Efficacy and safety of a low monthly dose of intravenous iron sucrose in peritoneal dialysis patients

Purpose

Scientific data regarding intravenous iron supplementation in peritoneal dialysis (PD) patients are scarce. In attempting to administer the minimum monthly IV iron dose that could improve erythropoiesis, we wanted to assess the safety and efficacy of monthly maintenance intravenous administration of 100 mg iron sucrose in PD patients.

Methods

In a 9-month prospective study, all clinically stable PD patients received intravenously 200 mg of iron sucrose as a loading dose, followed by monthly doses of 100 mg for five consecutive months. Levels of hemoglobin (Hb), ferritin, transferrin saturation (TSAT), reticulocyte hemoglobin content (CHr) and C-reactive protein (CRP) were measured before each administration and 3 months after the last iron infusion. Also, doses of concurrent erythropoietin administration were recorded.

Results

Eighteen patients were eligible for the study. Mean levels of Hb and ferritin increased significantly (from 10.0 to 10.9 mg/dL, p?=?0.01 and from 143 to 260 ng/mL, p?=?0.005), as well as the increase in TSAT levels approached borderline significance (from 26.2 to 33.1%, p?=?0.07). During the 6 months of iron administration, the erythropoietin dose was reduced in five patients and discontinued in one. During the 3 months following the last iron infusion, three of them again raised the erythropoietin dose to previous levels. None of the patients experienced any side effects related to IV iron administration.

Conclusions

A monthly maintenance intravenous dose of 100 mg iron sucrose may be a practical, effective, and safe in the short term, treatment of anemia in PD patients resulting in improved hemoglobin levels, iron indices, and erythropoietin response.

     

Is oxidative stress an issue in peritoneal dialysis?

During the last two decades, oxidative stress (OS) has emerged as a novel risk factor for a variety of adverse events, including atherosclerosis and mortality in chronic kidney disease (CKD) patients. Increased OS occurs even in early stages of the disease, progresses with deterioration of renal function and is further aggravated by hemodialysis (HD), due to the bioincompatibility of the method. Compared to HD, peritoneal dialysis (PD) is a more biocompatible dialysis modality, characterized by a significantly reduced, but still high, OS status. The culprit for OS in PD is mainly the composition of PD solutions (low pH, lactate buffer, increased osmolarity and high glucose concentration). After heat sterilization of PD solutions, formation of glucose degradation products (GDPs) and advanced glycation end‐products (AGEs) trigger inflammation and enhance OS. Chronic exposure of the peritoneum to this toxic, hyperglycemic environment leads to OS‐derived morphologic damage of peritoneal cells, loss of ultrafiltration capacity and decreased technique survival. Moreover, OS is linked with peritonitis, loss of residual renal function, inflammation, atherosclerosis, cardiovascular (CV) disease, and increased mortality. To ameliorate OS status in PD, a multitargeted approach is necessary that includes use of neutral pH, low GDP, low lactate and iso‐ismolar PD solutions, strict glycemic control, optimal volume management and, probably supplementation with antioxidants, N‐acetylcysteine being the most promising among them.     

Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy.

