#3775 phosphate binders for patients with chronic kidney disease undergoing dialysis: a network meta-analysis of randomised controlled trials

Abstract Background and Aims Phosphate binders (PBs) are essential for proper serum phosphorus control in patients with chronic kidney disease (CKD) requiring dialysis along with adequate dialysis and phosphorus restriction. To evaluate the clinical efficacy and safety of each PBs, we conducted a systematic review (SR) using a network meta-analysis (NMA) of randomised controlled trials (RCTs). Method We searched published RCTs in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials (CENTRAL), and Clinical trial.gov databases using the search terms and text words relevant to this SR. We included RCTs involving adults (18 years and older) with at least 8 weeks of follow-up. Interventions and controls were the following: sevelamer-, bixalomer-, tenapanor-, iron- (ferric citrate, sucroferric oxyhydroxide), calcium-, magnesium-, lanthanum-, aluminium-, nicotinic acid-, and standard treatment or placebo). The outcomes were all-cause mortality, gastrointestinal adverse events (AEs), coronary artery calcium score (CACS), and serum calcium, phosphorus, and bicarbonate concentrations. Summary estimates were expressed as relative risk (RR) for binary outcomes and mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, respectively, with 95% confidence intervals (CI). The protocol of this study is registered in PROSPERO: CRD42022328388. Results All-cause mortality was identified and analysed in 29 trials involving 12,622 participants. Compared with calcium-containing PBs, sevelamer reduced the risk of all-cause mortality (RR 0.65, 95%CI 0.45 to 0.96). The risk of gastrointestinal AEs was higher for nicotinic acid (RR 3.79, 95%CI 1.29 to 11.12), sucroferric oxyhydroxide (RR 1.96, 95%CI 1.47 to 2.63), sevelamer (RR 1.47, 95%CI 1.14 to 1.88), and lanthanum (RR 1.36, 95%CI 1.14 to 1.64) than calcium-containing PBs. Lanthanum had an inhibitory effect on CACS progression compared to calcium-containing PBs (SMD -0.63, 95% CI -1.05 to -0.22). Serum calcium was lower than calcium-containing PBs in the following order: magnesium (MD -0.67, 95% CI -1.12 to -0.22), placebo (MD -0.64, 95% CI -1.22 to -0.67), nicotinic acid (MD -0.56, 95% CI -1.11 to -0.005), sevelamer (MD -0.35, 95% CI -0.47 to -0.23), and lanthanum (MD -0.24, 95% CI -0.38 to -0.095). No significant difference was observed in serum phosphorus decrease between any PBs and calcium-containing PBs. Serum bicarbonate concentration increased with ferric citrate (MD 1.16, 95% CI 0.36 to 1.96) and sucroferric oxyhydroxide (MD 1.06, 95% CI 0.29 to 1.82) but decreased with sevelamer (MD -1.24, 95% CI -1.71 to -0.77). Conclusion Our findings from SR based on NMA suggest that lanthanum may attenuate CACS and sevelamer may reduce the risk of all-cause mortality compared to calcium-containing PBs in patients with CKD requiring dialysis.