Iron Binding Capacity Research Articles

Preparation of Rehmanniae Radix Praeparata Polysaccharide Iron(III) Complex and Evaluation of Its Biological Activity.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

Iron Metabolism in Pediatric Living related Liver Transplantation

Abstract Introduction Iron deficiency is a frequent cause of anemia in liver transplant recipients, especially children. Rejection and infection are incriminated causes for occurrence of anemia after liver transplantation (LR). Aim of the Work We aimed to assess iron homeostasis in children who have undergone living related LT (LRLT) and its correlation with occurrence of rejection and infection. Patients and Methods The study was conducted on 35 children who have undergone LRLT. The patient characteristics, frequency of infection and rejection episodes, laboratory investigations including complete blood picture (CBC) and Iron profile (total iron binding capacity (TIBC),serum iron and ferritin) during the patient follow up visits were reported. Results Males were 68.58% of the studied patients and females were 31.42%. Their ages ranged from 1.3-15 years at time of LT with mean (SD) of 7.18 (3.8)years. The mean (SD) duration since LT was 4.83 (4.2) years. The commonest indication to LT was highgamma-glutamyl transferase (GGT) cholestasis (34.7%) followed by biliary atresia (21.7 %). Thirteen percent of patients had low hemoglobin (Hb) of whom 4.3% had normocytic normochromic anemia and 8.7% had microcytic hypochromic anemia. Serum iron was normal in 79.6% of patients and low in 20.4%, and ferritin was normal in 58.7% of patients and low in 41.3% while TIBC was normal in 82.6% of patients and low in 17.4%. Only serum iron showed significant negative correlation with white blood cells (WBCs) (P < 0.05). The iron parameters levels were not different in patients with no rejection or only one attack of rejection and the patients with multiple rejection episodes (P > 0.05). Conclusion Anemia is a reported complication after pediatric LT. Further studies are needed to assess the long term effect of post-LT anemia on patient outcome after LT.

Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis.

Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

Potential mediation effect of insulin resistance on the association between iron metabolism indicators and non-alcoholic fatty liver disease.

Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD. We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship. A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively. Higher levels ofserum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels.

Micronutrient-Associated Single Nucleotide Polymorphism and Mental Health: A Mendelian Randomization Study.

Previous studies have demonstrated the link between micronutrients and mental health. However, it remains uncertain whether this connection is causal. We aim to investigate the potential causal effects of micronutrients on mental health based on linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) analysis. Utilizing publicly available genome-wide association study (GWAS) summary datasets, we performed LDSC and MR analysis to identify candidate micronutrients with potential causal effects on mental health. Single nucleotide polymorphisms (SNPs) significantly linked with candidate micronutrients with a genome-wide significance level (p < 5 × 10-8) were selected as instrumental variables (IVs). To estimate the causal effect of candidate micronutrients on mental health, we employed inverse variance weighted (IVW) regression. Additionally, two sensitivity analyses, MR-Egger and weighted median, were performed to validate our results. We found evidence supporting significant causal associations between micronutrients and mental health. LDSC detected several candidate micronutrients, including serum iron (genetic correlation = -0.134, p = 0.032) and vitamin C (genetic correlation = -0.335, p < 0.001) for attention-deficit/hyperactivity disorder (ADHD), iron-binding capacity (genetic correlation = 0.210, p = 0.037) for Alzheimer's disease (AD), and vitamin B12 (genetic correlation = -0.178, p = 0.044) for major depressive disorder (MDD). Further MR analysis suggested a potential causal relationship between vitamin B12 and MDD (b = -0.139, p = 0.009). There was no significant heterogeneity or pleiotropy, indicating the validity of the findings. In this study, we identified underlying causal relationships between micronutrients and mental health. Notably, more research is necessary to clarify the underlying biological mechanisms by which micronutrients affect mental health.

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.

