[Iron Metabolism and Iron Therapy in Chronic Renal Failure].

Iron therapy in nephropathic patients can allow optimizing treatment with EPO identifying the minimum effective dose capable of improving the patient's quality of life. The most recent studies on iron metabolism and on the interference of iron deficiency syndrome on the performance of some organs, in particular the myocardium, suggest the need to intervene very early, especially in patients with cardiomyopathy and systolic deficit. Setting up an iron therapy in nephropathic patients requires a correct diagnosis. That is particularly difficult in comorbid and inflamed patients because of the poor diagnostic reliability of the main biomarkers (ferritin and transferrin saturation). We need to spread the use of biomarkers that are not influenced by the inflammatory state, not expensive and easily accessible: reticulocyte hemoglobin could meet these requirements. The Pivotal study has delineated the optimal iron treatment in incident hemodialysis patients, treated with EPO not inflamed with classical biomarkers. It is yet to be determined, however, whether the Pivotal results are reproducible in more comorbid patients, also considering new and different therapeutic scenarios that the use of hypoxia-inducible factor-prolyl hydroxyl inhibitors may determine.

Comparison of the Anaemia and Transfusion Rates of Pregnant Women Treated with Intravenous versus Oral Iron in the Third Trimester.

OBJECTIVE: To evaluate and compare the blood transfusion requirements during delivery in third-trimester pregnant women with iron deficiency anaemia (IDA) who were treated with intravenous (IV) ferric carboxymaltose (FCM) versus those treated with oral iron supplementation. STUDY DESIGN: Comparative study. Place and Duration of the Study: Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkiye, from January 2017 to December 2022. METHODOLOGY: Pregnant women with haemoglobin (Hb) levels <10 g/dL in their third trimester were included. One group (n = 50) received IV FCM, while the other group (n = 96) received oral iron therapy. Key outcome measures included Hb levels at delivery and the need for a postpartum blood transfusion. Inclusion criteria were third-trimester pregnancy with IDA, and exclusion criteria included haematological or chronic systemic diseases and high-risk pregnancies. RESULTS: The mean initial Hb levels in the third trimester of pregnancy in the FCM group and oral iron group were 8.31 ± 0.96 g/dL and 9.29 ± 1.20 g/dL, respectively (p <0.001). The mean Hb levels in the delivery room were 11.09 ± 1.38 and 9.44 ± 1.16 g/dL, respectively (p <0.001). The rates of postpartum erythrocyte transfusion requirement were 6% (n = 3) and 18.75% (n = 18), respectively (p = 0.037). CONCLUSION: IV FCM administration to pregnant patients with IDA during the third trimester was found to be more effective than oral iron treatment in reducing blood transfusion rates. KEY WORDS: Anaemia, Ferric carboxymaltose, Pregnancy, Iron deficiency, Intravenous iron.

Normalization of Fetal Cerebral and Hepatic Iron by Parental Iron Therapy to Pregnant Rats with Systemic Iron Deficiency without Anemia.

BACKGROUND/OBJECTIVES: Iron (Fe) is a co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe-deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and the expression of iron-relevant genes. METHODS: Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe, copper (Cu), and zinc (Zn) and gene expression of ferroportin, hepcidin, and ferritin H + L in pups on P0 and as adults on P70. RESULTS: Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin mRNA was significantly lower following ID. Cerebral hepcidin mRNA was hardly detectable irrespective of iron status. CONCLUSIONS: In conclusion, administering FDI subcutaneously to ID pregnant rats on E0 normalizes fetal cerebral and hepatic Fe. When applied at later gestational ages, supplementation with additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

Iron Treatment in Patients with Iron Deficiency Before and After Metabolic and Bariatric Surgery: A Narrative Review.

Iron is an essential nutrient in living organisms with multiple vital functions. Iron deficiency (ID) can cause long term health consequences beyond iron deficiency anemia (IDA). The high prevalence of ID and its long-term effects in patients with obesity and after metabolic and bariatric surgery (MBS) is recognized. Nevertheless, there is limited knowledge of the optimal route or dose for treatment of patients with obesity and post-MBS, and an evidence-based universal guideline for prevention and treatment of ID in short- and long-term post-MBS (PMBS) is not yet available. ID in the general population is currently treated with oral or parenteral iron, where oral iron treatment is considered the preferred option with parenteral iron as a second-line treatment in case there is intolerance or lack of response to oral iron. In patients with obesity with chronic low-grade inflammation and PMBS patients with altered gut anatomy and function, there are also alterations in the bioavailability and higher risks of side effects of available oral irons. The conclusions of current studies exploring effective treatment of iron deficiency in this population have been inconsistent and further well-planned randomized and prospective studies are needed. This is a narrative review of the literature on the available treatment options and strategies for treatment of ID in PMBS patients to recognize the knowledge gaps and provides topics of future research.

