静脉用右旋糖酐氢氧化铁注射液治疗血液透析患者肾性贫血的随机及多中心对照临床研究

目的 评价右旋糖酐氢氧化铁注射液治疗维持性血液透析(血透)患者铁缺乏的有效性与安全性。方法 159例维持性血透患者,肾性贫血程度:血红蛋白(Hb)60～90 g/L,或红细胞压积(Hct)0.18～0.27,随机分为静脉组与口服组,分别采用静脉注射右旋糖酐氢氧化铁及口服琥珀酸亚铁进行补铁治疗,总疗程8周。检测治疗前后血清铁指标、红细胞相关指标及生化指标,并对不良反应进行监测。结果 (1)共136例完成本研究,其中静脉组70例、口服组66例,两组患者年龄、性别、贫血程度、血清铁指标及EPO用量相匹配。(2)治疗8周时,静脉组Hb及Hct显著升高,分别上升(25.5±18.7)％和(28.9±21.1)％,幅度明显高于口服组[(12.0±16.8)％和(16.7±22.5)％],P<0.001。(3)治疗8周后两组血清铁蛋白(SF)与转铁蛋白饱和度(TSAT)均较治疗前显著升高,且静脉组升高幅度[SF(316.0±398.0)％,TSAT(89.7±99.0)％】明显高于口服组[SF(157.0±454.0)％,TSAT(35.2±57.0)％】,P<0.001。(4)治疗8周后静脉组血清白蛋白及血清钾较治疗前升高,白蛋白由(36.9±5.2)g/L升至(39.3±5.9)g/L,血清钾由(4.8±0.8)mmol/L升至(5.1±0.9)mmol/L,P<0.01。两组治疗前后血WBC及其它生化指标均相近。(5)静脉组4例有不良反应,1例出现药物相关皮疹,停药后消失,1例轻微心悸,2     

Intravenous iron therapy in pediatric hemodialysis patients: a meta-analysis

Dialysis guidelines recommend aggressive management of anemia, including the use of intravenous iron (IVFe) when indicated. However, few published data are available to guide the use of IVFe in children, and studies are difficult to compare. In this meta-analysis we sought to combine evidence by pooling clinical trial data to determine if IVFe therapy helped increase hematocrit, serum levels of hemoglobin, ferritin, and transferrin saturation (TSAT), and reduce erythropoietin use. We searched MEDLINE and other databases, publications, and other sources to identify as many published and unpublished trials as possible. Of 379 possible studies, nine met the criteria for inclusion and analysis. Across all nine studies, 141 patients were studied, for durations of 2 weeks to 12 months. Pooled results identified an increase in hemoglobin, hematocrit, ferritin, and TSAT levels, and reduced use of erythropoietin, with effect sizes (in standardized weighted mean differences) ranging from 0.62 (95% confidence interval 0.11–1.13) to 1.86 (1.58–2.15) standard deviation improvements. Current practice is based largely on extrapolation from adult data and a few small pediatric trials. The pooled pediatric data suggest that IVFe is effective and produces moderate to large effects on the reported outcomes. Prospective, multi-center trials are needed to determine the optimal utilization of IVFe in children.     

Effect of an intravenous iron dextran regimen on iron stores, hemoglobin, and erythropoietin requirements in hemodialysis patients

Iron deficiency is a common cause of delayed or diminished response to erythropoietin (EPO) in hemodialysis patients. Although oral iron is often prescribed to replete iron stores, this approach to iron supplementation may not be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an effective alternative approach to replete iron stores and may facilitate more cost-effective use of EPO. The purpose of this study was to evaluate an IV iron dextran regimen that consisted of a loading dose phase followed by monthly maintenance doses of iron dextran. The effect of this regimen on iron stores, hemoglobin, and EPO doses was evaluated. This was an open prospective study in adult hemodialysis patients who were iron deficient as defined by a serum ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%. Patients were loaded with 1 g iron dextran in five divided doses and then received monthly maintenance doses of 100 mg for the 4-month study period. Values of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month study period. Thirty hemodialysis patients receiving EPO were identified as being iron deficient and were enrolled in the study. The mean serum ferritin increased significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P = 0.002). Values for hemoglobin did not change significantly during the study period; however, there was a significant reduction in EPO dose from a mean baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P = 0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per year could be saved by use of IV iron dextran. The administration of the IV iron dextran regimen in the iron-deficient hemodialysis population was effective at repleting and maintaining iron stores and reducing EPO use.     

