Intravenous Iron Administration Research Articles

Reticulocyte Hemoglobin Equivalent: An Indicator of Reduced Iron Availability in Chronic Kidney Diseases during Erythropoietin Therapy

Anemia is a common complication of chronic kidney disease (CKD), particularly in dialysis patients. Correction of anemia in CKD patients includes the administration of both recombinant human erythropoietin and intravenous iron. An optimization of iron treatment requires obtaining a target hemoglobin level and avoiding an excessive body-iron overload. The reticulocyte hemoglobin content (CHr) has been shown to be an early indicator of iron-restricted erythropoiesis. The recent European guidelines for anemia treatment in CKD assessed the value for CHr >29 pg/cell as the reticulocyte parameter to evaluate a patient's iron needs. The reticulocyte hemoglobin equivalent (RET-He), recently introduced to determine the forward scatter of fluorescence-labeled reticulocytes, seems to be a sensitive indicator of iron-deficiency anemia. This study evaluates the concordance between the CHr parameter, used as a reference, and the new RET-He in a cohort of 57 dialysis patients referred to the Nephrology Unit of our hospital. All patients received erythropoietin, and iron was administered intravenously to maintain the hemoglobin level between 10 and 12 mg/dL. A total of 285 determinations were performed with both instruments. In the dialysis population, the 95% central range for CHr of 24.8 to 36.3 pg corresponds to a range for RET-He of 23.3 to 40.1 pg, with a mean bias of 1.12 pg between the 2 parameters. In comparison with CHr, the value of 30.5 pg for RET-He appeared to be the best cut-off point with a very good sensitivity and specificity to determine patients needing iron supplementation. Our study showed an excellent diagnostic efficiency of RET-He to evaluate patients needing iron support and demonstrated a strict correspondence between the classic CHr and the new Ret-He. This correspondence was independent of clinical changes, frequently occurring in dialysis patients. Both parameters could be used soon to guide and monitor iron treatment in dialysis patients.

Recent experience with high-dose intravenous iron administration

It is necessary to provide adequate amounts of bioavailable iron to correct any deficit and maintain body iron stores in anemic patients with chronic kidney disease (CKD). Although dosing regimens for intravenous iron sucrose exist, simplification of these regimens may produce financial savings and reduce the time commitment of both patients and clinicians. We have explored high-dose (500 mg or greater) intravenous iron sucrose regimens in patients with CKD and summarize our findings here. Three studies used 500 mg intravenous iron sucrose doses on 2 or more successive days, and one study examined the feasibility of a single total dose infusion of 1000 mg. We conclude that patients do not tolerate 1000 mg doses as a single infusion. On the other hand, a dosing regimen of 500 mg iron sucrose given intravenously over 3 h on successive days is safe and effective in replenishing and maintaining body iron stores. Finally, in anemic CKD patients not receiving erythropoietic hormone therapy, we found an increase in hemoglobin concentrations, and no deleterious effect on glomerular filtration rate 6 months after they were treated with iron sucrose.

Perioperative intravenous iron preserves iron stores and may hasten the recovery from post‐operative anaemia after knee replacement surgery

In unilateral total knee replacement (TKR), perioperative blood loss, low transfusion thresholds and short hospital stay result in patients being discharged with low haemoglobin (Hb). We assessed the effects of perioperative administration of intravenous iron, with or without erythropoietin, plus a restrictive transfusion threshold (Hb < 80 g L(-1)) both on transfusion rate and recovery from post-operative anaemia. TRK patients received iron sucrose (2 x 200 mg per 48 h, iv) (Group IVI, n = 129). Patients with admission Hb < 130 g L(-1), also received erythropoietin (1 x 40 000 IU, sc) (Group EPO, n = 19). Perioperative clinical and laboratory data were obtained. Mean Hb loss was 36 g L(-1), but only seven patients were transfused (5%). Pre-operatively, 66 (45%) patients did not have enough stored iron to compensate Hb loss. At post-operative day 30, only 15% were anaemic, 70% of Hb loss and 92% of pre-operative Hb were recovered and ferritin increased by 73 microg L(-1) (P < 0.01), although erythropoietic response was higher in patients receiving erythropoietin (P < 0.05). No adverse effects of iron sucrose or erythropoietin were witnessed. This protocol seems to reduce allogeneic blood transfusion rate and may hasten the recovery from post-operative anaemia in TKR patients, without depleting iron stores. Further studies are needed to ascertain which patients may benefit of extended intravenous iron and/or erythropoietin administration.

