Enhancing diagnostic accuracy for iron deficiency in pregnant women through mean reticulocyte volume.

BACKGROUND AND OBJECTIVES: Women are more prone to iron deficiency (ID) anemia when pregnant. The diagnostic use of mean reticulocyte volume (MRV) in identifying ID anemia during pregnancy has not been thoroughly investigated. The objective of this study is to evaluate the effectiveness of MRV in diagnosing ID in pregnant women. METHODS AND STUDY DESIGN: Firstly, MRV of 20 healthy female volunteers (healthy group) was measured on specific days for one month. Subsequently, clinical data from 724 pregnant women were thoroughly examined. These women were divided into two groups: 282 with ID (research group) and 442 without ID (control group). Parameters such as MRV, reticulocyte hemoglobin equivalent (RHE), red blood cell volume distribution width-standard deviation (RDW-SD), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), reticulocyte count (RET), MRV/MCV ratio, and serum ferritin (SF) were analyzed and compared. RESULTS: MRV remained consistent over a period of one month for 20 healthy individuals. In addition, there were significant differences in MRV, RHE, RDW-SD, MCV, MCH, MCHC, HCT, RET, and MRV/MCV between the research group and control group. The receiver operating characteristic (ROC) analysis showed that the areas under the curve (AUCs) for these measures were as follow: 0.840, 0.837, 0.676, 0.654, 0.639, 0.602, 0.571, 0.550, and 0.816, respectively. Ultimately, there was a substantial disparity in MRV prior to and following therapy with oral iron treatments. CONCLUSIONS: In healthy women, MRV remains stable and is a reliable ID marker, which can be used to assess oral iron treatment effectiveness during pregnancy.

Iron administered in the neonatal period changed memory, brain monoamine levels, and BDNF mRNA expression in adult Sprague-Dawley rats.

BACKGROUND: Iron is one of the key microelements in the mammalian body and is the most abundant metal in the brain. Iron, a very important chemical element in the body of mammals, is the most abundant metal in the brain. It participates in many chemical reactions taking place in the central nervous system acting as a cofactor in key enzymatic reactions involved in neurotransmitter synthesis and degradation, dendritic arborization, and myelination. Moreover, iron accumulation in the brain has been implicated in the pathogenesis of neurogenerative disorders. MATERIAL AND METHODS: The aim of our study was to assess the influence of iron administered orally (30 mg/kg) to rats in the neonatal period (p12-p14) by testing the performance of rats in the open field and social interaction tests, and by evaluating the recognition memory, monoamine levels in some brain structures, and BDNF mRNA expression. The behavioral and biochemical tests were performed in adult p88-p92 rats. RESULTS: Iron administered to rats in the neonatal period induced long-term deficits in behavioral tests in adult rats. It reduced the exploratory activity in the open field test. In the social interaction test, it induced deficits in the parameters studied, and decreased memory retention. Moreover, iron changed the brain monoamine levels in some studied brain structures and decreased the expression of BDNF mRNA in the hippocampus. CONCLUSIONS: All earlier and our present results indicated that iron administered to rats in the neonatal period induced an increase in oxidative stress which resulted in a change in the brain monoamine levels and decreased BDNF mRNA expression which may play a role in iron-induced memory impairment in adult rats.

Maternal Fatigue after Postpartum Anemia Treatment with Intravenous Ferric Carboxymaltose vs. Intravenous Ferric Derisomaltose vs. Oral Ferrous Sulphate: A Randomized Controlled Trial.

