肾性贫血治疗中静脉铁剂的应用

慢性肾脏病（chronic kidney disease，CKD）患者缺铁非常普遍。缺铁直接影响贫血纠正，使重组人促红细胞生成素（recombinant human erythropoietin，rHuEPO）的需要量增加。缺铁患者即使应用足量rHuEPO治疗，也无法达到目标血红蛋白水平。因此，监测铁代谢、有效的补充铁剂是纠正肾性贫血的重要环节。     

静脉铁剂对维持性血液透析患者贫血及微炎症、氧化应激的影响

肾性贫血是维持性血液透析患者常见的并发症，重组人红细胞生成素对肾性贫血有肯定的治疗效果，但同时需要常规补充铁剂，并且铁缺乏纠正后可以显著提高重组人红细胞生成素的治疗效果。研究表明静脉铁剂联合重组人红细胞生成素可以有效地纠正维持性血液透析患者的缺铁及贫血状态，     

慢性肾脏病贫血与炎症

肾性贫血是慢性肾脏病患者最常见的并发症之一,红细胞生成素产生不足是导致肾性贫血的主要原因。传统 改善肾性贫血的治疗手段如红细胞生成刺激剂、补充铁剂等治疗达标率低。主要原因在于肾性贫血病因复杂,受多 因素影响,尤其炎症、铁稳态失衡。因此,明确慢性肾脏病炎症与贫血关系,可以为改善炎症状态下肾性贫血提供新 的治疗思路。文章总结了慢性肾脏病患者炎症状态与肾性贫血的相关机制。     

大剂量右旋糖酐铁治疗维持性血液透析患者贫血的疗效

肾性贫血是促进慢性肾衰竭(CRF)进展、增加心脑血管并发症的发生率及病死率的重要危险因素.铁缺乏是导致肾性贫血的重要原因之一,约25％ ～ 33％的CRF贫血患者合并铁缺乏.有研究发现,在纠正铁缺乏及改善红细胞的生成方面静脉铁剂优于口服铁剂,因此K/DOQI工作组建议采用静脉补充铁剂的方法治疗肾性贫血[1].本研究对维持性血液透析(MHD)贫血患者采用两种不同的方法静脉补铁,观察其有效性及安全性.     

慢性肾脏病贫血与炎症

肾性贫血是慢性肾脏病患者最常见的并发症之一，红细胞生成素产生不足是导致肾性贫血的主要原因。传统
改善肾性贫血的治疗手段如红细胞生成刺激剂、补充铁剂等治疗达标率低。主要原因在于肾性贫血病因复杂，受多
因素影响，尤其炎症、铁稳态失衡。因此，明确慢性肾脏病炎症与贫血关系，可以为改善炎症状态下肾性贫血提供新
的治疗思路。文章总结了慢性肾脏病患者炎症状态与肾性贫血的相关机制。     

重视肾性贫血患者静脉铁剂的合理应用

重组人促红细胞生成素（rHuEPO）治疗肾性贫血已20余年，在临床应用中，确实纠正了大部分患者的贫血，改善了患者临床症状，提高了生活质量。但是临床发现不少患者应用足量EPO仍无法使Hb及Hct达到或维持于目标值，人们将这种现象称为EPO低反应性或EPO抵抗，其原因有多种，最常见的是机体缺铁。缺铁的主要原因是慢性肾脏病（CKD）患者摄入不足、隐匿的胃肠道出血、血液透析（HD）患者透析器和血路中血液残留、反复采帆、应用rHuEPO铁需要量增加以及服用磷酸盐结合剂十扰铁的吸收。合理补充足量铁剂不但能显著提高EPO的疗效，而且能减少EPO的用量。     

左卡尼汀在肾性贫血治疗中的应用及对氧化应激反应的影响

目的探讨左卡尼汀联合蔗糖铁注射液及促红细胞生成素（EPO）治疗肾性贫血疗效及对氧化应激反应的影响。方法实验组40例需长期血透并存在较严重肾性贫血患者采用左卡尼汀联合蔗糖铁注射液及EPO治疗,对照组40例采用蔗糖铁注射液及EPO治疗。结果治疗8周末时,实验组血红蛋白、红细胞比容、转铁蛋白饱和度、血清铁蛋白均较治疗前及对照组治疗后升高;实验组超氧化物歧化酶及谷胱甘肽过氧化物酶活性亦高于对照组,但丙二醛低于对照组（P均〈0.05）。结论左卡尼汀治疗肾性贫血疗效显著,且可缓解静脉铁剂引起的氧化应激反应。     

血管紧张素转换酶抑制剂对促红细胞生成素治疗贫血的影响

重组人红细胞生成素(rHuEPO)目前在世界应用于治疗贫血患者,许多调查已证实rHuEPO治疗贫血患者的效能和安全性。本研究检验肾性贫血患者应用血管紧张素转换酶抑制剂(ACEI)是否干扰rHuEPO治疗贫血。     

