Badve Sunil V, Beller Elaine M, Cass Alan, Francis Daniel P, Hawley Carmel, Macdougall Iain C, Perkovic Vlado, Johnson David W
Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia, 4102.
Cochrane Database Syst Rev. 2013 Aug 26;2013(8):CD006861. doi: 10.1002/14651858.CD006861.pub3.
People living with end-stage kidney disease (ESKD) often develop anaemia. Erythropoiesis-simulating agents (ESAs) are often given to people living with ESKD to maintain haemoglobin at a level to minimise need for transfusion. However, about 5% to 10% of patients with ESKD exhibit resistance to ESAs, and observational studies have shown that patients requiring high doses of ESA are at increased risk of mortality.
This review aimed to study the effects of interventions for the treatment of ESA-resistant anaemia in people with ESKD.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE for randomised controlled trials (RCT) that involved participants with ESKD on dialysis or who were pre-dialysis patients with chronic kidney disease (stage 5). Date of last search: April 2013.
ESA resistance was defined as failure to achieve or maintain haemoglobin/haematocrit levels within the desired target range despite appropriate ESA doses (erythropoietin ≥ 450 U/kg/wk intravenously or ≥ 300 U/kg/wk subcutaneously; darbepoetin ≥ 1.5 µg/kg/wk) in people who were not nutritionally deficient, or who had haematological or bleeding disorders. Extended inclusion criteria for ESA hyporesponsive state were: erythropoietin dose ≥ 300 U/kg/wk and ≥ 150 U/kg/wk for intravenous administration; or ≥ 200 U/kg/wk and ≥ 100 U/kg/wk for subcutaneous administration; or darbepoetin dose ≥ 1.0 µg/kg/wk).
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).
Titles and abstracts of 521 records were screened, of which we reviewed 99 from the full text. Only two studies matched our inclusion criteria. One study compared intravenous vitamin C versus no study medication for six months in 42 ESKD patients on haemodialysis who required intravenous erythropoietin (dose ≥ 450 U/kg/wk). The other included study compared high-flux dialyser versus low-flux dialyser for six months in 48 haemodialysis patients who required subcutaneous erythropoietin (dose ≥ 200 U/kg/wk). Because interventions differed, data could not be combined for quantitative meta-analysis.
AUTHORS' CONCLUSIONS: There was inadequate evidence identified to inform recommendation of any intervention to ameliorate ESA hyporesponsiveness. Adequately powered RCTs are required to establish the safety and efficacy of interventions to improve responsiveness to ESA therapy.
终末期肾病（ESKD）患者常出现贫血。促红细胞生成素类似物（ESAs）常用于ESKD患者，以维持血红蛋白水平，尽量减少输血需求。然而，约5%至10%的ESKD患者对ESAs耐药，观察性研究表明，需要高剂量ESA的患者死亡风险增加。
本综述旨在研究治疗ESKD患者对ESA耐药性贫血的干预措施的效果。
我们在Cochrane对照试验中心注册库（CENTRAL）、MEDLINE和EMBASE中检索了随机对照试验（RCT），这些试验的参与者为接受透析的ESKD患者或慢性肾病（5期）的透析前患者。最后检索日期：2013年4月。
ESA耐药定义为在无营养缺乏、血液学或出血性疾病的患者中，尽管给予适当剂量的ESA（静脉注射促红细胞生成素≥450 U/kg/周或皮下注射≥300 U/kg/周；达比加群≥1.5 µg/kg/周），仍未能达到或维持血红蛋白/血细胞比容水平在期望的目标范围内。ESA低反应状态的扩展入选标准为：静脉注射促红细胞生成素剂量≥300 U/kg/周和≥150 U/kg/周；或皮下注射≥200 U/kg/周和≥100 U/kg/周；或达比加群剂量≥1.0 µg/kg/周）。
两位作者独立评估研究质量并提取数据。采用随机效应模型进行统计分析，结果以风险比（RR）或平均差（MD）及95%置信区间（CI）表示。
筛选了521条记录的标题和摘要，其中99篇全文进行了综述。只有两项研究符合我们的纳入标准。一项研究在42例接受血液透析且需要静脉注射促红细胞生成素（剂量≥450 U/kg/周）的ESKD患者中，比较了静脉注射维生素C与不使用研究药物六个月的效果。另一项纳入研究在48例需要皮下注射促红细胞生成素（剂量≥200 U/kg/周）的血液透析患者中，比较了高通量透析器与低通量透析器六个月的效果。由于干预措施不同，数据无法合并进行定量荟萃分析。
没有足够的证据支持推荐任何改善ESA低反应性的干预措施。需要有足够样本量的RCT来确定改善对ESA治疗反应性的干预措施的安全性和有效性。