(1) Background: Postpartum anemia is a common maternal complication and is recognized as a cause of impaired quality of life, reduced cognitive abilities, and fatigue. Efficient iron supplementation for the treatment of postpartum anemia is an essential component of high-quality maternal care. The optimal mode of iron supplementation has not been determined yet, whether oral or intravenous. The objective of this study was to compare postpartum anemia treatment with intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate. (2) Methods: A single-center, open-label, randomized controlled trial. Women with hemoglobin < 100 g/L within 48 h postpartum were randomly allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose, or oral ferrous sulfate. Intravenous iron was given in one or two doses, while ferrous sulfate was given as two 80 mg tablets once daily. The primary outcome was maternal fatigue measured by the Multidimensional Fatigue Inventory (MFI) six weeks postpartum. Hemoglobin, ferritin, and transferrin saturation levels were analyzed as secondary outcomes. A Kruskal-Wallis test was used for group comparison (p < 0.05 significant). (3) Results: Three hundred women were included. The MFI score at six weeks postpartum did not differ between groups (median 38 (inter-quartile range (IQR) 29-47) in the ferric carboxymaltose group, median 34 (IQR 26-42) in the ferric derisomaltose group, and median 36 (IQR 25-47) in the ferrous sulfate group; p = 0.26). Participants receiving oral iron had lower levels of hemoglobin (135 (131-139) vs. 134 (129-139) vs. 131 (125-137) g/L; p = 0.008), ferritin (273 (198-377) vs. 187 (155-246) vs. 24 (17-37) µg/L; p < 0.001) and transferrin saturation (34 (28-38) vs. 30 (23-37) vs. 24 (17-37) %; p < 0.001) than those receiving ferric carboxymaltose or ferric derisomaltose. (4) Conclusions: Intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate had similar impacts on maternal fatigue at six weeks postpartum despite improved laboratory parameters in the intravenous groups.

Incidence of postpartum depression after treatment of postpartum anaemia with intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate: A randomized clinical trial.

Objectives: This study aimed to explore whether the type of iron preparation used to treat postpartum anaemia affects the incidence of postpartum depression and whether the risk of postpartum depression is higher in postpartum patients with anaemia who were adequately treated compared to the general postpartum population. Study design: Single-center, open-label, randomized trial. Women were allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate. Intravenous iron was given in one or two doses, while ferrous sulphate as two 80 mg tablets once daily. Primary outcome was postpartum depression measured by Edinburgh Postnatal Depression Scale (EPDS) six weeks postpartum. Haematological parameters were analyzed as secondary outcomes. Kruskal-Wallis test was used for group comparison (p < 0.05 significant). The chi-square test was applied to compare categorical variables as well as the group of all subjects treated for anaemia in the study with the historical data for the Slovenian postpartum population. Results: Three-hundred women with postpartum anemia (hemoglobin < 100 g/L within 48-hours postpartum) were included between September 2020 and March 2022 in tertiary perinatal center. Most characteristics were similar across groups. EPDS score at six weeks postpartum did not differ between groups. The treatment modality of postpartum anaemia did not have a statistically significant effect on the EPDS score six weeks after treatment (p = 0.10), nor did it have a statistically significant effect on the difference in EPDS scores before and after treatment (p = 0.68). The proportions of participants who scored 10 or more points on the EPDS scores at six weeks postpartum were not statistically different between the groups (p = 0.79). The proportion of participants with an EPDS score of 10 or more at six weeks postpartum in the total study population did not differ significantly from previously reported proportion of postpartum women with EPDS score of 10 or more in the general population (12 % vs. 21 %; p < 0.001). Conclusions: Maternal depression at 6 weeks postpartum did not differ in women treated for postpartum anemia with intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate. Participants with postpartum anaemia who are adequately treated with either oral or intravenous iron preparations are not at a higher risk of postpartum depression than the general population at six weeks postpartum.

Preoperative intravenous iron treatment - a cohort study on colorectal cancer recurrence.

Background: Intravenous (i.v.) iron treatment has been speculated to increase the malignant potential of colorectal malignancies but also to enhance the immune systems potential to fight the invasive tumor. Clinical data however is very limited. We investigate if preoperative i.v. iron treatment is associated with colorectal cancer (CRC) recurrence. Methods: Retrospective cohort study on surgical CRC patients with iron deficiency anemia (1st March 2013 - 31st December 2019). Patients were grouped based on whether they had received preoperative treatment with i.v. iron. Local data was combined with data from the National Danish Health registries to identify recurrences, death, and emigration. Survival analysis, including Kaplan-Meyer curves and multivariate competing risk analysis adjusting for sex, age, ASA-group, tumor stage, surgical radicality, and miss match repair status was performed. Results: Of 1228 patients, 125 were available for analysis. 89 patients had received preoperative i.v. iron and 36 had not. The two groups were comparable on baseline and surgical characteristics. Median follow-up times were 4.74 in iron treated patients and 5 years in patients not receiving iron treatment. Five-year rate of non-recurrence was 85 % (0.74-0.91) in the i.v. iron treated group vs. 82 % (0.64-0.91) in the control group, non-significant difference. Multivariate survival analysis did not find iron treatment to be associated with recurrence rates (Hazard Ratio 0.88 (95 % ci; 0.31-2.51). Conclusion: No association between preoperative i.v. iron treatment and the five-year cancer recurrence rate in iron deficient anemic CRC patients was found.