Adjudication of Hospitalizations and Deaths in the IRONMAN Trial of Intravenous Iron for Heart Failure.

BACKGROUND: Patients with heart failure and iron deficiency have diverse causes for hospitalization and death that might be affected by iron repletion. OBJECTIVES: The purpose of this study was to explore causes of hospitalizations and deaths in a randomized trial (IRONMAN) of heart failure comparing intravenous ferric derisomaltose (FDI) (n = 568) and usual care (n = 569). METHODS: Patients with heart failure, left ventricular ejection fraction ≤45%, and either transferrin saturation <20% or serum ferritin <100 µg/L were enrolled. Median follow-up was 2.7 years (Q1-Q3: 1.8-3.6 years). A committee adjudicated the main and contributory causes of unplanned hospitalizations and deaths. RRs (rate ratios) for selected recurrent events with 95% CIs are also reported. RESULTS: Compared with usual care, patients randomized to FDI had fewer unplanned hospitalizations (RR: 0.83; 95% CI: 0.71-0.97; P = 0.02), with similar reductions in cardiovascular (RR: 0.83; 95% CI: 0.69-1.01) and noncardiovascular (RR: 0.83; 95% CI: 0.67-1.03) hospitalizations, as well as hospitalizations for heart failure (RR: 0.78; 95% CI: 0.60-1.00), respiratory disease (RR: 0.70; 95% CI: 0.53-0.97), or infection (RR: 0.82; 95% CI: 0.66-1.03). Heart failure was the main cause for 26% of hospitalizations and contributed to or complicated a further 12%. Infection caused or contributed to 38% of all hospitalizations, including 27% of heart failure hospitalizations. Patterns of cardiovascular and all-cause mortality were similar for patients assigned to FDI or usual care. CONCLUSIONS: In IRONMAN, FDI exerted similar reductions in cardiovascular and noncardiovascular hospitalizations, suggesting that correcting iron deficiency might increase resistance or resilience to a broad range of problems that cause hospitalizations in patients with heart failure. (Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency; NCT02642562).

Safety and efficacy of iron supplementation with 3 months of daily ferrous sulphate in children living with HIV and mild-to-moderate anaemia in Uganda: a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Iron deficiency is the most common nutritional deficiency in the world, but iron supplementation can increase risk of opportunistic infections, especially in children living with HIV. We aimed to assess the effect of supplemental iron on haemoglobin concentration in children living with HIV and mild-to-moderate anaemia in Uganda. METHODS: We did a double-blind, randomised, placebo-controlled trial of iron supplementation in children aged 6 months to 12 years living with HIV at two sites (ie, Kampala and Fort Portal, Uganda). Inclusion criteria were confirmed diagnosis of HIV and stable treatment with antiretroviral therapy for at least 6 months. Exclusion criteria were already taking iron supplementation, acute illness, current opportunistic infection, fever, known sickle cell disease, severe undernutrition, or any chronic illness requiring medical attention. Children were randomly assigned (1:1) via simple randomisation to an 84-day course of either ferrous sulphate or identical placebo tablets once per day. Randomisation codes were computer-generated and stratified by age (ie, 6-23 months or 24 months and older) by the Toronto Institute of Pharmaceutical Technology, the tablet manufacturer. Participants and all individuals giving the interventions, assessing outcomes, and analysing data were masked to group assignment. Children aged 6-23 months received tablets of 12·5 mg ferrous sulphate or identical placebo; children aged 24 months or older received tablets of 30·0 mg ferrous sulphate or identical placebo. Caregivers were instructed to give the supplement after a meal, preferably after an evening meal. The primary outcome was mean haemoglobin concentration at day 84. All analyses were intention to treat. This trial is registered at ClinicalTrials.gov (NCT03596996). FINDINGS: Between May 5, 2018, and Nov 6, 2019, 973 children living with HIV were screened, of whom 200 (20%) met all inclusion criteria and were enrolled. 102 (51%) were randomly assigned to receive iron and 98 (49%) to receive placebo. In the iron group, 57 (56%) of 102 children were male and 45 (44%) were female. In the placebo group, 44 (45%) of 98 children were male and 54 (55%) were female. Iron supplementation was associated with improvement in haemoglobin in unadjusted analysis (p=0·029), but not adjusted analysis (p=0·10), and with improvement in ferritin and hepcidin in both adjusted (p=0·0046; p=0·0079) and unadjusted (p<0·0001; p<0·0001) analyses at day 84. There were four hospital admissions, all for children in the iron group; none were fatal: two children were admitted to hospital with pneumonia, one with severe malaria, and one with hepatitis. Frequency of admissions was not significantly different between groups (p=0·12). INTERPRETATION: Iron could have haematological benefit and improve iron status in children living with HIV in Uganda. Future studies powered for morbidity outcomes with longer follow-up are needed, as are those that evaluate the effects of iron supplementation on neurocognitive outcomes. FUNDING: Minnesota Masonic Charities, the Department of Pediatrics at the University of Minnesota, the Hennepin Healthcare Research Institute, and the US National Institutes of Health.

