Potential cost savings of erythropoietin administration in end-stage renal disease

BACKGROUND: In a Department of Veterans Affairs randomized controlled trial, a lower dose of recombinant human erythropoietin (epoetin) was shown to attain target hematocrit levels when administered subcutaneously compared with intravenously. Since epoetin is expensive, optimizing the therapeutic effect of epoetin using a strategy that includes subcutaneous administration could lead to substantial cost savings. METHODS: We used an economic cost projection model to estimate potential savings to the Medicare End-Stage Renal Disease Program that could occur during a transition from intravenous to subcutaneous administration of epoetin among hemodialysis patients. Data included clinical results from the Department of Veterans Affairs randomized controlled trial, the 1998 Centers for Medicare and Medicaid Services' End-Stage Renal Disease Core Indicators Survey, and the 1997-1998 Medicare claims files. In sensitivity analyses, we varied the expected dose reductions (10% to 50%) and the proportion of patients (25% to 100%) who switched to subcutaneous administration. RESULTS: Medicare cost savings were estimated at $47 to $142 million annually as 25% to 75% of hemodialysis patients who received epoetin intravenously switched to subcutaneous administration while reducing the dose by 32%. A minimal reduction (10%) in epoetin dose would result in Medicare cost savings of an estimated $15 to $44 million annually. CONCLUSION: Administering epoetin subcutaneously would provide substantial cost savings to Medicare. For the transition to occur, consensus among stakeholders is needed, especially among patients whose treatment satisfaction and health-related quality of life would be most affected.     

EPO促进胚胎神经干细胞向神经元分化的形态学研究

目的：探讨促红细胞生成素（erythropoietin ,EPO）促进神经干细胞（neural stem cells ,NSCs）分化的形态学表现,为细胞移植治疗脑部疾病和脑损伤提供实验依据。方法取大鼠14 d胚胎脑皮质先增殖培养,后贴壁分化培养。适时镜下观察,免疫细胞化学染色,用nestin鉴定NSCs ,GFAP鉴定神经胶质细胞、MAP2鉴定神经元。选取第3代 NSCs ,向培养基中分别添加不同剂量的 EPO ,浓度分别为0．5u/ml ,5u/ml ,50u/ml ,500u/ml ,并设不添加EPO的对照组,MAP2免疫荧光共聚焦显微镜观察NSCs向神经元方向的分化。结果1）鼠胚脑皮质在无血清悬浮培养形成大量神经球,并可传代,球内细胞均表达 nestin。分化培养,可检测出MAP2或GFAP阳性细胞。2）EPO≥5u/ml各组分化培养,表达MAP2阳性细胞显著升高（P＜0．05）。结论大鼠胚胎脑皮质体外培养可获得NSCs ;适当浓度EPO可提高NSCs向神经元的分化。     

促红细胞生成素对新生儿缺氧性心肌损伤的影响

目的探讨促红细胞生成素（EPO）对新生儿缺氧性心肌损伤的治疗效果和保护作用,分析其对预后的影响及作用机制,为临床治疗提供依据。方法选择2010年5月-2013年5月宁波大学医学院附属医院缺氧性心肌损伤的新生儿42例,随机分为观察组和对照组,每组各21例,对照组进行常规治疗;观察组在常规治疗基础上应用EPO治疗。检测两组患儿治疗前后的肌酸激酶（CK）及同工酶（CK-MB）、肌钙蛋白Ⅰ、血红蛋白（Hb）、网织红细胞（Ret）,并进行心电图（ECG）检查。观察患儿呼吸急促消失、精神状态好转和ECG恢复时间等指标。结果治疗后两组患儿CK、CK-MB和肌钙蛋白Ⅰ水平均低于治疗前,差异均有统计学意义（P〈0.05）;治疗后观察组CK、CK-MB和肌钙蛋白Ⅰ分别为（198.26±69.04）U/L、（26.9±9.56）U/L、（0.16±0.38）μg/L,均低于对照组[（242.30±103.41）U/L、（37.40±12.30）U/L、（0.54±0.17）μg/L],差异均有统计学意义（P〈0.05）。治疗后观察组Hb和Ret%分别为（171.52±20.83）g/L和（3.55±0.65）,均高于对照组[（155.43±21.42）g/L、（2.51±0.63）],差异均有统计学意义（P〈0.05）。观察组ECG异常率为19.05%,低于对照组（47.62%）,差异有统计学意义（P〈0.05）;观察组呼吸急促消失、精神状态好转时间和ECG恢复时间分别为（1.28±0.14）、（2.56±0.21）、（5.32±0.40）d,均低于对照组[（2.86±0.32）、（4.05±0.41）、（7.38±0.74）d],差异均有统计学意义（P〈0.05）。结论 EPO对新生儿缺氧性心肌损伤的治疗效果较好,能够促进心功能恢复,改善症状或体征,减少症状改善时间,改善预后。     

