Comparative Effectiveness and Safety of Phosphorus-Lowering Drugs for CKD Stages 3-5

Objective: To evaluate the efficacy and safety of 12 phosphorus-lowing drugs for hyperphosphatemia in chronic kidney disease (CKD) stages 3-5.Study Design & Methods: Systematic review and network meta-analysis of randomized controlled trials (RCTs).We searched three databases from inception through September for 2023 RCTs evaluating 12 phosphorus-lowing drugs.We performed frequentist random-effects network meta-analyses and present MD and 95% CIs.Subgroup analyses were performed between the dialysis and non-dialysis patients to assess robustness, source of heterogeneity, and risk of bias using the Cochrane RoB 2 tool. Results:We included 121 trials (18376 subjects) and compared 13 drugs or placebo.In terms of efficacy, except for SFC, all drugs lowered the level of serum phosphorus compared with placebo.PA21, NA and TE were most likely to be ranked the best, second best or third best.CaMg, NA and CO posed lower risks for hypercalcemia than calcium-based phosphorus binder.All phosphorus-lowing drugs significantly affect serum iPTH levels compared with placebo.CO, TE and PA21 posed a higher risk for gastrointestinal discomfort.In addition, iron-containing drugs showed positive effects on iron parameters.Limitations: Few high-quality RCTs; Unclear allocation concealment and blinding; Low evidence quality reduced reliability.Conclusions: PA21 has the best phosphorus-lowering effect in hyperphosphatemia adults with CKD; considering efficacy and safety, CC shows evidence to be the most J o u r n a l P r e -p r o o f appropriate drug with or without dialysis.