Serum Iron-binding Capacity Research Articles

8454 Iron deficiency as a cause of euthyroid syndrome

Abstract Disclosure: O.V. Samburskaya: None. S. Kalinchenko: None. L. Vorslov: None. Annotation: The prevalence of euthyroid pathology syndrome is increasing, and the cause of its occurrence remains unknown, despite the decrease in the quality of life of these patients, there is no treatment for this pathology. One of the reasons may be iron deficiency, which not only reduces the activity of thyroid enzymes, but also disrupts the feedback between a decrease in triiodothyronine and the level of thyroid-stimulating hormone (TSH). Materials and methods: There are 6 patients under observation, aged from 25 to 55 years, average age 38.4±12.67 years, gender distribution: 4 women 67% and 2 men 33%, who are undergoing treatment to compensate for iron deficiency and simultaneously control thyroid function. The analysis of iron deficiency is performed according to blood test parameters: total blood count, total serum iron binding capacity, transferrin, ferritin, serum iron. The function of the thyroid gland is determined by blood test parameters: T4 free, T3 free, TSH.The received data. According to the results of the data obtained, latent iron deficiency was found in all 6 patients. All patients have a decrease in thyroid hormone levels: T3 free 3.87±0.45 pmol/l (reference range 3.69-8.46 pmol/L) and T4 free 14.17±1.23 pmol/L (reference range 12.3-22.8 pmol/L) is closer to the lower limit of normal, but TSH is also closer to the lower limit of the norm is 1.46±0.33 µm/ml (reference range 0.70-5.9 µm/ml). Discussion: The existing iron deficiency leads to the development of chronic hypoxia, which leads to a violation of the functioning of many endocrine glands, including a violation of the work of thyroid enzymes: thyroid peroxidase and deiodinases, with a decrease in the synthesis of thyroid hormones (T4 and T3), and according to the feedback principle, an decrease in the level of thyroxine and triiodothyronine is expected raising the level of TSH. However, with chronic hypoxia, iron deficiency, hypoxic dysfunction develops not only of the peripheral endocrine glands, but also hypoxic hypothalamic-pituitary dysfunction, which leads to an inadequate response of the pituitary gland, i.e. the absence of an increase in TSH in response to a decrease in thyroid hormones. Conclusion: All patients with euthyroid syndrome need to evaluate the biochemical parameters of the body's iron supply, and the elimination of deficiency of which may be the necessary treatment for patients with euthyroid pathology. Presentation: 6/2/2024

Mendelian Randomization Analysis of Systemic Iron Status and Risk of Different Types of Kidney Disease.

With rapid increases in incidence, diverse subtypes, and complicated etiologies, kidney disease remains a global public health problem. Iron, as an essential trace element, has pleiotropic effects on renal function and the progression of kidney diseases. A two-sample Mendelian randomization (MR) analysis was implemented to determine the potential causal effects between systemic iron status on different kidney diseases. Systemic iron status was represented by four iron-related biomarkers: serum iron, ferritin, transferrin saturation (TfSat), and total iron binding capacity (TIBC). For systemic iron status, 163,511, 246,139, 131,471, and 135,430 individuals were included in the genome-wide association study (GWAS) of serum iron, ferritin, TfSat, and TIBC, respectively. For kidney diseases, 653,143 individuals (15,658 cases and 637,485 controls), 657,076 individuals (8160 cases and 648,916 controls), and 659,320 individuals (10,404 cases and 648,916 controls) were included for immunoglobulin A nephropathy (IgAN), acute kidney disease (AKD), and chronic kidney disease (CKD), respectively. Our MR results showed that increased serum iron [odds ratio (OR): 1.10; 95% confidence interval (95% CI): 1.04, 1.16; p < 0.0042], ferritin (OR: 1.30; 95% CI: 1.14, 1.48; p < 0.0042), and TfSat (OR: 1.07; 95% CI: 1.04, 1.11; p < 0.0042)] and decreased TIBC (OR: 0.92; 95% CI: 0.88, 0.97; p < 0.0042) were associated with elevated IgAN risk. However, no significant associations were found between systemic iron status and AKD or CKD. In our MR study, the genetic evidence supports elevated systemic iron status as a causal effect on IgAN, which suggests a potential protective effect of iron chelation on IgAN patients.

Association among attention-deficit hyperactivity disorder, restless legs syndrome, and peripheral iron status: a two-sample Mendelian randomization study.

