A Review of Phosphate Binders in Chronic Kidney Disease: Incremental Progress or Just Higher Costs?

• Published in: Drugs (New York, N.Y.) Vol. 77; no. 11; pp. 1155 - 1186
• Main Authors: Peter, Wendy L. St, Wazny, Lori D., Weinhandl, Eric, Cardone, Katie E., Hudson, Joanna Q.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.07.2017; Springer Nature B.V
• Subjects: Acetic acid; Binders; Body burden; Bone (long); Bone diseases; Calcification; Calcification (ectopic); Calcium; Calcium acetate; Calcium carbonate; Calcium Compounds - adverse effects; Calcium Compounds - metabolism; Calcium Compounds - therapeutic use; Calcium phosphates; Cardiovascular diseases; Central nervous system; Chelating Agents - adverse effects; Chelating Agents - economics; Chelating Agents - pharmacology; Chelating Agents - therapeutic use; Citric acid; Clinical outcomes; Drug Costs; Ferric citrate; Ferric Compounds - adverse effects; Ferric Compounds - metabolism; Ferric Compounds - therapeutic use; Fractures; Gender differences; Humans; Hypercalcemia; Hyperphosphatemia; Hyperphosphatemia - drug therapy; Hyperphosphatemia - etiology; Internal Medicine; Intolerance; Iron; Kidney diseases; Kidney transplantation; Lanthanum; Lanthanum - metabolism; Lanthanum - pharmacology; Lanthanum - therapeutic use; Medicine; Medicine & Public Health; Meta-Analysis as Topic; Mortality; Peritoneal dialysis; Pharmacology/Toxicology; Pharmacotherapy; Phosphate; Phosphates; Phosphates - blood; Phosphates - metabolism; Phosphorus; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - drug therapy; Review Article; Reviews; Sevelamer - therapeutic use; Studies; Systematic review
• ISSN: 0012-6667; 1179-1950
• DOI: 10.1007/s40265-017-0758-5

As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. However, studies included in meta-analyses show significant heterogeneity, and exclusion or inclusion of specific studies alters results. Since no long-term studies have been conducted to determine whether treatment with any phosphate binder is better than placebo on any hard clinical endpoint (including mortality), it is unclear whether possible benefit with sevelamer represents net benefit of sevelamer, net harm with calcium-containing phosphate binders, or both. Although one meta-analysis suggested that calcium acetate may be more efficacious gram for gram than calcium carbonate as a binder, calcium acetate did not reduce hypercalcemia, and gastrointestinal intolerance was higher. Data are insufficient to determine whether calcium acetate provides lower risk of vascular calcification than calcium carbonate. Fears of lanthanum accumulation in the central nervous system or bone with long-term treatment do not appear to be warranted. Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.