The Effects of Sevelamer and Calcium Acetate on Proxies of Atherosclerotic and Arteriosclerotic Vascular Disease in Hemodialysis Patients

Abstract

Background: We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. Methods: To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. Results: The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate –2.5 ± 1.8 mg/dl vs. sevelamer –2.8 ± 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium ≧10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 ± 2.1 g/day – equivalent to 1.2 ± 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 ± 350, median change +20, p = 0.002) and aorta (mean change 181 ± 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. Conclusion: Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.

Vascular Calcification Mechanisms

“…Indeed, when sevelamer was compared to commonly used Ca-based P binders in a large hemodialysis patient group it was found that patients receiving sevelamer had unchanged median coronary artery and aorta calcification scores after 1 yr as opposed to Ca-treated patients whose arterial calcification scores increased 28% over baseline (12). Significantly, although both treatments controlled P levels equivalently, treatment with Ca containing binders led to an increased frequency of hypercalcemic episodes and greater suppression of serum parathyroid hormone (PTH) levels in hemodialysis patients (54,55). Similar effects of sevelamer were also noted in a rat uremia model, where renal calcification was greatly reduced compared to Ca carbonate treatment (56).…”

Analisi costo/efficacia di sevelamer nel trattamento dell’iperfosforemia del paziente in dialisi

“…La probabilità di essere trattati con una statina è stata ricavata dallo studio di Chertow e collaboratori: nella coorte sevelamer tale probabilità è del 22%, mentre nella coorte del calcio è del 46% [35]. Tale differenza è in relazione all'efficacia di sevelamer nel ridurre i livelli di LDL-colesterolo.…”

“…A differenza del calcio, però, l'uso di sevelamer comporta minori livelli di calcemia, la riduzione dei livelli di PCR, il rallentamento della progressione delle calcificazioni vascolari, una minore incidenza di infarto del miocardio, di angina pectoris e di altre vasculopatie periferiche [34][35][36].…”

“…Questo risultato può contribuire alla riduzione del rischio cardiovascolare e ad aumentare la sopravvivenza dei pazienti in dialisi. Inoltre, la riduzione del colesterolo comporta anche la riduzione della percentuale di pazienti che devono essere trattati con una statina [35].…”

Low Calcidiol Levels and Coronary Artery Calcification

“…This step has not been proved. Notably, studies of sevelamer hydrochloride showed less progression of calcification compared with calcium-based binders, but no randomized clinical trial showed a survival benefit to sevelamer in intention-to-treat analyses 22 ; therefore, although CAC associates with coronary events and is considered a measure of subclinical atherosclerosis, it is unclear whether regression or less progression of CAC links with improved outcomes. It may be that CAC is yet another critical cardiovascular risk factor, which, like diabetes and hypertension, is now related to low calcidiol levels.…”