Impact of vitamin D deficiency on iron status in children with type I diabetes

Vitamin D deficiency (VDD) and anemia are both public health nutrition concerns. An association between VDD and anemia has been suggested in various healthy and diseased populations. The current study aimed to elucidate the effect of VDD on iron status in children with type I diabetes mellitus (T1DM). The study recruited two groups of children with T1DM: control group comprised of 38 T1DM children with sufficient vitamin D (> 30 ng/ml) and a case group, consisted of 52 T1DM children with VDD (< 20 ng/ml). Both groups had comparable gender, age, BMI, and disease duration. The laboratory measurements included analysis of blood indices, markers of iron metabolism, hepcidin and inflammatory markers included interleukin 6 (IL-6) and C-reactive protein (CRP). Compared to control group, T1DM children with VDD differs specifically in terms of some markers of blood indices, such as decreased hemoglobin and increased red blood cell distribution width. Moreover, decreased serum iron, ferritin, total iron-binding capacity and transferrin along with elevated inflammatory markers were observed in case group. Results of the study indicated that VDD had increased the risk of iron deficiency anemia in children with T1DM as well as inflammatory related anemia. Furthermore, in T1DM children, VDD had raised the incidence of both absolute and functional iron deficiency, with greater incidence of the former. This study may indicate that VDD may be a risk factor that may worsen iron deficiency anemia in T1DM.

Improvement of in vivo iron bioavailability using mung bean peptide-ferrous chelate

There is an increasing amount of research into the development of a third generation of iron supplementation using peptide-iron chelates. Peptides isolated from mung bean were chelated with ferrous iron (MBP-Fe) and tested as a supplement in mice suffering from iron-deficiency anemia (IDA). Mice were randomly divided into seven groups: a group fed the normal diet, the IDA model group, and IDA groups treated with inorganic iron (FeSO4), organic iron (ferrous bisglycinate, Gly-Fe), low-dose MBP-Fe(L-MBP-Fe), high-dose MBP-Fe(H-MBP-Fe), and MBP mixed with FeSO4 (MBP/Fe). The different iron supplements were fed for 28 days via intragastric administration. The results showed that MBP-Fe and MBP/Fe had ameliorative effects, restoring hemoglobin (HGB), red blood cell (RBC), hematocrit (HCT), and serum iron (SI) levels as well as total iron binding capacity (TIBC) and body weight gain of the IDA mice to normal levels. Compared to the inorganic (FeSO4) and organic (Gly-Fe) iron treatments, the spleen coefficient and damage to liver and spleen tissues were significantly lower in the H-MBP-Fe and MBP/Fe mixture groups, with reparative effects on jejunal tissue. Gene expression analysis of the iron transporters Dmt 1 (Divalent metal transporter 1), Fpn 1 (Ferroportin 1), and Dcytb (Duodenal cytochrome b) indicated that MBP promoted iron uptake. These findings suggest that mung bean peptide-ferrous chelate has potential as a peptide-based dietary supplement for treating iron deficiency.

Associations Between Genetically Predicted Iron Status and Cardiovascular Disease Risk: A Mendelian Randomization Study.

Mendelian randomization (MR) studies suggest a causal effect of iron status on cardiovascular disease (CVD) risk, but it is unknown if these associations are confounded by pleiotropic effects of the instrumental variables on CVD risk factors. We aimed to investigate the effect of iron status on CVD risk controlling for CVD risk factors. Iron biomarker instrumental variables (total iron-binding capacity [n=208 422], transferrin saturation [n=198 516], serum iron [n=236 612], ferritin [n=257 953]) were selected from a European genome-wide association study meta-analysis. We performed 2-sample univariate MR of each iron trait on CVD outcomes (all-cause ischemic stroke, cardioembolic ischemic stroke, large-artery ischemic stroke, small-vessel ischemic stroke, and coronary heart disease) from MEGASTROKE (n=440 328) and CARDIoGRAMplusC4D (Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus the Coronary Artery Disease Genetics) (n=183 305). We then implemented multivariate MR conditioning on 7 CVD risk factors from independent European samples to evaluate their potential confounding or mediating effects on the observed iron-CVD associations. With univariate MR analyses, we found higher genetically predicted iron status to be associated with a greater risk of cardioembolic ischemic stroke (transferrin saturation: odds ratio, 1.17 [95% CI, 1.03-1.33]; serum iron: odds ratio, 1.21 [95% CI, 1.02-1.44]; total iron-binding capacity: odds ratio, 0.81 [95% CI, 0.69-0.94]). The detrimental effects of iron status on cardioembolic ischemic stroke risk remained unaffected when adjusting for CVD risk factors (all P<0.05). Additionally, we found diastolic blood pressure to mediate between 7.1 and 8.8% of the total effect of iron status on cardioembolic ischemic stroke incidence. Univariate MR initially suggested a protective effect of iron status on large-artery stroke and coronary heart disease, but controlling for CVD factors using multivariate MR substantially diminished these associations (all P>0.05). Higher iron status was associated with a greater risk of cardioembolic ischemic stroke independent of CVD risk factors, and this effect was partly mediated by diastolic blood pressure. These findings support a role of iron status as a modifiable risk factor for cardioembolic ischemic stroke.

