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

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

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.

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.

Few high-quality RCTs; unclear allocation concealment and blinding; low evidence quality reduced reliability.

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.

Registered at PROSPERO (CRD42024500243).