Real-world efficacy and safety of intravenous ferric carboxymaltose for the management of iron deficiency anaemia in Malaysia: A single centre cohort study.

INTRODUCTION: Up to 24.2% Malaysians are estimated to be affected by anaemia. Iron deficiency is the most common nutritional deficiency leading to anaemia. Oral iron therapy may not be well tolerated or efficient. Ferric carboxymaltose (FCM), a non-dextran intravenous iron formulation, may be an appealing alternative for iron replacement therapy. This retrospective study aimed to investigate the efficacy and safety of intravenous FCM infusion for the management of iron deficiency anaemia in a single centre in Malaysia. MATERIALS AND METHODS: All patients who received at least one dose of 500 mg intravenous FCM infusion from January to December 2023 in Bukit Tinggi Medical Centre (BTMC) were identified from the electronic medical record database. Inclusion criteria were patients: (1) ≥ 14 years old and (2) with iron deficiency anaemia. The primary outcome was the mean change in haemoglobin level before treatment and 30 day after treatment. Secondary outcomes included reasons for intravenous FCM infusion, median dose, adverse drug reactions, mean change in haemoglobin levels for different subgroups and percentage of patients with normalised haemoglobin after treatment. The efficacy outcome was analysed using per-protocol analysis while the safety outcome used intention-to-treat analysis. Paired t-test was used to compare the mean difference between the haemoglobin measurements before and 30-day after treatment. RESULTS: A total of 144 administrations were given to 141 patients requiring intravenous iron replacement therapy during the 1-year study period in BTMC. Intravenous FCM infusion was administered for the management of iron deficiency related to: (1) increased blood loss, including menorrhagia, haemorrhoids and GI-related surgery, (2) low iron intake, including poor nutrition and gastrointestinalrelated malabsorption and (3) haematological disorders, including autoimmune haemolytic anaemia, myelodysplastic syndrome, diffuse large B-cell lymphoma and idiopathic thrombocytopaenia purpura. The median dose of intravenous FCM infusion was 1000 mg. At 30 day post-infusion, the mean haemoglobin level increased significantly from 8.9 g/L to 11.6 g/L (p < 0.05), an increase of 2.68 g/L (95% CI: 2.45 - 2.90 g/L). No adverse drug reactions were reported. Subgroup analysis showed that patients with haematological disorders had significantly higher improvement in haemoglobin levels after intravenous iron infusion compared to those without. At 7-day, 14-day, 21-day post-infusion, 33% (33/99), 34% (34/99) and 36% (36/99) patients had a normalised haemoglobin level, respectively. The proportion of patients with a normalised haemoglobin level increased to 36% (36/99) and 42% (42/99) at 30-day and 90-day post-infusion. CONCLUSION: Within the limit of this single-centre retrospective study, intravenous FCM infusion was well tolerated and effective in increasing the haemoglobin level among patients with iron deficiency anaemia.

Do Parenteral Iron Therapies Preserve or Deteriorate Kidney Functions? "Iron Carboxy Maltose or Iron Sucrose?"

