. In particular, it is recommended that the use of calcium-based phosphate binders should be restricted in patients with hypercalcaemia, vascular calcification, low levels of parathyroid hormone (PTH) or adynamic bone disease. In this respect, it should be underscored that treatment with phosphate-binding agents can normalise the levels of phosphate and PTH, but the use of calcium carbonate can favour the progression of vascular calcifications. There is evidence of reduced progression of vascular calcification in patients treated with sevelamer compared with high doses of calcium-based binders, but there is as yet no strong evidence regarding hard outcomes, such as mortality or hospitalization, to support the use of one treatment over another. Nevertheless, a number of experimental and observational findings seem to suggest that sevelamer should be preferred over calcium-based binders, in as much as these can increase cardiovascular mortality when used in high doses. A threshold dose below which calcium-based binders can be used safely in CKD patients with hyperphosphatemia has yet to be established.

Keywords: chronic kidney disease; hyperphosphataemia; phosphate binders; vascular calcification.

Figure 1.

Nonclassical effects of sevelamer. Potentially positive effects are in white boxes while negative ones are in grey boxes. FGF, fibroblast growth factor.