Hemodialysis (HD) patients with hyperphosphatemia who receive sevelamer as an adjunct to calcium-based phosphate binders or a substitution have lower mortality, a new study finds.

Calcium-based binders such as calcium carbonate and calcium acetate have been associated with arterial calcification. However, previous trials have not consistently shown benefit from switching from calcium-based binders. Furthermore, in real-world practice, the non-calcium, resin-based binder sevelamer frequently is taken in conjunction with calcium-based binders.

To address outstanding questions, Hirotaka Komaba, MD, of Tokai University School of Medicine in Isehara, Japan, and colleagues examined data from DOPPS (Dialysis Outcomes and Practice Patterns Study) phases 3 (2005–2008) and phase 4 (2008–2011) in 12 countries. Of 12,564 patients with hyperphosphatemia taking calcium-based phosphate binders, 2606 subsequently received sevelamer hydrochloride or sevelamer carbonate as either add-on or alternative therapy.

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In the initial 4 months of treatment, mean serum phosphorus levels in patients receiving sevelamer fell by 0.3 mg/dL, followed by slower declines, according to results published online ahead of print in the Clinical Journal of the American Society of Nephrology. Serum levels of calcium and parathyroid hormone did not change meaningfully.

To assess survival, the investigators matched 2501 sevelamer-treated patients with one or more patients not treated with sevelamer with similar estimated risks of death. Patients treated with sevelamer had a 14% lower risk for mortality than patients not receiving sevelamer.

“Our results extend the findings from recent observational studies showing the survival benefit of phosphate-lowering therapy … and provide a new rationale for using sevelamer as a switch or add-on therapy in patients on hemodialysis being treated with calcium-based phosphate binders,” Dr Komaba and the team wrote.

The authors noted that several possible mechanisms could explain why sevelamer was associated with improved survival. “The most plausible mechanism is that the improved control of serum phosphorus, along with decreases in the calcium load, was associated with attenuation of vascular calcification and thereby led to improved cardiovascular outcomes,” they stated.

The investigators also discussed additional possibilities, including reductions in malnutrition, fibroblast growth factor 23, uric acid, low-density lipoprotein levels, and/or advanced glycation end products.

In their discussion of study limitations, the team noted that sevelamer hydrochloride and sevelamer carbonate have different profiles for metabolic acidosis, which might affect survival. In addition, the researchers said they had scant data on phosphate binder dosages and adherence, and no information on over-the-counter calcium carbonate use. The investigators also lacked information regarding dietary intake of phosphate or protein. “It is likely that patients who were prescribed sevelamer had higher intake of both phosphate and protein than those not treated with sevelamer.”

“Future studies should focus on determining whether better or more intensive management of hyperphosphatemia might reduce mortality risk in patients on hemodialysis,” Dr Komaba and colleagues said.

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1. Komaba H, Wang M, Taniguchi M, et al. Initiation of Sevelamer and Mortality Among Hemodialysis Patients Treated With Calcium-Based Phosphate Binders. Clin J Am Soc Nephrol. doi: 10.2215/CJN.13091216 [Epub ahead of print]