Epidemiological evidence indicates a high correlation and comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and Restless Legs Syndrome (RLS). We aimed to investigate the causal relationship and shared genetic architecture between ADHD and RLS, as well as explore potential causal associations between both disorders and peripheral iron status. We performed two-sample Mendelian randomization (MR) analyses using summary statistics from genome-wide meta-analyses of ADHD, RLS, and peripheral iron status (serum iron, ferritin, transferrin saturation, and total iron binding capacity). Additionally, we employed linkage disequilibrium score regression (LDSC) to assess genetic correlations between ADHD and RLS using genetic data. Our MR results supports a causal effect from ADHD (as exposure) to RLS (as outcome) (inverse variance weighted OR = 1.20, 95% CI: 1.08-1.34, p = 0.001). Conversely, we found no a causal association from RLS to ADHD (inverse variance weighted OR = 1.04, 95% CI: 0.99-1.09, p = 0.11). LDSC analysis did not detect a significant genetic correlation between RLS and ADHD (Rg = 0.3, SE = 0.16, p = 0.068). Furthermore, no evidence supported a causal relationship between peripheral iron deficiency and the RLS or ADHD onset. However, RLS may have been associated with a genetic predisposition to reduced serum ferritin levels (OR = 1.20, 95% CI: 1.00-1.04, p = 0.047). This study suggests that ADHD is an independent risk factor for RLS, while RLS may confer a genetic predisposition to reduced serum ferritin levels. The GWAS summary data utilized originated from populations of European ancestry, limiting the generalizability of conclusions to other populations. The potential co-occurrence of RLS in individuals with ADHD should be considered during diagnosis and treatment. Moreover, iron supplementation may be beneficial for alleviating RLS symptoms.

The Administration of Intradialytic Parenteral Nutrition Does Not Affect the Anemia Status of Chronic Kidney Disease Patients Undergoing Hemodialysis

Background: Hemodialysis (HD) patients are susceptible to malnutrition, and there is a close relationship between malnutrition and the incidence of anemia. Parenteral nutrition plays a role in treating malnutrition. Objective: This study aims to determine the effect of parenteral nutrition on anemia in HD patients. Methods: Quasi-experimental research which is part of the nutritional research tree at the Hemodialysis Unit of RSUP Dr. Soetomo Surabaya for 3 months. A total of 45 malnourished CKD patients (SGA B &amp; C) undergoing routine HD were included in this study (n=26 received regular diet &amp; education, n=17 received regular diet, education and intradialytic parenteral nutrition, and n=2 dropped out of school due to blood transfusion). Measurements of body mass index (BMI), hemoglobin (Hb), serum iron (SI), and total iron binding capacity (TIBC) were carried out before and 8 weeks after therapy. Between groups used the Mann-Whitney test, while pre and post used the Wilcoxon matched-pairs sign rank test. Results: The treatment group was older than the control group. There was no difference in duration of HD between groups. Intradialytic parenteral nutrition had no effect on BMI (24.71±3.939 vs 24.71±4.026; p=0.3802), Hb (9.746±1.309 vs 9.162±1.960; p= 0.3525), SI (62.33±34.74 vs. 53.78±24.89; p=0.3594), and TIBC (242.8±119.0 vs. 197.3±43, 65; p=0.4258). Conclusion: In HD patients, intradialytic parenteral nutrition for 8 weeks did not affect Hb, SI and TIBC levels. Long-term observations with larger samples are needed to confirm these findings.

Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.

Point Shear Wave Elastography Detected Liver Stiffness Increased in Pediatric Patient With Thalassemia Major.

Transient elastography (TE) and point shear wave elastography (pSWE) are 2 elastographic ultrasound examinations used in liver stiffness (LS) measurement. It was shown that the LS value detected by TE in pediatric β-thalassemia major patients has increased, and there was no LS evaluation obtained with pSWE in literature. Thus, in this study, it was aimed to evaluate LS with pSWE examination in children with thalassemia major and to determine LS-related parameters in these patients. Sixty-three schoolchildren with a diagnosis of β-thalassemia major and 21 healthy controls between the ages of 7 and 18 years were included. In addition to routine anamnesis, physical examination, and laboratory examinations, renal and liver ultrasounds were performed. Liver stiffness values were measured by pSWE examination. Serum levels of urea, aspartate-aminotransferase, alanine-aminotransferase, iron, and ferritin were significantly higher in patients, and serum creatinine, iron binding capacity, and hemoglobin levels were found to be significantly lower (P < 0.05 for each). Liver stiffness values were significantly higher in patients compared with healthy controls. In linear regression analysis, serum iron and iron binding capacity values were found to be closely related with LS (P < 0.001 vs. β = 0.482 and P = 0.047 vs. β = 0.237, respectively). Liver stiffness values obtained by pSWE examination increase significantly in patients. According to the results of our study, in addition to the previously known TE method, we think that the LS evaluation obtained by pSWE, a new method that can make more accurate measurements, can be used in the possible early detection of target organ damage in children with thalassemia major.

