The role of calcium and non calcium-based phosphate binders in chronic kidney disease

Abstract

Rising levels of serum phosphate occur late in the course of chronic kidney disease (CKD) and have been easy targets for nephrologists to treat using phosphate binding drugs, as well as fertile ground for the pharmaceutical industry, for meta-analysis and for the earnest pontifications of guideline writers. Unfortunately, the evidence does little to support this focus, which might be better applied to earlier, adaptive hormonal changes, and to phosphate balance rather than serum phosphate levels. Nevertheless, phosphate binders are ubiquitously prescribed to patients on dialysis, and often prescribed to patients with earlier stages of CKD; for which there is no evidence of benefit and some evidence that calcium-based binders (CBBs) and possibly non-CBBs may cause more harm than placebo. For patients on dialysis, observational studies suggest that phosphate binder use may reduce mortality. Meta-analyses report reduced hypercalcaemia for non-CBBs versus CBBs, and compared with CBBs sevelamer has been reported to significantly reduce vascular calcification progression and, in some but not all studies, overall mortality. However, limitations include study heterogeneity. For patients on dialysis, CBBs appear to have no advantages over the non-CBBs, apart from lower cost. In general, it seems prudent to avoid prescribing calcium-based drugs to patients who are pre-dialysis, and to use non-CBBs preferentially in CKD stage 5D. Current draft Kidney Disease Improving Global Outcomes guidelines suggest that CBB dosage be minimized in CKD stages 3 to 5D.