BACKGROUND: Treatment of end stage renal disease (ESRD) is based on preserving renal functions. Since renal anemia is frequently detected, we use parenteral iron treatments in patients with chronic kidney disease (CKD). However, there need to be more precise and sufficient studies on the effect of these treatments on the rate of decrease in the glomerular filtration rate (GFR). Therefore, we conducted a study comparing the rates of change in renal function in patients who had used parenteral iron for at least five years. METHODS: Our study is a retrospective cohort study, and 180 patients with CKD (86 women, 94 men, mean age: 63.5 ± 11.4 years) who had been followed and treated in nephrology outpatient clinics for at least five years and met the study criteria were included in the study. Patients were divided into three groups for iron therapy: not receiving iron therapy, iron carboxy maltose (ICM), and iron sucrose (IS) parenterally. Each group consisted of 60 people. The first and last creatinine and GFR values were compared for a 5-year follow-up in each group. RESULTS: There was no significant difference between the two groups, those using and those not using iron, regarding creatinine increase and GFR decrease rate. Additionally, no significant difference was detected in the GFR decline rates of patients using ICM and IS. CONCLUSIONS: This study reduces the concerns that correcting anemia through parenteral iron therapy in patients with CKD may harm renal function.

Intravenous versus oral iron for anaemia among pregnant women in Nigeria (IVON): an open-label, randomised controlled trial.

BACKGROUND: Oral iron for anaemia in pregnancy is often not well tolerated, with poor adherence. Iron administered intravenously might address these tolerance and adherence issues. We investigated the effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate on anaemia and iron deficiency among pregnant women in Nigeria. METHODS: We did a multicentre, open-label, parallel, randomised controlled trial of pregnant women (aged 15-49 years) with haemoglobin (Hb) concentrations of less than 10 g/dL at 20-32 weeks' gestation from 11 primary, secondary, or tertiary health facilities in Nigeria (five in Lagos and six in Kano). Exclusion criteria included vaginal bleeding, blood transfusion or major surgery within the past 3 months, symptomatic anaemia, anaemia known to be unrelated to iron deficiency, clinically confirmed malabsorption syndrome, previous hypersensitivity to any form of iron, pre-existing maternal depression or other major psychiatric illness, immune-related diseases, such as systemic lupus erythematosus or rheumatoid arthritis, or severe allergic reactions. Participants were randomly assigned (1:1) by nurses and doctors using a web-based randomisation service to either receive a single dose of intravenous ferric carboxymaltose (20 mg/kg to a maximum of 1000 mg) or oral ferrous sulphate (200 mg; 65 mg elemental iron) three times daily until 6 weeks postpartum. The study was primarily unmasked. Primary outcomes were maternal anaemia (Hb <11 g/dL) at 36 weeks' gestation and preterm birth at before 37 weeks' gestation, with analysis by intention to treat in participants with available data. This study was registered at the ISRCTN registry on Dec 10, 2020 (ISRCTN63484804) and on ClinicalTrials.gov (NCT04976179) on April 7, 2021. FINDINGS: Between Aug 10, 2021, and Dec 15, 2022, 13 724 pregnant women were screened for eligibility. 12 668 were excluded due to ineligibility for inclusion, and 1056 provided consent to participate and were randomly assigned to either the intravenous or oral administration groups. 527 were assigned to the intravenous ferric carboxymaltose group and 529 were assigned to the oral ferrous sulphate group. 518 in the intravenous group were assessed at 36 weeks' gestational age and after 518 deliveries, and 511 completed the 6 weeks postpartum visit. 513 in the oral ferrous sulphate group were assessed at 36 weeks' gestational age and after 512 deliveries, and 501 completed the 6 weeks postpartum visit. No significant difference was found in anaemia at 36 weeks (299 [58%] of 517 in the intravenous group vs 305 [61%] of 503 in the oral group; risk ratio 0·95, 95% CI 0·85-1·06; p=0·36), nor in preterm birth (73 [14%] of 518 vs 77 [15%] of 513; 0·94, 0·70-1·26; p=0·66). There were no significant differences in adverse events. The most common adverse events were diarrhoea (in six participants) and vomiting (in three participants) in the oral group and fatigue (in two participants) and headache (in two participants) in the intravenous group. INTERPRETATION: Although the effect on overall anaemia did not differ, intravenous iron reduced the prevalence of iron deficiency to a greater extent than oral iron and was considered to be safe. We recommend that intravenous iron be considered for anaemic pregnant women in Nigeria and similar settings. FUNDING: Bill & Melinda Gates Foundation.

