Supplementary Material for: Erythropoiesis-Stimulating Agents (ESA) for Preventing the Progression of Chronic Kidney Disease: A Meta-Analysis of 19 Studies

<b><i>Background:</i></b> The effect of anemia correction on kidney function in chronic kidney disease (CKD) patients remains unclear. As 19-40% of patients with CKD receive an erythropoiesis-stimulating agent (ESA), this is a potentially important consideration. <b><i>Summary:</i></b> We conducted a systematic review and meta-analysis of randomized trials to January 1, 2014 in adult patients with CKD stages 1 to 4. Selection criteria for studies: randomized controlled trials of at least 2 months duration. Patients were allocated to ESA versus placebo, no treatment, or different ESA doses with the purpose of achieving a higher versus a lower hemoglobin target. The analyzed outcomes were the need for renal replacement therapy, doubling of serum creatinine, change in GFR (ml/min), mortality and withdrawal of treatment due to adverse events. A total of 19 trials (n = 8,129 participants with CKD stage 1-4) were reviewed. There was no difference in the risk of end-stage kidney disease (RR, 0.97 [CI 0.83-1.20], 17 trials, 8,104 participants), change in GFR (Mean Difference [MD] -0.45 [-2.21, 1.31], 9 trials, 1,848 participants) or withdrawal of treatment due to adverse events (RR, 1.18 [CI 0.77-1.81], 10 trials, n = 1,958 participants) for patients at higher hemoglobin (Hb) targets. Furthermore, no statistically significant differences in mortality (Risk Ratio [RR] 1.10 [CI 0.90-1.35], 16 trials, n = 8,082 participants) were observed. <b><i>Key Messages:</i></b> There is no evidence that ESA treatment affects renal function in patients with CKD. Use of these agents should not therefore be influenced by considerations about influencing CKD progression.**背景**：慢性肾病(CKD)患者的贫血纠正对肾功能的影响目前尚不明确。鉴于19%~40%的CKD患者会接受促红细胞生成素刺激剂(ESA)治疗，该问题具有重要的临床研究价值。 **研究概述**：本研究针对2014年1月1日前发表的、纳入1~4期CKD成年患者的随机试验开展了系统综述与荟萃分析。研究纳入标准如下：时长至少2个月的随机对照试验；患者被分配至ESA组与安慰剂组、无治疗组，或不同ESA剂量组，以实现更高或更低的血红蛋白靶标水平。本研究分析的结局指标包括肾替代治疗需求、血清肌酐翻倍情况、肾小球滤过率(GFR, ml/min)变化、全因死亡率以及因不良事件终止治疗的情况。最终共纳入19项试验，涉及8129名1~4期CKD患者。对于血红蛋白靶标水平更高的患者群体，其终末期肾病发病风险（相对危险度 RR (Risk Ratio)=0.97，置信区间 CI (Confidence Interval)=0.83~1.20；17项试验，8104名患者）、GFR变化（均差 MD (Mean Difference)=-0.45，CI=-2.21~1.31；9项试验，1848名患者）以及因不良事件终止治疗的比例（RR=1.18，CI=0.77~1.81；10项试验，1958名患者）均未出现显著差异。此外，全因死亡率也未观察到统计学显著差异（RR=1.10，CI=0.90~1.35；16项试验，8082名患者）。 **核心结论**：目前尚无证据表明促红细胞生成素刺激剂(ESA)治疗会影响CKD患者的肾功能。因此，临床应用此类药物时，无需顾虑其对CKD病情进展的潜在影响。