Efficacy and Safety of Phosphate-Lowering Agents for Adult Patients with Chronic Kidney Disease Requiring Dialysis: A Network Meta-Analysis.

Abstract

Background: It is necessary to update the evidence of each phosphate-lowering agent on dialysis patients.

Methods: From the CENTRAL, MEDLINE, EMBASE, and ClinicalTrial.gov databases, randomized controlled trials (RCTs) using oral phosphate-lowering agents on adult patients requiring maintenance dialysis were extracted. The treatment period was required for eight or more weeks, and the risk of bias was assessed according to the Cochrane Collaboration method. The outcomes were all-cause mortality, cardiovascular mortality, gastrointestinal (GI) events, fracture, coronary artery calcium score (CACS), serum calcium, phosphate, intact parathyroid hormone (iPTH), and bicarbonate levels. A network meta-analyses using multivariate random-effects models were performed for assessing the comparative effectiveness. The ranking of the phosphate-lowering agents was assessed using a surface under the cumulative ranking curve (SUCRA).

Results: A total of 70 RCTs involving 15,551 participants were included. Eleven phosphate-lowering agents including calcium-based agents, sevelamer, bixalomer, lanthanum, sucroferric oxyhydroxide, ferric citrate, tenapanor, magnesium, nicotinamide, aluminum, and sucralfate were assessed. Sevelamer was significantly associated with lower all-cause mortality compared with calcium-based agents [risk ratio (95% Confidence Interval {CI}): 0.59 (0.37-0.94)], and sucroferric oxyhydroxide and tenapanor were estimated to rank high in terms of lowering all-cause mortality based on the SUCRA. The risk of GI events was the highest with nicotinamide, followed by sucroferric oxyhydroxide. Compared with calcium-based agents, CACS were significantly lower among those on lanthanum and sucroferric oxyhydroxide [standardized mean difference (95% CI): -0.26 (-0.52 to -0.01) and -0.50 (-0.95 to -0.06), respectively]. Serum calcium levels were higher and serum iPTH levels were lower in patients treated with calcium-based agents. Except for sevelamer, serum bicarbonate levels for all other agents were higher compared with placebo.

Conclusions: Compared with calcium-based agents, sevelamer was associated with lower all-cause mortality, and sucroferric oxyhydroxide and lanthanum were associated with slower progression of CACS. Potential benefits and harms should be considered when selecting phosphate-lowering agents (PROSPERO: CRD42022328388).