Calcium-based phosphate binders (CBPB) are associated with greater mortality compared with non-calcium phosphate binders (NCBPB), a new review and meta-analysis confirms.

Nigar Sekercioglu, PhD, of McMaster University in Hamilton, Ontario, Canada, and colleagues, updated a 2013 systematic review by Sophie A. Jamal et al. published in the Lancet (382(9900):1268–77).

They identified 15 additional randomized controlled trials published 1996 to 2016 and combined the data with that from 13 trials vetted by Jamal et al. After their review, the investigators rated the studies as low to moderate in quality.

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In the trials, a total of 8335 dialysis and non-dialysis patients (mean age 47 to 69 years) with chronic kidney disease (CKD) were randomly assigned to receive CBPB (calcium acetate, calcium citrate, or calcium carbonate); NCBPB (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide, or ferric citrate); or a control (placebo, low phosphorus diet, or no treatment).

After their analyses, the investigators found an 89% higher risk of mortality from any cause with CBPB compared with sevelamer based on moderate-level evidence. Compared with NCBPB generally, the risk of death was 76% higher. In absolute terms, that represents a mortality increase of 43 cases per 1000 patients.

The results agree with findings from the 2013 review. Rather than pointing to a benefit of NCBPB, Dr Sekercioglu and his team suggested the findings reflect a potential negative effect of calcium-based binders, such as vascular calcification. When the investigators performed a conventional meta-analysis for cardiovascular mortality based on 5 studies, they found no difference between CBPB and NCBPB, however. They did observe higher hospitalization rates with CBPB. Both sets of results were non-significant.   

“Our results raise questions about whether administration of calcium as an intervention for CKD-MBD remains ethical,” Dr Sekercioglu and colleagues concluded. “Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life.” They added that future research should involve patients at earlier stages of CKD who haven’t yet developed irreversible calcification to see whether particular treatments lead to target attainment and clinically meaningful improvement.

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1. Sekercioglu N, Thabane L, Pablo Díaz Martínez J, et al. Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis. PLOS One. doi:10.1371/journal.pone.0156891.