Calcium-free Phosphate Binders: Sevelamer
The anion exchanger compound sevelamer represented the first nonabsorbable, calcium-free and metal-free phosphate binder approved for the treatment of hyperphosphatemia in dialysis patients. In addition to the initial formulation sevelamer-HCl, the more acid/base-neutral compound sevelamer carbonate is meanwhile available.
A number of key studies compared the effects between sevelamer and calcium-containing binders on the progression of vascular, and especially coronary artery, calcification in different stages of CKD. The majority of these trials demonstrated that sevelamer treatment stopped or slowed calcification progression, whereas calcium-containing binders accelerated this process, but a recent meta-analysis (n = 3271) could not confirm a significant superiority of sevelamer in this context. Trials addressing the effect of sevelamer on patient mortality in dialysis patients were inconclusive: in the Dialysis Clinical Outcomes Revisited (DCOR) study (n = 2.103) no differences were found between sevelamer and calcium-containing binder treatment concerning the primary endpoint all-cause mortality, while in a posthoc analysis of the RIND study, a survival advantage in favor of sevelamer was found. A recent randomized, open-label study in patients not on dialysis (CKD stage 3–4; n = 212) investigated the effects of sevelamer carbonate and calcium carbonate on all-cause mortality and dialysis inception, and demonstrated a reduced all-cause mortality with sevelamer treatment.
Of note, there are additional studies demonstrating pleiotropic effects associated with sevelamer treatment, with regard to elevations in serum fetuin-A levels, lowering of serum FGF23 levels and reductions in inflammation in addition to its well known cholesterol-lowering properties.