Addition of oral iron bisglycinate to intravenous iron sucrose for the treatment of postpartum anemia-randomized controlled trial.

BACKGROUND: Studies that have compared the effectiveness of oral with intravenous iron supplements to treat postpartum anemia have shown mixed results. The superiority of one mode of treatment vs the other has yet to be demonstrated. Therefore, despite guidelines and standards of care, treatment approaches vary across practices. A single 500 mg dose of iron sucrose, which is higher than what is usually administered, has not been evaluated to treat postpartum moderate to severe anemia. OBJECTIVE: This study aimed to compare the efficacy of intravenous iron sucrose alone with intravenous iron sucrose in combination with oral iron bisglycinate supplementation in treating moderate to severe postpartum anemia. STUDY DESIGN: A randomized controlled trial was conducted between February 2015 and June 2020. Women with postpartum hemoglobin level of ≤9.5 g/dL were treated with 500 mg intravenous iron sucrose after an anemia workup, which ruled out other causes for anemia. In addition to receiving intravenous iron, women were randomly allocated to receive either 60 mg of oral iron bisglycinate for 45 days or no further iron supplementation. The primary outcome was hemoglobin level at 6 weeks after delivery. Secondary outcomes were iron storage parameters and quality of life. RESULTS: Of 158 patients who participated, 63 women receiving intravenous and oral iron, and 44 women receiving intravenous iron-only, completed the study and were included in the analysis. Baseline and obstetrical characteristics were similar between the study cohorts. Although statistically significant, postpartum hemoglobin levels were only 0.4 g/dL higher in the intravenous and oral iron than intravenous iron-only cohort (12.4 g/dL vs 12.0 g/dL, respectively; P=.03), with a respective increase from baseline of 4.2 g/dL vs 3.7 g/dL (P=.03). There was no difference in the rate of women with hemoglobin level of <12.0 or 11.0 g/dL. Iron storage and health quality were not different between the cohorts. Oral iron treatment was associated with 29% rate of adverse effects. Compliance and satisfaction from treatment protocol were high in both cohorts. CONCLUSION: Intravenous 500 mg iron sucrose treatment alone is sufficient to treat postpartum anemia without the necessity of adding oral iron treatment.

Intravenous Iron-Induced Hypophosphatemia: An Emerging Syndrome.

Some, but not all, intravenous iron formulations have been recognized to induce renal phosphate wasting syndrome. Most commonly this has been reported following treatment of iron deficiency anemia (IDA) with ferric carboxymaltose (FCM). A search of PubMed identified relevant randomized controlled trials (RCTs), and case studies evaluating hypophosphatemia (HPP) resulting from intravenous iron treatment. While more recent larger comparative RCTs have confirmed that the majority of patients receiving FCM, especially those with normal renal function, may experience severe HPP, complete documentation is hampered by inconsistent reporting of serum phosphate in such trials. Similarly, while case series and RCTs have documented the persistence of HPP for several weeks or even months, the lack of studies lasting beyond 5-6 weeks has constrained full understanding of the duration of effect. Clinical trials have established that the mechanism involves the bone/metabolic axis with the elevation of intact fibroblast growth factor 23 playing the central role. Reports continue to accumulate of the clinical consequences of severe HPP which are, most commonly, bone abnormalities following repetitive dosing. Case reports and studies, however, have also shown that symptomatic hypophosphatemia can occur after a single FCM dose. The frequency of such events remains unknown, in part due to lack of awareness of hypophosphatemia coupled with the fact that the most common acute symptoms of HPP (fatigue and weakness) are the same for IDA and for many of the chronic diseases that cause IDA. Changes to US and European prescribing information for FCM should raise awareness of the potential for HPP and need to monitor patients at risk for it.

