Meta-analysis of the efficacy and safety of sevelamer as hyperphosphatemia therapy for hemodialysis patients

Abstract

This study was designed to examine the relative safety and efficacy of sevelamer in the treatment of chronic kidney disease (CKD) patients in comparison to placebo, calcium carbonate (CC), or lanthanum carbonate (LC). The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were searched for articles published through 18 June 2022. The quality of relevant studies was independently analyzed by two investigators who also extracted data from these manuscripts as per Cochrane Collaboration Handbook 5.3. The safety and efficacy of sevelamer as a treatment for hyperphosphatemia in CKD patients were then examined through a meta-analysis, with the primary patient-level outcomes of interest in this analysis being all-cause mortality and the incidence of gastrointestinal adverse effects. Vascular calcification score was also examined as an intermediate outcome, while serum biochemical parameters including levels of phosphate (P), calcium (Ca), intact parathyroid hormone (iPTH), lipids, C-reactive protein (CRP), or fibroblast growth factor-23 (FGF-23) were additionally assessed. In total, this meta-analysis incorporated data from 34 randomized controlled trials (RCTs) enrolling 2802 patients. Sevelamer was associated with reduced all-cause mortality (RR 0.28, CI 0.19 - 0.41, very low certainty) and Vessel calcification score (RR -0.58, CI -1.11 to -0.04, low certainty) and induced less hypercalcemia (MD -0.28, CI 0.40 to -0.16, low certainty) and hyperphosphatemia (MD -0.22, CI -0.32 to -0.13, low certainty) when compared with Ca-based binders in CKD5D individuals. No significant differences in gastrointestinal adverse events (GAEs) incidence were observed. These data suggest that sevelamer may represent a beneficial means of protecting CKD patients against death and vessel calcification when used to treat hyperphosphatemia, while we found no clinically important benefits in decreasing gastrointestinal adverse effects.

Keywords: Sevelamer; chronic kidney disease; hyperphosphatemia; meta-analysis.

Figure 1.

Quality analyses of the included studies. (a) Risk of bias chart; (b) risk of bias summary for all RCTs. Red: high risk; yellow: unclear risk; green: low risk.

Figure 2.

PRISMA flowchart.

Figure 3.

(a) All-cause mortality; (b) Vessel calcification score.

Figure 4.

Serum phosphorus level.

Figure 5.

Serum calcium level.

Figure 6.

Ca × P product.

Figure 7.

iPTH.

Figure 8.

(a) TC (b) LDL-c.

Figure 9.

Laboratory outcomes (a) CRP; (b) FGF-23.

Figure 10.

Gastrointestinal adverse effects.

Figure 11.

Funnel plots of (a) serum phosphorus; (b) calcium; (c) Ca × P product; (d) iPTH; and (e) GAEs for the sevelamer vs. CC comparison.