Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis.
Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis.
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CKD 中红细胞生成刺激剂的剂量和不良后果：荟萃回归分析。
DOI：
10.1053/j.ajkd.2012.07.014
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Jaber BL
中科院分区：
文献类型：
--
作者：
Koulouridis I;Alfayez M;Trikalinos TA;Balk EM;Jaber BL
用促红细胞生成素(ESA)治疗慢性肾脏病(CKD)贫血会增加心血管风险。Meta回归分析检验ESA剂量与不良结果的关系，与目标或已实现的血红蛋白无关。CKD贫血患者，与透析状态无关。我们检索了MEDLINE(启动至2010年8月)和已发表的荟萃分析和随机对照试验的书目，以评估ESA治疗成人慢性肾脏病贫血的疗效，至少持续3个月。两位作者独立筛选了引文并提取了相关数据。个别研究人员被视为队列，并构成分析单位。ESA剂量标准化为每周等值的促红细胞生成素和血红蛋白水平。全因和心血管死亡率、心血管事件、肾脏疾病进展或输血需求。31项试验(12,956名患者)符合标准。全因死亡率与较高的前3个月平均ESA剂量(发生率比[IRR]，1.42；95%CI，1.10-1.83)和较高的总研究期间平均ESA剂量(IRR，1.09；95%CI，1.02-1.18)有关。在调整了头3个月的平均血红蛋白后，前3个月的ESA剂量仍然显著(IRR，1.48；95%CI，1.02-2.14)，整个研究期的平均ESA剂量调整后的目标血红蛋白(IRR，21.41；95%CI，1.08-1.82)也是显著的。ESA剂量和心血管死亡率之间的参数估计在大小和方向上相似，但没有统计学意义。较高的总研究期间平均ESA剂量也与高血压、中风和血栓事件(包括与透析血管通路相关的血栓事件)的发生率增加相关。使用研究水平的汇总数据；使用促红细胞生成素的等量剂量；缺乏对混杂因素的调整。在CKD患者中，较高的ESA剂量可能与全因死亡率和心血管并发症相关，而与血红蛋白无关。
Targeting higher hemoglobin with erythropoiesis-stimulating agents (ESAs) to treat anemia of chronic kidney disease (CKD) is associated with increased cardiovascular risk. Meta-regression analysis examining the association of ESA dose with adverse outcomes, independent of target or achieved hemoglobin. Patients with anemia of CKD, irrespective of dialysis status. We searched MEDLINE (inception to August 2010) and bibliographies of published meta-analyses and selected randomized controlled trials assessing the efficacy of ESAs for treatment of anemia in adults with CKD, with minimum 3-month duration. Two authors independently screened citations and extracted relevant data. Individual study arms were treated as cohorts and constituted the unit of analysis. ESA dose standardized to a weekly epoetin alfa equivalent, and hemoglobin levels. All-cause and cardiovascular mortality, cardiovascular events, kidney disease progression or transfusion requirement. 31 trials (12,956 patients) met criteria. All-cause mortality was associated with higher (per epoetin-alfa–equivalent 10,000-U/wk increment) first-3-month mean ESA dose (incidence rate ratio [IRR], 1.42; 95% CI, 1.10–1.83) and higher total-study-period mean ESA dose (IRR, 1.09; 95% CI, 1.02–1.18). First-3-month ESA dose remained significant after adjusting for first-3-month mean hemoglobin (IRR, 1.48; 95% CI, 1.02- 2.14), as did total-study-period mean ESA dose adjusting for target hemoglobin (IRR, 2 1.41; 95% CI, 1.08–1.82). Parameter estimates between ESA dose and cardiovascular mortality were similar in magnitude and direction but not statistically significant. Higher total-study-period mean ESA dose was also associated with increased rate of hypertension, stroke, and thrombotic events including dialysis vascular access-related thrombotic events. use of study-level aggregated data; use of epoetin alfa–equivalent doses; lack of adjustment for confounders. In patients with CKD, higher ESA dose might be associated with all-cause mortality and cardiovascular complications independent of hemoglobin.
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