Retrospective Evaluation of Effects of Preoperative Anaemia Treatment in Gynaecological and Obstetric Surgical Patients.

OBJECTIVE: In anemic patients undergoing surgery, there is an increase in the requirement of blood transfusion, longer hospital stay and higher intensive care unit adimission. In this study we aimed to evaluate the efficacy of iv iron treatment before elective obstetric or gynecological operations retrospectively. METHODS: After obtaining approval of ethics committee, records of 5688 patients underwent either obstetric or gynecological surgery between January 1st of 2016 to December 31st of 2018 were documented retrospectively and 241 anemic cases were identified. Eighty-one anemic patients who did not receive any iv iron treatment preoperatively were excluded and 160 cases treated with either iv iron (either sucrose or ferric carboxy maltose) were included. The laboratory results including haemoglobin (Hb), MCV,MCH and serum iron binding capacities, ferritin, iron and transferrin levels were documented before (preoperative) and after iv iron treatment (postoperative 10th day) were collected from files. Difference between preoperative and postoperative Hb, MCV, MCH, TIBC, serum ferritin, iron and transferrin levels of these cases were determined. RESULTS: In 97 obstetric cases, the differences of Hb, MCV, MCH, serum iron, ferritin, iron binding capacity values before surgery and postoperative 10th day were respectively found as 1.3 g dL-1 (p=0.000); 1.9 fL (p=0.000); 0.3 pg (p=0.01); 44.4 µg dL-1 (p=0.008); 85.9 µg L-1 (p=0.009); 211.7 µg dL-1 (p=0.001). In 63 gynecologic cases, same measurements were evaluated and similar differences in Hb, MCV, MCH, serum ferritin and transferrin saturation values were 1.25 g dL-1 (p=0.000); 2.2 fL (p=0.000); 0.8 pg (p=0.000); 215.6 µg L-1 (p=0.002); 41.5% (p=0.044). Two obstetric patients and 7 gynaecologic patients were transfused erytrocyte suspensions after surgery. CONCLUSION: Efficacy of preoperative iv iron therapy in gynaecologic-obstetric patients with IDA has been demonstrated and its importance has been revisited once again.

Impact of treating iron deficiency, diagnosed according to hepcidin quantification, on outcomes after a prolonged ICU stay compared to standard care: a multicenter, randomized, single-blinded trial.

BACKGROUND: Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnose in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. METHODS: In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥ 5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm, patients were treated with intravenous iron (1 g of ferric carboxymaltose) when hepcidin was < 20 µg/l and with intravenous iron and erythropoietin for 20 ≤ hepcidin < 41 µg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue, day 90 mortality and 1-year survival. RESULTS: Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). A total of 220 patients (55%) had ID at discharge (i.e., a hepcidin < 41 µg/l). Primary endpoint was not different (medians (IQR) post-ICU LOS 33(13;90) vs. 33(11;90) days for intervention and control, respectively, median difference - 1(- 3;1) days, p = 0.78). D90 mortality was significantly lower in intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference - 8.7 (- 15.1 to - 2.3)%, p = 0.008, OR 95% IC, 0.46, 0.22-0.94, p = 0.035), and one-year survival was improved (p = 0.04). CONCLUSION: Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but was associated with a significant reduction in D90 mortality and with improved 1-year survival in critically ill patients about to be discharged after a prolonged stay. TRIAL REGISTRATION: www.clinicaltrial.gov NCT02276690 (October 28, 2014; retrospectively registered).

Detection of Common Deletional of α-Thalassemia 3.7 Kb from Metropolitan Region of Manaus, Amazonas, Brazil.