促红细胞生成素对心肺复苏后大鼠神经功能及脑细胞凋亡的影响

目的 探讨促红细胞生成素（EPO）对心肺复苏后大鼠神经功能及脑细胞凋亡的影响.方法 将成年雄性SD大鼠随机分为对照组和EPO组,每组24只,采用窒息法制备心肺复苏模型,神经功能缺损评分（NDS）法评价复苏后12 h、24 h大鼠的神经功能,于复苏后0h、12 h、24 h用RT-PCR法检测大脑皮层组织凋亡诱导因子（AIF）、caspas-3 mRNA的水平.结果 EPO组心肺复苏后12 h、24h NDS评分分别为（70.50±4.04）分和（65.88±2.64）分,与对照组[12 h：（60.00±3.38）分;24h：（54.50±2.56）分]比较,差异有统计学意义（P＜0.01）;EPO组AIF基因mRNA表达水平在复苏后12h和24 h分别为（1.31±0.26）、（1.87±0.17）,与对照组[12h：（1.88±0.18）;24h：（2.71±0.24）]比较显著降低（均P＜0.01）;EPO组caspase-3基因的mRNA表达水平在复苏后12h和24 h分别为（1.49±0.15）、（1.56±0.10）,与对照组[12 h：（1.68±0.10）;24h：（1.84±0.16）]比较显著降低（均P＜0.01）;结论 EPO可降低AIF、caspase-3 mRNA的转录,减少脑缺血和再灌注损伤导致的皮层神经细胞凋亡,改善心肺复苏后大鼠的脑功能.     

Decreased levels of ferritin,mild thrombocytosis,and increased erythropoietin are sequential events among frequent plateletpheresis donors: Implication for a ferritin screen

BackgroundIt is generally recognized that repeat apheresis increases the risk for iron deficiency, thus may impact on the blood homeostasis. With regard to donor vigilance, we clarified the mid- to long-term effects of plateletapheresis by comparing the most frequent donors with the first-time ones in hematological and biochemical tests.MethodsLevels of erythropoietin (EPO), hemoglobin (Hb) and ferritin were analyzed in double-unit (500 mL whole blood or 6 × 10¹¹ apheresis platelets) donations in three male cohorts, with identifiers of first-time whole-blood donors (n = 30), first-time platelet donors transited from maximal whole blood to apheresis (n = 30) and frequent donors subjected to extreme plateletpheresis (n = 90), respectively. According to the number of donations, the last earnest cohort, who donate almost 24 times a year, was further subdivided into three groups– casual (76–120 life-time donations in 5 years), mediocre (121–168 within 7 years) and enthusiastic (≥169 within 7 years and a month).ResultsRegardless of the donation experience in whole blood or plateletpheresis, iron deficiency (serum ferritin concentrations <15 μg/L) was identified in all earnest cohorts. The ferritin means were significantly lower in plateletpheresis groups, with the lowest values in the enthusiastic group. EPO levels showed a significant inverse correlation with ferritin (p = 0.015, r = –0.224). Long-term earnest donors had the lowest iron stores accompanied by a later thrombocytosis and a final increase in EPO was revealed.ConclusionRegular ferritin screens are crucial to ensure a high level of donor health protection.     

促红细胞生成素联用参附注射液治疗慢性心力衰竭合并贫血的临床观察

目的观察促红细胞生成素（EPO）联合参附注射液治疗合并贫血的慢性心力衰竭（CHF）的临床疗效。方法将160例合并贫血的CHF患者随机分成4组：对照组（常规治疗组）、EPO组、参附注射液组和EPO加参附注射液组,每组各40例。记录治疗前、后各组患者的心功能分级（NYHA）、明尼苏达心衰生活质量评分、左心室射血分数（LVEF）、左心室舒张末期内径（LVEDD）、血浆N末端B型利钠肽原（NT-pro-BNP）水平及血红蛋白（Hb）浓度,统计再住院率,观察不良反应。结果治疗后各组患者的心功能分级和生活质量评分均明显下降,LVEF提高,LVEDD缩小,NT-pro-BNP水平降低,Hb浓度升高,而EPO组、参附注射液组和EPO加参附注射液组的疗效较对照组又有显著提高,再住院率显著低于对照组（尸〈0．05）。各组治疗后未见明显不良反应。结论EPO联合参附注射液治疗慢性心力衰竭合并贫血能显著提高临床疗效。     