BACKGROUND: Iron balance is critical for adequate erythropoiesis and there remains much debate concerning the optimal timing and dosage of iron therapy for haemodialysis patients receiving recombinant human erythropoietin therapy. METHODS: In this study, we examined the influence of baseline ferritin level and intravenous infusion of 100 mg ferric saccharate on the oxidative status of the patients on maintenance haemodialysis. The levels of antioxidant enzymes and lipid peroxides were determined in erythrocytes and plasma of 50 uraemic patients on haemodialysis. These patients were divided into groups 1, 2, and 3, based on their baseline serum ferritin levels of <300, 301-600, and >601 microg/l, respectively. RESULTS: We found that the mean superoxide dismutase (SOD) activities in the erythrocytes were similar in the three groups of patients and did not differ from those of the age-matched controls. On the other hand, all the haemodialysis patients showed significantly higher plasma SOD activity as compared to controls. After intravenous iron infusion, group 3 patients showed the largest decrease in plasma SOD activity. The plasma glutathione peroxidase (GSHPx) activities of the patients in all three groups and the erythrocyte GSHPx activities of the patients in the groups 2 and 3 were lower than those of the healthy controls. In all three groups of patients, no difference in GSHPx activity was found before and after intravenous iron infusion. On the other hand, we found that the average baseline levels of plasma lipid peroxides of all three groups of patients were significantly higher than that of the controls. The patients in group 3 with the highest serum ferritin levels showed the highest levels of plasma lipid peroxides. More importantly, we found that after iron infusion, the patients in all three groups, particularly those in group 3, showed significantly elevated levels of plasma lipid peroxides. CONCLUSION: We demonstrated that increased oxidative stress in the blood circulation of the uraemic patients on haemodialysis is exacerbated by the elevated baseline serum ferritin levels and intravenous iron infusion. The resultant oxidative damage may contribute to the increased incidence of atherosclerosis in the patients with end-stage renal disease on long-term haemodialysis.     

Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis

BACKGROUND: Several medications have been tested with the aim of decreasing oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The aim of the present study was to assess the influence of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: This was a placebo-controlled study. The study was performed on 34 HD patients, 13 PD patients and 22 healthy volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into 2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300 mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were examined before and after treatment. RESULTS: Before the treatment, the levels of EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001) were significantly higher in the healthy group than PD and HD groups. Serum vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/- 0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment (p=0.021). CONCLUSION: Vitamin E therapy is effective in decreasing the levels of EOF in patients on HD and PD, and it is also effective in decreasing lipid peroxidation in patients on HD.     

Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis

Intravenous iron application to anemic patients on hemodialysis leads to an "oversaturation" of transferrin. As a result, non-transferrin-bound, redox-active iron might induce lipid peroxidation. To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(III) hydroxide sucrose complex intravenously during a hemodialysis session, 22 patients were investigated in a randomized cross-over design, either with or without a single oral dose of 1200 IU of all-rac-alpha-tocopheryl acetate taken 6 h before the hemodialysis session. Blood was drawn before and 30, 60, 90, 135, and 180 min after the start of the iron infusion, and areas under the curve (AUC0-180 min) of ratios of plasma malondialdehyde (MDA) to cholesterol and plasma total peroxides to cholesterol (two markers of lipid peroxidation) were determined as the outcome variables. At baseline of the session without vitamin E supplementation, plasma alpha-tocopherol concentrations (27.6 +/- 1.8 micromol/L) and ratios of alpha-tocopherol to cholesterol (5.88 +/- 1.09 mmol/mol) were normal, plasma MDA concentrations were above normal (1.20 +/- 0.28 micromol/ L), and bleomycin-detectable iron (BDI), indicating the presence of redox-active iron, was not detectable. Upon iron infusion, BDI and MDA concentrations increased significantly (P < 0.001). BDI concentrations explained the increase over baseline in MDA concentrations (MDA = 1.29 +/- 0.075 x BDI). Vitamin E supplementation, leading to a 68% increase in plasma alpha-tocopherol concentrations, significantly reduced the AUC0-180 min of MDA to cholesterol (P = 0.004) and peroxides to cholesterol (P = 0.002). These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron. Given that intravenous iron is applied repeatedly to patients on hemodialysis, this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term.     

Pharmacokinetics of intravenous ceftizoxime in patients on continuous ambulatory peritoneal dialysis

The pharmacokinetics of ceftizoxime (CZM) were determined in 16 non-infected CAPD patients. Patients received either 500 mg or 1000 mg CZM by i.v. bolus. The dialysate exchange volume was 2 l. Serum CZM concentrations at 10 min were 69.7 +/- 19.7 micrograms/ml (1000 mg dose) and 39.2 +/- 8.4 micrograms/ml (500 mg dose), and declined to 33.7 +/- 13.9 micrograms/ml and 16.9 +/- 3.2 micrograms/ml respectively at 360 min. Dialysate CZM levels at 10 and 360 min were 1.8 +/- 1.3 and 19.9 +/- 6.6 micrograms/ml respectively (1000 mg dose) and 1.4 +/- 0.9 and 12.6 +/- 3.5 micrograms/ml (500 mg dose). The half-time of CZM was 14.1 +/- 4.6 h. Peritoneal clearance of CZM was low and equilibrium was not achieved in 6 h. However peritoneal CZM concentrations were adequate within 1 h for the treatment of most organisms which cause CAPD-related peritonitis.     