Correlation of iron deficiency indexes with Eradication and Recurrence of Helicobacter Pylori Infection in Children.

To explore the correlation of iron deficiency (ID) indexes with eradication and recurrence of Helicobacter pylori (Hp) infection in children. This is a clinical comparative study. One hundred and twenty-six children who were first diagnosed as Hp infection in Baoding Children's Hospital (Hp infection group); and the control group included 200 children without Helicobacter Pylori infection (negative stool Hp antigen test and/or 13C-urea breath test) in local region at the same time from January 2020 to January 2022. Enrolled children were subjected to routine blood test, serum ferritin (SF), serum iron (SI) and total iron binding capacity (TIBC) detection. Meanwhile, children with Hp infection were given triple therapy for eradication and followed up for one year. The levels of SI, SF and Hb in non-eradication group were lower than those in eradication group (P<0.05); while TIBC level in the former group was higher than that in the latter group (P<0.05). Furthermore, SF level in the recurrence group was lower than that in the non-recurrence group (P<0.05). While there was no significant difference in Hb, SI and TIBC levels between the recurrence group and the non-recurrence group (P>0.05). Low level of SF may be a risk factor for difficulty in eradication and recurrence after eradication in children with Hp infection. Meanwhile, low levels of Hb and SI are influential factors for difficulty in eradication in children with Hp infection.

Reticulocyte hemoglobin content associated with the risk of iron deficiency anemia

Background/ObjectiveReticulocyte hemoglobin content (MCHr) was recognized as a rapid and reliable marker for investigating iron deficiency (ID). We hypothesized that MCHr was associated with the risk of iron deficiency anemia in adults. MethodsThis is a dual-center case-control study. A total of 806 patients and healthy individuals were recruited from Ruijin Hospital and Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine between January 2021 and December 2021. The participants were categorized into iron deficiency anemia (IDA) group (n = 302), non-IDA group (n = 366), and healthy control group (n = 138). According to the MCHr level, the participants were divided into two groups, i.e. normal MCHr (≥25 pg) and decreased MCHr (<25 pg) group. Multivariate logistic regression analysis and adjusted subgroup analysis were conducted to estimate the relative risk between MCHr and IDA, with confounding factors including age, sex, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), Hematocrit (HCT), serum iron (Fe), ferritin (Ferrit), and total iron binding capacity (TIBC). ResultsCompared with the non-IDA, the MCHr level with IDA decreased significantly. ROC curve analysis showed that MCHr had the largest area under the AUC curve. After comprehensive adjustment for confounding factors, individuals with normal level of MCHr exhibited a decreased risk of IDA (OR = 0.68 [0.60, 0.77], P < 0.01), while the risk of IDA was up to 5 times higher for those with decreased MCHr. ConclusionOur findings supported the hypothesis that MCHr was associated with the risk of IDA in adults and could serve as an indicator of IDA severity. MCHr holds clinical value as an auxiliary diagnostic indicator, providing valuable insights into whether invasive examinations are warranted in the assessment of IDA.

Relationship between iron homeostasis and prognosis in patients with heart failure: a retrospective study based on the MIMIC-IV database.

The role of iron homeostasis has become increasingly recognized as a key factor in determining a prognosis of patients with heart failure (HF). Disruptions in iron balance, encompassing deficiency and overload, can affect patient prognosis, and therefore, significantly impact treatment and management strategies. The study investigated possible associations between iron homeostasis-related indicators and long‑term mortality as well as first‑admission mortality in individuals with HF. Data on 3483 HF patients from the MIMIC‑IV database were retrospectively analyzed. The relationship between iron homeostasis-related indicators (ferritin, serum iron, transferrin, and total iron binding capacity [TIBC]) and the first-admission and long-term mortality of HF patients was discerned utilizing the Cox proportional hazards model and the Kaplan-Meier survival analysis. Additionally, the predictive capability of these indicators for patient prognosis was assessed using the receiver operating characteristic curve. Fourth quartile levels of ferritin and serum iron were obviously associated with poor long‑term outcomes in HF patients. Conversely, fourth quartile levels of transferrin and TIBC served as protective factors and were associated with a lower mortality. Additionally, iron homeostasis indicators exhibited a certain predictive value for both long‑term mortality and first‑admission mortality in HF patients. This study underscores a significant association between iron homeostasis indicators and the prognosis of HF patients, providing valuable insights into risk stratification and clinical decision‑making for this population. Future studies should focus on dynamic fluctuations in iron homeostasis and explore interventions to improve the prognosis of HF patients.