BACKGROUND: Alpha Thalassemia (α-thal) is a heterogeneous group of hereditary alterations caused by deletions that affect alpha regulatory genes, and the 3.7Kb deletion is the most frequent worldwide. The prevalence ranges from 20% and 35% in Brazil, depending mainly on race, predominant in Afro-descendants. PURPOSE: The aim was to determine α-thal -α3.7Kb and -α4.2Kb deletions, estimating their frequency in individuals from six regions of Amazonas State. METHODS: Volunteers age between 18-59 years old of both genders participated in the study. Blood was collected from March 2014 to September 2017 at the health centers of each participant city. α-thal3.7Kb was performed by GAP-PCR, while α-thal4.2Kb by Multiplex-PCR. The total samples collected from each city were: Manaus (capital), 356 (19.7%); Iranduba 232 (12.8%); Manacapuru, 287 (15.9%); Presidente Figueiredo, 370 (20.5%); Itacoatiara, 301 (16.6%); and Coari, 263 (14.5%). RESULTS: The average age among males was 35.3±14.8, while for females, it was 36.7±14.9 years old. Microcytosis (MCV <80fL) was found in 158 individuals (8,46%) and α-thal diagnosed in 143 individuals (7.9%), and all of these individuals carried the 3.7Kb deletion 5.95% in heterozygous and 1.95% in homozygous. α-thal4.2kb was not found in any volunteer. The association analyses to the α-thal3.7kb genotypes were statistically significant for all hematological parameters (p<.001), except serum iron and serum ferritin analyses. CONCLUSION: This study highlights α-thal 3.7kb deletion as an important public health problem, especially in a population not yet characterized about this disease. Thus, epidemiological studies using molecular tools become relevant in regions where the disease is underestimated, contributing to a better understanding of thalassemia incidence and iron deficiency anemias incidence of the participating cities. We reinforce that future molecular studies in North Region from Brazil can be utilized to describe other genetic anemias as structural hemoglobinopathies that have already proven to be highly prevalent in Brazil.

Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial.

BACKGROUND: The optimal intravenous (IV) iron would allow safe correction of iron deficiency at a single infusion over a short time. The FERWON-NEPHRO trial evaluated the safety and efficacy of iron isomaltoside 1000/ferric derisomaltose (IIM) in patients with non-dialysis-dependent chronic kidney disease and iron deficiency anaemia. METHODS: In this randomized, open-label and multi-centre trial conducted in the USA, patients were randomized 2:1 to a single dose of 1000 mg IIM or iron sucrose (IS) administered as 200 mg IV injections up to five times within a 2-week period. The co-primary endpoints were serious or severe hypersensitivity reactions and change in haemoglobin (Hb) from baseline to Week 8. Secondary endpoints included incidence of composite cardiovascular adverse events (AEs). RESULTS: A total of 1538 patients were enrolled (mean estimated glomerular filtration rate 35.5 mL/min/1.73 m2). The co-primary safety objective was met based on no significant difference in the incidence of serious or severe hypersensitivity reactions in the IIM and IS groups [0.3% versus 0%; risk difference: 0.29% (95% confidence interval: -0.19; 0.77; P > 0.05)]. Incidence of composite cardiovascular AEs was significantly lower in the IIM versus IS group (4.1% versus 6.9%; P = 0.025). Compared with IS, IIM led to a more pronounced increase in Hb during the first 4 weeks (P ≤ 0.021), and change in Hb to Week 8 showed non-inferiority, confirming that the co-primary efficacy objective was met. CONCLUSIONS: Compared with multiple doses of IS, a single dose of IIM induced a non-inferior 8-week haematological response, comparably low rates of hypersensitivity reactions, and a significantly lower incidence of composite cardiovascular AEs.

A Review of Clinical Guidelines on the Management of Iron Deficiency and Iron-Deficiency Anemia in Women with Heavy Menstrual Bleeding.

