How is chronic hyperphosphatemia treated?
Chronic hyperphosphatemia as seen with end-stage kidney disease should be treated with phosphorus binders. Binders are cationic compounds that bind phosphate anions in the gut and prevent absorption. One of the first phosphorus binders used was aluminum hydroxide. The use of aluminum hydroxide was associated with adynamic bone disease and dementia. Aluminum gave way to calcium-based binders, primarily calcium acetate and calcium carbonate. Additional binders include sevelamer, lanthanum carbonate, and two iron-based binders: sucroferric oxyhydroxide and ferric citrate. All of these have shown efficacy in lowering serum phosphorus. In multiple meta-analyses sevelamer has demonstrated a survival advantage over calcium-based binders. However, this finding is largely dependent on the positive results of a single large trial, Di Lori’s open-label INDEPENDENT Trial. INDEPENDENT showed a huge reduction in cardiovascular mortality with sevelemer (hazard ratio [HR] 0.09; total mortality HR 0.23) that other studies were unable to detect.
The use of phosphate binders in CKD is less clear. The drugs appear to be effective and reduce both serum phosphorus and 24-hour urine phosphorus; however, vascular calcification, an important surrogate endpoint, actually increased rather than decreased. No randomized trials have demonstrated survival or improved kidney function through the use of phosphorus binders in CKD.