Erythrocyte Iron Incorporation but Not Absorption Is Increased by Intravenous Iron Administration in Erythropoietin-Treated Premature Infants1–3

Because critically ill premature infants experience significant iron loss due to phlebotomy and have high iron needs for growth, Fe absorption and incorporation studies are clinically important. A prospective, controlled, randomized, open 21-d study was conducted in infants with birth weight <1300 g and gestational age < 31 wk to assess the efficacy of combining intravenous (IV) sucrose iron (Fe) with erythropoietin (EPO) for increasing Fe absorption, RBC Fe incorporation, and erythropoiesis. Three clinically stable groups were enrolled at 3-4 wk of age: Control, EPO [2100 U EPO/(kg.wk)]; and IV Fe+EPO [2 mg IV sucrose Fe/(kg.d) plus 2100 U EPO/(kg.wk)]. All subjects received 9 mg/(kg.d) of oral Fe polymaltose. Subjects were not allowed RBC transfusions. Indicators of iron status and erythropoiesis were assessed before and 18 d after treatment. On d 4, tracer doses of oral polymaltose (57)Fe and IV sucrose (58)Fe were administered, and stool and blood samples were collected for Fe absorption and incorporation determinations. Compared with the Control group, the EPO group demonstrated greater hemoglobin (Hb) concentration and reticulocyte count, but no difference in Fe incorporation. In contrast, the IV Fe+EPO group demonstrated greater total Fe incorporation, Hb concentration, plasma ferritin, and reticulocyte count compared with the Control and EPO groups. Absorption of (57)Fe and nonisotopic polymaltose Fe did not differ among the groups (range: 48-58%, and 41-47%, respectively). We conclude that IV sucrose Fe administered in combination with EPO to very-low-birth weight premature infants significantly increases RBC Fe incorporation and erythropoiesis more than EPO alone, but without increasing iron absorption.

A randomized open-label study of darbepoetin alfa administered every 3 weeks with or without parenteral iron in anemic subjects with nonmyeloid malignancies receiving chemotherapy

8612 Background: Patients (pts) with cancer receiving chemotherapy often have chemotherapy-induced anemia (CIA) and reduced quality of life. Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) that can effectively treat CIA when administered once every 3 weeks (Q3W). In patients with CIA, limited data in the literature suggest that administration of intravenous (IV) iron with ESA therapy may increase clinical response. Methods: This randomized, multicenter, open-label, 16-week study evaluated the safety and efficacy of DA 500 mcg administered Q3W using the SureClick injection device in pts with CIA (Hb &lt; 11 g/dL) who received either IV iron or standard practice for iron administration (oral iron or no iron). The dose of IV iron was 200 mcg administered either Q3W with DA Q3W or, if required, as 2 doses (200 mcg total) within a 3-week period. Pts who received ≥ 1 dose of DA and who completed the 16-week study period by October 19, 2005 are included in this interim analysis (planned sample size = 400 pts). Accrual will have finished by conference time. Randomization was stratified by tumor type and baseline (BL) Hb (&lt; 10 or ≥ 10 g/dL). The incidence of adverse events and serious adverse events, in particular embolic/thrombotic events, was summarized. Efficacy endpoints were estimated using the crude % of pts (95% CI). Hb values within 28 days of a transfusion were not included in any efficacy analysis. Results: Of the 114 pts included in this interim analysis, 65% were women, 99% were Caucasian, the mean (SD) age was 60 years (12), and 26% had lung or gynecological tumors; study endpoints are shown in the table. Conclusions: Based on the interim results, the safety profile for pts receiving DA 500 mcg Q3W with IV iron appears to be comparable to pts receiving DA 500 mcg Q3W with oral iron or no iron. The % pts who achieved the target Hb (≥ 11 g/dL) appeared higher, and the % pts who required transfusions appeared lower, in the group receiving IV iron. [Table: see text] [Table: see text]

Effect of Intravenous Ascorbic Acid in Hemodialysis Patients With EPO-Hyporesponsive Anemia and Hyperferritinemia

Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis patients most commonly results from iron deficiency, the contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We conducted an open-label prospective study to assess the effect of vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia. Forty-six of 262 patients in an inner-city hemodialysis center met the inclusion criteria (administration of intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk, average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%). Patients were excluded if they had a clear explanation for the EPO hyporesponsiveness. Four patients refused to participate. The remaining patients were randomly assigned; 20 patients to receive standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 22 patients to receive standard care only (group 2). Study duration was 6 months. During the study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from final analysis. Monthly assessment included Hb level, mean corpuscular volume, iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive protein (CRP), and liver enzymes were measured every 3 months. Age, sex, race, and time on dialysis therapy were similar in both groups. At 6 months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased significantly in group 1, but not in controls. Changes in Hb content in reticulocytes and ferritin level also were statistically significant in group 1. There was no change in biointact parathyroid hormone levels. Although serum iron levels and intravenous iron doses changed within each group, changes were equal between the 2 groups. In hemodialysis patients with refractory anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either by augmenting iron mobilization from its tissue stores or through antioxidant effects.

Effect of Intravenous Iron Sucrose in Peritoneal Dialysis Patients Who Receive Erythropoiesis-Stimulating Agents for Anemia

Although iron therapy is essential to optimize use of erythropoiesis-stimulating agents (ESA), randomized, controlled trials have heretofore been unavailable to evaluate reliably the efficacy of intravenous iron as an adjuvant to ESA treatment in peritoneal dialysis (PD) patients. In a multicenter trial, patients who had anemia, PD-dependent chronic kidney disease, stable ESA therapy, and a broad range of iron status (ferritin < or = 500 ng/ml, transferrin saturation < or = 25%) were randomly assigned to receive either 1 g of iron sucrose intravenously in three divided doses (300 mg over 1.5 h on days 1 and 15, 400 mg over 2.5 h on day 29) or no supplemental iron. No serious adverse drug events occurred after intravenous iron administration. The primary end point, peak hemoglobin increase, was higher (1.3 +/- 1.1 versus 0.7 +/- 1.1, mean +/- SD; P = 0.0028), and anemia intervention (transfusion, increase in ESA dose, or intravenous iron therapy not called for in protocol) occurred later (P = 0.0137) and less often in intravenous iron-treated patients compared with untreated control subjects (one of 66 [1.3%] versus five of 30 [16.7%]). Among patients who did not require intervention, iron-treated patients showed a calculated net ESA dose decrease compared with untreated control subjects. Baseline iron status did not predict responsiveness to intravenous iron therapy. Intravenous iron sucrose is an effective adjunct to ESA therapy in anemic patients with PD-dependent chronic kidney disease and is administered safely as 300 mg over 1.5 h or 400 mg over 2.5 h. Evidence of iron deficiency at baseline is not required to demonstrate intravenous iron efficacy.

Is there a role for perioperative intravenous iron therapy in orthopedic and trauma surgery? Clinical experience in major lower limb surgery

SUMMARYPerioperative anemia is a common condition among orthopedic and trauma surgery patients. Preoperative anemia is most frequently caused by iron deficiency or chronic inflammatory disease and is one of the major predictive factors for perioperative blood transfusion. In addition to preoperative anemia, perioperative blood loss is a major cause of postoperative anemia although blunted erythropoiesis attributable to inflammation‐induced inhibition of erythropoietin (EPO) action and decreased iron availability may also play a role. We assessed the safety and effectiveness of perioperative intravenous iron administration, with or without EPO, to stimulate erythropoiesis in patients undergoing trauma (hip fracture) or elective orthopedic surgery (knee and hip replacement). Overall, no side effects were observed. The treatment resulted in lower transfusion requirements, decreased postoperative infection and mortality rates, and shorter length of hospital stay. If confirmed by large randomized clinical trials, these findings will provide a rationale to treat orthopedic and trauma patients with intravenous iron, alone or in combination with EPO, in order to attain higher postoperative hemoglobin concentrations, reduce postoperative complications and shorten hospital stay while limiting exposure to allogeneic blood.

Hierro por vía intravenosa en cirugía general

Preoperative anemia is the main cause of blood transfusion in surgical patients. In digestive surgery high blood loss and allogenic blood transfusion (ABT) are associated with serious adverse events and higher mortality. Consequently, we believe that intravenous iron administration is justified to correct perioperative anemia. We present the case of a woman with metastatic colorectal adenocarcinoma in whom intravenous iron administration avoided the use of ABT. Subsequently, the iron metabolism profile improved. This had previously corresponded to a mixed pattern of iron deficiency, that is, to the association of organic and functional iron deficiency.

