|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.
Novel and potentially practice-changing. We currently use calcium-based phosphate binders to control lab abnormalities, usually switching to sevalamer when hypercalcaemia becomes an issue. This review shows that the mortality in RCTs is higher in people treated with calcium binders rather than sevalamer. Whether sevalamer is protective or calcium binders harmful is not addressed by this work, and there are no data to answer this important question. The cost of sevalamer compared with calcium is another important issue. We also do not know whether the harms associated with calcium could be mitigated by a different strategy with the calcium concentration in the dialysate. Finally, this meta-analysis has substantial heterogeneity, only 70 events separating the groups, and borderline statistical significance. Is this good enough evidence on which to change practice?
Although previous meta-analyses suggested similar results favouring non-calcium-containing phosphate binders on patient survival, this update appears to confirm it. It, therefore, has a stronger message about the need for changing clinical practice about first-choice phosphate binders. I do not necessarily agree with the phrasing in the conclusion about harm of calcium-containing phosphate binders per se, since many patients do not always like or tolerate the first-choice binder and could end up requiring a calcium-containing binder that nevertheless is probably better than not taking any binding at all. A good quality meta-analysis.