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Evidence-Based Supplement Research
Evidence-Based Supplement Research

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

  • 2026-05
  • Kidney medicine 8(5)
    • Wenping Hou
    • Peitao Xie
    • Ya Fu
    • Cen Wang
    • Kun Wang
    • Yang Sun
    • Wei Wei
    • Lei Xu
    • Changhai Su

Study Design

Type
Review
Sample size
n = 376
Population
hyperphosphatemic adults with chronic kidney disease
Methods
Systematic review and network meta-analysis of randomized controlled trials (RCTs). We searched 3 databases from inception through September 2023 for RCTs evaluating 12 phosphorus-lowering drugs. We performed frequentist random-effects network meta-analyses and present mean differences and 95% CIs.
Funding
Unclear

Objective

To evaluate the efficacy and safety of 12 phosphorus-lowering drugs for hyperphosphatemia in chronic kidney disease 3-5 stages.

Study design & methods

Systematic review and network meta-analysis of randomized controlled trials (RCTs). We searched 3 databases from inception through September 2023 for RCTs evaluating 12 phosphorus-lowering drugs. We performed frequentist random-effects network meta-analyses and present mean differences and 95% CIs. Subgroup analyses were performed between the dialysis and nondialysis patients to assess robustness, source of heterogeneity, and risk of bias using the Cochrane risk of bias assessment tool.

Results

We included 121 trials (18,376 participants) and compared 13 drugs or placebo. In terms of efficacy, except for sodium ferrous citrate, all drugs lowered the level of serum phosphorus compared with placebo. Sucroferric oxyhydroxide (PA21), nicotinic acid, and tenapanor were most likely to be ranked the best, second best, or third best. Calcium/magnesium carbonate, nicotinic acid, and colestilan posed lower risks for hypercalcemia than calcium-based phosphorus binders. All phosphorus-lowering drugs significantly affect serum intact parathyroid hormone levels compared with placebo. Colestilan, tenapanor, 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 hyperphosphatemic adults with chronic kidney disease; considering efficacy and safety, calcium carbonate shows evidence of being the most appropriate drug with or without dialysis.

Registration

Registered at PROSPERO (CRD42024500243).

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