Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of noncalcium-based phosphate-lowering treatment in nondialysis CKD.

We conducted a systematic review and meta-analyses of RCTs involving noncalcium-based phosphate-lowering therapy compared with placebo, calcium-based binders, or no study medication, in adults with CKD not on dialysis or post-transplant. RCTs had ≥3 months follow-up and outcomes included biomarkers of mineral metabolism, cardiovascular parameters, and adverse events. Outcomes were meta-analyzed using the Sidik–Jonkman method for random effects. Unstandardized mean differences were used as effect sizes for continuous outcomes with common measurement units and Hedge’s g standardized mean differences (SMD) otherwise. Odds ratios were used for binary outcomes. Cochrane risk of bias and GRADE assessment determined the certainty of evidence.

In total, 20 trials involving 2498 participants (median sample size 120, median follow-up 9 months) were eligible for inclusion. Overall, risk of bias was low. Compared with placebo, noncalcium-based phosphate binders reduced serum phosphate (12 trials, weighted mean difference -0.37; 95% CI, -0.58 to -0.15 mg/dl, low certainty evidence) and urinary phosphate excretion (eight trials, SMD -0.61; 95% CI, -0.90 to -0.31, low certainty evidence), but resulted in increased constipation (nine trials, log odds ratio [OR] 0.93; 95% CI, 0.02 to 1.83, low certainty evidence) and greater vascular calcification score (three trials, SMD, 0.47; 95% CI, 0.17 to 0.77, very low certainty evidence). Data for effects of phosphate-lowering therapy on cardiovascular events (log OR, 0.51; 95% CI, -0.51 to 1.17) and death were scant.

Noncalcium-based phosphate-lowering therapy reduced serum phosphate and urinary phosphate excretion, but there was an unclear effect on clinical outcomes and intermediate cardiovascular end points. Adequately powered RCTs are required to evaluate benefits and risks of phosphate-lowering therapy on patient-centered outcomes.

降磷干预对 CKD 患者临床结局的益处尚不清楚；系统评价主要涉及透析患者。本研究旨在总结随机对照试验 (RCT) 中有关非透析 CKD 中非钙基降磷治疗的益处和风险的证据。

我们对 RCT 进行了系统回顾和荟萃分析，这些随机对照试验涉及非钙基降磷疗法与安慰剂、钙基结合剂或无研究药物的比较，用于未接受透析或移植后的 CKD 成人患者。RCTs 有≥3 个月的随访，结果包括矿物质代谢、心血管参数和不良事件的生物标志物。使用 Sidik-Jonkman 随机效应方法对结果进行荟萃分析。非标准化均值差被用作具有共同测量单位的连续结果的效应量，否则使用 Hedge's g 标准化均值差 (SMD)。比值比用于二元结果。Cochrane 偏倚风险和 GRADE 评估决定了证据的确定性。

总共涉及 2498 名参与者的 20 项试验（中位样本量 120，中位随访 9 个月）符合纳入条件。总体而言，偏倚风险很低。与安慰剂相比，非钙基磷酸盐结合剂可降低血清磷酸盐（12 项试验，加权平均差 -0.37；95% CI，-0.58 至 -0.15 mg/dl，低确定性证据）和尿磷排泄（8 项试验，SMD -0.61 ；95% CI，-0.90 至 -0.31，低确定性证据），但导致便秘增加（九项试验，对数优势比 [OR] 0.93；95% CI，0.02 至 1.83，低确定性证据）和更高的血管钙化评分（三项试验，SMD，0.47；95% CI，0.17 至 0.77，极低质量证据）。降磷疗法对心血管事件（log OR，0.51；95% CI，-0.51 至 1.17）和死亡的影响数据很少。

非钙基降磷疗法减少了血清磷酸盐和尿磷酸盐的排泄，但对临床结果和中间心血管终点的影响尚不清楚。需要足够有力的随机对照试验来评估降磷疗法对以患者为中心的结果的益处和风险。