Effects of Hypoxia and Inflammation on Hepcidin Concentration in Non-Anaemic COVID-19 Patients.

Background/Objectives: This study aimed to explore the influence of hypoxia, inflammation, and erythropoiesis on hepcidin and other iron status parameters in non-anaemic COVID-19 patients admitted to the emergency unit before the introduction of therapeutic interventions. Methods: Ninety-six COVID-19 patients and 47 healthy subjects were recruited. Patients were subdivided into hypoxic or normoxic groups and, after follow-up, into mild and moderate, severe or critical disease severity groups. Iron, unsaturated iron-binding capacity (UIBC), ferritin, C-reactive protein (CRP), and interleukin 6 (IL-6) were measured on automatic analysers. ELISA kits were used for hepcidin and erythropoietin (EPO) determination. We calculated total iron-binding capacity (TIBC) and ratios of hepcidin with parameters of iron metabolism (ferritin/hepcidin, hepcidin/iron), inflammation (hepcidin/CRP, hepcidin/IL-6), and erythropoietic activity (hepcidin/EPO). Results: Hepcidin, ferritin, EPO, CRP, IL-6, ferritin/hepcidin, and hepcidin/iron were increased, while UIBC, TIBC, hepcidin/CRP, and hepcidin/IL-6 were decreased in hypoxic compared to normoxic patients as well as in patients with severe or critical disease compared to those with mild and moderate COVID-19. Regarding predictive parameters of critical COVID-19 occurrence, in multivariable logistic regression analysis, a combination of EPO and ferritin/hepcidin showed very good diagnostic performances and correctly classified 88% of cases, with an AUC of 0.838 (0.749-0.906). Conclusions: The hypoxic signal in our group of patients was not strong enough to overcome the stimulating effect of inflammation on hepcidin expression. EPO and ferritin/hepcidin might help to identify on-admission COVID-19 patients at risk of developing a critical form of the disease.

Hematological parameters of healthy pregnant women in three trimesters compared with parameters of non-pregnant women

Anemia is a public health problem, especially in developing countries. All over the world iron deficiency is the main cause of anemia, especially during pregnancy. Pregnant women belong to the most vulnerable population group in Iraq.The objective: to determine the impact of pregnancy on hematological parameters and to compare the hematological indicators in different periods of gestation with the indicators of non-pregnant women.Materials and methods. The study was conducted over a three-month period at Baghdad hospitals and medical centers, including Baghdad Teaching Hospital, Al-Karam Hospital, and a health center in Al-Dorrah and Al-Shaab, Baghdad province, from September 1 to December 1, 2022. 60 pregnant women, 20 persons in each trimester, and 25 non-pregnant women (control) aged 18–35 years were included in the study. All participants were examined for hematological parameters: hemoglobin, erythrocytes, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), measured of the concentration of hemoglobin in red blood cells (MCHC) and determined the level of iron in the blood (serum iron – SI, total iron binding capacity – TIBC, transferrin saturation – TS and serum ferritin – SF).Results. A significant decrease in the hematological indicators of pregnant women in the first trimester of pregnancy compared to non-pregnant women was established – hemoglobin, erythrocytes, PCV, MCH, MCHC. The dynamics of the decrease in the level of these parameters increases in the second trimester, and also progressively decreases in the third trimester, which leads to anemia.Starting from the first trimester and during the second and third trimesters, a decrease in the level of serum iron, transferrin saturation and serum ferritin was found in pregnant women compared to non-pregnant women, but the level of TIBC increased. During the second trimester, the need for iron begins to increase and continues to growth until the end of pregnancy. In addition, these research results indicate the importance of iron deficiency in the development of iron deficiency anemia.Conclusions. During pregnancy, anemia and a decrease in the level of some hematological parameters were determined, which progresses with increasing gestational age and is less compared to that in non-pregnant women. A decrease in the level of iron in the blood serum was established from the first to the third trimester of pregnancy. The severity of anemia is related to many factors, especially age, education level, low income, type of diet and parity.

