Ten-Year Experience with Sevelamer and Calcium Salts as Phosphate Binders

Abstract

Most patients with chronic kidney disease experience abnormalities in serum calcium, phosphorus, parathyroid hormone, and vitamin D metabolism. These can lead to vascular calcification (VC), which has been associated with increased risk for cardiovascular disease and mortality. Although hyperphosphatemia is believed to be a risk factor for mortality and VC, no randomized trial was ever designed to demonstrate that lowering phosphate reduces mortality. Nonetheless, binders have been used extensively, and the preponderance of evidence shows that sevelamer slows the development of VC whereas calcium salts do not. Four studies have demonstrated a slower progression of VC with sevelamer than with calcium-containing binders, although a fifth study showed nonsuperiority. Conversely, the results on mortality with sevelamer have been variable, and data on calcium-based binders are nonexistent. Improved survival with sevelamer was demonstrated in a small randomized clinical trial, whereas a larger randomized trial failed to show a benefit. In addition, preclinical models of renal failure and preliminary clinical data on hemodialysis patients suggest a potential benefit for bone with sevelamer. Meanwhile, several randomized and observational studies suggested no improvement in bone density and fracture rate, and a few noted an increase in total and cardiovascular mortality in the general population given calcium supplements. Although additional studies are needed, there are at least indications that sevelamer may improve vascular and bone health and, perhaps, mortality in hemodialysis patients, whereas data on calcium-based binders are lacking.

Effects of Sevelamer Carbonate on Advanced Glycation End Products and Antioxidant/Pro-Oxidant Status in Patients with Diabetic Kidney Disease

“…Mild constipation and occasional cramping were present in approximately 10% of patients and did not differ between the SC and CC arms, consistent with previous clinical trials (26,27). There were no serious adverse events in either the SC or CC treatment arm.…”

“…Pill count did not differ by drug assignment, and compliance was 55% in the SC arm and 60% in the CC arm at study end, a finding similar to other studies of these interventions (25,26).…”

Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

“…Little is known about the role of CaSR in the effects of serum calcium on this pathway. To directly test the effects of increased serum calcium level on FGF23 production, mice were injected ip with calcium gluconate, which will not alter bioavailability of phosphorus in the gastrointestinal tract and will bypass any intestinal factor that might be altered with dietary manipulations (30,44). There was a sustained increase in serum calcium for PTH KO and PTH-CaSR DKO mice, whereas there was only a slight, insignificant elevation in WT mice.…”

Phosphate control in dialysis

“…The efficacy of this binder in reducing P levels is well established. 45 Sevelamer can reduce the impact of calcium overload in dialysis patients, also allowing prevention of cardiovascular complications by its nonclassical pleiotropic effects. 46 In the Treat to Goal Study, 47 administration of sevelamer HCl was associated with a reduction in the progression of coronary calcification, compared with the administration of calcium-based binders.…”