Phosphate binder therapy for attainment of K/DOQI bone metabolism guidelines

Hyperphosphatemia in patients with chronic kidney disease leads to secondary hyperparathyroidism and renal osteodystrophy, and it is independently associated with mortality risk. The exact mechanism by which hyperphosphatemia increases mortality risk is unknown, but it may relate to enhanced cardiovascular calcification. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease recommends maintenance of serum phosphorus below 5.5 mg/dL, calcium-phosphorus (Ca x P) product less than 55 mg(2)/dL(2), intact parathyroid hormone (iPTH) 150 pg/mL to 300 pg/mL, and bicarbonate (HCO(3)) greater than 22 mEq/L. Although calcium-based phosphate binders (CBPB) are cost effective, there are long-term safety concerns pertaining to their postulated role in the progression of cardiovascular calcification. Sevelamer hydrochloride has been recommended as an alternative noncalcium phosphate binder. Results from the Calcium Acetate Renagel Evaluation (CARE) study indicate that calcium acetate is more effective than sevelamer hydrochloride in controlling serum phosphorous, Ca x P product, and HCO(3) in hemodialysis patients. In the Treat-to-Goal study, dialysis patients treated with sevelamer hydrochloride had slower progression of coronary and aortic calcification than patients treated with CBPB. The mechanism underlying the beneficial effect of sevelamer hydrochloride is unknown but may relate to decreased calcium loading, or to dramatic reductions in low-density lipoprotein (LDL) cholesterol in sevelamer hydrochloride-treated patients. At present, evidence incriminating CBPB in the progression of cardiovascular calcification in end-stage renal disease (ESRD) remains largely circumstantial. As calcium acetate is more efficacious and cost effective than sevelamer hydrochloride, it remains an accepted first-line phosphate binder. This review examines these issues and provides rational guidelines for the use of CBPB in patients on maintenance hemodialysis.