INTRODUCTION: Up to one-third of women of reproductive age experience heavy menstrual bleeding (HMB). HMB can give rise to iron deficiency (ID) and, in severe cases, iron-deficiency anemia (IDA). AIM: To review current guidelines for the management of HMB, with regards to screening for anemia, measuring iron levels, and treating ID/IDA with iron replacement therapy and non-iron-based treatments. METHODS: The literature was searched for English-language guidelines relating to HMB published between 2010 and 2020, using the PubMed database, web searching, and retrieval of clinical guidelines from professional societies. RESULTS: Overall, 55 guidelines mostly originating from North America and Europe were identified and screened. Twenty-two were included in this review, with the majority (16/22) focusing on guidance to screen women with HMB for anemia. The guidance varied with respect to identifying symptoms, the criteria for testing, and diagnostic hemoglobin levels for ID/IDA. There was inconsistency concerning screening for ID, with 11/22 guidelines providing no recommendations for measurement of iron levels and four contrasting guidelines explicitly advising against initial assessment of iron levels. In terms of treatment, 8/22 guidelines provided guidance on iron therapy, with oral iron administration generally recommended as first-line treatment for ID and/or IDA. Four guidelines recommended intravenous iron administration for severe anemia, in non-responders, or before surgery. Three guidelines provided hemoglobin thresholds for choosing between oral or intravenous iron treatment. Four guidelines discussed the use of transfusion for severe IDA. CONCLUSION: Many of the guidelines for managing HMB recognize the importance of treating anemia, but there is a lack of consensus in relation to screening for ID and use of iron therapy. Consequently, ID/IDA associated with HMB is likely to be underdiagnosed and undertreated. A consensus guidance, covering all aspects of screening and management of ID/IDA in women with HMB, is needed to optimize health outcomes in these patients.

Women who bleed heavily during menstruation are at risk of iron deficiency and anemia. This can have a negative effect on the well-being of women and can cause serious complications after surgery. Iron is an important part of the hemoglobin in red blood cells that carries oxygen around the body. Bleeding causes iron to be lost from the body. If there is heavy blood loss, iron stores in the body can become low, leading to iron deficiency. If the iron deficiency is severe enough to impair red blood cell production, iron-deficiency anemia can develop. We reviewed the current guidelines for the care of women with heavy menstrual bleeding, focusing on the detection and treatment of iron deficiency and anemia. Most guidelines include routine testing for anemia. Fewer guidelines consider measuring iron levels. Not all the guidelines include advice on the best way to treat iron deficiency and anemia. For those that do, the recommendations vary and sometimes offer conflicting advice. There is little agreement on when to give iron therapy, and whether this should be given by mouth or by infusion. A lack of clear guidance on detecting and treating iron deficiency and anemia caused by heavy menstrual bleeding puts women at risk of being undiagnosed and untreated. To address these concerns, the authors recommend the development of consensus guidelines. These should contain comprehensive recommendations on all aspects of the diagnosis and management of iron deficiency and anemia in women with heavy menstrual bleeding.

Impact of immediate post-transplant parenteral iron therapy on the prevalence of anemia and short-term allograft function in a cohort of pediatric and adolescent renal transplant recipients.

Anemia is common but under-diagnosed and often inadequately treated in KTX recipients. ID is the major cause of early-onset anemia. We introduced routine use of parenteral (IV) iron in patients (2-18 years) who had KTX between January 2011 and December 2015. We explored the clinical benefits of this practice by comparing the iron-treated subjects [TX] with historical controls who had KTX between 2005 and 2010. The prevalence of anemia at 6 months (early-onset) for the cohort (both the study group and controls) was 55% and for anemia at 12 months (late-onset) was 60%. Although cause-effect relationship may not be proven in a retrospective study design, there was a significant greater frequency of ID and anemia at 3 (P < .02) and 6 months (P < .04), and a reduced allograft function (eGFR < 60 mL/min/1.73 m2 ) at 12 (P = .03) and 24 months (P = .04) of KTX in the control arm. Furthermore, a greater proportion of the control arm required either ESA (P = .03) or blood transfusion (P = .04) as a rescue treatment for moderate-to-severe anemia. In conclusion, routine parenteral iron treatment was associated with a lower prevalence of early- and late-onset anemia, and a lower requirement for either ESA rescue or blood transfusion.

Intravenous ferric carboxymaltose for iron deficiency anemia in dialysis patients: Effect of a new protocol adopted for a hemodialysis limited assistance center.

