Supplementary Material for: Conversion from Epoetin and Darbepoetin to C.E.R.A. in Non-Dialysis CKD Patients: A Multicenter Italian Prospective Study in Nephrology Practice

<i>Background:</i> In non-dialysis patients (ND-CKD), C.E.R.A. has been extensively investigated in ESA-naïve subjects but no data are available on its efficacy after switch from other ESA. <i>Methods:</i> In this prospective, multicenter, open-label study lasting 24 weeks, ND-CKD patients (n = 157) receiving ESA were converted to C.E.R.A. at doses lower than recommended. Primary outcome was the prevalence of Hb target (11-12.5 g/dl). <i>Results:</i> Age was 73 ± 13 years and GFR was 26.2 ± 9.4 ml/min/1.73 m2; male gender, diabetes and prior cardiovascular disease were 49, 33 and 19%, respectively. Doses of darbepoetin (25 ± 16 µg/week, n = 124) and epoetin (5,702 ± 3,190 IU/week, n = 33) were switched to low dose C.E.R.A. (87 ± 17 µg/month). During the study, prevalence of Hb target increased from 60% to 68% at week-24, while that of Hb &lt; 11 g/dl declined from 32% to 16% (p &lt; 0.001). Hb increased from 11.3 ± 0.8 at baseline to 11.7 ± 0.9 g/dl at week-24 (p = 0.01) without changes in C.E.R.A. dose. Significant predictors of Hb increase were low BMI, low Hb and longer dosing intervals before switch. These factors also predicted the risk of Hb overshooting (Hb &gt; 12.5 g/dl) occurring in 57 patients. <i>Conclusions:</i> In ND-CKD, conversion from other ESAs to C.E.R.A. is associated with a better anemia control induced by a greater Hb increase in patients previously treated with ESAs at extended dosing interval. This parameter should be considered when switching to long-acting ESA for its potential impact on the risk of overshooting.

背景：在非透析慢性肾脏病（non-dialysis chronic kidney disease, ND-CKD）患者中，针对促红细胞生成素刺激剂（Erythropoiesis-Stimulating Agents, ESA）初治人群对C.E.R.A.的研究已较为广泛，但尚无关于其从其他ESA转换给药后的疗效数据。
方法：本项为期24周的前瞻性多中心开放标签研究，纳入157例正在接受ESA治疗的ND-CKD患者，将其转换为低于推荐剂量的C.E.R.A.进行治疗。主要结局指标为血红蛋白（hemoglobin, Hb）达标（11~12.5 g/dl）的患者占比。
结果：患者平均年龄为73±13岁，估算肾小球滤过率（estimated glomerular filtration rate, GFR）为26.2±9.4 ml/min/1.73m²；男性、合并糖尿病及既往心血管疾病患者占比分别为49%、33%及19%。原接受达贝泊汀（25±16 μg/周，n=124）和促红细胞生成素（5702±3190 IU/周，n=33）的患者，均转换为低剂量C.E.R.A.（87±17 μg/月）。研究期间，Hb达标率从基线的60%升至第24周的68%，而Hb<11 g/dl的患者占比从32%降至16%（p<0.001）。患者Hb水平从基线的11.3±0.8 g/dl升至第24周的11.7±0.9 g/dl（p=0.01），且C.E.R.A.剂量未发生调整。Hb水平升高的显著预测因素包括低体质量指数（body mass index, BMI）、基线Hb水平较低以及转换前更长的给药间隔时间。上述因素同时可预测Hb超靶（Hb>12.5 g/dl）的发生风险，本研究中共57例患者出现该情况。
结论：在ND-CKD患者中，对于既往接受长间隔给药方案ESA治疗的人群，转换为C.E.R.A.治疗可通过提升Hb水平实现更好的贫血控制。鉴于该参数对Hb超靶风险存在潜在影响，在转换为长效ESA治疗时应将其纳入考量。