Maintenance intravenous iron therapy in pediatric hemodialysis patients

Iron supplementation is required for optimal response to erythropoietin (EPO) in hemodialysis patients. This is due to blood lost in the dialysis tubing after dialysis and the increased demand for iron by EPO therapy. Maintenance intravenous (IV) iron was administered according to a standardized protocol to pediatric patients on hemodialysis in our institution. The effect of this protocol on EPO dose, iron indices, anemia, and medication costs was evaluated. Data on two groups of patients were retrieved from the health records. Group 1 (n=14) consisted of patients treated in the 18 months prior to the protocol. These patients received oral iron supplements and occasional IV iron. Group 2 (n=5) consisted of all patients treated with the IV iron protocol. There was no difference in clinical characteristics and mean values for monthly hemoglobin, serum iron, ferritin, and transferrin saturation between groups. The dose of EPO was significantly reduced in group 2 compared with group 1 (193.9±121.4 vs. 73.9±39.0 units/kg per week, P<0.05). Medication costs were reduced by 26% in group 2. No significant adverse events were seen. Maintenance IV iron reduced the dose of EPO required to maintain blood hemoglobin levels. Our results also suggest that maintenance IV iron is a more-economic method of iron supplementation for pediatric hemodialysis patients. Received: 13 November 2000 / Revised: 23 April 2001 / Accepted: 24 April 2001     

Reduction in erythropoietin doses by the use of chronic intravenous iron supplementation in iron-replete hemodialysis patients

BACKGROUND: Iron deficiency is the most common cause of suboptimal response to recombinant human erythropoietin (rHuEPO) in chronic hemodialysis (HD) patients. Iron supply can correct this situation, however, optimal dosage, route of administration, and monitoring of iron status during rHuEPO therapy in maintenance HD patients remains controversial. METHODS: We conducted a 12-month intravenous iron substitution trial in 149 iron-replete chronic HD patients receiving subcutaneous rHuEPO therapy. The available iron pool was maintained with 100 mg iron every 2 weeks or 1 month depending on serum ferritin and transferrin saturation levels, the rHuEPO dosage titrated depending on hematocrit (Hct) levels. RESULTS: After 12-month protocol, the Hct increased (28.7 +/- 4.1 vs 27.7 +/- 2.6, p = 0.003), rHuEPO requirement reduced 25% (46.1 +/- 28.9 vs 61.5 +/- 67.8 U/kg/week, p = 0.006), serum ferritin increased (1,383 +/- 727 vs 930 +/- 857 ng/ml, p < 0.001), so did the transferrin saturation (36.1 +/- 12.7 vs 27.5 +/- 12.8%, p < 0.001). The serum albumin decreased slightly but reached statistical significance (4.1 +/- 0.48 vs 4.2 +/- 0.36 g/dl, p = 0.006), so did the cholesterol levels (166 +/- 41 vs 173 +/- 38 mg/dl, p = 0.044) and pre-dialysis creatinine (11.3 +/- 2.3 vs 11.5 +/- 2.4 mg/dl, p = 0.015). Besides, the iPTH levels did not interfere with the rHuEPO dosage reduction and Hct increment in our patients. CONCLUSION: We conclude that maintaining high levels of serum ferritin and transferrin saturation could further reduce the requirement of rHuEPO in chronic HD patients, but the long-term effect of iron overloading to patients' nutritional status must be further evaluated in contrast to the economic saving.     