Iron and erythropoietin deficiencies are determinants of anemia in chronic kidney disease. In hemodialysis (HD) patients, intravenous (IV) iron is associated with a greater hemoglobin (Hb) production and better erythropoietin response but may be associated to hypersensitivity reaction. After the 2013 European Medicines Agency report regarding early detection/management of iron allergic reactions, IV iron administration dramatically reduced in Italian Hemodialysis-Limited-Assistance-Centre (HD-CAL) where a physician is present only once a week. Objective of the study was providing an effective and secure IV iron administration protocol for HD-CAL patients. IV ferric carboxymaltose (FCM) administration was more effective and better tolerated than sodium ferric gluconate for iron deficiency correction and resolution of anemia in 24 patients undergoing HD in our HD-CAL. Six months of FCM IV treatment once a week increased ferritin and Hb compared to sodium ferric gluconate once a week leading to decreased erythropoietin consumption from 24 000 to 15 000 U/patient/week with an erythropoietin annual expense reduction. No blood transfusions, gastrointestinal intolerance or other adverse effects were reported. The FCM IV administration protocol for our HD-CAL patients was safe and no adverse events were reported, resulting in significantly increased ferritin, transferrin saturation, and Hb levels, reduction of erythropoietin requirements, and consequently reduction of erythropoietin expenses.

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial.

BACKGROUND: The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder. METHODS: CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements. RESULTS: Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group. CONCLUSION: L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006).

Impact and management of iron deficiency and iron deficiency anemia in women's health.

INTRODUCTION: Iron deficiency and iron deficiency anemia are highly prevalent among women throughout their lives. Some females are particularly vulnerable to iron deficiency/iron deficiency anemia, including those with heavy menstrual bleeding (HMB) and pregnant/postpartum women. Despite the high prevalence of iron deficiency/iron deficiency anemia in women, the condition is still underdiagnosed and therefore undertreated, with serious clinical consequences. Areas covered: The following review examines the impact of iron deficiency and iron deficiency anemia on clinical outcomes and quality of life in women from adolescence to post-menopause, paying particular attention to guidelines and current recommendations for diagnostic tests and management. Expert commentary: There are numerous adverse health consequences of an iron-deficient state, affecting all aspects of the physical and emotional health and well-being of women. Guidelines must be developed to help clinicians better identify and treat women at risk of iron deficiency or iron deficiency anemia, particularly those with HMB, or who are pregnant or postpartum. Replacement therapy with oral or intravenous iron preparations is the mainstay of treatment for iron deficiency/iron deficiency anemia, with red blood cell transfusion reserved for emergency situations. Each iron therapy type is associated with benefits and limitations which impact their use.

Oral versus intravenous iron therapy in patients with inflammatory bowel disease and iron deficiency with and without anemia in Germany - a real-world evidence analysis.

BACKGROUND: Iron-deficiency anemia and iron deficiency are common comorbidities associated with inflammatory bowel disease (IBD) resulting in impaired quality of life and high health care costs. Intravenous iron has shown clinical benefit compared to oral iron therapy. AIM: This study aimed to compare health care outcomes and costs after oral vs intravenous iron treatment for IBD patients with iron deficiency or iron deficiency anemia (ID/A) in Germany. METHODS: IBD patients with ID/A were identified by ICD-10-GM codes and newly commenced iron treatment via ATC codes in 2013 within the InGef (formerly Health Risk Institute) research claims database. Propensity score matching was performed to balance both treatment groups. Non-observable covariates were adjusted by applying the difference-in-differences (DID) approach. RESULTS: In 2013, 589 IBD patients with ID/A began oral and 442 intravenous iron treatment. After matching, 380 patients in each treatment group were analyzed. The intravenous group had fewer all-cause hospitalizations (37% vs 48%) and ID/A-related hospitalizations (5% vs 14%) than the oral iron group. The 1-year preobservation period comparison revealed significant health care cost differences between both groups. After adjusting for cost differences by DID method, total health care cost savings in the intravenous iron group were calculated to be €367. While higher expenditure for medication (€1,876) was observed in the intravenous iron group, the inpatient setting achieved most cost savings (€1,887). CONCLUSION: IBD patients receiving intravenous iron were less frequently hospitalized and incurred lower total health care costs compared to patients receiving oral iron. Higher expenditures for pharmaceuticals were compensated by cost savings in other domains.

Kidney injury in infants and children with iron-deficiency anemia before and after iron treatment.

