Effect of different phosphate binders on fibroblast growth factor 23 levels in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials

Background: Serum intact fibroblast growth factor 23 (FGF23) levels are progressively increased in relation to the severity of kidney dysfunction. High serum intact FGF23 concentration is associated with the increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Clinically, phosphate binders are commonly used to reduce serum intact FGF23 levels in CKD patients by lowering serum phosphate levels. It is not clear whether all kinds of phosphate binders can reduce serum intact FGF23 levels, or which kind of phosphate binders is more effective in reducing serum intact FGF23 levels in patients with CKD. The aim of this systematic review and meta-analysis was to compare the efficiency of different kinds of commonly used phosphate binders on serum intact FGF23 levels in patients with CKD.

Methods: Systematic searches were performed through PubMed, Cochrane Central Register of Controlled Trials and Embase from 1999 to 2020. We included the studies performed only in human subjects. All randomized clinical trials (RCTs) were included. Reviews, case reports, letters, commentaries, abstracts and unpublished articles were excluded. Risk of bias was assessed by the Cochrane Collaboration's tool. Random effect was performed in meta-analysis. Meta-regression was used to investigate heterogeneity.

Results: Of 1,895 articles, 15 RCTs (comprising 1,098 participants) were included. Common sources of bias were selection bias. Phosphate binders could reduce serum intact FGF23 levels in patients with CKD [standard mean difference (SMD) of total change in serum intact FGF23 levels was 0.91 PG/mL (95% confidence interval: 0.38 to 1.44 PG/mL]. Meta-regression explained 89.02% of heterogeneous sources, indicating that dietary phosphate intake could weaken the effect of phosphate binders on reducing serum intact FGF23 levels, and the effect of phosphate binders on reducing serum intact FGF23 levels in dialysis patients was better than that in early-to-middle CKD patients.

Discussion: Phosphate binders can effectively reduce serum intact FGF23 levels in CKD patients, and iron-based phosphate binders have better effect on reducing serum intact FGF23 levels than other phosphate binders.