The authors of this systematic review note that clinicians are uncertain as to which type of phosphate binder (calcium-based on non-calcium-based) should be prescribed for patients with advanced chronic kidney disease. They conducted a previous meta-analysis in 2009 in order to address this uncertainty – the results suggested a mortality benefit for non-calcium-based binders but this was inconclusive. They therefore performed an updated analysis.
A total of 8 new studies (5 RCTs, 4 of which were open-label) meeting the inclusion criteria were identified from an updated search of the literature. The main results of the updated meta-analysis (based on 11 randomised studies reporting mortality) were as follows:
• Patients randomised to non-calcium-containing phosphate binders had a reduction in all-cause mortality compared to those randomised to calcium-based phosphate binders (RR 0.78; 95% CI 0.61-0.98). This seemed to be independent of serum phosphate reduction.
• The results were similar when all studies were considered (RR 0.87; 0.77-0.97). The reduction in mortality was seen regardless of haemodialysis status.
• The reduction in mortality was only statistically significant in the 5 studies that reported outcomes at 24 months (the authors suggest this was because there was insufficient power to assess the outcome at 36-42 months).
• Analyses of differences in mortality according to type of non-calcium-based binder found that the reductions were not statistically significant (sevelamer [12 studies]: RR 0.89; 95% CI 0.78-1.01; lanthanum [2 studies]: 0.74; 0.49-1.13).
• The authors were unable to show whether the increase in mortality in those taking calcium-based binders was due to an increase in cardiovascular events, as the 8 new studies did not report these outcomes.
• The reduction in vascular calcification was greater in patients randomised to non-calcium-based phosphate binders.
The authors suggest, based on their findings, that first-line therapy for phosphate lowering should be non-calcium-based binders (sevelamer or lanthanum). They note however the non-significant results for lanthanum and sevelamer when assessed individually, and say that further research is required to determine whether outcome differs by specific type of non-calcium-based binder.
The authors go on to discuss the strengths and limitations of their systematic review. Weaknesses highlighted include the following:
• Calcium carbonate and calcium acetate were assumed to be equivalent• Only one study reported specifically on the use of sevelamer carbonate (the rest were sevelamer hydrochloride or the type was specified)• The inability to comment on the effect of other non-calcium-containing binders• The funnel plot indicated potential publication bias • None of the studies formally assessed adverse events • Follow-up was short • A moderate degree of heterogeneity was noted between studies• Due to the design of the studies, the authors were not able to establish whether non-calcium-based binders are inherently beneficial, or if calcium-based binders are harmful, or both