Use of Calcium-Free Binders Justified
Michal L. Melamed, MD, MHS
Elevated serum phosphate levels are associated with all-cause and cardiovascular mortality in patients on dialysis, as demonstrated in a 2004 study by Block and colleagues (J Am Soc Nephrol. 2004;15:2208-2218).
Moreover, a recent analysis showed that incident hemodialysis (HD) patients who were taking any phosphate binder experienced better survival compared with those who were not taking phosphate binders (J Am Soc Nephrol. 2009;20:388-396).
While this study did not evaluate different binder types, it seems clear that phosphate binding has an important role in the health and well-being of dialysis patients.There are several potential reasons to choose noncalcium phosphate binders, although randomized clinical trials using primarily sevelamer hydrochloride have not demonstrated a consistent benefit for the use of such agents. This review will summarize that evidence.
The primary argument for the use of noncalcium-based phosphate binders is the fear that calcium itself may help promote vascular calcification. Several lines of evidence suggest that high serum levels of calcium are detrimental. Elevated calcium levels were shown in the previously cited study by Block et al to be associated with a higher risk of mortality in dialysis patients.
Moreover, elevated phosphate levels and calcium levels induce calcification in in vitro models (Kidney Int. 2004;66:2293-2299). A higher dose of oral calcium from calcium-based phosphate binders was associated with more coronary artery calcification (CAC) in young HD patients (N Engl J Med. 2000;342:1478-1483).
Current therapy with calcium binders probably leads to calcium loading, explaining why National Kidney Foundation Dialysis Outcomes Quality Initiative Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease include suggestions about maximum daily doses of elemental calcium (Am J Kidney Dis. 2003;42:S1-S202).
This fear is especially justified in patients with adynamic bone disease in whom calcium and phosphate are not being deposited into bone but potentially into the vasculature. The currently available noncalcium-based phosphate binders are sevelamer hydrochloride or sevelamer carbonate (an anion exchange resin), lanthanum carbonate, and aluminum hydroxide. Side effects preclude the use of aluminum hydroxide for long-term control of phosphate.