Investigating the binding affinity, molecular dynamics, and ADMET properties of curcumin-IONPs as a mucoadhesive bioavailable oral treatment for iron deficiency anemia.

Iron deficiency anemia (IDA) is a common health issue, and researchers are interested in overcoming it. Nanotechnology green synthesis is one of the recent approaches to making efficient drugs. In this study, we modeled curcumin-coated iron oxide nanoparticles (cur-IONPs) to study their predicted toxicity and drug-likeness properties, then to investigate mucoadhesive behavior by docking cur-IONPs with two main mucin proteins in gastrointestinal tract (GIT) mucosa (muc 5AC and muc 2). Furthermore, the stability of cur-IONPs/protein complexes was assessed by molecular dynamics. Our in-silico studies results showed that cur-IONPs were predicted to be potential candidates to treat IDA due to its mucoadhesive properties, which could enhance the bioavailability, time residency, and iron absorbance through GIT, in addition to its high safety profile with high drug-likeness properties and oral bioavailability. Finally, molecular dynamic simulation studies revealed stable complexes supporting strength docking studies. Our results focus on the high importance of in-silico drug design studies; however, they need to be supported with in vitro and in vivo studies to reveal the efficacy, toxicity, and bioavailability of cur-IONPs.

Comparison of the efficacy and adverse effects of oral ferrous succinate tablets and intravenous iron sucrose: a retrospective study.

OBJECTIVE: To analyse the clinical efficacy and adverse drug reactions (ADRs) of iron preparations. METHODS: A total of 374 patients with iron deficiency anaemia admitted to our hospital between 1 January and 31 December 2020 were included in this study. They were divided into 2 groups based on their medication regimens: Group A (n = 187) took oral ferrous succinate tablets, and Group B (n = 187) received intravenous iron sucrose. The remission of major symptoms, laboratory test results, ADRs and other related data were collected after 4 weeks of treatment. RESULTS: Compared with the pre-treatment baseline, haemoglobin (Hb), serum iron (SI), serum ferritin (SF) and the mean corpuscular volume (MCV) increased in both groups at 4 weeks of treatment (P < 0.05). After treatment, Group A had lower levels of Hb (108.41 ± 8.39 vs. 122.31 ± 6.04 g/L, t = 6.293, P < 0.001), SI (9.72 ± 4.24 vs. 15.62 ± 5.41 µmol/L, t = 5.482, P < 0.001) and SF (27.1 ± 10.82 vs. 39.82 ± 10.44 ug/L, t = 6.793, P < 0.001) compared with Group B. In contrast, there was no significant difference in the post-treatment level of MCV (P > 0.05). The overall response rate significantly differed between the 2 groups (78.61% vs. 90.91%, χ2 = 10.949, P < 0.001). The incidence of ADRs of both groups were similar, and the difference was not statistically significant (χ2 = 0.035, P = 0.851). CONCLUSION: Iron sucrose demonstrates favourable efficacy and safety in treating iron deficiency anaemia.

Effects of beetroot (Beta vulgaris) supplements on selective enzymatic and non-enzymatic antioxidants in iron deficiency anemia.

Iron deficiency anemia (IDA) is not only associated with iron deficiency but has shown strong association with the over production of free radicles and deficiency of antioxidant enzymes. The result of this imbalance is oxidative stress (OS) which is now considered as an important associated factor with various diseases. Treating IDA in most of cases with oral iron supplements results in more OS as iron is a transition metal. A more suitable alternate for iron supplementation is Beta vulgaris supplement, which being herbal in origin is far less associated with side effects. We studied effects of beta vulgaris supplements on enzymatic and non-enzymatic antioxidants in IDA patients. A significant increase in all study parameters were observed after treatment (p <0.05). When pre-supplemental values of super oxide dismutase (SOD) and reduced glutathione (GSH-PX) of IDA were compared with post-supplemental values, they were significantly low (p <0.05). A positive correlation was noted between the two antioxidants and hemoglobin (Hb) values suggesting a direct relationship between antioxidant status and Hb levels. Non enzymatic antioxidants included vitamin A,C and E. We also found a significant improvement (p <0.05) of these vitamins when compared with their initial values and the control group. Our study shows improvement of antioxidant status of anemic patients with 12 week supplementation of Beta vulgaris.

