Phosphate-Binding Agents in Adults With CKD: A Network Meta-analysis of Randomized Trials
Phosphate-Binding Agents in Adults With CKD: A Network Meta-analysis of Randomized Trials
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DOI：
10.1053/j.ajkd.2016.05.015
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发表时间：
2016-11-01
影响因子：
13.2
通讯作者：
Strippoli, Giovanni F. M.
中科院分区：
文献类型：
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作者：
Palmer, Suetonia C.;Gardner, Sharon;Strippoli, Giovanni F. M.
背景：指南优先推荐患有慢性肾病（CKD）的成人使用非磷酸钙结合剂。我们对 CKD 的磷酸盐结合剂策略进行比较和排名。研究设计：网络荟萃分析。设置和人群：患有 CKD 的成人。研究选择标准：分配磷酸盐结合剂的随机试验。干预措施：司维拉姆、镧、铁、钙、考乐替兰、双沙洛姆、烟酸和镁。结果：主要结果是全因死亡率。其他结局包括心血管死亡率、心肌梗死、中风、不良事件、血清磷和钙水平以及冠状动脉钙化。 结果：纳入 77 项试验（12,562 名受试者）。大多数研究（11,009 名患者中的 62 项试验）是在透析人群中进行的。试验通常持续时间较短（中位数为 6 个月），并且存在较高的偏倚风险。 20 项研究在 86,744 个患者月的随访期间确定了全因死亡率。没有证据表明任何药物类别与安慰剂相比可以降低死亡率或心血管事件。与钙剂相比，司维拉姆降低了全因死亡率（OR，0.39；95% CI，0.21-0.74），而镧、铁和考来替兰的治疗效果并不显着（OR 为 0.78 [95% CI，0.16-3.72]、0.37 [95% CI，0.09-1.60] 和 0.55 [95% CI，0.07-4.43]，分别）。镧会引起恶心，司维拉姆引起便秘的风险最高，铁会引起腹泻。与安慰剂相比，所有磷酸盐结合剂都能更大程度地降低血清磷水平，其中铁剂被列为最佳治疗方法。司维拉姆和镧引起高钙血症的风险明显低于钙。局限性：一致性测试有限；结论：目前没有证据表明磷酸盐结合剂治疗与安慰剂相比可以降低成人 CKD 患者的死亡率。目前尚不清楚钙剂与司维拉姆相比较高的死亡率是否反映了钙剂的净危害、司维拉姆的净效益、两者兼而有之或两者都没有。铁基粘合剂显示出更大程度降低磷酸盐的证据，值得在随机试验中进行进一步检查。 Am J 肾病杂志。 68（5）：691-702。 (C) 2016 年作者。由 Elsevier Inc. 代表国家肾脏基金会 (National Kidney Foundation, Inc.) 出版。
Background: Guidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD.Study Design: Network meta-analysis.Setting & Population: Adults with CKD.Selection Criteria for Studies: Randomized trials with allocation to phosphate binders.Interventions: Sevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium.Outcomes: The primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification.Results: 77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium.Limitations: Limited testing of consistency; short follow-up.Conclusions: There is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD. It is not clear whether the higher mortality with calcium versus sevelamer reflects whether there is net harm associated with calcium, net benefit with sevelamer, both, or neither. Iron-based binders show evidence of greater phosphate lowering that warrants further examination in randomized trials. Am J Kidney Dis. 68(5): 691-702. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.