Effect Of Intravenous Iron Supplementation Research Articles

Iron management and exercise training in individuals with chronic kidney disease: lived experiences.

Non-anaemic iron deficiency is highly prevalent in people living with chronic kidney disease (CKD) but is underdiagnosed and undertreated, especially in earlier stages of CKD. A multicentre trial assessing the effect of intravenous iron supplementation in iron-deficiency but not anaemic people with CKD included a qualitative sub-study that aimed to explore the patient experience and psychosocial impact of living with CKD and iron deficiency, and the experience of the therapeutic intervention (intravenous iron and exercise). Semi-structured interviews were conducted with 23 trial participants blinded to treatment. Topics explored included experiences of living with CKD and iron deficiency, symptoms, social and leisure activities, quality of life, and participants' views and experiences of receiving the therapeutic intervention. Thematic analysis was used to identify and report themes. Six overarching themes were identified: lack of awareness of iron deficiency; overwhelming feelings of tiredness; feeling limited; balancing emotions; perceptions and experiences of therapeutic treatment received; and impact of trial participation on life participation. Trial participation, specifically the exercise training, was perceived to be beneficial, with improvements in life participation and psychological wellbeing experienced. However, there were no clear differences between treatment groups, with mixed perceptions about which therapeutic treatment was received. The impact of tiredness on individuals with CKD is profound and can result in reduced vitality, impaired ability to engage in life activities and emotional conflict. Improved communication and support about psychosocial impact and management of symptoms, particularly fatigue, for people with CKD may be required, alongside effective therapeutic interventions, to improve symptom management and quality of life.

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial

BackgroundMany people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics.MethodsThis is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3–4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken.ResultsSeventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) μg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m.ConclusionThe results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme.Trial registrationEudraCT: 2018–000,144-25 Registered 28/01/2019.

Effect of Intravenous Iron Supplementation on Hospitalization for Heart Failure in Hemodialysis Patients

Effect of Intravenous Iron Supplementation on Hospitalization for Heart Failure in Hemodialysis Patients

Long-term Effect of Intravenous Iron Carboxymaltose Treatment on Oxidative Stress in Women with Iron Deficiency Anemia

Objective: This study aims to clarify the effects of intravenous iron supplementation on biomarkers for oxidative stress in women with iron deficiency anemia.
 Methods: This is a cross-sectional review of 40 healthy women and 40 women who underwent intravenous iron treatment due to anemia. Biochemical markers for oxidative stress were determined for both healthy controls and anemic patients. These markers were also evaluated at hour 1 and day 30 of intravenous iron treatment.
 Results: The patients with anemia had significantly higher catalase activity and total oxidant status (TOS) but significantly lower nitrate and total anti-oxidant status (TAS) than the healthy controls (p=0.0245, p<0.0001, p=0.0437 and p<0.0001 respectively). At hour 1 of intravenous iron treatment, nitrate, nitrite, nitric oxide, total thiol and TAS values were significantly lower and TOS values were significantly higher than those before the administration of treatment (p=0.0322, p=0.0003, p=0.0005, p<0.0001, p<0.0001 and p=0.004). At day 30 of intravenous iron treatment, catalase activity, nitrate, total thiol and TOS values were significantly lower than those before the administration of treatment (p=0.0332, p=0.0015, p=0.0391 and p<0.0001 respectively) and at hour 1 of treatment (p=0.0498, p<0.0001, p=0.0004 and p<0.0001 respectively). At day 30 of intravenous iron treatment, nitric oxide and TAS values were significantly higher than those before the administration of treatment (p=0.0480 and p=0.001 respectively) and at hour 1 of treatment (p<0.0001 for both).
 Conclusion: Intravenous iron replacement prompts oxidative stress at hour 1 of infusion in adults with anemia but this increase resolves partially in the following 30 days.

Iron Supplementation Interferes With Immune Therapy of Murine Mammary Carcinoma by Inhibiting Anti-Tumor T Cell Function.

Iron is both, an essential compound for many metabolic processes, and iron deficiency can impact on the proliferation of cells including lymphocytes but also tumor cells. On the other hand, excess iron-catalyzed radical formation can induce cellular toxicity which has been previously demonstrated for T cells in hereditary iron overload. Despite these interconnections, little is known on the effects of clinically approved intravenous iron supplements for curing cancer-related anemia, on T cell differentiation, tumor proliferation, anti-tumor T cell responses and, of clinical importance, on efficacy of cancer immunotherapies. Herein, we analyzed the effects of intravenous iron supplementation on T cell function and on the effectiveness of anti-cancer chemotherapy with IL-2/doxorubicin or immunotherapy with checkpoint-inhibitor anti-PD-L1 in C57Bl/6N female mice with implanted E0771 mammary carcinomas. We found that iron application resulted to an increased availability of iron in the tumor microenvironment and stimulation of tumor growth. In parallel, iron application inhibited the activation, expansion and survival of cytotoxic CD8+ T cells and of CD4+ T helper cells type 1 and significantly reduced the efficacy of the investigated anti-cancer treatments. Our results indicate that iron administration has a tumor growth promoting effect and impairs anti-cancer responses of tumor infiltrating T lymphocytes along with a reduced efficacy of anti-cancer therapies. Iron supplementation in cancer patients, especially in those treated with immunotherapies in a curative setting, may be thus used cautiously and prospective studies have to clarify the impact of such intervention on the outcome of patients.

