Non-calcium-containing phosphate binders: comparing efficacy, safety, and other clinical effects

Phosphate-binder therapy for hyperphosphataemia is key to the treatment of patients with chronic kidney disease (CKD)-mineral and bone disorder (MBD). Calcium-free phosphate binders are increasingly favoured since calcium-based agents potentially cause harmful calcium overload and vascular calcification that confound the benefits of reducing serum phosphorus. Several calcium-free phosphate binders are available, including the non-absorbed agent sevelamer and the absorbed agents, e.g. lanthanum and magnesium salts. Randomised controlled studies consistently show that sevelamer and lanthanum carbonate offer equivalent lowering of serum phosphorus and often effectively achieve phosphorus targets versus calcium salts, with sevelamer having a positive effect on bone disease, vascular calcification, and patient-level outcomes in dialysis patients in several trials. There is also evidence that lanthanum carbonate can improve bone health, but data are limited to its effects to vascular calcification or patient-level outcomes. Magnesium salts have also been shown to reduce serum phosphorus levels, but clear evidence is lacking on bone, vascular, or clinical outcomes. It also remains to be established whether long-term systemic accumulation of lanthanum and magnesium, in tissues including bone, has clinically relevant toxic effects. This review summarises the evidence of efficacy and safety for newer calcium-free phosphate binders in CKD-MBD management.