维持透析时间对腹膜透析患者CKD-MBD的影响

目的 对维持腹膜透析患者的骨代谢指标进行横断面调查,并探讨腹膜透析时间对腹膜透析患者慢性肾脏疾病矿物质骨代谢异常(Chronic kidney disease-mineral and bone disorder,CKD-MBD)的影响.方法 以60例腹膜透析患者和30例健康体检者(对照组)作为研究对象,腹膜透析患者分为A组(腹膜透析时间＜24个月)和B组(腹膜透析时间≥24个月),比较各组间骨代谢指标,如血钙,血磷,25-羟维生素D3[25-hydroxyl vitamin D3,25 (OH) D3]、血清全段甲状旁腺素(intact parathyroid hormone,iPTH)和骨碱性磷酸酶(bone alkaline phosphatase,BALP)的变化.结果 与对照组相比,腹膜透析组的血磷升高,血钙降低且差异具有统计学意义(P1.40±0.29mmol/L vs 1.75±0.57mmol/L;Ca 2.33±0.19mmol/L 2.02±0.2mmol/L,P＜0.叭),iPTH,25 (OH) D3,BALP具有显著性差异[iPTH 436.41±368.28pg/mL vs 53.31±23.71pg/mL;25(OH)D3199.28±139.52ng/mL vs 36.04±14.17ng/mL;BALP80.24±39.41ng/mL vs 173.76±52.38ng/mL,P＜0.01].腹膜透析患者一项或多项骨代谢指标异常的发生率为100％.与对照组相比,A组、B组的血钙降低,血磷升高,且具有统计学意义;但A组与B组的血钙、血磷水平差异无统计学意义(P＞0.05).与对照组相比,A组、B组的iPTH显著升高(53.31±23.71pg/mL vs 596.57±449.91 pg/mL & 276.25±148.23pg/mL,P＜0.05);25(OH)D3显著减低[173.76±52.38ng/mL vs 58.99±25.79ng/mL & 101.48±39.67ng/mL,P＜0.05],A组BALP明显减低(36.04±14.18ng/mL vs 264.58±114.24ng/mL);与A组相比,B组的iPTH升高,25(OH)D3降低,BALP降低,且差异均具有统计学意义(BALP:133.97±133.90ng/mL vs 264.58±114.24ng/mL,P＜0.05).结论 腹膜透析患者存在明显的矿物质骨代谢异常.随着腹膜透析时间的增加,骨转化类型可能会发生变化,由于常规行骨活检较困难,需动态的检测患者的骨代谢血清学指标来辅助判断骨转化类型.腹膜透析患者矿物质骨代谢异常的治疗方案需根据骨转化类型进行调整.     

慢性肾小球肾炎患者血清新蝶呤的水平及其意义

静脉使用蔗糖铁已被广泛地用于血液透析患者肾性贫血的治疗,但在非透析慢性肾脏病(NDCKD)患者中使用不多,大剂量蔗糖铁在NDCKD患者中使用的研究报道更少.我科对使用大剂量蔗糖铁治疗肾性贫血伴铁缺乏的NDCKD患者的安全性及有效性进行了观察.     