The effects of intravenous iron supplementation on fatigue and general health in non-anemic blood donors with iron deficiency: a randomized placebo-controlled superiority trial

We investigated whether intravenous iron supplementation improves fatigue and general health in non-anemic repeat adult blood donors with iron deficiency (ferritin ≤ 50 µg/L). Of 1,487 potentially eligible participants, 203 were randomly assigned to a single intravenous dose of 800 mg iron-carboxymaltose and 202 to placebo; 393 participants completed the trial. At 6 to 8 weeks after intervention, self-rated mean fatigue scores (numeric rating scale from 1–10, primary outcome) were 3.9 ± 1.8 in the iron supplementation group and 4.0 ± 2.2 in the placebo group, showing no group difference (p = 0.819). Pre-specified subgroup analyses of gender, ferritin < 25 µg/L and fatigue ≥ 4 points, as well as exploratory analyses of lower ferritin cut-offs did not reveal any between-group differences. In terms of secondary outcomes, the mean differences were 114.2 µg/L for ferritin (95% CI 103.1–125.3) and 5.7 g/L for hemoglobin (95% CI 4.3–7.2) with significantly higher values in the iron supplementation group. No group differences were observed for different measures of general well-being and other clinical and safety outcomes. Intravenous iron supplementation compared with placebo resulted in increase of ferritin and hemoglobin levels in repeat blood donors with low iron stores, yet had no effect on fatigue and general well-being.

Effect of Intravenous Iron Supplementation in Reducing Allogenic Blood Transfusion

Effect of Intravenous Iron Supplementation in Reducing Allogenic Blood Transfusion

Effect of Intravenous Iron Supplementation on Hepcidin Levels in Iron Deficient Pregnant Females in Second and Third Trimester.

Objective of the study was to assess effect of iron therapy on serum hepcidin levels in iron deficient pregnant women and its correlation with hemoglobin, serum iron profile and C-reactive protein (CRP). A total of 100 pregnant women were enrolled in the study; 25 were included in the "control group" having normal hematological and biochemical parameters while 75 iron deficient pregnant women were enrolled in the "patient group" with low hematological and biochemical parameters. CRP was done to rule out inflammation and to observe its association with hepcidin. Intravenous iron was administered to the patient group. Post treatment CBC, serum iron, serum ferritin and serum hepcidin were determined. Difference between pre and post treatment hemoglobin, serum iron, serum ferritin and serum hepcidin levels were determined and correlation among them was calculated. Post treatment serum hepcidin levels were significantly higher than pretreatment level (p=0.001). However, no correlation was seen between serum hepcidin, serum iron, serum ferritin and hemoglobin. Hepcidin levels remain low during pregnancy as there is increased demand for iron in pregnancy. Iron supplementation results in increased hepcidin levels; however no mathematical correlation was found between serum hepcidin level and serum iron profile.

Effect of Intravenous Iron Supplementation on Iron Stores in Non-Anemic Iron-Deficient Patients with Hereditary Hemorrhagic Telangiectasia.

In hereditary hemorrhagic telangiectasia (HHT), frequent episodes of nasal and gastrointestinal bleeding commonly lead to iron-deficiency with or without anemia. In the retrospective study presented here we assessed the iron stores, as determined by analysis of plasma ferritin, during oral and intravenous iron supplementation, respectively, in a population of iron-deficient non-anemic HHT patients who were inadequately iron-repleted by oral supplementation. A switch from oral to intravenous iron supplementation was associated with a significant increase in ferritin in this patient population.