Atg4a Promotes Mitochondrial Quality Control and Hemoglobin Production In Vivo

Mitochondrial quality control is essential for maintaining cellular homeostasis and contributes to the regenerative capacity of hematopoietic stem cells and the differentiation of lineage-committed progeny. During red blood cell (RBC) production, mitochondria contribute to the production of hemoglobin and are the site for heme synthesis. Mitochondrial dysfunction is found in patients with mtDNA mutations, sickle cell disease, and myelodysplastic syndromes; therefore, it is critical to delineate the molecular mediators of mitochondrial quality control during erythropoiesis. While it is established that autophagy contributes to mitochondrial clearance during reticulocyte maturation, less is known about the regulation of mitochondrial quality control in erythroid progenitors. Our previous study identified an erythroid-specific role for the autophagy-related protease ATG4A in human erythropoiesis (Stolla MC et al., Blood Advances, 2022). To better understand the contribution of Atg4a-dependent autophagy to erythropoiesis in vivo, we have developed a new genetically modified mouse model . To evaluate the role of Atg4a in vivo, we disrupted the expression of Atg4a by targeting exons 5/6 using CRISPR/Cas9 in C57/BL6 embryos. Analysis of the peripheral blood of adult Atg4a-/- (KO) and Atg4a+/+ (WT) mice revealed a normal hematocrit (47.5% WT vs. 47% KO), but elevated numbers of red blood cells (10.7 M/μL WT vs. 11.2 M/μL KO, p=0.012) and a compensatory 5.8 % decrease in RBC volume (MCV: 44.3 fl WT vs. 41.7 fl KO, p=0.0004). Consistent with a reduction in RBC size, we observed a modest reduction in total hemoglobin (16.8 g/dl WT vs. 16.0 g/dl KO, p=0.054) and a profound decrease in the mean corpuscular hemoglobin concentration (MCHC: 35.39 g/dl WT vs. 34.17 g/dl KO, p=0.038) in Atg4a -/- (KO) mice. To determine if Atg4a-/- mice are iron deficient, we evaluated iron parameters in peripheral blood. While Atg4a-/- mice had slightly lower values of serum iron (152 μg/dl WT vs. 128.7 μg/dl KO, p=0.21) and total-iron binding capacity (511 μg/dl WT vs. 456 μg/dl KO, p=0.04) they had comparable levels of transferrin saturation (29.9% WT vs. 28.1% KO, p=0.65). Furthermore, we found similar amounts of EPO in the serum of Atg4a-/- and Atg4a+/+ mice (314 pg/ml WT vs. 345 pg/ml KO, p=0.78). Thus, loss of Atg4a leads to a reduction in hemoglobin production and RBC size without overt iron deficiency. To determine if alterations in erythroid maturation contributed to the decrease in MCV and MCHC, we used flow cytometry to quantify bone marrow erythroid progenitors (I), basophilic erythroblasts (II), polychromatic and orthochromatic erythroblasts (III), and reticulocytes (IV) using CD44, Ter119, CD71, and lineage markers (CD11b, B220, Gr-1) in Atg4a-/- mice. Similar numbers of erythroid populations (I-IV) were observed in the bone marrow and spleen of Atg4a-/- and Atg4a+/+ mice suggesting that erythroid maturation was not significantly altered in vivo. Since Atg4a is known to facilitate mitochondrial clearance during human erythropoiesis, we next evaluated mitochondrial dynamics in murine erythroid populations I-IV using dyes for active (TMRM) and total mitochondria (Mitotracker Green, MTG). Compared to Atg4a+/+ mice, Atg4a-/- mice had increased MTG fluorescence in erythroid populations I and II and a 25% decrease in TMRM fluorescence. Therefore, loss of Atg4a significantly reduces the ratio of active-to-total mitochondria in erythroid progenitors and basophilic erythroblasts, indicating that elimination of inactive mitochondria promotes mitochondrial function early in erythropoiesis. Since mitochondria are the site for heme synthesis, we sorted erythroid populations from Atg4a-/- and Atg4a+/+ mice and measured total heme content. While in Atg4a +/+ mice heme content increased by 3-fold between erythroid populations III and IV, heme content did not increase between erythroid populations III and IV from Atg4a-/- mice resulting in significantly reduced heme content in reticulocytes. Our study highlights an important protective role for autophagy in erythropoiesis where it mediates the elimination of dysfunctional mitochondria. Loss of mitochondrial quality control restricts heme production reducing the hemoglobin concentration of circulating RBCs. Further investigation will determine if the absence of Atg4a compromises the response to stress erythropoiesis.