肾性贫血铁剂的合理应用

在肾性贫血的临床治疗中，导致红细胞生成刺激药物（ESA）抵抗的原因中，最常见的是铁缺乏和铁利用障碍，而足够的铁储存，是ESA发挥最大作用的基本保证。近年来，欧美发达国家制定的肾性贫血铁剂应用指南，为合理使用铁剂提供了可靠的依据，本文通过对相关指南的学习和解读，结合临床实践提出一些临床合理使用铁剂的体会。     

影响肾性贫血治疗效果的因素

肾性贫血是慢性肾脏病的常见并发症,可加速肾功能进展,并增加患者的心血管疾病发生率及病死率。促红细 胞生成素联合铁剂是目前临床一线治疗方案,但仍有患者疗效欠佳。影响肾性贫血治疗可能的因素包括铁缺乏、继 发性甲状旁腺功能亢进症、炎症状态、透析不充分、血管紧张素转换酶抑制剂或血管紧张素受体拮抗剂应用、纯红细 胞再生障碍性贫血等。低氧诱导因子-脯氨酰羟化酶抑制剂作为新一类口服药物,治疗肾性贫血的有效性得到证 实,其长期应用的副反应及耐受性尚需进一步研究。     

Nononcologic use of human recombinant erythropoietin therapy in hospitalized patients

BACKGROUND: Human recombinant erythropoietin (rHuEPO) is widely used to stimulate red blood cell production in patients with anemia due to cancer, renal disease, and other medical conditions, but concern has grown about its overuse and potential for harm. Little is known about the nature of rHuEPO use in hospitalized patients who receive rHuEPO therapy for nononcologic indications. METHODS: We reviewed the drug utilization data from a large academic medical center for all patients admitted during 3 years to identify all patients without cancer who received at least 1 dose of rHuEPO, including their age and sex; diagnoses; hematocrit and hemoglobin and iron levels; and use of supplemental iron. We also compared the rates of laboratory testing and iron supplementation in patients with and without chronic kidney disease (CKD). RESULTS: A total of 1360 distinct patients with 3094 hospitalizations received at least 1 dose of rHuEPO. In 2959 admissions for which hematocrit was determined within 14 days before rHuEPO use, mean values were less than 33% in 1792 (61%) and greater than 36% in 553 (19%). Patients with CKD were more likely than patients without CKD to receive rHuEPO with hematocrit greater than 36% (22% vs 8%; P<.001). Monitoring of iron status was more common in patients with CKD than in those without CKD (64% vs 45%; P <.001). Almost one fourth (23%) of rHuEPO recipients in whom iron levels were measured had absolute iron deficiency (serum ferritin concentration <100 ng/mL). In patients with CKD, only about half (54%) had adequate iron stores at the time of rHuEPO administration; this rate was even lower in patients without CKD (33%; P<.001). Only 66% of patients with documented iron deficiency who were receiving rHuEPO also received concomitant iron supplementation; this rate did not differ between patients with or without CKD. CONCLUSIONS: There is significant variability in the degree of anemia, completeness of iron measurement, and use of iron supplementation in hospitalized patients without cancer who are prescribed rHuEPO. Our results identify potential targets for quality improvement in patients both with and without CKD.     

Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin

PURPOSE: The purpose of this study was to determine the efficacy of recombinant human erythropoietin (rHuEPO) given subcutaneously three times/week in patients with chronic renal failure and anemia (predialysis). PATIENTS AND METHODS: Eleven patients with predialysis chronic renal failure participated in a double-blind, placebo-controlled study of subcutaneously administered erythropoietin. For 12 weeks, patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo. After 12 weeks of placebo, patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved. Throughout the study, blood pressure was monitored closely and blood work was obtained regularly for hemoglobin, hematocrit, reticulocyte count, and iron profile determinations. RESULTS: At 12 weeks, the hematocrit of the treated group had risen from 29% +/- 2% to 35% +/- 2% (p less than 0.001). The placebo group baseline hematocrit was 28% +/- 2% and at 12 weeks 26% +/- 2% After 12 weeks of rHuEPO therapy, the hematocrit of the prior placebo group was 32% +/- 2% (p less than 0.001 versus baseline). No significant change in biochemical parameters was noted. Mean blood pressure values were comparable before and after treatment. All protein ultimately required iron supplementation. In two patients, the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued. CONCLUSIONS: It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis.     

Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial.