Maternal ketone supplementation throughout gestation improves neonatal cardiac dysfunction caused by perinatal iron deficiency.

Iron deficiency (ID) is common during gestation and in early infancy and has been shown to adversely affect cardiac development and function, which could lead to lasting cardiovascular consequences. Ketone supplementation has been shown to confer cardioprotective effects in numerous disease models. Here, we tested the hypothesis that maternal ketone supplementation during gestation would mitigate cardiac dysfunction in ID neonates. Female Sprague-Dawley rats were fed an iron-restricted or iron-replete diet before and throughout pregnancy. Throughout gestation, iron-restricted dams were given either a daily subcutaneous injection of ketone solution (containing ß-hydroxybutyrate [ßOHB]) or saline (vehicle). Neonatal offspring cardiac function was assessed by echocardiography at postnatal days (PD)3 and 13. Hearts and livers were collected post-mortem for assessments of mitochondrial function and gene expression profiles of markers oxidative stress and inflammation. Maternal iron restriction caused neonatal anemia and asymmetric growth restriction at all time points assessed, and maternal ßOHB treatment had no effect on these outcomes. Echocardiography revealed reduced ejection fraction despite enlarged hearts (relative to body weight) in ID offspring, resulting in impaired oxygen delivery, which was attenuated by maternal ßOHB supplementation. Further, maternal ketone supplementation affected biochemical markers of mitochondrial function, oxidative stress and inflammation in hearts of neonates, implicating these pathways in the protective effects conferred by ßOHB. In summary, ßOHB supplementation confers protection against cardiac dysfunction in ID neonates and could have implications for the treatment of anemic babies.

An Electrolytic Elemental Iron Powder Effectively Regenerates Hemoglobin in Anemic Rats and Is Relatively Well Absorbed When Compared to Ferrous Sulfate Monohydrate.

Elemental iron powders are used as food fortificants to reduce the incidence of iron deficiency anemia. However, many commercially available iron powders are relatively untested in vivo. The purpose of this study was to determine the hemoglobin regeneration efficiency (HRE) and relative iron bioavailability (RBV) of an electrolytic elemental iron powder (EIP), by treating anemic rats with 14 d iron repletion diets fortified with four different concentrations (12, 24, 36, or 48 mg iron/kg diet) of EIP and bakery-grade ferrous sulfate monohydrate (FS; FeSO4•H2O), or no added iron (control); n = 9-12/group. The HRE of FS was significantly higher (p ≤ 0.05) than EIP at each concentration of dietary iron tested. For EIP, the HREs (ratios) of diets containing 12, 24, 36, and 48 mg iron/kg were 0.356, 0.205, 0.197, and 0.163, respectively. For both EIP and FS, HRE was inversely associated with increasing dietary iron. The RBVs (%) of iron from EIP in diets at 12, 24, 36, and 48 mg iron/kg as compared to FS were 64.5, 59.1, 50.6, and 54.3%, respectively. Overall, findings show that at the concentrations of iron tested, EIP has RBVs greater than 50% and is an effective fortification agent to replenish hemoglobin and correct iron deficiency anemia.

Ferric citrate hydrate improves transferrin saturation in patients with low levels of transferrin saturation undergoing hemodialysis.

Although it has been established that patients with chronic kidney disease and iron deficiency, as indicated by a transferrin saturation of < 20%, are at increased risk of all-cause mortality and cardiovascular events, the optimal management of such patients has not yet been determined. In this post hoc subgroup analysis, we aimed to clarify the effect of ferric citrate hydrate on transferrin saturation in patients with chronic kidney disease and low transferrin saturation (< 20%) undergoing hemodialysis. To accomplish this, we extracted the relevant data on a subset of patients drawn from two previous studies: the ASTRIO study (A Study examining the contribution to Renal anemia treatment with ferric citrate hydrate, Iron-based Oral phosphate binder, UMIN000019176) and a post-marketing surveillance study. The subset of patients used for the present study were those with baseline transferrin saturation < 20%. We found that administration of ferric citrate hydrate increased transferrin saturation and maintained transferrin saturation at approximately 30%. However, because we did not have access to data on all-cause mortality or cardiovascular events, we could not ascertain whether the frequency of these outcomes was reduced in parallel with improvements in transferrin saturation. Further large studies are required.

