Slowing the progression of vascular calcification in hemodialysis.
Hyperphosphatemia and secondary hyperparathyroidism are common complications of ESRD (chronic kidney disease stage 5) that, when untreated, may result in increased morbidity and mortality. Hyperphosphatemia and hypercalcemia have been associated with increased coronary artery calcification. Achieving control of serum phosphorus without increasing serum calcium is an important goal for patients with ESRD. Although calcium-based phosphate binders effectively reduce serum phosphorus and parathyroid hormone concentrations, these agents can lead to hypercalcemia and have been associated with increased vascular calcification. The phosphorus binder sevelamer was developed to overcome the limitations associated with the usual management of hyperphosphatemia and secondary hyperparathyroidism (i.e., mineral salts). Sevelamer, a nonabsorbable hydrogel, is as efficacious as calcium-based phosphate binders for reducing serum phosphorus but does not cause hypercalcemia or other adverse metabolic effects. Sevelamer also exhibits beneficial effects on lipids, consistently and significantly decreasing LDL cholesterol and increasing HDL cholesterol in most studies. In a head-to-head randomized clinical trial, sevelamer and calcium-based binders achieved similarly excellent phosphorus control, but the use of calcium-based binders led to significantly higher serum calcium concentrations and an increased incidence of hypercalcemia and unintended suppression of parathyroid hormone. Treatment with calcium-based binders also led to the progression of coronary artery and aortic calcification, whereas sevelamer attenuated or arrested progression. Strategies that use oral calcium and vitamin D in patients with ESRD should be reexamined, and the potential advantages of sevelamer should be considered when selecting a primary agent to reduce serum phosphorus in hemodialysis patients.
Chertow
Glenn M
GM
Department of Medicine, University of California San Francisco, San Francisco, California 94118-1211, USA. chertowg@medicine.ucsf.edu
D001018:Aortic Diseases / Q000209:etiology / Q000517:prevention & control*; D002114:Calcinosis / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy*; D002118:Calcium / Q000097:blood; D004852:Epoxy Compounds / Q000627:therapeutic use*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000150:complications*; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000097:blood; D011073:Polyamines; D011095:Polyethylenes / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000379:methods*; D000069603:Sevelamer
D004852:Epoxy Compounds; D010281:Parathyroid Hormone; D010710:Phosphates; D011073:Polyamines; D011095:Polyethylenes; D000069603:Sevelamer; D002118:Calcium