We have used recombinant human erythropoietin (rHuEPO) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders. rHuEPO was administered subcutaneously 5 days per week at escalating doses (50 to 150 U/kg per day). The aim of treatment was a hemoglobin (Hb) level greater than or equal to 10 g/dL without blood transfusion. Of 25 patients treated, 17 were evaluable, most of them with a regular need for transfusion. Eight of these had lymphoproliferative disorders (three cases of malignant lymphoma and five of monoclonal gammopathy) and were exposed to cytotoxic therapy. The other nine patients had hematopoietic stem cell disorders (four cases of myelodysplastic syndrome, three of idiopathic myelofibrosis, and two of chronic myelogenous leukemia). All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia, while patients with stem cell disorder showed variable values. Erythroid marrow activity was inadequate in all cases. Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion. The median dose of rHuEPO required for correction of anemia was 75 U/kg. In four cases response was maintained with 50 U/kg, three times per week. There was no complete response among patients with hematopoietic stem cell disorder, although transfusion requirement was eliminated or reduced in four cases. Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response. Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder. We conclude that: (1) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia; (2) this is less likely in hematopoietic stem cell disorders, although favorable responses may be observed in occasional patients; and (3) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia.     

Use of agents stimulating erythropoiesis in digestive diseases

Anemia is the most common complication of inflammatory bowel disease （IBD）. Control and inadequate treatment leads to a worse quality of life and increased morbidity and hospitalization. Blood loss, and to a lesser extent, malabsorption of iron are the main causes of iron deficiency in IBD. There is also a variable compo- nent of anemia related to chronic inflammation. The anemia of chronic renal failure has been treated for many years with recombinant human erythropoietin （rHuEPO）, which significantly improves quality of life and survival. Subsequently, rHuEPO has been used progressively in other conditions that occur with anemia of chronic processes such as cancer, rheumatoid arthritis or IBD, and anemia associated with the treatment of hepatitis C virus. Erythropoietic agents complete the range of available therapeutic options for treatment of anemia associated with IBD, which begins by treating the basis of the inflammatory disease, along with intravenous iron therapy as first choice. In cases of resistance to treatment with iron, combined therapy with erythropoietic agents aims to achieve near-normal levels of hemoglobin/hematocrit （11-12 g/dL）. New formulations of intravenous iron （iron carboxymaltose） and the new generation of erythropoietic agents （darbepoetin and continuous erythropoietin receptor activator） will allow better dosing with the same efficacy and safety.     

Parenteral iron supplementation for the treatment of iron deficiency anemia in children

Iron-deficiency anemia impairs growth and intellectual development in children, which can be reversed only by early diagnosis and iron supplementation. Oral supplementation can efficiently replace stores, but in many cases parenteral iron is needed. Unfortunately some adverse reactions have limited its use in children. We compared the efficacy and safety of intramuscular and intravenous administration in 33 evaluable children with severe iron deficiency and/or iron-deficiency anemia who failed to respond to oral iron supplementation. Nineteen children received intravenous infusion and 14 intramuscular injections. All children showed recovery from iron-deficiency anemia, with statistically similar improvement in hemoglobin levels. The duration of treatment was longer in those receiving intramuscular injection. Parenteral iron therapy for the treatment of iron-deficiency anemia is a rapid, easy, and definitive solution to a long-troubling situation. We suggest the use of parenteral iron, in particular intravenous iron, in children who do not recover from severe iron-deficiency anemia after oral therapy. We should consider the physical and neuropsychological sequelae of long-lasting iron deficiency in children and the fact that oral supplementation is less likely to replace iron stores.     

肾性贫血患者血红蛋白波动与预后关系

慢性肾脏病(CKD)患者血红蛋白波动性大于正常人。CKD患者的血红蛋白高波动性是否与死亡预后直接有关?针对这个问题，当前已经发表了大量基于观察性数据的分析结果，但结果互相矛盾。本文对已经发表的数个有代表性的观察性研究进行深入的剖析，提出血红蛋白波动与患者预后关系的独到见解。     

Evaluation of erythroid marrow response to recombinant human erythropoietin in patients with cancer anaemia.

BACKGROUND. Anaemia is a frequent finding in patients with cancer and may be due to different causes, including blunted erythropoietin production. MATERIALS AND METHODS. In a pilot study, we administered recombinant human erythropoietin (rHuEPO) to twelve patients with solid tumours and secondary anaemia. rHuEPO was given subcutaneously 5 d per week at escalating doses (75 to 150 U/kg per day): the aim of treatment was a Hb level > or = 10 g/dl without blood transfusion. We evaluated endogenous EPO production through serum EPO levels and erythroid marrow activity by means of serum transferrin receptor (TfR). RESULTS. Six out of 12 subjects had defective endogenous EPO production. All patients but two responded to treatment with steady increases in Hb levels above 10 g/dl, and the median dose of rHuEPO required for correction of anaemia was 75 U/kg. Response was associated with an early increase in serum TfR. Six patients developed functional iron deficiency and required iron supplementation to obtain response. Treatment improved functional ability in 4/10 responders. CONCLUSIONS. Subcutaneous rHuEPO can stimulate erythroid marrow activity in cancer anaemia, even in patients with advanced disease, and marrow response can be adequately monitored by serum TfR. Functional iron deficiency as a cause of nonresponse to rHuEPO is frequent in these patients and may require parenteral iron administration. Although erythropoietin can improve the anaemia of cancer, the decision to treat should be individualised for each patient, looking more at the quality of life and cost-effectiveness than at cosmetic increases in the haemoglobin level.     