Evaluation of oxidative stress after repeated intravenous iron supplementation

Parenteral iron has been recommended for the treatment of iron deficiency in the majority of maintenance hemodialyzed (HD) patients. However, iron supplementation and consequent over saturation of transferrin and high iron levels, may aggravate oxidative stress already present in these patients. This study aimed to further clarify the role of repeated intravenous iron therapy as a supplementary cause of oxidative stress in HD patients. Markers of free radical activities (carbonyl reactive derivatives, CRD, thiol groups, SH, malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase, SOD and glutathione peroxidase, GPX) were determined in plasma and red blood cells (RBC) of 19 hemodialysis patients given a total iron dose of 625 mg (ferrogluconat, Ferrlecit, 62.5 mg). Blood samples were taken before the first and after the last dose of iron. Twenty apparently normal subjects served as healthy controls. Before iron treatment, HD patients exhibited increased concentrations of MDA and CRD in plasma and red blood cells, accompanied with impaired antioxidant capacity. All patients responded to iron therapy with a significant increase in their serum ferritin, serum iron, hemoglobin, and red blood cells levels. However, iron treatment resulted in enhanced oxidative stress in plasma of HD patients, since significant increase in plasma MDA and CRD concentrations, together with a decrease in nonprotein SH groups levels were detected. Supplementation with iron did not significantly influence plasma SOD and GPX activities, nor did any of the red blood cell parameters tested. Our data show that, despite improvement in hematological parameters, an increase in iron stores due to supplementation could also contribute to increased free radical production in HD patients.     

A prospective crossover trial comparing intermittent intravenous and continuous oral iron supplements in peritoneal dialysis patients.

BACKGROUND: Concomitant iron supplementation is required in the great majority of erythropoietin (Epo)-treated patients with end-stage renal failure. Intravenous (i.v.) iron supplementation has been demonstrated to be superior to oral iron therapy in Epo-treated haemodialysis patients, but comparative data in iron-replete peritoneal dialysis (PD) patients are lacking. METHODS: A 12-month, prospective, crossover trial comparing oral and i.v. iron supplementation was conducted in all Princess Alexandra Hospital PD patients who were on a stable dose of Epo, had no identifiable cause of impaired haemopoiesis other than uraemia, and had normal iron stores (transferrin saturation >20% and serum ferritin 100-500 mg/l). Patients received daily oral iron supplements (210 mg elemental iron per day) for 4 months followed by intermittent, outpatient i.v. iron infusions (200 mg every 2 months) for 4 months, followed by a further 4 months of oral iron. Haemoglobin levels and body iron stores were measured monthly. RESULTS: Twenty-eight individuals were entered into the study and 16 patients completed 12 months of follow-up. Using repeated-measures analysis of variance, haemoglobin concentrations increased significantly during the i.v. phase (108+/-3 to 114+/-3 g/l) compared with each of the oral phases (109+/-3 to 108+/-3 g/l and 114+/-3 to 107+/-4 g/l, P<0.05). Similar patterns were seen for both percentage transferrin saturation (23.8+/-2.3 to 30.8+/-3.0%, 24.8+/-2.1 to 23.8+/-2.3%, and 30.8+/-3.0 to 26.8+/-2.1%, respectively, P<0.05) and ferritin (385+/-47 to 544+/-103 mg/l, 317+/-46 to 385+/-47 mg/l, 544+/-103 to 463+/-50 mg/l, respectively, P=0.10). No significant changes in Epo dosages were observed throughout the study. I.v. iron supplementation was associated with a much lower incidence of gastrointestinal disturbances (11 vs 46%, P<0.05), but exceeded the cost of oral iron treatment by 6.5-fold. CONCLUSIONS: Two-monthly i.v. iron infusions represent a practical alternative to oral iron and can be safely administered to PD patients in an outpatient setting. Compared with daily oral therapy, 2-monthly i.v. iron supplementation in PD patients was better tolerated and resulted in superior haemoglobin levels and body iron stores.     

Effect of haemodiafiltration with online regeneration of ultrafiltrate on oxidative stress in dialysis patients.