Intravenous iron gluconate administration increases circulating PAPP-A in hemodialysis patients

BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is a proatherosclerotic molecule, interrelated with oxidative stress in hemodialysis (HD) patients. As intravenous (IV) iron might enhance oxidative stress in HD patients, this study investigates circulating PAPP-A during HD session and after IV iron administration. METHODS: In 20 HD patients, plasma PAPP-A concentration was assessed immunochemically during 2 HD sessions (prior to HD and at 60, 130, and 240 min of HD session). Sodium ferric gluconate (62.5 mg) was given IV to all patients 65 min after the start of the second HD. RESULTS: Sixty-five min after IV iron application, there was a significant increase in plasma PAPP-A (from 36.0+/-9.9 to 79.6+/-28.9 mU/L, p<0.0001). At the end of this HD session, PAPP-A decreased significantly (p<0.0001), but still remained 1.5-fold greater compared with predialysis levels (p<0.0005). CONCLUSION: IV iron increases circulating PAPP-A, and in this way, it might contribute to more pronounced cardiovascular complications in HD patients.     

Impact of iron dextran on polymorphonuclear cell function among hemodialysis patients

BACKGROUND: Polymorphonuclear cell (PMN) dysfunction and the increased use of parenteral iron may be important contributory factors to bacterial infections among patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). We compared the in vitro impact of a commonly used parenteral iron preparation, iron dextran, on PMN function and viability between a group of HD patients with normal iron indices and healthy subjects. METHODS: Eleven patients with ESRD on HD and 10 healthy subjects were studied. PMN harvested from heparinized blood were incubated with iron dextran (0 - 20 mM) in culture medium (RPMI) for 24 hours at 37 degrees C with 5% CO2 following which function and viability were assessed by flow cytometry using appropriate fluorescent labels. RESULTS: Unstimulated, S. aureus and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated hydrogen peroxide (H2O2) production was significantly higher in PMN unexposed to iron dextran from HD patients compared to those from healthy subjects. Iron dextran had no impact on unstimulated PMN H2O2 production in either group. In the healthy group, the only significant change occurred with 4-beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) stimulation, where cells exposed to 0.2 and 2.0 mM iron dextran produced less H2O2 relative to PMN unexposed to iron dextran (p < 0.05). In the HD group, all concentrations of iron dextran significantly attenuated H2O2 production stimulated by S. aureus, fMLP and PMA compared to PMN unexposed to iron dextran. Although PMN phagocytosis decreased with exposure to increasing concentration of iron dextran in both healthy subjects and HD patients, these changes did not achieve statistical significance. No significant changes in PMN viability or apoptosis were seen in either group after exposure to iron dextran. CONCLUSIONS: These results indicate that iron dextran, a standard parenteral iron preparation, attenuates PMN function in HD patients with normal iron indices at clinically relevant concentrations. Further studies are required to evaluate and compare the impact of newer preparations of parenteral iron, such as iron sucrose and ferric gluconate, on PMN function.     

Intravenous iron treatment in paediatric chronic kidney disease patients not on erythropoietin

Intravenous (IV) iron treatment reduces erythropoietin (EPO) dose in paediatric haemodialysis patients. The efficacy in paediatric nonhaemodialysis patients is less well established. IV iron is routinely given in our institution to these patients, including some who have not started EPO. The effect of this strategy was examined. Patients with chronic kidney disease (CKD) or peritoneal dialysis (PD) not on EPO were identified. Case notes were reviewed for haemoglobin (Hb), red cell and iron indices for 6 months before and at least 3 months after IV iron. Five patients were identified. Mean age was 13.3 years and mean IV iron (Venofer) dose = 3.1 mg/kg. Median number of doses = 7 (range 3–10). Hb increased significantly after IV iron from 11.4 ± 0.7 to 12.8 ± 1.3 g/dl (p = 0.02). Mean cell volume increased from 87.7±3.4 to 90.1 ± 3.7 fl (p = 0.01), and mean cell Hb remained unchanged: 29.2 ± 1.2 to 29.7 ± 1.0 pg (p = 0.12). Absolute and percentage reticulocyte count remained unchanged. There was no change in iron indices: ferritin 55.1 ± 31.3 to 97.3 ± 46.5 ng/ml (p = 0.3), iron 18.9 ± 6.9 to 18.1 ± 4.2 μmol/l (p = 0.7), transferrin 1.9 ± 1.6 to 2.0 ± 0.1 g/l (p = 1.0), transferrin saturation 35.7 ± 8.1 to 40.3 ± 18.0% (p = 0.5). IV iron slightly improved Hb levels in five paediatric CKD and PD patients not receiving EPO. This strategy may delay the need for EPO treatment and deserves further evaluation.     