Ferritin Reference Ranges in an Adult Population of Working-Age Adults without Anemia

Introduction Considerable controversy has surrounded the creation of reference intervals for ferritin within tested populations. This is particularly true for women and has been attributed to a high prevalence of nonanemic iron deficiency due to physiologic blood loss during menses and physiologic iron transfer during pregnancy. The Quest Blueprint for Wellness (BFW) program is an annual health screening that provides a range of testing to Quest employees and families. Using deidentified data on 24,812 individuals (55% female; age range 18-80 years old) collected as part of this program, we studied the relationship between serum ferritin and characteristics of the study population, red blood cell parameters, and iron saturation in order to better define normal reference ranges for serum ferritin. Methods Test results of participants in the annual BFW screening program conducted between January 2022 and May 2023 were identified (26,535 [53% female]); tests included hematocrit, hemoglobin, RBC indices (including RDW), total serum iron and total iron binding capacity and CRP. Individuals with abnormalities of hemoglobin, hematocrit or RBC indices (including RDW); serum iron or serum TIBC; or elevated CRP were successively excluded, leaving 24,812 participants (55% female). None of these remaining individuals had a personal history of anemia or an identified ICD-10 code associated with anemia or other RBC disorder. This study population was used in subsequent analyses. Multimodal decomposition (MMD) in R (version 4.2.2) was used to calculate reference intervals based on the distribution of results associated with the healthy study subpopulation that was defined. To address the possibility that the TIBC saturation initially employed (20%) was too low, reference intervals were also determined when varying TIBC saturations from 20%-25%. Results As shown in Table 1, the lower limits of the ranges identified did not vary significantly as the TIBC saturation percent was increased from 20% to 25%. The lower limit for women below 50 years of age ranged from 11-13 ng/mL, which was substantially lower than the lower limits for men of the same age. Over the age of 50, the lower limit of the ferritin reference ranges for women increased, approaching but not equaling or exceeding the values observed for men until ages greater than 70. This may reflect the end of menses and the gradual repletion of iron stores. In contrast, the lower limits of the reference ranges for serum ferritin for men increased at ages 30-40 and then declined and fell below that of women in the eighth decade. Conclusions Comparing the lower range of ferritin values between men and women, these data suggest that iron deficiency may be present in a large proportion of working age women in the absence of anemia or abnormal RBC indices. These data also suggest that normal ferritin values are age dependent for both men and women. These conclusions are tempered by the unavailability of a physiologic reference standard able to demonstrate that iron deficiency is in fact present. The lower limit of the ferritin range for women under the age of 60 and for men over the age of 70 approximates the ferritin values associated with the absence of stainable bone marrow iron. While this test is the traditional “gold standard” it is rarely performed for the evaluation of iron status. The evaluation of iron deficiency at present lacks a physiologic indicator, analogous to the relationship between parathyroid hormone and calcium levels which permitted the definition of blood levels of 25 hydroxyvitamin D that represented sufficiency, or methylmalonic acid concentration in B12 deficiency. The broader availability of measures to assess the functional status of reticuloendothelial iron stores available to support erythropoiesis, such as measurements of hepcidin, would facilitate such an assessment.

Vitamin D Levels in Children Presenting with Breath-Holding Spells: An Example of A University Hospital

Aim: This study aimed to examine the vitamin D levels in children who experience breath-holding spells (BHS) and to compare these levels with those of a healthy control group. The goal was to establish a connection between BHS and vitamin D levels.&#x0D; Method: The records of 98 patients, who presented to the Pediatric Neurology and Pediatric Cardiology polyclinics of Adıyaman University Training and Research Hospital between December 2019 and October 2022, were retrospectively reviewed. Fifty-two patients who did not meet the inclusion criteria were excluded. The study included forty-six patients with BHS whose laboratory results were assessed and a healthy control group of fifty-three individuals. Fe, serum iron binding capacity, ferritin, vitamin B12, and vitamin D levels were measured in all patients.&#x0D; Results: The study group comprised 46 patients (female/male ratio = 1.4), consisting of 27 girls (58.6%) and 19 boys (41.3%). Within our patient cohort, 39 individuals (84.8%) were diagnosed with cyanotic-type spells, three (6.5%) with pallid-type spells, and four (8.7%) with mixed-type spells. For patients experiencing BHS, a comprehensive analysis was conducted on parameters including complete blood count, iron levels, iron-binding capacity, ferritin levels, vitamin B12, and vitamin D levels. Although no significant correlation was identified with vitamin D levels in this study, noteworthy connections were established with lower hemoglobin levels, decreased vitamin B12 levels, and reduced ferritin levels. Moreover, upon exclusion of patients exhibiting low vitamin B12 values from the analysis, a statistically significant relationship emerged between iron deficiency anemia and the occurrence of BHS (p

Assessment of erythroferrone levels in children with chronic kidney disease on regular hemodialysis