BACKGROUND: Increased oxidative stress (OxSt) as well as inflammation are risk factors for cardiovascular events and determinant of cardiovascular disease which remains the most common cause of excess morbidity and mortality for end-stage renal disease ESRD patients. Haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) has been shown to have a positive impact on markers of inflammation while its effect on OxSt is not known. METHODS: This study evaluates in haemodialysis patients the effect of HFR on the plasma level of oxidized LDL (OxLDL), a marker of OxSt, and mononuclear cell gene and protein expression of OxSt-related proteins such as p22phox (subunit of NAD(P)H oxidase), PAI-1 (induced by OxSt and atherothrombogenetic) and haeme-oxygenase-1 (HO-1) (induced by OxSt). Fourteen patients were randomized into two groups in a crossover design, treated for 6 month periods with HFR (SG8 Plus-Bellco, Mirandola, Italy) or low-flux bicarbonate dialysis (HD) using a polysulphone dialyser 1.8 m2. Blood samples were collected at the beginning of the study, after 6 months (crossover) and after 12 months. RESULTS: ANOVA analysis of the data performed to rule out any crossover effect in either sequence was not significant and thus data from both sequences were combined and then analysed further statistically. HFR reduced mRNA production and protein expression of p22phox and PAI-1 compared with HD (-9+/-5 vs 2+/-6 Delta%, P<0.0001 and -15+/-20 vs 3+/-17 Delta%, P<0.05 for p22phox; -19+/-6 vs -5+/-5 Delta%, P<0.0001 and -24+/-12 vs 9+/-15 Delta%, P<0.0001 for PAI-1). HO-1 was unchanged (-12+/-8 vs -10+/-8 Delta% and -21+/-12 vs -14+/-8 Delta%) while plasma OxLDL was reduced (-14+/-19 vs 1+/-14 Delta%, P<0.01). CONCLUSIONS: The results of our study indicate that HFR treatment, compared with standard dialysis, has a lower impact on OxSt. Given, the strong relationship between OxSt and inflammation and their impact on the long-term cardiovascular complications in end-stage renal disease patients, HFR might have a more beneficial impact in reducing the risk of atherosclerotic cardiovascular disease in dialysis patients.     

Effect of ACEI/ARBs on peritoneal protein loss in peritoneal dialysis patients

Objective To observe the effect of ACEI/ARBs on peritoneal protein loss in peritoneal dialysis patients. Methods Total of 81 peritoneal dialysis patients were included in the study. Thirty-seven cases were treated with ACEI/ARBs(ACEI/ARBs group), forty-four cases did not receive any ACEI/ARBs (Control group). After 6 mouths, the effect of ACEI/ARBs on peritoneal protein loss was evaluated, and the effects of residual renal function and dialysis age on the peritoneal protein loss were statistically analyzed. Results (1) The peritoneal protein loss was reduced in ACEI/ARBs group, the difference was 1.2(0, 1.6) g/24 h, while in the control group, the protein loss had no statistically significant change, the difference between the two group was statistically significant (P＜0.05). (2) When the patients’ eGFR＞2 ml•min-1•(1.73 m2)-1, the difference of the protein loss in ACEI/ARBs group was 1.4(1.2, 2.3) g/24 h , the difference between the two group was statistically significant(P＜0.01); when patients’ eGFR＜2 ml•min-1•(1.73 m2)-1, the differences of the protein loss between the two groups had no significant difference (P＞0.05). (3) When the dialysis ages＜12 months , the difference of the protein loss was 1.0(0.8, 1.4) g/24 h in ACEI/ARBs group，the differences between the two groups was statistically significant (P＜0.05); when the dialysis ages was from 12 months to 24 months or more than 24 months, The differences of the protein loss between the two groups and control group were both not statistically significant (P＞0.05). Conclusion ACEI/ARBs can reduce peritoneal protein loss in PD patient，the effect was better when patients’ residual renal function was better or dialysis age was shorter.     