静脉补铁对维持性血液透析患者微炎症及氧化应激状态的影响

目的探讨静脉补铁对维持性血液透析(MHD)患者微炎症及氧化应激状态的影响。方法选择MHD患者71例,随机分为静脉组(24例)、口服组(27例)和未补铁组(20例)。观察用药前后血红蛋白(Hb)浓度、红细胞压积(Hct)、血清铁(SI)、血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)等疗效指标以及血清C反应蛋白(CRP)、白介素-1β(IL-1β)、白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)等炎症指标和血浆及红细胞中丙二醛(MDA)、过氧化物歧化酶(SOD)、谷胱苷肽过氧化物酶(CSH-px)、全血过氧化氢酶(CAT)等氧化应激指标,并监测不良反应。结果8周后,静脉组Hb水平及SF较治疗前明显改善(P<0.01);血浆及红细胞中MDA较治疗前显著升高(P<0.01),SOD、GSH-px和全血中的CAT均较治疗前显著降低(P<0.01或P<0.05);血清CRP、IL-1β、TNF-α均较治疗前显著升高(P<0.01或P<0.05)。相关性分析发现,8周后静脉组血浆MDA与SF呈正相关,MDA与TNF-α呈正相关(P<0.01)。结论静脉补铁可有效改善患者贫血及缺铁,但也加剧了其炎症及氧化应激状态。MHD患者体内炎症及氧化应激之间具有相关性,氧化应激似乎是形成慢性炎症的关键因素之一。     

Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients

BACKGROUND: Intravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients. However, it may also enhance the generation of hydroxyl radicals. Recently, plasma proteins have been demonstrated to be extremely susceptible to oxidative stress. Therefore, we investigated the effect of IVIR on the oxidative status of albumin, a major plasma protein, in HD patients. METHODS: Eleven hemodialysis (HD) patients were treated with 40 mg of saccharated ferric oxide intravenously after every dialysis session for four weeks, and 11 age-/gender-matched HD patients were treated with vehicle. We performed high performance liquid chromatography (HPLC) analysis of serum albumin and determined the levels of reduced and oxidized albumin. Carbonyl formation of plasma proteins were also measured using an anti-2,4 dinitrophenylhydrazine antibody in patients with or without IVIR. RESULTS: IVIR resulted in an increase in both disulfide form (f(HNA-1)) and oxidized form (f(HNA-2)) of albumin in HD patients (36.0 +/- 6.03 vs. 41.7 +/- 6.27; 5.46 +/- 1.50 vs. 8.7 +/- 2.22, respectively, P < 0.05). The findings here also show that IVIR substantially increased plasma protein carbonyl content by oxidizing albumin. In addition, we found a strong correlation between plasma carbonyl content and the levels of oxidized albumin (f(HNA-1) and f(HNA-2)) in HD patients (R= 0.674 and R= 0.724, respectively, P < 0.01). CONCLUSION: The results of this study indicate that the HPLC analysis of serum albumin represents a potentially useful method for the quantitative and qualitative evaluation of oxidative stress in HD patients, and strongly suggest the possibility that oxidative stress, generated by IVIR, enhances the oxidation of albumin in those patients.     