Sodium ferric gluconate complex therapy in anemic children on hemodialysis

Pediatric patients with end-stage renal disease undergoing hemodialysis (HD) frequently develop anemia. Administration of recombinant human erythropoietin (rHuEPO) is effective in managing this anemia, although the additional demand for iron often results in iron deficiency. In adult patients undergoing HD, intravenous (IV) iron administration is known to replenish iron stores more effectively than oral iron administration. Nevertheless, IV iron supplementation is underutilized in pediatric patients, possibly because of unproved safety in this population. This international, multicenter study investigated the safety and efficacy of two dosing regimens (1.5 mg kg(-1) and 3.0 mg kg(-1)) of sodium ferric gluconate complex (SFGC) therapy, during eight consecutive HD sessions, in iron-deficient pediatric HD patients receiving concomitant rHuEPO therapy. Safety was evaluated in 66 patients and efficacy was evaluated in 56 patients. Significant increases from baseline were observed in both treatment groups 2 and 4 weeks after cessation of SFGC dosing for mean hemoglobin, hematocrit, transferrin saturation, serum ferritin, and reticulocyte hemoglobin content. Efficacy and safety profiles were comparable for 1.5 mg kg(-1) and 3.0 mg kg(-1) SFGC with no unexpected adverse events with either dose. Administration of SFGC was safe and efficacious in the pediatric HD population. Given the equivalent efficacy of the two doses, an initial dosing regimen of 1.5 mg kg(-1) is recommended for pediatric HD patients.

Intravenous iron-gluconate during haemodialysis modifies plasma β2-microglobulin properties and levels

Intravenous iron replacement therapy is routinely used for correction of anaemia in patients with end-stage renal failure. Free or labile iron, present both in parenteral iron formulations and in blood of haemodialysis (HD) patients, has the potential to induce severe oxidative processes. This study evaluated the acute in vivo effect of intravenous iron administration on the oxidation of plasma beta2-microglobulin (beta2m) and on its plasma levels after HD. Iron-gluconate was administered intravenously to 14 patients receiving HD with low-flux cellulose-triacetate membranes during the first hour of the 4 h HD treatment. Each patient underwent three different dialysis treatments, during which an infusion of 62.5, 125 or 0 mg (control) of iron-gluconate was administered in random order. Plasma beta2m levels and iron parameters were monitored immediately before and after each HD treatment. The molecular isoforms of beta2m were studied by two-dimensional gel electrophoresis and western analysis. Levels of oxidized beta2m were evaluated by reaction with 2,4-dinitrophenylhydrazine and western analysis. Both doses of iron-gluconate caused remarkable changes in the molecular properties of beta2m, including shift in isoelectric point, molecular mass and degree of oxidation. Iron administration also limited the decline in plasma beta2m levels to <7.5%, compared with 27.9+/-2.7% during HD without iron. Intravenous iron-gluconate led to a characteristic increase in molecular weight and in negative charge of beta2m, both of which can be assumed to be consistent with reduced membrane sieving coefficients and membrane adsorption, and thus with reduced clearance of beta2m.

Influence of Parenteral Iron Therapy and Oral Vitamin E Supplementation on Neutrophil Respiratory Burst in Chronic Hemodialysis Patients

Background. Bioincompatibility of hemodialysis (HD) membranes is responsible for neutrophil activation leading to oxidative stress, which can be further increased by intravenous (IV) iron (Fe) administration. The aim of our study was to monitor neutrophil respiratory burst during HD and to find out whether this process is influenced by IV Fe and oral vitamin E administration. Methods. Within four HD sessions, blood samples were taken from seven chronic HD patients at time 0 (before HD), 60, 70, and 130 min of HD session. Neutrophil respiratory burst was assessed by luminol-enhanced chemiluminescence (CL). Plasma advanced oxidation protein products (AOPP) concentration was measured spectrophotometrically. During the second and the fourth HD, 62.5 mg of sodium ferric gluconate was applied IV in the 65th minute of HD. Before the last two HD, the patients were given orally 200 mg of vitamin E daily for 7 days. Patient's results were compared with healthy controls. Results. Predialysis CL is higher in patients than in controls (1,926 ± 436 vs. 1,083 ± 325 RLU, p < .01). CL decreases in the 60th min of HD (1,926 ± 436 vs. 1,220 ± 599 RLU, p < .05); thereafter, it remains stable. After Fe application, CL increases at time 130 compared with CL at time 60 (1,303 ± 269 vs. 877 ± 292 RLU, p < .05). AOPP concentration is higher in patients than in controls (137.5 ± 42.7 vs. 88.9 ± 24.8 µmol/L, p < .01) and remains unaffected by vitamin E supplementation. After vitamin E intake, predialysis CL remains significantly higher than in controls, and changes in CL during HD are minimal despite Fe administration. Conclusion. HD patients' neutrophils generate more oxygen radicals than in healthy individuals. This production decreases during HD and then increases after IV Fe administration. Short-term vitamin Eadministration attenuates this fluctuation of neutrophil oxidative metabolism, without affecting the total degree of oxidative stress.