Efficacy of ferric carboxymaltose therapy in celiac patients

Aims: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. IDA can be caused by reduced iron intake, impaired iron absorption or losses. Celiac disease can cause iron malabsorption by decreasing the surface absorption area in the duodenum and consequently can cause IDA. Oral or intravenous iron preparations are used in the treatment of IDA. In this study, we wanted to investigate the efficacy of ferric carboxymaltose (FCM) in celiac patients with RIA. Methods: Twenty-three patients who were followed up in the gastroenterology outpatient clinic of İnönü University Medical Faculty Hospital Turgut Özal Medical Center with the diagnosis of CD and who received FCM were included in the study. The hemogram, ferritin, iron and iron binding levels of the patients were retrospectively screened through the hospital medical record system. Results: Of the 23 patients included in the study, 3 (13.05%) were male and 20 (86.95%) were female. Hemoglobin concentration, iron and iron binding capacity before and after treatment showed a significant increase in all parameters after treatment. Ferritin value increased, although not significantly. Conclusion: In our study, we found that FCM is an effective and safe treatment modality in the treatment of IDA in celiac patients.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study.

This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

#2896 Malnutrition is prevalent in hemodialysis patients—results from Croatian multicenter hemodialysis study

Abstract Background and Aims Malnutrition is a usually observed condition among patients on hemodialysis (HD) and is considered one of studiest indicators of mortality and morbidity. Malnutrition inflammation score (MIS) is associated with inflammation, nutritional status, quality of life, and 5-year prospective mortality. Also, phase angle (PhA) measured by bioelectrical impedance analysis (BIA) has been studied as indicator of nutritional status or muscle function in HD patients and lower PhA was associated with a greater risk of malnutrition. The aims of this study are to analyze the prevalence of malnutrition in hemodialysis (HD) patients in Croatia using MIS, and to assess the association of MIS and PhA with body mass composition, sociodemographic characteristics and laboratory parameters related to HD. Method 166 HD patients aged 68.5 (58.8-76) years, 55 women (33%) and 111 (67%) men with mean HD duration of 4 (2-6) years from 6 HD center were included in this study. For each study participant, data about body composition measured with BIA, laboratory, sociodemographic and clinical parameters were obtained. Also, body mass index (BMI) was calculated, and the Malnutrition Inflammation Score (MIS) used to assess nutritional status. Results Using an MIS cut-off point of 5 for malnutrition, 53% of patients were malnourished (MIS≥5). Therefore, those malnourished HD patients were significantly older (p = 0.001), with longer HD duration (p = 0.002), lower residual renal function (p = 0.02), waist circumference (p = 0.001), BMI (p &amp;lt; 0.001), muscle (p = 0.002) and fat mass (p = 0.001) in kg, phase angle PhA (p &amp;lt; 0.001), serum creatinine (p = 0.002), albumin (p = 0.008), phosphate (p = 0.01), and urate (p = 0.008) level but have significantly higher ferritin (p = 0.004), and mean cellular volume level (p = 0.02). Therefore, total MIS score significantly negatively correlated with HD duration (r = −0.247, p &amp;lt; 0.001), waist circumference (r = −0.323, p &amp;lt; 0.001),muscle mass (r = −0.236, p &amp;lt; 0.001), fat mass (r = −0.352, p &amp;lt; 0.001), serum creatinine (r = −0.271, p &amp;lt; 0.001), phosphor (r = −0.245, p &amp;lt; 0.001), urate (r = −0.344, p &amp;lt; 0.001), and TIBC (r = −0.376, p &amp;lt; 0.001), albumin (r = 0.241, p &amp;lt; 0.001), ferritin (r = 0.273, p &amp;lt; 0.001). In contrast, PhA significantly positively correlated with muscle mass (kg) (r = 0.311, p &amp;lt; 0.001), creatinine (r = 0.313, p &amp;lt; 0.001), phosphate (r = 0.208, p = 0.01), urate (r = 0.305, p = 0.01) and Total Iron Binding Capacity (TIBC) (r = 0.245, p &amp;lt; 0.001) while significantly negative correlation with ferritin (r = −0.182, p = 0.03) was found. Also, there was a significant negative correlation between PhA and MIS (r = −0.362, p &amp;lt; 0.001). A multivariate regression analysis showed that age (ß = 0.09, p = 0.005), waist circumference (ß = −0.09, p = 0.004), serum albumin (ß = −0.23, p = 0.04), and urate (ß = −0.01, p = 0.02), were predictive factors for malnutrition. Conclusion The prevalence of malnutrition in HD patients in Croatian HD population was high. These results indicate and highlight the urgent need for individualized and structural nutritional screening (using MIS score and PhA) and nutritional support in Croatian HD patients, especially for older HD patients and those with longer HD duration.

