Malgorzewicz S, Lichodziejewska-Niemierko M, Lizakowski S, Liberek T, Lysiak-Szydlowska W, Rutkowski B
Department of Nephrology, Transplantation and Internal Medicine, Medical University Gdansk, Gdansk, Poland.
Clin Nephrol. 2010 Mar;73(3):210-5. doi: 10.5414/cnp73210.
Recombinant human erythropoetin beta; (rHuEPO) has not only an erythropoietic effect but also appears to affect production of cytokines and may improve nutritional status of dialysis patients. Darbepoetin alpha; is a new erythropoiesis-stimulating protein with a threefold longer serum half-life when compared with rHuEPO. The objective of this prospective study was to assess oxidative stress, inflammation, nutrition and hematological response in peritoneal dialysis (PD) patients who were switched from rHuEPO beta to darbepoetin alpha. 12 stable PD patients (6 M, 6 F; mean age 56.2 +/- 15.1 yr.) were evaluated during this study together with 22 healthy volunteers serving as a control group. All patients had been receiving erythropoetin beta subcutaneously once a week before they were reassigned to darbepoetin. The new drug was administered every other week for 6 months, in a dose equivalent to a weekly dose of previously taken rHuEPO. Hematology, iron status and biochemical profiles were evaluated monthly. Markers of oxidative stress: malondialdehyde/ 4-hydroxynoneal (MDA/4HNE), carbonyl groups (CG), oxyLDL and AGEs and markers of inflammation: CRP, TNF alpha, IL-6 were measured on rHuEPO beta before the switch to darbepoetin, and after 1st and 6th month of darbepoetin treatment. The assessment of nutritional status was determined by body mass index (BMI), serum albumin concentration and Subjective Global Assessment (SGA).
Mean levels of Hb and Hct were stable during 6 months of observation and not significantly different from the data observed for on rHuEPO. Nutritional status was good in 9 patients, 3 patients were malnourished at the beginning of this study as assessed by SGA and this status persisted to the end of observation. The levels of markers of oxidative stress and inflammation were statistically higher than in the control group (p < 0.05).
Darbepoetin alpha given subcutaneously once every 2 weeks is effective for the treatment of anemia in PD patients. Less frequent administration of darbepoetin has a biological response similar to weekly administration of rHuEPO.
重组人促红细胞生成素β（rHuEPO）不仅具有促红细胞生成作用，而且似乎还会影响细胞因子的产生，并可能改善透析患者的营养状况。α-达贝泊汀是一种新型促红细胞生成刺激蛋白，与rHuEPO相比，其血清半衰期长三倍。这项前瞻性研究的目的是评估从rHuEPOβ转换为α-达贝泊汀的腹膜透析（PD）患者的氧化应激、炎症、营养和血液学反应。在本研究中评估了12例稳定的PD患者（6例男性，6例女性；平均年龄56.2±15.1岁），并以22名健康志愿者作为对照组。所有患者在重新分配使用α-达贝泊汀之前，每周皮下注射一次促红细胞生成素β。新药每隔一周给药一次，共6个月，剂量相当于之前每周服用的rHuEPO的剂量。每月评估血液学、铁状态和生化指标。在从rHuEPOβ转换为α-达贝泊汀之前以及α-达贝泊汀治疗的第1个月和第6个月后，测量氧化应激标志物：丙二醛/4-羟基壬烯醛（MDA/4HNE）、羰基（CG）、氧化型低密度脂蛋白（oxLDL）和晚期糖基化终末产物（AGEs）以及炎症标志物：C反应蛋白（CRP）、肿瘤坏死因子α（TNFα）、白细胞介素-6（IL-6）。通过体重指数（BMI）、血清白蛋白浓度和主观全面评定法（SGA）来确定营养状况评估。
在6个月的观察期内，血红蛋白（Hb）和血细胞比容（Hct）的平均水平保持稳定，与使用rHuEPO时观察到的数据无显著差异。根据SGA评估，9例患者营养状况良好，3例患者在本研究开始时营养不良，且这种状况一直持续到观察结束。氧化应激和炎症标志物水平在统计学上高于对照组（p<0.05）。
每2周皮下注射一次α-达贝泊汀对治疗PD患者贫血有效。α-达贝泊汀给药频率较低时的生物学反应与每周注射rHuEPO相似。