Weekly subcutaneous recombinant human erythropoietin corrects anemia of progressive renal failure

PURPOSE: The purpose of this study was to analyze data retrospectively from our use of weekly subcutaneous recombinant human erythropoietin (rHuEPO) in predialysis and peritoneal dialysis patients with anemia. PATIENTS AND METHODS: All anemic patients with progressive renal failure (12 predialysis and seven home peritoneal dialysis) in whom subcutaneous rHuEPO therapy was begun at, or was reduced to, a weekly dose were studied retrospectively. Patients were not selected for, nor excluded from, these observations for any other reason. Hematocrit and endogenous creatinine clearance were monitored regularly, and no other new treatment for anemia was given except oral iron. Iron-deficiency anemia was considered improbable because of normal red blood cell mean corpuscular volume. Unfortunately, iron parameters were not monitored. RESULTS: The hematocrit increased 4 to 9 percentage points in 4 to 13 weeks in all but two patients who were initially treated with weekly doses, and a hematocrit of 31% was achieved in these patients within 6 to 12 weeks. The mean effective dose to accomplish this was 150 U/kg. All but three patients could be maintained on weekly doses at a hematocrit of 31% or higher. The mean effective dose was 75 U/kg. CONCLUSION: It is concluded that subcutaneous rHuEPO administered weekly can correct the anemia of predialysis and peritoneal dialysis patients. Weekly dosing is more convenient for patients and may be less costly for Medicare providers.     

合理应用人促红细胞生成素治疗肾性贫血

基因重组人促红细胞生成素(rHuEPO)是治疗肾性贫血的主要药物,2012年改善全球肾脏病预后组织(KDIGO)贫血治疗指南根据最新的研究结果对EPO在慢性肾脏病的应用规范提出了建议。本文将从血红蛋白目标值、EPO治疗的启动时机、给药方案、EPO的反应性等方面进行讨论,探寻更加合理的EPO应用策略。在纠正贫血的过程中,应兼顾EPO治疗的获益和风险。     

Improvement of anemia in hemodialysis patients treated by hemodiafiltration with high-volume on-line-prepared substitution fluid

BACKGROUND: Hemodiafiltration (HDF) is associated with a lower incidence of neuropathy, carpal tunnel syndrome, joint pain, and partial correction of anemia. HDF with on-line-prepared substitution fluid (OL HDF), as compared with conventional hemodialysis, increases the treatment tolerance and, as compared with standard HDF, avoids storage problems and allows a higher substitution volume at low cost. METHODS: Thirty-two hemodialysis patients treated by OL HDF for at least 9 months were studied. Hemoglobin, hematocrit, iron metabolism, serum albumin, dialysis dose and dry body weight were determined under a settled condition with regular hemodialysis 3 months before the transfer to OL HDF. The same parameters were analyzed 3, 6 and 9 months after the beginning of the new treatment modality. RESULTS: During OL HDF, hemoglobin values significantly increased in patients without addition of recombinant human erythropoietin (rHuEPO): baseline vs. 6 months 11 +/- 1.7 vs. 12 +/- 1.8 g/dl (p < 0.01); baseline vs. 9 months 11 +/- 1.7 vs. 12 +/- 1.6 g/dl (p < 0.05). In patients on a maintenance dose of rhuEPO, this could be significantly reduced, while the target hemoglobin levels were maintained (10.6 +/- 0.9 g/dl): baseline 99.8 +/- 50.4 U/kg/week, 3rd month 76.2 +/- 43 U/kg/week, 6th month 64.3 +/- 37 U/kg/week, and 9th month 59.4 +/- 38.6 U/kg/week (p = 0.007, p = 0.0006, and p = 0.0007, respectively, vs. baseline). Iron metabolism, dialysis dose, dry body weight and serum albumin levels did not significantly change during the follow-up period. Further, a stability of the rHuEPO supplementation was observed in 14 patients followed up for 24 months. CONCLUSIONS: OL HDF influences anemia and rHuEPO dose. It allows considerable anemia correction in patients without rHuEPO treatment, while it significantly reduces rHuEPO doses in those on rHuEPO treatment as compared with standard hemodialysis. The rHuEPO costs are consequently reduced.