#406 High ferritin is not needed in hemodialysis patients: a retrospective study of total body iron and oral iron replacement therapy

Abstract Background and Aims In vivo iron levels can be adjusted through intestinal iron absorption to be maintained at a suitable level; however, optimal iron levels in hemodialysis (HD) patients are unclear. Although serum ferritin is useful as an indicator of iron stores, it does not necessarily reflect body iron levels in HD patients with unstable hematopoiesis since iron metabolism is a semi-closed system in vivo. In this study, we investigated total body iron (TBI), new index calculated as the sum of red blood cell (RBC) iron and iron stores, during courses of low-dose oral iron replacement therapy, and evaluated in vivo iron sufficiency and its indicators in HD patients. Method We analyzed data on 105 courses of low-dose iron replacement therapy (50–120 mg of iron daily) administered to 83 patients with serum ferritin &amp;lt;60 ng/mL and Hb &amp;lt;12 g/dL undergoing maintenance hemodialysis at our institution. Low-dose oral iron replacement therapy was initiated between August 2016 and June 2023 and continued for at least seven months. All blood samples were collected at the start of hemodialysis at the beginning of the week. Blood examinations were performed twice a month, and patients were given darbepoetin alfa (DA), long-acting ESAs to maintain Hb at the target level of 10–12 g/dL, in accordance with the guidelines of the Japanese Society for Dialysis Therapy. Iron-related parameters were determined based on blood samples collected once a month, with TSAT calculated from serum iron (Fe) and total iron-binding capacity (TIBC), using the following equation. TSAT=Fe/TIBC × 100. We evaluated changes in TBI, RBC iron, and iron stores from the initiation of treatment to month 7, in two groups of patients, namely, iron-therapy responders and non-responders. Furthermore, we investigated factors associated with steady-state TBI. TBI was regarded as achieving a steady state during the course of therapy when the trend shifted from an increase and the difference from the value at one month was less than or equal to zero. TBI was calculated using the formula proposed by Cable et al (Transfusion. 2016, 56, 2005). Results Mean age was 68.1±12.6 years and median time on hemodialysis was 6.6 years. Of the 105 courses of therapy, 75 were delivered to men and 30 to women, and 66.7% of the patients had diabetic nephropathy. The patients had a mean Hb level of 10.4±0.7 g/dL, a mean serum ferritin level of 27.3±12.5 ng/mL, mean transferrin saturation (TSAT) of 18.1%±5.9%, and a median C-reactive protein level of 0.1 mg/dL at the start of each course. TBI showed significant increases until month 4 and plateaued thereafter in iron-therapy responders, and tended to increase and then reached a similar plateau in non-responders (month 7: 1900±447 vs. 1900±408 mg, Fig. 1). As for RBC iron, iron-therapy responders showed significant monthly increases up to month 3, whereas non-responders showed constant values. Regarding iron stores, iron-therapy responders showed significant monthly increases up to month 5, while non-responders showed a significant increase only at month 1. DA per body weight showed a significant decrease at month 3 and 4 in the effective group, but a slight increase in the non-responder group. Steady-state TBI did not correlate with Hb or serum ferritin, but was strongly correlated with body surface area (BSA) using the Du Bois formula [TBI=−791.914 + 1628.606 × BSA (m2); R2=0.88, p&amp;lt;0.001, Fig. 2]. Conclusion This study showed that hemodialysis patients can increase their body iron levels during oral iron replacement therapy and maintain them at the same level after sufficiency has been achieved, suggesting activation of a “mucosal block.” Furthermore, this result also suggests that determining iron sufficiency based on serum ferritin alone is difficult in HD patients with fluctuations in Hb. However, regression equations using steady-state TBI and BSA showed a high degree of fit. Therefore, BSA might potentially be used in estimations of TBI sufficiency, which may be useful for avoiding excessive iron dosage.

Prognostic Impact of Iron Metabolism Changes in Patients with Acute Coronary Syndrome and its Correlation with TIMI Risk Score and 6-month Left Ventricular Performance