The effect of oxidative stress inhibition with trimetazidine on the peritoneal alterations induced by hypertonic peritoneal dialysis solution

BACKGROUND: Chronic peritoneal dialysis (PD) can result in several peritoneal alterations of varying degree, which lead to progressive reduction in dialytic efficacy. Although its pathogenesis has not been clarified yet, it has been proposed that high glucose induced oxidative stress generation within the peritoneal membrane plays an important role in leading to membrane alterations. The aim of this study was to investigate the effect of oxidative stress inhibition on peritoneal alterations induced by hypertonic PD solutions in rats. METHODS: The rats were divided into three groups receiving no treatment (the control group), hypertonic PD solution intraperitoneally (ip) only (the hypertonic dextrose group) and hypertonic PD solution ip plus trimetazidine (TMZ) orally (TMZ group). After 4 weeks, a one-hour peritoneal equilibration test (PET) was performed. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D(1)/D(0) glucose), ultrafiltration volume (UF) and the level of dialysate protein were determined. The levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF) and the activity of glutathione peroxidase (GPx) were investigated in the peritoneal tissue lysates. The peritoneal membrane was evaluated histologically by light microscopy. RESULTS: Compared to the control group, peritoneal function tests (UF: 3.6 +/- 0.4 vs. 1.2 +/- 0.6 mL, D/P urea: 0.57 +/- 0.03 vs. 0.76 +/- 0.04, D(1)/D(0) glucose: 0.46 +/- 0.02 vs. 0.33 +/- 0.05) and morphology (thickness: 4.4 +/- 0.5 vs. 61 +/- 14 micro m and neovascularisation: 0.2 +/- 0.4 vs 2.4 +/- 0.8 number/field) were dramatically altered in the hypertonic PD solution-treated rats. Likewise, higher levels of VEGF, MDA and decreased activity of GPx were determined in the hypertonic PD solution-treated rats. Although peritoneal thickness (37 +/- 17 micro m) was not completely decreased, peritoneal functions were protected in the TMZ group (UF: 4.0 +/- 0.4 mL, D/P urea: 0.62 +/- 0.06, D(1)/D(0) glucose: 0.43 +/- 0.02). In the TMZ group, MDA and VEGF levels and neoangiogenesis were significantly less than those of the hypertonic dextrose group. In addition, GPx activity significantly increased in the TMZ group. CONCLUSIONS: These data demonstrated that not only generating oxidative stress but also attenuating antioxidative system and high glucose concentration can cause structural and functional alterations within the peritoneal membrane. TMZ can preserve these alterations by inhibiting the oxidative stress within the peritoneal membrane.     

Short-term small-dose intravenous iron trial to detect functional iron deficiency in dialysis patients

BACKGROUND/AIM: Management of renal anemia in end-stage renal disease requires careful evaluation of the iron status before and in particular during erythropoietin treatment. However, there is no simple and practical iron index accurately predictive of functional iron deficiency in these patients till now. The purpose of this prospective study, therefore, is to evaluate whether a short course of low-dose intravenous iron challenge can detect functional iron deficiency in hemodialysis patients. METHODS: Twenty-four patients with baseline serum ferritin levels between 100 and 500 ng/ml were treated with intravenous saccharated ferric oxide, 960 mg over 24 hemodialysis treatments, and the hemoglobin level was checked every week. RESULTS: Patients whose hemoglobin value increased at least by 1 g/dl within the 8-week period were classified as having functional iron deficiency or as responders (n = 26; 81.2%). All other subjects were classified as having adequate iron levels or as nonresponders (n = 6; 18.8%). There were no significant differences in age, sex, dialysis years, Kt/V, dialyzers, hemoglobin, and basal and final transferrin saturation and ferritin between responders and nonresponders. In addition, there were no iron indices with acceptable levels of sensitivity and specificity. On the contrary, the cutoff value of increments of hemoglobin of at least 0.2 g/dl after a 2-week intravenous iron trial had a sensitivity of 96.2% and a specificity of 100% in all patients (n = 32) and a sensitivity of 100% and a specificity of 100% after patients with transferrin saturation <20% were excluded (n = 24). These values had the greatest utility of the tests studied in this work. CONCLUSION: A 240-mg intravenous iron challenge during a 2-week period may be a simple, accurate, and straightforward method to detect a functional iron deficiency status in hemodialysis patients undergoing erythropoietin therapy.