Anemia is a common comorbidity in children with chronic kidney disease (CKD) and is associated with adverse outcomes. Erythroferrone (ERFE) is a hepcidin inhibitor whose synthesis is stimulated by erythropoietin, which increases iron absorption and mobilization. Aim of the study: to assess the levels of ERFE hormone in children with CKD on regular hemodialysis. This case–control study was carried out at Menoufia University Hospital and included 70 subjects: 38 healthy individuals (controls) and 32 children with CKD on regular dialysis (cases). The study was approved by the Faculty of Medicine Ethics Committee at Menoufia University. All children were subjected to full history taking, complete clinical examination, blood tests such as complete blood count, reticulocyte count, serum iron, ferritin, and total iron binding capacity, liver and renal function tests, and an immunoassay to measure human ERFE. There was a statistically significant difference in the levels of ERFE between the cases and controls (p &lt; 0.001). There was a significant, strong correlation between the levels of hemoglobin and serum iron and the level of ERFE (r = –0.655, p &lt; 0.001). There was no significant correlation between the administered dose of exogenous erythropoietin and the level of ERFE (p = 0.460). Serum ERFE levels in the children with CKD on regular hemodialysis were significantly higher than in the controls and were negatively correlated with hemoglobin and iron levels. There was no significant correlation between ERFE levels and both serum ferritin and total iron binding capacity levels.

The use of iron-containing drugs for the prevention of alimentary anemia in sows and their offspring

As a result of a scientific and economic experiment conducted in the conditions of the industrial pig complex of Bryansk Meat Processing Plant LLC in Vygonichi district, the effectiveness of the use of iron–containing preparations Ferrolong and Ferzaks-forte for the prevention of alimentary anemia of pregnant sows and piglets was studied. The object of the study was pregnant sows of a large white breed with an average live weight of 150-160 kg at the age of two years, and piglets obtained from them. At the first stage of the research, two groups of sows were formed, 3 heads each. 15 days before farrowing, the sows of the experimental group received the drug Ferrolong (iron content III 200 mg/ml, vitamin B12 - 0.1 mg/ml) at a dose of 4 ml intramuscularly. Sows of the control group did not receive injections of iron-containing preparations.The effect of the drugs on the growth and safety of piglets, on biochemical (iron, total iron binding capacity of serum (OHSS), % saturation of transferrin) and hematological parameters was analyzed. Based on the conducted step-by-step studies, it was found that the introduction of Ferrolong 15 days before farrowing stimulates hematopoiesis in sows, but does not significantly affect the red blood indicators of suckling piglets. Intramuscular administration of Ferrolong to piglets at a dose of 1 ml in the first three days of life is accompanied by a pronounced antianemic effect, and is characterized by a high content of hemoglobin in erythrocytes and a saturation coefficient of serum transferrin. This scheme is recommended for the prevention of iron deficiency anemia in the household. Ferzaks-forte, due to its vitamins, has a broader effect on metabolic processes, but laboratory indicators indicate that a single intramuscular injection of this drug is not enough to prevent anemia.

DIAGNOSTIC ACCURACY OF RDWI TO DIFFERENTIATE IRON DEFICIENCY ANEMIA AND THALASSEMIA TRAIT IN BORDERLINE HBA2

Background: Thalassemia is an inherited hemoglobin disorders in which there is reduction or absence of α or β chains due to mutations in α or β genes. Microcytic hypochromic anemia is hallmark of beta thalassemia trait and the patient is usually asymptomatic. It is important to differentiate it from iron deficiency anemia (IDA) which also shows similar peripheral blood picture. The diagnosis is based on quantification of HbA2 and serum ferritin. If the level of HbA2 is more than 3. 5%, then diagnosis of beta thalassemia trait is made. The problem arises with borderline HbA2 i. e 3.1% - 3.4%. There is also diagnostic difficulty when concomitant iron deficiency anemia is present.&#x0D; Objectives: To determine the diagnostic accuracy of RDWI in borderline HbA2 to distinguish the beta thalassemia trait from IDA and to diagnose beta thalassemia trait when genetic analysis is not easily available.&#x0D; Methods: It was a cross sectional validation study. A total of 90 patients were included in this study, having HbA2 between 3.1-3.4%. Tests for serum ferritin, serum iron and total iron binding capacity (TIBC) were done on all samples. RBC morphology, RBC count, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC) and RDW of all samples were noted. RDWI of all samples was calculated. Mutational analysis by ARMS- PCR was done for confirmation of β thalassemia trait.&#x0D; Results: Out of 90 samples with borderline HbA2, 30 cases were diagnosed as β thalassemia trait. Out of these, 15(50 %) had concomitant IDA along with beta thalassemia trait and 15 were non iron deficient beta thalassemia carriers. 43 samples were not iron deficient and were also negative for β thalassemia trait, whereas 17 samples had only IDA without beta thalassemia trait. The sensitivity of RDWI was 76.6% and specificity was 56.6% in borderline HbA2.&#x0D; Conclusion: RDWI is a good indicator to differentiate between IDA and beta thalassemia trait (sensitivity 76.6% specificity 56.6%). But in all cases of borderline HbA2 genetic analysis should be done to see the mutation and to confirm the diagnosis.