Safety of intravenous iron in clinical practice: implications for anemia management protocols.

Optimizing anemia management is the sole indication for intravenous (IV) iron administration in the patient with chronic kidney disease (CKD): Achieving and maintaining iron sufficiency is crucial to achieving and maintaining target-range hemoglobin (Hgb). Although pica (geophagia) ([1][1]) and

Strategien zur Bluteinsparung in der Chirurgie: Der Stellenwert von Erythropoetin und der parenteralen Eisensubstitution

Recombinant human erythropoietin (rHuEPO) and intravenous (i.v.) iron administration may be useful tools to save blood in surgery. In the perioperative period, rHuEPO should be used in slightly anemic patients for whom an autologous predonation program is not recommended (or feasible). In such cases, i.v. iron is only given if there is a functional or real iron deficiency state. In the post-operative period, i.v. iron is administered in association with rHuEPO in an attempt to rapidly correct severe post-operative anemia. The same regimen is used for patients undergoing surgery for inflammatory bowel disease and rheumatoid arthritis. Finally, other particular categories of patients, such as those with reduced body weight (< 50 kg), candidates for surgery with increased blood needs (> 5 units), or those with a too-short period of time before surgery, also benefit from the administration of these two drugs.

Treatment for women with postpartum iron deficiency anaemia

Postpartum anaemia is associated with breathlessness, tiredness, palpitations and maternal infections. Blood transfusions or iron supplementation have been used in the treatment of iron deficiency anaemia. Recently other anaemia treatments, in particular erythropoietin therapy, have also been used. To assess the clinical effects of treatments for postpartum anaemia, including oral, intravenous or subcutaneous iron/folate supplementation and erythropoietin administration, and blood transfusion. We searched the Cochrane Pregnancy and Childbirth Group trials register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), Current Contents and ACP Journal Club (from inception to March 2003). Randomised controlled trials (RCTs) comparing therapy for postpartum iron deficiency anaemia (oral, intravenous or subcutaneous administration of iron, folate, erythropoietin or blood transfusion) with placebo, another treatment or no treatment. Two reviewers independently assessed trial quality and extracted data. Six included RCTs involving 411 women described treatment with erythropoietin or iron as their primary interventions. No RCTs were identified that assessed treatment with blood transfusion. Few outcomes relating to clinical maternal and neonatal factors were reported: studies focused largely on surrogate outcomes such as haematological indices. Overall, the methodological quality of the included RCTs was reasonable; however, their usefulness in this review is restricted by the interventions and outcomes reported. When compared with iron therapy only, erythropoietin increased the likelihood of lactation at discharge from hospital (1 RCT, n = 40; relative risk (RR) 1.90, 95% confidence interval (CI) 1.21 to 2.98). No apparent effect on need for blood transfusions was found, when erythropoietin plus iron was compared to treatment with iron only (2 RCTs, n = 100; RR 0.20, 95% CI 0.01 to 3.92), although the RCTs may have been of insufficient size to rule out important clinical differences. Haematological indices (haemoglobin and haemocrit) showed some increases when erythropoietin was compared to iron only, iron and folate, but not when compared with placebo. There is some limited evidence of favourable outcomes for treatment of postpartum anaemia with erythropoietin. However, most of the available literature focuses on laboratory haematological indices, rather than clinical outcomes. Further high-quality trials assessing the treatment of postpartum anaemia with iron supplementation and blood transfusions are required. Future trials may also examine the significance of the severity of anaemia in relation to treatment, and an iron-rich diet as an intervention.

Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients

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. 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. 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). 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.

