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

Summary

Across 70 RCTs in 15,551 dialysis patients, sevelamer reduced all-cause mortality versus calcium-based binders. Lanthanum and sucroferric oxyhydroxide slowed coronary artery calcium progression, while nicotinamide and sucroferric oxyhydroxide had higher gastrointestinal adverse events.

Key Findings

• Sevelamer reduced all-cause mortality versus calcium-based agents (RR 0.59, 95% CI 0.37–0.94).
• Lanthanum and sucroferric oxyhydroxide slowed CACS progression vs calcium-based agents (SMD −0.26 and −0.50, respectively).
• GI events were highest with nicotinamide, followed by sucroferric oxyhydroxide.
• Calcium-based agents increased serum calcium and reduced iPTH compared with other agents; bicarbonate levels were higher with most agents except sevelamer.

Clinical Implications

Prefer sevelamer over calcium-based binders when mortality reduction is prioritized; consider lanthanum or sucroferric oxyhydroxide to slow coronary calcification while balancing GI tolerability. Tenapanor may be favorable for mortality ranking but requires individual risk–benefit assessment.

Limitations

• Indirect comparisons and heterogeneity across trials and treatment durations (≥8 weeks).
• Adverse event reporting and outcomes varied between studies; potential publication bias cannot be fully excluded.

Future Directions

Head-to-head pragmatic trials and patient-level network meta-analyses are needed to validate mortality and calcification findings and to clarify GI tolerability trade-offs.