Acquired red cell aplasia in association with the use of recombinant erythropoietin in chronic renal failure

Acquired pure red cell aplasia (PRCA) is a rare condition. Traditionally it has been described in association with various etiologies such as parvovirus B19 infection, auto-immune disorders and drugs. Immunologically mediated PRCA is by far the commonest cause in adults, particularly since 1998, when a marked increased incidence of PRCA was noted in chronic renal failure patients receiving subcutaneous (SC) recombinant erythropoietin (rEpo). Typically these patients had been given erythropoietin for correction of anemia of renal failure and subsequently present with severe transfusion dependent anemia. Most cases were associated with SC administration of human serum albumin (HSA) free erythropoieitin alfa product (Eprex). Early recognition and withdrawal of erythropoietin therapy is essential. Treatment with immunosuppressive therapy, particularly in conjunction with renal transplant results in good response with resolution in the majority of cases. The pathogenesis is related to interaction of multiple factors such as formulation change and improper storage leading to increased immunogenicity of the recombinant product. The incidence peaked in 2001 and 2002, subsequently dropping considerably from 2003. This can be explained by the institution of measures such as more stringent handling and storage conditions, improvements in formulation of HSA free Eprex and switch to intravenous (IV) administration for Eprex in dialysis patients. The evidence to date on this condition is summarized in this review.     

Uremia Enhances the Blood Pressure Response to Erythropoietin

To investigate the role of uremia in the development of human recombinant erythropoietin (r-HuEPO)-induced hypertension, Wistar rats were divided into a uremic (subtotal nephrectomy) and a control group. After three weeks, both groups were again divided and each subgroup received either r-HuEPO (100 u/kg s.c., 3 times weekly) or the vehicle for a further 3 weeks. Hematocrit, blood pressure and blood chemistry were measured prior to surgery, before either vehicle or r-HuEPO treatment and before euthanasia. The uremic group developed anemia, hypertension and all the biochemical features observed in humans with end-stage renal disease. r-HuEPO therapy increased hematocrit from 29 ± 2.5% to 46 ± 2% (p < 0.01) in the uremic rats. The mean baseline blood pressure was 119 ± 10 mmHg. At week 3, mean blood pressure was unchanged in control rats, but it was increased to 151 & 5 mmHg (p CO.01) in the nephrectomized group. At week 6, mean blood pressure in the untreated uremic rats remained unchanged from week 3, but blood pressure in the uremic animals treated with r-HuEPO increased significantly to 187 & 8 mmHg (p CO.01). There was no significant correlation between hematocrit and blood pressure in the r-HuEPO treated uremic group (r=0.01, NS). r-HuEPO had no effect on blood pressure in control rats despite a significant increase in hematocrit. These results indicate that the blood pressure response to r-HuEPO is enhanced in rats with chronic renal failure.     

Correction of anaemia of chronic renal failure with recombinant human erythropoietin: safety and efficacy of one year's treatment in a European multicentre study of 150 haemodialysis-dependent patients

One hundred and fifty patients undergoing regular haemodialysis for end-stage renal failure entered a trial of treatment for anaemia with recombinant human erythropoietin (r-HuEPO). At data cut-off 37 patients (24.6%) had dropped out for various reasons; most of them (n = 22) discontinued because of kidney transplantation (after 3-17 months of treatment). The initial dose was 24 U/kg i.v. thrice weekly, with subsequent dose escalations after a minimum of 2 weeks if the haemoglobin (Hb) was less than 10% above the pretreatment baseline. One hundred and forty-three patients who were eligible for efficacy analysis achieved an Hb increase of greater than or equal to 2 g/dl, and all 139 patients eligible for 'full response' analysis (Hb between 10 and 12 g/dl) were dose titrated to reach this arbitrarily defined optimal range. Patients' response to r-HuEPO treatment was independent of age, weight, nephric state or duration of dialysis treatment. To maintain the Hb within the range of 10-12 g/dl during 1 year's treatment (n = 96) a median weekly r-HuEPO dose of 200 U/kg (range 150-300) divided into one, two, or three administrations appeared to be adequate. This maintenance dose depends slightly on the patient's baseline Hb. The study provides evidence that long-term treatment with r-HuEPO is safe. In 48 patients (of whom 12 had no history of hypertension) elevation of blood pressure required additional treatment, which was effective in all but one who was withdrawn from the study. Four patients had seizures and one suffered hypertensive encephalopathy without convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)