A Cost-Utility Analysis of Ferric Derisomaltose Versus Ferric Carboxymaltose in Patients with Iron Deficiency Anemia in China.

INTRODUCTION: Intravenous (IV) iron is the recommended treatment for patients with iron deficiency anemia (IDA) unresponsive to oral iron treatment, in whom oral iron is contraindicated, or where rapid iron replenishment is required. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), which showed significantly higher incidence of hypophosphatemia after administration of FCM than FDI. The present study objective was to evaluate the cost-utility of FDI versus FCM in a population of patients with IDA in China. METHODS: A previously-published patient-level simulation model was used to model the cost-utility of FDI versus FCM in China. The number of infusions of FDI and FCM was modeled based on the approved posology of the respective formulations using simplified tables of iron need in a population of patients with body weight and hemoglobin levels informed by a Chinese RCT of FCM. Data on the incidence of hypophosphatemia was obtained from the PHOSPHARE-IDA RCT, while data on disease-related quality of life were obtained from SF-36v2 data from the PHOSPHARE-IBD RCT. RESULTS: Over the 5-year time horizon, patients received 3.98 courses of iron treatment on average, requiring 0.90 fewer infusions of FDI than FCM (7.69 vs. 6.79). This resulted in iron procurement and administration cost savings of renminbi (RMB) 206 with FDI (RMB 3,519 vs. RMB 3,312). Reduced incidence of hypophosphatemia-related fatigue resulted in an increase of 0.07 quality-adjusted life years and further cost savings of RMB 782 over 5 years, driven by reduced need for phosphate testing and replenishment. FDI was therefore the dominant intervention. CONCLUSIONS: The results showed that FDI would improve patient quality of life and reduce direct healthcare expenditure versus FCM in patients with IDA in China.

Ferric carboxymaltose-induced hypophosphatemia - a case series.

Hypophosphatemia may cause serious complications. Depending on its severity and duration, signs and symptoms range from fatigue to life-threatening events, like severe rhabdomyolysis and mental status changes. Long-term consequences include osteomalacia. Hypophosphatemia may be secondary to the use of parental iron, mostly associated with ferric carboxymaltose (FCM), with an incidence of around 45% to 70%. We describe three cases of hypophosphatemia in patients with chronic iron deficiency anemia, requiring repeated FCM infusions. The patients' presentation to the Rheumatology department included musculoskeletal symptoms of severe hypophosphatemia and long-term hypophosphatemic osteomalacia, with fractures. We aim to raise awareness for ferric carboxymaltose-induced hypophosphatemia, an entity increasingly described in the literature that can be responsible for severe disability or potentially life-threatening adverse events.

Intravenous iron supplementation in pulmonary hypertension groups 1 to 4.

Background: Iron deficiency (ID) is common in patients with pulmonary arterial hypertension and has been associated with increased morbidity and mortality. We aimed to evaluate the therapeutic effects of iron supplementation in iron deficient patients with group 1 to 4 pulmonary hypertension (PH). Methods: A total of 85 PH patients (mean age 69.8 ± 12.0 years, 56.5% female) were included in this prospective trial. Patients were screened for ID at baseline. PH patients with ID received intravenous iron supplementation (500-1000 mg ferric carboxymaltose). PH patients without ID served as control group. At baseline and 16-week follow up, six-minute walk test (6MWT), laboratory testing and echocardiography were performed. Additionally, World Health Organization (WHO) functional class, fatigue score and quality of life (QoL) by the SF-36 questionnaire were assessed. Results: Overall, ID was present in 26.7% (n=8/30), 37.5% (n=9/24), 45.5% (n=10/22) and 44.4% (n=4/9) of patients in PH groups 1-4, respectively. In the total study population, iron restoration led to a significant mitigation of fatigue (p=0.01). However, 6MWT, WHO function class, NT-proBNP levels, QoL and right ventricular function did not change significantly. With regard to the underlying PH group, only PH group 3 patients experienced significant improvements in 6MWT distance (p=0.019), WHO functional class (p=0.017), fatigue (p=0.009) and some QoL domains, as compared to controls. Conclusions: ID was common in PH groups 1 to 4. Though intravenous iron supplementation adequately restored iron status and improved fatigue throughout all patients, in the underlying PH groups treatment was accompanied by improvements in exercise capacity, WHO function class and fatigue only in group 3 PH.