Fujiwara Nobuharu, Nakamura Tsukasa, Sato Eiichi, Kawagoe Yasuhiro, Hikichi Yutaka, Ueda Yoshihiko, Node Koichi
Department of Cardiovascular Medicine, Saga University, Japan.
Intern Med. 2011;50(18):1929-34. doi: 10.2169/internalmedicine.50.5145. Epub 2011 Sep 15.
BACKGROUND/AIMS: Erythropoietin (EPO) has been widely used for the treatment of anemia in chronic kidney disease (CKD). A growing body of evidence indicates that the therapeutic benefits of EPO could extend beyond the improvement of anemia. The aim of the present study was to determine whether EPO affects renovascular and oxidative stress biomarkers in pre-dialysis CKD patients with anemia.
The study was a single-arm prospective study. Fifteen CKD patients (9 males and 6 females, mean age 63 years) with anemia (mean Hb: 8.1 g/dL) were treated with recombinant human EPO; 12,000 U administered subcutaneously once every 2 weeks. Various parameters were measured before and 6 months after treatment. These included serum hemoglobin (Hb), creatinine, estimated glomerular filtration rate (eGFR), proteinuria, urinary liver-type fatty acid binding protein (L-FABP--a biomarker of renal injury), urinary 8-hydroxydeoxyguanosine (8-OHdG--a marker of oxidative stress), serum asymmetrical dimethylarginine (ADMA), carotid artery intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) as vascular markers and plasma brain natriuretic peptide (BNP) levels and left ventricular ejection fraction (LVEF) as cardiac function markers and cardio-thoracic ratio (CTR) and inferior vena cava dimension (IVCS) as extra fluid retention markers.
After 6 months, serum Hb was significantly increased (p<0.001) and urinary levels of protein, L-FABP and 8-OHdG, carotid IMT, baPWV, plasma BNP and serum ADMA levels were significantly decreased (p<0.001). Serum creatinine, eGFR, LVEF, CTR and IVCS showed little difference throughout the experimental period.
These data suggest that recombinant human EPO may ameliorate renal injury, oxidative stress and progression of atherosclerosis in addition to improving anemia in CKD patients.
背景/目的：促红细胞生成素（EPO）已被广泛用于治疗慢性肾脏病（CKD）中的贫血。越来越多的证据表明，EPO的治疗益处可能超出改善贫血的范围。本研究的目的是确定EPO是否会影响透析前贫血的CKD患者的肾血管和氧化应激生物标志物。
该研究为单臂前瞻性研究。15例贫血（平均血红蛋白：8.1g/dL）的CKD患者（9例男性，6例女性，平均年龄63岁）接受重组人EPO治疗；每2周皮下注射12,000U。在治疗前和治疗6个月后测量各种参数。这些参数包括血清血红蛋白（Hb）、肌酐、估计肾小球滤过率（eGFR）、蛋白尿、尿肝型脂肪酸结合蛋白（L-FABP，一种肾损伤生物标志物）、尿8-羟基脱氧鸟苷（8-OHdG，一种氧化应激标志物）、血清不对称二甲基精氨酸（ADMA）、颈动脉内膜中层厚度（IMT）和臂踝脉搏波速度（baPWV）作为血管标志物，以及血浆脑钠肽（BNP）水平和左心室射血分数（LVEF）作为心功能标志物，心胸比率（CTR）和下腔静脉内径（IVCS）作为额外液体潴留标志物。
6个月后，血清Hb显著升高（p<0.001），尿蛋白、L-FABP和8-OHdG水平、颈动脉IMT、baPWV、血浆BNP和血清ADMA水平显著降低（p<0.001）。血清肌酐、eGFR、LVEF、CTR和IVCS在整个实验期间变化不大。
这些数据表明，重组人EPO除了改善CKD患者的贫血外，还可能改善肾损伤、氧化应激和动脉粥样硬化进展。
