Department of Medicine, Division of Nephrology, Kidney and Dialysis Research Laboratory, St. Elizabeth's Medical Center, Boston, MA 02135, USA.
Am J Kidney Dis. 2013 Jan;61(1):44-56. doi: 10.1053/j.ajkd.2012.07.014. Epub 2012 Aug 22.
Targeting higher hemoglobin levels with erythropoiesis-stimulating agents (ESAs) to treat the anemia of chronic kidney disease (CKD) is associated with increased cardiovascular risk.
Metaregression analysis examining the association of ESA dose with adverse outcomes independent of target or achieved hemoglobin level.
SETTING & POPULATION: 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 the treatment of anemia in adults with CKD, with a 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 the 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 level (IRR, 1.48; 95% CI, 1.02-2.14), as did total-study-period mean ESA dose adjusting for target hemoglobin level (IRR, 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 also was 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 level.
用促红细胞生成素刺激剂（ESA）来提高血红蛋白水平以治疗慢性肾脏病（CKD）的贫血与心血管风险增加有关。
荟萃回归分析，检查 ESA 剂量与目标或实际血红蛋白水平无关的不良结果的关联。
患有 CKD 贫血的患者，不论其透析状态如何。
我们检索了 MEDLINE（从建立到 2010 年 8 月）和已发表的荟萃分析的参考文献，并选择了评估 ESA 治疗 CKD 成人贫血疗效的随机对照试验，试验持续时间至少为 3 个月。两位作者独立筛选引文并提取相关数据。个别研究臂被视为队列，构成分析单位。
每周促红素 alfa 当量标准化的 ESA 剂量和血红蛋白水平。
31 项试验（12956 名患者）符合标准。全因死亡率与较高的（每 10000-U/周促红素 alfa 当量增加）前 3 个月平均 ESA 剂量（发生率比 [IRR]，1.42；95%可信区间，1.10-1.83）和整个研究期间的平均 ESA 剂量（IRR，1.09；95%可信区间，1.02-1.18）相关。在前 3 个月调整平均血红蛋白水平后，前 3 个月 ESA 剂量仍有意义（IRR，1.48；95%可信区间，1.02-2.14），在前 3 个月调整目标血红蛋白水平后，整个研究期间平均 ESA 剂量也有意义（IRR，1.41；95%可信区间，1.08-1.82）。ESA 剂量与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。较高的整个研究期间的平均 ESA 剂量也与高血压、中风和血栓形成事件（包括透析血管通路相关的血栓形成事件）的发生率增加相关。
使用研究水平的汇总数据；使用促红素 alfa 当量剂量；缺乏混杂因素的调整。
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有关，而与血红蛋白水平无关。
