DeFrancisco A L M, Macdougall I C, Carrera F, Braun J, Bárány P, Bridges I, Wheeler T, Tran D, Dietrich A
Hospital Universitario Valdecilla, Servicio de Nefrologia, Santander, Spain.
Clin Nephrol. 2009 Apr;71(4):397-404. doi: 10.5414/cnp71397.
To help identify factors contributing to intra-patient Hb variability, pooled records were analyzed from 5,592 patients undergoing hemodialysis (HD) in European, multicenter, open-label, single-arm Phase 3b trials.
Patients previously treated with recombinant human erythropoietin (rHuEPO) were switched to darbepoietin-alpha administered once a week (QW) or once every 2 weeks (Q2W), maintaining the same dosing schedule and route of ESA administration (intravenous or subcutaneous) up to and through the evaluation period. Patients were treated with darbepoietin-alpha to maintain Hb levels between 10 and 13 g/dl. Intrapatient variability was calculated using the SD model, taking all of an individual patient's Hb values during the evaluation period (Weeks 21 - 24 after conversion) and calculating the SD of these Hb values. Adverse events (AE) of infection or inflammation were recorded.
Smaller variability was seen for patients 65 years of age or older compared with younger patients (p = 0.0044) and greater variability for patients less than 40 years of age compared with older patients (p < 0.01). Little difference in variability was seen in relation to sex overall or to the presence or absence of diabetes. Intra-patient Hb variability was greater in the presence of intercurrent conditions, including infection or inflammation (p = 0.0032), blood transfusion (p < 0.0001), hospitalization (p < 0.0001), or hospitalization for cardiovascular (CV) causes (p = 0.0012), than in their absence. Iron status differences had little detectable effect on intra-patient Hb variability. A larger number of changes made to the ESA dose during the evaluation period was also associated with greater Hb variability compared with fewer dose changes, but this association could not be proved as being causative. Although p values were calculated for some comparisons, statistical significance might not indicate clinical significance because of the large sample size. Multivariable analysis to assess the association between AE status and intra-patient Hb variability, adjusting for age, sex, diabetes status, number of dose changes and iron status showed that AE status was significantly associated with Hb variability.
Additional studies would be needed to further investigate causes and effects of Hb variability and intercurrent events.
为了帮助确定导致患者血红蛋白（Hb）变异性的因素，对欧洲多中心、开放标签、单臂3b期试验中5592例接受血液透析（HD）患者的汇总记录进行了分析。
先前接受重组人促红细胞生成素（rHuEPO）治疗的患者改为每周一次（QW）或每2周一次（Q2W）给予α-达贝泊汀，在整个评估期内维持相同的给药方案和促红细胞生成素类似物（ESA）给药途径（静脉内或皮下）。给予患者α-达贝泊汀治疗以维持Hb水平在10至13 g/dl之间。使用标准差（SD）模型计算患者内变异性，采用评估期内（转换后第21 - 24周）某一患者的所有Hb值并计算这些Hb值的标准差。记录感染或炎症的不良事件（AE）。
65岁及以上患者的变异性小于年轻患者（p = 0.0044），40岁以下患者的变异性大于老年患者（p < 0.01）。总体而言，性别及是否患有糖尿病对变异性的影响不大。在并发疾病（包括感染或炎症，p = 0.0032）、输血（p < 0.0001）、住院（p < 0.0001）或因心血管（CV）原因住院（p = 0.0012）的情况下，患者内Hb变异性高于无这些情况时。铁状态差异对患者内Hb变异性几乎没有可检测到的影响。与较少的剂量变化相比，评估期内对ESA剂量进行更多次更改也与更大的Hb变异性相关，但这种关联不能被证明具有因果关系。尽管对一些比较计算了p值，但由于样本量较大，统计学显著性可能并不表明具有临床意义。多变量分析评估AE状态与患者内Hb变异性之间的关联，对年龄、性别、糖尿病状态、剂量变化次数和铁状态进行校正后显示，AE状态与Hb变异性显著相关。
需要进一步的研究来进一步调查Hb变异性和并发事件的原因及影响。