Correlation of HbA1c with Serum Iron & Transferrin Saturation in Non-Diabetic Patients with Iron Deficiency.

To determine correlation of HbA1c with serum iron and transferrin saturation in non-diabetic patients with iron deficiency. This cross-sectional comparative study was conducted at Dr Ruth KM Pfau Civil Hospital Karachi from 15th September 2021 to 14th March 2022, on non-diabetic patients based on fasting blood sugar (FBS) of <100 mg/dl. Patients were divided into two groups. Group one included patients having iron deficiency anemia (ID), whereas group two included same number of age and sex matched healthy subjects taken as controls, without ID. Blood sample was taken for HbA1c, CBC, serum iron and total iron binding capacity. Transferrin saturation (TSAT) was calculated. Comparison of quantitative variables with ID and non-ID group was done by Student's t-test. Correlation of HbA1c with iron &TSAT was done in both groups using Kendal tau-b test, as data was not normally distributed. Out of 230 patients, 83 (36.1%) were males while 147(63.9%) were females. Mean age of patients was 43.7±13.28 years. Mean HbA1c level was significantly high in ID group (5.89±0.43) as compared to non-ID group (5.52±0.50) with a p-value <.001. The HbA1c levels correlated negatively with hemoglobin, serum iron levels and transferrin saturation with a p-value <.001. Low serum Iron and TSAT was related to elevation in HbA1c value. Iron deficiency needs to be corrected before HbA1c interpretation.

The effect of systemic iron status on osteoarthritis: A mendelian randomization study.

Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron; transferrin saturation; ferritin; total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-sample Mendelian randomization (MR) design. Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associated with all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 individuals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches. Results: Based on liberal instruments, genetically predicted serum iron and transferrin saturation were significantly associated with hip OA and total hip replacement, but not with knee OA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80). Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor.

Роль бактерий рода Desulfovibrio sp. в патологии человека

Bacteria of the genus Desulfovibrio sp. They are widespread in the environment – they are found in soil, wastewater, bottom sediments. The effect of these microorganisms on the development of pathological conditions in humans has not been fully established. Bacteria of the genus Desulfovibrio sp., gram-negative, curved microorganisms,non-spore – forming, slow-growing, anaerobic. Objective. Identification of pathogenetic features of the effect of sulfate-reducing bacteria of the genus Desulfovibrio sp. on the human. Patients and methods.167 patients who signed a voluntary informed consent was conducted among patients who applied to the Federal State Budgetary Institution "Central Research Institute of Epidemiology" for an examination of intestinal microbiocenosis. Microbiological examination of the biomaterial was carried out using traditional microbiological methods. The following blood parameters were used to assess iron metabolism in the body: hemoglobin, serum iron, ferritin, transferrin, unsaturated iron binding capacity of serum and the percentage of transferrin saturation with iron. Statistical data analysis was performed using standard descriptive statistics methods using Excel (Microsoft Corporation, 2019, USA). The statistical significance of the differences in the compared indicators was assessed using the Student's t-test the significance level of p &lt; 0.05 (t &gt; 2). Results. Bacteria of the genus Desulfovibrio sp. were found in 66 patients (39.5%). In the group of patients whose examination revealed bacteria of the genus Desulfovibrio sp., the number of people with anemia was 16, without anemia was 50. Among patients with the absence of bacteria of the genus Desulfovibrio sp. in the microbiocenosis. laboratory-confirmed iron metabolism disorder with the development of anemia was detected in 11 people, the absence of anemia in 90. The calculation of the odds ratio showed that the risk of anemia increases 2.6 times [95% CI 1.13–6.08] in the presence of bacteria of the genus Desulfovibrio sp in the intestine. Conclusion. It can be assumed that bacteria of the genus Desulfovibrio sp. is one of the etiological factor of the development of iron deficiency anemia in humans. Key words: microbiocenosis, iron deficiency anemia, Desulfovibrio desulfuricans

Preclinical Pharmacokinetics and Pharmacodynamics of DISC-0998, a Humanized Anti-Hemojuvelin (HJV) Monoclonal Antibody to Suppress the Production of Hepcidin