BACKGROUND: Our study aimed to investigate the effects of iron-deficiency anemia (IDA) on renal tubular functions before and after iron treatment for infants and children with IDA. We measured urinary levels of two kidney injury markers: neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP). MATERIAL AND METHODS: Thirty-six infants and children with IDA and 20 matched healthy controls were included. We assessed different laboratory parameters, estimated glomerular filtration rate, urinary levels of NGAL, and L-FABP. Urinary kidney injury markers were measured in IDA patients before and after 3 months of oral iron therapy. RESULTS: IDA patients had significantly higher urinary NGAL and L-FABP levels compared to their healthy controls. After 3 months of oral iron treatment, there was a significant improvement (decrease) in urinary NGAL and L-FABP in infants and children with IDA. Urinary markers returned to normal levels (healthy control levels) in children with IDA, but not for infants with IDA compared to their healthy controls. CONCLUSION: Subclinical kidney injury was found in infants and children with IDA. This injury was completely reversible in older children with IDA and partially reversible in infants with IDA after iron therapy. Higher urinary levels of kidney injury molecules in IDA infants after iron treatment are suggestive of more sensitivity of these infants to oxidative stress caused by iron therapy or may be due to the immaturity of the kidney and more damage caused by IDA which may require more time to recover.

The influence of restoration measures on phosphorus internal loading from the sediments of a hypereutrophic lake.

Uzarzewskie Lake was a hypereutrophic, dimictic lake characterized by low water transparency, high chlorophyll-a concentration and intense phytoplankton blooms; thus, restoration treatment was started. A chemical treatment, based on phosphorus inactivation with small doses of iron sulphate, was undertaken in 2006-2007. Nitrate-rich groundwater flowing from seepage springs was directed into the lake hypolimnion to increase redox potential since 2008. Phosphorus internal loading was reduced by more than 80% as a result of restoration treatment. In the profundal zone, where P release from the bottom sediments prevailed throughout the year, it decreased from 13.02 mg P m-2 day-1 in 2010 to 2.81 mg P m-2 day-1 in 2015. Meanwhile, in the littoral zone, P accumulation in bottom sediments predominated; hence, the mean value of internal loading was increasing from 2.61 mg P m-2 day-1 in 2011 to 10.24 mg P m-2 day-1 in 2015. The annual P load from the bottom sediments in the profundal zone was much higher than from the littoral zone as a result of (i) a higher P release in most years and (ii) the greater area of this zone (82% of the lake's area). The fraction of residual phosphorus (Res-P) has the largest share, and in recent years, this has shown a tendency to decrease. The sum of bioavailable fractions was low (average 5.7%) showing a downward trend in recent years. Sustainable restoration of the lake resulted in a slow but steady decreasing trend in internal phosphorus loading.

Experimental iron amendment suppresses toxic cyanobacteria in a hypereutrophic lake.

The effects of reducing nutrient inputs to lakes and reservoirs are often delayed by hysteresis resulting from internal phosphorus (P) loading from sediments. Consequently, controlling harmful algal blooms (HABs) in many eutrophic ecosystems requires additional management to improve water quality. We manipulated iron (Fe) concentrations in a hypereutrophic lake to determine if Fe amendment would suppress HABs by inhibiting P release from sediments. Our experiment consisted of 15 in situ mesocosms, 12 of which each received a different dose of Fe (ranging from 2 to 225 g/m2 ); the remaining three were unmanipulated to serve as controls. Iron amendment decreased P accumulation in porewaters and the flux of P from sediments, which significantly lowered P concentrations in the water column. Iron exerted significant dose-dependent negative effects on the biomass of phytoplankton and periphyton, and reduced the dominance of cyanobacteria. Even at the lowest doses, Fe appeared to reduce the toxicity of cyanobacterial blooms, as measured by concentrations of hepatotoxic microcystins. Overall, our findings highlight the potential for Fe treatment as an effective strategy for minimizing HABs in eutrophic lakes and reservoirs. More broadly, our study reinforces the importance of Fe in regulating the trophic state of freshwaters, and the sensitivity of certain ecosystems to changes in Fe supply. Finally, we hypothesize that decreases in natural Fe supplies to lakes associated with anthropogenic activities may worsen outbreaks of toxic cyanobacteria.