Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis

Lancet. 2013 Oct 12;382(9900):1268-77. doi: 10.1016/S0140-6736(13)60897-1. Epub 2013 Jul 19.


Background: Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease.

Methods: We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model.

Findings: Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0·78, 95% CI 0·61-0·98).

Interpretation: Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder.

Funding: None.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Acetates / therapeutic use
  • Aged
  • Calcium Carbonate / therapeutic use
  • Calcium Compounds / therapeutic use*
  • Cause of Death
  • Chelating Agents / therapeutic use*
  • Female
  • Humans
  • Hyperphosphatemia / etiology
  • Hyperphosphatemia / mortality
  • Hyperphosphatemia / prevention & control*
  • Male
  • Middle Aged
  • Phosphates / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Renal Dialysis / adverse effects
  • Renal Dialysis / mortality
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / mortality*


  • Acetates
  • Calcium Compounds
  • Chelating Agents
  • Phosphates
  • Calcium Carbonate
  • calcium acetate