Background Anemia of inflammation (AI) is an immune-driven disorder that displays reduced erythropoietic activity and dysregulation of iron homeostasis. It is associated with a number of underlying diseases including myelofibrosis (MF) and chronic kidney disease (CKD) and caused by inflammatory cytokines which increase hepcidin levels. Increased hepcidin leads to sequestered iron in macrophages, decreased iron absorption and decreased serum iron. Interfering with HJV function and suppressing the production of hepcidin results in increases in serum iron in healthy volunteers has been observed with another humanized monoclonal antibody (mAb, DISC-0974). PK/PD results from a Phase 1 clinical trial with DISC-0974 in healthy volunteers support monthly subcutaneous (SC) dosing. DISC-0998 is a potent and highly selective HJV mAb with an engineered Q and L mutation (QL-mutation) in the Fc region, aimed to alter binding to the FcRn receptor, resulting in an increased PK half-life. Preclinical studies have demonstrated that DISC--0998 has biological activity, low immunogenicity potential and desirable pharmacokinetic (PK) and pharmacodynamic (PD) properties. Objectives To evaluate the PK/PD relationships of DISC-0998 with hepcidin, serum iron, and TSAT in male cynomolgus monkeys to inform drug development strategy. Methods Male cynomolgus monkeys were randomized to different dose groups and received a single SC (0.1, 0.3, 1.0, and 3.0 mg/kg) or intravenous (IV, 6 mg/kg) dose of DISC-0998. Blood samples were obtained at predefined time points for PK, hepcidin-25, serum iron, and total iron binding capacity (TIBC) measurements. Concentration of serum hepcidin-25 was analyzed using a qualified LC-MS/MS method. Concentrations of serum iron and TIBC were analyzed using a HITACHI7180 Chemistry Analyzer. Serum DISC-0998 concentrations were analyzed using a qualified MSD method. For comparison purposes, the results from DISC-0974 monkey PK/PD studies following 0.3, 1, and 6 mg/kg SC were also included. WinNonlin (PhoenixTM, v8.1) was used for PK/PD calculations. Results Following a single SC or IV dose, DISC-0998 exhibited low clearance (SC CL/F 0.14 - 0.83 mL/hr/kg; IV CL 0.14 mL/hr/kg), small volume of distribution (Vz 50 -104 mL/kg), and nonlinear PK typical for a mAb. Compared to DISC-0974, DISC-0998 exhibited lower clearance (~30 -40%), higher volume of distribution (30 - 70%), and a longer half-life (~ 2 times), which translated to longer duration of downstream PD effects. Dose-dependent hepcidin-25 reduction, along with elevations in serum iron and TSAT were also demonstrated. Based on PK and serum iron response, DISC-0998 has similar or slightly better potency in monkey compared to DISC-0974 (EAUC50 of 1495 hr*ug/mL vs. 3918 hr*g/mL, respectively). Conclusion DISC-0998 demonstrated a favorable PK/PD profile in monkeys, allowing prediction of its PKPD profiles in humans. These data support further development of DISC-0998 for anemia of inflammation related disorders, with the potential of long intervals in between dosing. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effect of inulin, galacto oligosaccharides and iron fortification on iron deficiency anemia among women of reproductive age; a randomized controlled trial

Iron supplementation and fortification are the well-known approaches to treat iron deficiency anemia (IDA) in women of reproductive age. The objective of the current randomized controlled trial (RCT) was to evaluate the cumulative effects of prebiotics and iron fortification among women of reproductive age. For this purpose, a total of 75 iron deficient women of childbearing age were recruited and randomly divided into 5 groups (4 treatment groups and 1 control group). Four different types of fortified wheat flour were prepared using two iron fortificants (NaFeEDTA and FeSO4) and two prebiotics [inulin and galacto oligosaccharides (GOS)], while control group was treated with iron fortified flour without any prebiotics. Blood samples were collected from overnight fasted women on monthly basis up to 90 days. Hematological indices such as Hemoglobin (Hb), Hematocrit, Red Blood Cell (RBC) Count and Mean Corpuscular Volume (MCV), as well as iron biomarkers including serum iron, ferritin, transferrin, and Total Iron Binding Capacity (TIBC) were evaluated for analyses. The results showed a considerable positive improvement in all iron biomarkers as well as hematological indices among the treatment groups (P-value < 0.05), as compared to the control group. A maximum Hb (11.86 ± 0.24 mg/dL) and hematocrit value (35.06 ± 1.32%), was reported in group G3 which was treated with fortified wheat flour at a dose of 963 mg/kg GOS + 15 ppm FeSO4. On the other hand, highest mean values for RBC Count (4.73 ± 0.41 mil/mm3), MCV (81.41 ± 3.21 fL), serum iron (75.62 ± 2.79 μg/dL), serum transferrin (16.82 ± 0.30 mg/dL), and TIBC (403.68 ± 7.27 μg/dL) were observed in G4 group receiving the fortified wheat flour at a dose of 963 mg/kg GOS + 30 ppm FeSO4 level. The study concluded that prebiotic fortification along with iron salts helps to enhance iron absorption among iron deficiency anemic women of reproductive age.