Objectives: Iron is vital for human metabolism and function. One major cause of anemia is a shortage of iron. On the other hand, a low blood iron level does not always indica te an abnormal hemoglobin concentration. Left ventricular function, ferritin, and blood iron levels were investigated 6 months following the acute coronary syndrome (ACS) index event. In addition, we searched for correlations between thrombolysis in myocardial infarction (TIMI) risk score, cytokines such as C-reactive protein (CRP), and serum iron content. Materials and Methods: From August 2021 to July 2022, 100 consecutive patients with ACS who were requesting admission to the critical care unit of the Cardiology Department at SCB Medical College in Cuttack, Odisha, were the subject of this study. Participants in our research with ST-elevation or non-ST-elevation myocardial infarction (ST elevation myocardial infarction [STEMI] or Non ST elevation myocardial infarction [NSTEMI]) ranged in age from 18 to 70 years. We measured CRP, transferrin saturation, total iron binding capacity, ferritin, and blood iron at baseline. The left ventricular ejection fraction (LVEF %) difference was assessed 6 months after baseline echocardiography and follow-up. Various factors were considered while calculating the short- and long-term prognoses, including the patient’s heart failure at admission and any deaths that took place in hospitals within 6 months after the index event. Results: There was no improvement in LVEF for 56.25% of patients (36 out of 66) 6 months after the index event; however, for 43.75% (28 patients) of the 66 STEMI patients, LVEF improved. Out of 34 NSTEMI patients, 14 (42.42%) improved their LVEF 6 months after ACS, whereas 19 (57.58%) did not. Serum iron levels and LVEF at 6 months were shown to be significantly correlated in all patients (overall P &lt; 0.001, STEMI P &lt; 0.001, and NSTEMI P = 0.001). Serum iron levels are positively correlated with improvements in LVEF after 6 months in both patients with STEMI; P &lt; 0.001, and NSTEMI P = 0.006. Serum iron levels and hospitalized STEMI patients’ TIMI risk scores showed a significant connection (P &lt; 0.001). Conclusion: Regardless of hemoglobin content, patients with &lt;10% improvement in LVEF from baseline had considerably lower blood iron levels. Six months after their initial ACS incident, patients with ACS who had lower blood iron concentrations at baseline recovered less well in terms of left ventricular systolic function. In our study, 48% of men and 68% of women were found to be iron deficient. In addition to being an indicator of inflammation, hypoferremia may be the target of a novel biomarker with potential applications in medicine in the near future. It could be useful in predicting left ventricular function following ACS.

Exploring the Biological Pathways of Siderophores and Their Multidisciplinary Applications: A Comprehensive Review.

Siderophores are a class of small molecules renowned for their high iron binding capacity, essential for all life forms requiring iron. This article provides a detailed review of the diverse classifications, and biosynthetic pathways of siderophores, with a particular emphasis on siderophores synthesized via nonribosomal peptide synthetase (NRPS) and non-NRPS pathways. We further explore the secretion mechanisms of siderophores in microbes and plants, and their role in regulating bioavailable iron levels. Beyond biological functions, the applications of siderophores in medicine, agriculture, and environmental sciences are extensively discussed. These applications include biological pest control, disease treatment, ecological pollution remediation, and heavy metal ion removal. Through a comprehensive analysis of the chemical properties and biological activities of siderophores, this paper demonstrates their wide prospects in scientific research and practical applications, while also highlighting current research gaps and potential future directions.

Evaluation of the Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantations in ALS Patients by Investigating Patients' Specific Immunological and Biochemical Biomarkers.

Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell (MSC) therapy cohort as a promising novel treatment modality by estimating some additional new parameters, such as immunological and biochemical factors. This study was designed as an open-label, one-arm cohort retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous-bone marrow-derived mesenchymal stem cells (BM-MSCs) in 15 confirmed patients with ALS, administered at a dose of 1 × 106 cells/kg BW with a one-month interval, in equal amounts in both an intravenous (IV) and intrathecal (IT) capacity simultaneously, via various biochemical (iron (Fe), ferritin, total-iron-binding capacity (TIBC), transferrin, and creatine kinase (CK)) and immunological parameters (tumor necrosis factor-alpha (TNF-α), neurofilament light chain (NFL), and glial-cell-derived neurotrophic factor (GDNF) levels, evaluated during the three-month follow-up period in serum and cerebrospinal fluid (CSF). Our study indicated that, in the case of immunological biomarkers, TNF-α levels in the CSF showed a significant decrease at month three after transplantation compared with levels at month zero, and the p-value was p < 0.01. No statistically significant changes were observed for other immunological as well as biochemical parameters and a p-value of p > 0.05. These results can indicate the potential benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results.

Serum iron level is independently associated with sarcopenia: a retrospective study

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67–7.98), age > 65 years (OR 5.40, 95% CI 2.25–12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08–0.36), and serum iron < 10.95 μmol/L (OR 0.39, 95% CI 0.16–0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.

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.