Effect of Intravenous Iron Supplementation on Acute Mountain Sickness: A Preliminary Randomized Controlled Study

BackgroundThe aim of this study was to assess the role of intravenous iron supplementation in the prevention of AMS.Material/MethodsThis was a randomized, double-blinded, placebo-controlled study. Forty-one (n=41) healthy Chinese low-altitude inhabitants living in Beijing, China (altitude of about 50 meters) were randomly assigned into intravenous iron supplementation (ISS group; n=21) and placebo (CON group; n=20) groups. Participants in the ISS group received iron sucrose supplement (200 mg) before flying to Lhasa, China (altitude of 4300 meters). Acute mountain sickness (AMS) severity was assessed with the Lake Louise scoring (LLS) system within 5 days after landing on the plateau (at high altitude). Routine check-ups, clinical biochemistry, and blood tests were performed before departure and 24 h after arrival.ResultsA total of 38 participants completed the study (ISS group: n=19; CON group: n=19). The rate of subjects with AMS (LLS>3) was lower in the ISS group compared with the CON group, but no significant differences were obtained (P>0.05). There were no differences in patients’ baseline characteristics. The physiological indices were similar in both groups except for serum iron concentrations (19.44±10.02 vs. 85.10±26.78 μmol/L) and transferrin saturation rates (28.20±12.14 vs. 68.34±33.12%), which were significantly higher in the ISS group (P<0.05). Finally, heart rate was identified as a contributing factor of LLS.ConclusionsThese preliminary findings suggest that intravenous iron supplementation has no significant protective effect on AMS in healthy Chinese low-altitude inhabitants.

Four weeks of IV iron supplementation reduces perceived fatigue and mood disturbance in distance runners.

PurposeTo determine the effect of intravenous iron supplementation on performance, fatigue and overall mood in runners without clinical iron deficiency.MethodsFourteen distance runners with serum ferritin 30–100 µg·L−1 were randomly assigned to receive three blinded injections of intravenous ferric-carboxymaltose (2 ml, 100 mg, IRON) or normal saline (PLACEBO) over four weeks (weeks 0, 2, 4). Athletes performed a 3,000 m time trial and 10×400 m monitored training session on consecutive days at week 0 and again following each injection. Hemoglobin mass (Hbmass) was assessed via carbon monoxide rebreathing at weeks 0 and 6. Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score (TFS) and Total Mood Disturbance (TMD) using the Brief Fatigue Inventory and Brunel Mood Scale. Data were analyzed using magnitude-based inferences, based on the unequal variances t-statistic and Cohen's Effect sizes (ES).ResultsSerum ferritin increased in IRON only (Week 0: 62.8±21.9, Week 4: 128.1±46.6 µg·L−1; p = 0.002) and remained elevated two weeks after the final injection (127.0±66.3 µg·L−1, p = 0.01), without significant changes in Hbmass. Supplementation had a moderate effect on TMD of IRON (ES -0.77) with scores at week 6 lower than PLACEBO (ES -1.58, p = 0.02). Similarly, at week 6, TFS was significantly improved in IRON vs. PLACEBO (ES –1.54, p = 0.05). There were no significant improvements in 3,000 m time in either group (Week 0 vs. Week 4; Iron: 625.6±55.5 s vs. 625.4±52.7 s; PLACEBO: 624.8±47.2 s vs. 639.1±59.7 s); but IRON reduced their average time for the 10×400 m training session at week 2 (Week 0: 78.0±6.6 s, Week 2: 77.2±6.3; ES–0.20, p = 0.004).ConclusionDuring 6 weeks of training, intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency, without concurrent improvements in oxygen transport capacity or performance.

Effect of Intravenous Iron Supplementation for Acute Postoperative Anemia in Patients Undergoing Gastrectomy for Gastric Carcinoma: A Pilot Study

Several previous studies have concluded that iron supplementation is not beneficial for correcting acute postoperative anemia. However, little data are available about the effect of intravenous (i.v.) iron supplementation for acute postoperative anemia in patients undergoing gastrectomy. Between February 2009 and May 2012, 527 patients underwent gastrectomy for gastric carcinoma. From February 2011, we began i.v. iron supplementation for patients with acute postoperative anemia (hemoglobin (Hb) ≤10 g/dL) at our institute. This study compared the changes of serum Hb up to postoperative 6 months between the patients treated before and after the introduction of i.v. iron supplementation. A total of 142 patients had acute postoperative anemia (Hb ≤10 g/dL). Of these, 68 patients (47.9%) received i.v. iron supplementation. There were no significant differences in age, gender, operation type, tumor stage, and the presence of postoperative chemotherapy between the i.v. iron supplementation and no-supplementation group. Postoperatively, the serum Hb increase over time was significantly better in the i.v. iron supplementation group (repeated measures ANOVA, p = .009). The mean increase of Hb at postoperative 6 months was 3.2 g/dL in the i.v. supplementation group and 2.5 g/dL in the no-supplementation group (p = .029). Multivariate analysis revealed that i.v. iron supplementation was an independent factor of increased serum Hb at postoperative 6 months. Unlike non-gastrointestinal surgery, i.v. iron significantly increased serum Hb in patients developing acute postoperative anemia after gastrectomy. A prospective randomized trial is warranted to confirm the role of i.v. iron supplementation in patients with gastrectomy.

