Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia.
Department of Medicine, University of Melbourne, Parkville, Australia.
J Am Soc Nephrol. 2022 Jan;33(1):59-76. doi: 10.1681/ASN.2021040554. Epub 2021 Oct 13.
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.
目前尚不清楚降低磷酸盐干预对慢性肾脏病（CKD）患者临床结局的益处；系统评价主要涉及透析患者。本研究旨在总结非钙基降磷治疗在非透析或移植后 CKD 患者中的随机对照试验（RCT）的获益和风险的证据。
我们对非钙基降磷治疗与安慰剂、钙基结合剂或无研究药物治疗的 RCT 进行了系统评价和荟萃分析，纳入对象为未接受透析或移植的 CKD 成人患者。RCT 随访时间≥3 个月，结局包括矿物质代谢生物标志物、心血管参数和不良事件。使用 Sidik-Jonkman 法进行随机效应荟萃分析。采用均数差值（MD）作为具有共同测量单位的连续结局的效应量，采用 Hedge's g 标准化均数差值（SMD）表示其他情况。采用比值比（OR）表示二分类结局。Cochrane 偏倚风险和 GRADE 评估确定证据的确定性。
共纳入 20 项涉及 2498 名参与者（中位样本量 120 名，中位随访时间 9 个月）的试验。总体而言，偏倚风险较低。与安慰剂相比，非钙基磷结合剂降低了血清磷（12 项试验，加权均数差-0.37；95%CI，-0.58 至-0.15mg/dl，低确定性证据）和尿磷排泄量（8 项试验，SMD-0.61；95%CI，-0.90 至-0.31，低确定性证据），但导致便秘发生率增加（9 项试验，对数优势比[OR]0.93；95%CI，0.02 至 1.83，低确定性证据）和血管钙化评分增加（3 项试验，SMD 0.47；95%CI，0.17 至 0.77，极低确定性证据）。关于降磷治疗对心血管事件（OR 对数，0.51；95%CI，-0.51 至 1.17）和死亡率的影响的数据很少。
非钙基降磷治疗可降低血清磷和尿磷排泄量，但对临床结局和中间心血管终点的影响尚不清楚。需要进行充分的 RCT 来评估降磷治疗对患者为中心结局的获益和风险。
