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Slowing the progression of vascular calcification in hemodialysis
1Department of Medicine, University of California San Francisco, San Francisco, California 94118-1211, USA. chertowg@medicine.ucsf.edu
Insights
Sevelamer effectively controls phosphorus in end-stage renal disease (ESRD) without causing hypercalcemia, unlike calcium-based binders. This non-hydrogel binder also improves lipid profiles and reduces vascular calcification progression in ESRD patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Pharmacology
Background:
- Hyperphosphatemia and secondary hyperparathyroidism are prevalent complications in end-stage renal disease (ESRD), contributing to increased morbidity and mortality.
- Both hyperphosphatemia and hypercalcemia are linked to heightened coronary artery calcification.
- Effective management of serum phosphorus without elevating serum calcium is crucial for ESRD patients.
Purpose of the Study:
- To evaluate sevelamer, a non-hydrogel phosphorus binder, as an alternative to calcium-based binders for managing hyperphosphatemia in ESRD.
- To compare the efficacy and safety of sevelamer versus calcium-based binders regarding phosphorus control, calcium levels, parathyroid hormone suppression, and vascular calcification.
Main Methods:
- A head-to-head randomized clinical trial comparing sevelamer with calcium-based phosphate binders.
- Assessment of serum phosphorus, calcium, and parathyroid hormone levels.
- Evaluation of lipid profiles and monitoring of coronary artery and aortic calcification progression.
Main Results:
- Sevelamer demonstrated comparable phosphorus control to calcium-based binders.
- Sevelamer did not cause hypercalcemia or adverse metabolic effects, unlike calcium-based binders which led to higher serum calcium and hypercalcemia.
- Sevelamer use was associated with attenuated or arrested progression of coronary artery and aortic calcification, while calcium-based binders showed progression.
Conclusions:
- Sevelamer is an effective alternative to calcium-based phosphate binders for phosphorus control in ESRD patients.
- Sevelamer offers advantages over calcium-based binders by avoiding hypercalcemia, improving lipid profiles, and mitigating vascular calcification.
- Reevaluation of oral calcium and vitamin D strategies is warranted, with consideration for sevelamer as a primary agent in hemodialysis patients.
Abstract:
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.