Intravenous iron supplementation in children on hemodialysis

BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in children with ESRD on HD and the effect on iron status measured. METHODS: Fourteen patients were divided into three groups according to their actual iron status. Group A--iron deficient (ferritin (F)<100 microg/L, or F 100-400 microg/L and transferrin saturation (TSAT)<20%). These patients were treated with i.v. iron-sucrose 3 mg/kg/dialysis. Group B--iron-replete (F 100-400 microg/L and TSAT> or =20%, or TSAT>50%). These patients received 0.3 mg/kg/dialysis iron-sucrose. Group C--possible iron-overloaded (F>400 microg/L). These patients were not treated with iron. RESULTS: Group A--3 mg/kg/dialysis of iron-sucrose resulted in a major increase in F, indicating possible iron overload. Therefore, the iron-deficient patients received 1 mg/kg/dialysis iron-sucrose during 22 periods of 2-14 (mean 5) weeks: the median F increased from 186 to 343 microg/L (p<0.001). Group B--0.3 mg/kg/dialysis iron-sucrose resulted in adequate iron levels during 22 periods of 2-60 (mean 9) weeks. CONCLUSION: In children, 3 mg/kg/dialysis iron-sucrose complex results in a possible iron overload. Dosage of 1 mg/kg/dialysis and 0.3 mg/kg/dialysis seem adequate for correction and maintenance therapy respectively.     

Short stature and growth hormone use in pediatric hemodialysis patients

End-stage renal disease (ESRD) causes growth retardation in children, and poor growth has been linked to worse outcomes. Recombinant human growth hormone (rhGH) can increase growth velocity and final adult height in pediatric ESRD patients. We aimed to identify clinical predictors of short stature (height standard deviation score (Ht SDS) <-1.88) and rhGH use in short stature pediatric hemodialysis patients. In 2002, the Centers for Medicare & Medicaid Services (CMS) Clinical Performances Measures (CPM) ESRD Project collected demographic, clinical and laboratory data as well as rhGH use on all in-center hemodialysis patients in the US aged <18 years. The odds ratios (OR) of short stature and rhGH use for individual predictors were determined by multivariate logistic regression modeling. Six-hundred and fifty-one (92%) of 710 eligible patients were included for analysis. Of these, 266 (41%) had Ht SDS <-1.88. After adjustment, short stature was predicted by congenital/urologic causes of ESRD ((OR 5.4; 95% confidence interval [CI], 2.1-13.8; p <0.001) in patients aged 10-14 years; (OR 2.8; 95% CI, 1.5-5.4; p <0.01) in patients aged 15-18 years) and increasing years on dialysis ((OR 1.2; 95% CI, 1.1-1.4; p <0.01) in patients aged 10-14 years; (OR 1.2; 95% CI, 1.1-1.4; p <0.001) in patients aged 15-18 years). Of 266 short stature patients, 214 (80.5%) had data on rhGH use. Of these, 80 (37%) had been prescribed rhGH. After adjustment, use of rhGH in short-stature patients was predicted by white race (OR 2.1; 95% CI, 1.1-4.0; p <0.05), increasing years on dialysis (OR 1.13; 95% CI, 1.05-1.22; p <0.01) and patients with BMI <16.6 kg/m(2) (OR 3.1; 95% CI, 1.2-8.4; p <0.05). Increasing age and level of intact parathyroid hormone were not associated with rhGH use among short stature patients. A significant proportion of pediatric hemodialysis patients have short stature. The majority of short-stature patients are not receiving rhGH. Patients with short stature who are white, have longer durations on dialysis and have lower BMI are more likely to receive rhGH.     

Intravenous ascorbic acid administration for erythropoietin-hyporesponsive anemia in iron loaded hemodialysis patients

Intravenous ascorbic acid administration (IVAA) could override recombinant human erythropoietin (rHuEPO) resistance in hemodialysis patients with iron overload. We investigated the hematopoietic response to IVAA in iron-overloaded hemodialysis patients. We included 36 patients whose ferritin levels were higher than 500 microg/L and who needed more than 100 U/kg/week of rHuEPO. The study included an initial phase (500 mg IVAA twice weekly was administered to all of the patients for 8 weeks) and a maintenance phase (patient groups were formed; Group 1 received IVAA 500 mg/week for 8 weeks and Group 2 received no therapy). We observed a significant increase in hematocrit and transferrin saturation and a decrease in the percentage of hypochromic red cells and ferritin levels at the end of the initial phase. The total weekly-required rHuEpo dose and rHuEpo/hemoglobin also fell significantly after the initial phase. The response remained stable in patient groups during the maintenance phase. In 6 nonresponders, the hypochromic red cells were <10%. In conclusion, IVAA effectively overrides rHuEPO resistance in iron-overloaded hemodialysis patients.     