Efficacy and toxicity of intravenous iron in a mouse model of critical care anemia*

Anemia is common in critically ill patients, due to inflammation and blood loss. Anemia can be associated with iron deficiency and low serum hepcidin levels. However, iron administration in this setting remains controversial because of its potential toxicity, including oxidative stress induction and sepsis facilitation. The objective of this work was to determine the efficacy and toxicity of iron administration using a mouse model mimicking critical care anemia as well as a model of acute septicemia. Prospective, randomized, open label controlled animal study. University-based research laboratory. C57BL/6 and OF1 mice. Intraperitoneal injection of zymosan inducing generalized inflammation in C57BL/6 mice, followed in our full model by repeated phlebotomies. A dose equivalent to 15 mg/kg of ferric carboxymaltose was injected intravenously on day 5. To assess the toxicity of iron in a septicemia model, OF1 mice were simultaneously injected with iron and different Escherichia coli strains. To investigate the effect of iron on oxidative stress, we measured reactive oxygen species production in the blood using luminol-amplified chemiluminescence and superoxide dismutase 2 messenger RNA levels in the liver. These markers of oxidative stress were increased after iron administration in control mice but not in zymosan-treated mice. Liver catalase messenger RNA levels decreased in iron-treated control mice. Iron administration was not associated with increased mortality in the septicemia model or in the generalized inflammation model. Iron increased hemoglobin levels in mice fed with a low iron diet and subjected to phlebotomies and zymosan 2 wks after treatment administration. Adverse effects of intravenous iron supplementation by ferric carboxymaltose seem to be minimal in our animal models. Furthermore, iron appears to be effective in correcting anemia, despite inflammation. Studies of efficacy and safety of iron in critically ill patients are warranted.

Effects of intravenous iron supplementation on non-hematological symptoms in inflammatory bowel disease patients

Background/aim: Iron deficiency anemia (IDA) represents the most common systemic complication in inflammatory bowel disease (IBD). Evidence from studies in nephrology show that the treatment of anemia improves not only hematological parameters, but also non-hematological symptoms, i.e. cognitive functions (CF), loss of hair, and restless leg syndrome (RLS). These improvements were mainly seen in patients with iron deficiency. The present non-interventional study (NIS) examined the association between changes in hemoglobin (Hb) and non-hematological symptoms in IBD patients suffering from IDA.

Effect of intravenous iron supplementation on hepatic cytochrome P450 3A4 activity in hemodialysis patients: A prospective, open-label study

Background: Cytochrome P450 (CYP) 3A4 is an enzyme with activity dependent on the reduction of heme iron that is responsible for the metabolism of many drugs. CYP3A4 activity is reduced in hemodialysis (HD) patients and thus may be related to functional iron deficiency. Objective: The purpose of this study was to investigate the effect of IV iron supplementation on hepatic is CYP3A4 activity in HD patients. Methods: This prospective, open-label study was conducted in 12 iron-deficient (transferrin saturation <20% or ferritin <100 ng/L) HD patients on stable medication regimens. To probe for hepatic CYP3A4 activity, an erythromycin breath test (ERMBT) was administered before and after 1 g IV iron sucrose (administered as a 100-mg dose [20 mg/mL]), at each of 10 consecutive HD sessions). CYP3A4 activity was estimated by the percentage of administered 14C exhaled in a single-breath collection after the test dose of erythromycin underwent demethylation by CYP3A4. The ERMBT was also administered to 7 age-, sex-, and race-matched healthy controls. Results: Twelve HD patients (6 Hispanic, 3 white, 3 Native American; 8 men, 4 women; mean [SEM] age, 56.2 [5.0] years; mean [SEM] weight, 77.0 [5.6] kg; and 7 controls (4 men, 3 women; mean [SEM] age, 51.3 [5.0] years; mean [SEM] weight, 77.5 [7.4] kg) were enrolled in the study. In the total HD population studied, mean (SEM) CYP3A4 activity did not change significantly after IV iron replacement (1.46 [0.27] vs 1.57 [0.24] 14C exhaled/h). A subgroup of 7 HD patients had significantly lower CYP3A4 activity before IV iron replacement compared with the other 5 HD patients and controls (mean [SEM] 0.86 [0.24] vs 2.30 [0.26] and 2.10 [0.26] 14C exhaled/h; P < 0.01). After IV iron replacement, mean (SEM) CYP3A4 activity increased in these 7 HD patients (120.1% [67.1%]); P = 0.04) and it was not statistically different from that of controls (1.50 [0.36] vs 2.10 [0.26]). Conclusions: Overall, IV iron administration had no significant effect on hepatic CYP3A4 activity. However, in a subset of HD patients with low baseline CYP3A4 activity indicated by low ERMBT values, IV iron supplementation was associated with a potentially clinically relevant increase in hepatic CYP3A4 activity. Further studies are needed to clarify mechanisms and clinical implications of this interaction.