The effects of iron dextran on the oxidative stress in cardiovascular tissues of rats with chronic renal failure

Redox-active iron can promote oxidative stress and tissue injury by catalyzing hydroxyl radical generation and lipid peroxidation. Intravenous iron preparations are routinely administered in conjunction with erythropoietin to treat anemia in patients with chronic renal failure (CRF), a condition that is marked by oxidative stress and inflammation. This treatment frequently elevates iron burden, which can potentially intensify oxidative stress and, thus, cardiovascular disease in this population. We studied renal function and oxidative stress parameters in the cardiovascular tissues of CRF (5/6 nephrectomized) and sham-operated control rats 3 months after a single intravenous infusion of iron dextran (500 mg/kg). Arterial pressure was equally elevated and creatinine clearance was equally reduced in both iron-treated and -untreated CRF groups. Iron administration significantly raised the blood hemoglobin, serum iron concentration, and transferrin saturation in both CRF and control groups. Iron administration resulted in a significant rise in plasma concentration of lipid peroxidation product, malondialdehyde in the CRF rats, and an insignificant rise in the control group. Plasma oxidized low-density lipoprotein (LDL) concentration was increased in the CRF groups, and was not affected by iron administrations. Iron administration raised nitrotyrosine abundance in the aorta of CRF but not in the control group. Left ventricular tissue abundance of p22(phox) subunit of NAD(P)H oxidase was elevated in CRF group and was not affected, whereas p67(phox) subunit abundance was raised by prior iron administration. Iron administration insignificantly lowered aorta p22(phox), but had no effect on p67(phox) subunit abundance in the treated CRF group. Previous iron administration significantly lowered superoxide dismutase and catalase abundance in the aorta and glutathione peroxidase in the left ventricle of CRF animals, but did not significantly change these parameters in the iron-treated control animals. A single intravenous injection of iron dextran increased oxidative stress in the cardiovascular tissues in the CRF group, but not the control rats, pointing to heightened susceptibility to iron-mediated toxicity in CRF. However, administration of iron dextran did not adversely affect kidney function, and favorably affected hemoglobin concentration in rats with CRF induced by renal mass reduction. Further studies are needed to explore the effects of other parenteral iron preparations, repeated intravenous iron administration, and presence of comorbid conditions such as diabetes.

The New Reticulocyte Parameter (RET-Y) of the Sysmex XE 2100

To verify their clinical usefulness in diagnosis and early response to therapy of sideropenic anemia, we compared the behavior of the reticulocyte parameter (RET-Y), a raw measure dependent on size and content of the cell, generated by the Sysmex XE 2100, with the mean reticulocyte volume (MCVr) and mean reticulocyte hemoglobin content (CHr) from the Bayer ADVIA 120 in healthy subjects and patients with iron deficiency anemia. Correlations were high ( r = 0.88 and r = 0.94, respectively). All parameters varied significantly as early as 48 hours after the start of intravenous iron therapy (mean differences of 17.4% [RET-Y], 4.5% [MCVr], and 9.5% [CHr]). Sudden decreases in those parameters at interruption of therapy indicate the reappearance of sideropenic erythropoiesis. The receiver operating characteristic curve demonstrated a high degree of efficiency in differentiating moderate or severe iron deficiency anemia from the healthy state. The best association between sensitivity and specificity was at a cutoff of channel 1,624 for RET-Y and 104.5 fL for MCVr (negative and positive predictive values, respectively, of 99.6% and 96.5% for RET-Y and 98.7% and 93.3% for MCVr). RET-Y is correlated closely with CHr and is useful for diagnosis and early monitoring after the administration of intravenous iron.

Bench-to-bedside review: Iron metabolism in critically ill patients

Critically ill patients frequently develop anemia due to several factors. Iron-withholding mechanisms caused by inflammation contribute to this anemia. The iron metabolism imbalances described or reported in all intensive care studies are similar to the values observed in anemia of inflammation. The administration of iron could be useful in the optimization of recombinant human erythropoietin activity, but this could be at the expense of bacterial proliferation. Since there is a lack of evidence to support either oral or intravenous iron administration in intensive care patients, further studies are necessary to determine the efficacy and safety of iron supplementation in conjunction with recombinant human erythropoietin in critically ill patients. We review the mechanisms leading to iron sequestration in the presence of inflammation. The present article also reviews the literature describing the iron status in critically ill patients and explores the role of iron supplementation in this setting.

Transient Severe Thrombocytopenia in a Patient on CAPD after Intravenous Iron Administration

Transient Severe Thrombocytopenia in a Patient on CAPD after Intravenous Iron Administration