Low-dose intravenous iron administration in chronic hemodialysis patients treated with recombinant human erythropoietin

We conducted a prospective study to determine the effect of intravenous low-dose iron administration in chronic hemodialysis patients treated with recombinant human erythropoietin (rHuEPO). Sixteen hemodialysis patients (8 males and 8 females; mean age 63.1+/-9.8 years) on maintenance rHuEPO therapy were included in the study. Patients with <100 ng/ml of ferritin received 50 mg iron during every hemodialysis session. Patients with 100-200 ng/ml of ferritin were given 50 mg iron fortnightly. Iron was not supplemented in patients with ferritin levels >200 ng/ml. Mean hematocrit, serum iron levels and transferrin saturations were significantly higher at 6 and 12 months. There was a significant reduction in weekly rHuEPO doses between the start and the 6th and 12th months. Our study shows intravenous iron administration of 100 mg/month may be sufficient to achieve a satisfactory iron status in dialysis patients on maintenance rHuEPO therapy.     

血液透析红细胞生成素抵抗患者pro-hepcidin与炎性反应和铁代谢的关系

目的 研究维持性血液透析(MHD)红细胞生成素(EPO)抵抗患者pro-hepcidin与炎性反应和铁代谢的关系.方法 40例MHD患者为研究对象,其中20例EPO低反应和20例EPO正常反应.20例健康体检者为对照组.检测参试者的血红细胞计数(RBC)、血红蛋白(Hb)、网织红细胞计数(Ret)、红细胞比容(Hct)、血清铁蛋白(SF)、转铁蛋白(TF)、血清铁和总铁结合力、转铁蛋白饱和度(TSAT)(TSAT=血清铁/总铁结合力)、血清pro-hepcidin、血清超敏C反应蛋白(hs-CRP),并比较组间差异.Pearson相关法分析pro-hepcidin的影响因素.ROC曲线预测pro-hepcidin对EPO抵抗的价值.结果 MHD患者SF、血清pro-hepcidin、hs-CRP显著高于健康对照者(P＜0.01),TF显著低于健康对照者(P＜0.05).EPO抵抗患者血清铁蛋白、血清pro-hepcidin、hs-CRP明显高于反应正常的患者(P＜0.01).Pearson相关分析显示MHD EPO抵抗患者血清pro-hepcidin水平与血清铁蛋白(r=0.843,P=0.000)和hs-CRP(r=0.695,P=0.001)呈正相关.预测EPO抵抗的ROC曲线显示,pro-hepcidin、SF、hs-CRP曲线下面积分别为0.713、0.769和0.958.结论 EPO抵抗与炎性反应和铁代谢相关.血清pro-hepcidin、SF、hs-CRP有可能成为EPO抵抗的标志.     

Recombinant human erythropoietin and phlebotomy in the treatment of iron overload in chronic hemodialysis patients

Five long-term hemodialysis patients with clinical iron overload were treated with 300 U/kg of recombinant human erythropoietin (rHuEPO) intravenously (IV) after each hemodialysis. The patients were phlebotomized after each hemodialysis at any time the predialysis hematocrit was 35% or greater. Over a period of 1 year, the average phlebotomy rate varied from 0.5 to 1.1 U/wk with a mean phlebotomy rate of 45.8 +/- 5.6 U/yr (range, 27 to 57 U). The mean serum ferritin decreased from 8,412 +/- 1,599 micrograms/L (ng/mL) to 3,007 +/- 1,129 micrograms/L (ng/mL), and the mean iron removal over this period was 9.5 g. Liver iron deposition, as measured by density on computed tomographic (CT) scan, improved, while skin color lightened significantly. Patients tolerated phlebotomy with no major symptoms or complications and exhibited no change in the hemogram or serum chemistries. In patients with severe iron overload, changes in serum ferritin with erythropoietin treatment alone may not reflect true change in iron burden. Use of high-dose erythropoietin and phlebotomy is an effective and safe (at least for 1 year) method of reducing iron overload in long-term hemodialysis patients.