Soluble Transferrin Receptor Levels Research Articles

Immature reticulocyte fraction: A novel biomarker of hemodynamic severity in pulmonary arterial hypertension.

Various erythropoietic abnormalities are highly prevalent among patients with pulmonary arterial hypertension (PAH) and associated with worse disease severity. Given the poorly understood yet important roles of dysregulated erythropoiesis and iron metabolism in PAH, we sought to further characterize the hematologic and iron profiles in PAH and their relationship to PAH severity. We recruited 67 patients with PAH and 13 healthy controls. Hemodynamics attained within 1 year of blood sample collection were available for 36 patients. Multiple hematologic, iron, and inflammatory parameters were evaluated for their association with hemodynamics. The subset with hemodynamic data consisted of 29 females (81%). The most common etiologies were idiopathic PAH (47%) and connective tissue disease-related PAH (33%). 19 (53%) had functional class 3 or 4 symptomatology, and 12 (33%) were on triple pulmonary vasodilator therapy. Immature reticulocyte fraction (IRF) had significant positive correlations with mean pulmonary artery (PA) pressure (mPAP) (0.59, p < 0.001), pulmonary vascular resistance (0.52, p = 0.001), and right atrial pressure (0.46, p = 0.005), and significant negative correlations with cardiac index (-0.43, p = 0.009), PA compliance (PAC) (-0.60, p < 0.001), stroke volume index (SVI) (-0.57, p < 0.001), and mixed venous oxygen saturation (-0.51, p = 0.003). IRF correlated with markers of iron deficiency (ID) and erythropoiesis. On multivariable linear regression, IRF was associated with elevated mPAP and reduced SVI and PAC independent of EPO levels, transferrin saturation, and soluble transferrin receptor levels. We identified IRF as a novel and potent biomarker of PAH hemodynamic severity, possibly related to its associations with erythropoiesis, ID, and tissue hypoxia.

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.

Iron deficiency and all-cause mortality after myocardial infarction

BackgroundData on the clinical significance of iron deficiency (ID) in patients with myocardial infarction (MI) are conflicting. This may be related to the use of various ID criteria.We aimed to compare the association of different ID criteria with all-cause mortality after MI. MethodsConsecutive patients hospitalized for their first MI at a large tertiary heart center were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality. ResultsFrom the 1,156 patients included (aged 64±12 years, 25 % women), 194 (16.8 %) patients died during the median follow-up of 3.4 years. After multivariate adjustment, iron level ≤13 µmol/L (HR 1.67, 95 % CI 1.19–2.34) and the combination of iron level ≤12.8 µmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L (HR 2.56, 95 % CI 1.64–3.99) termed as PragueID criteria were associated with increased mortality risk and had additional predictive value to the GRACE score. Compared to the model including iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95 % CI 0.52–0.69) by reclassifying patients into a higher-risk group. No association between ferritin level and mortality was found. 51 % of patients had low iron levels, and 58 % fulfilled the PragueID criteria. ConclusionIron deficiency is common among patients with the first MI. The PragueID criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality and should be evaluated in future interventional studies for the identification of patients potentially benefiting from intravenous iron therapy.

Association between obesity and anemia in an nationally representative sample of United States adults: a cross-sectional study.

Few studies are about the relationship between anemia and obesity, and previous studies have only paid attention to BMI. We first included body fat percentage (BF%) as an assessment indicator and divided it into quartiles, grouped participants into obesity and non-obesity used data from NHANES database. After adjustment for age, gender, ethnicity, education and family income, the level of soluble transferrin receptor (sTfR), and incidence of elevated CRP or HsCRP were progressively higher with increased BF%, whereas mean cell volume (MCV), natural logarithm (Ln) serum ferritin (SF), and Ln SF/sTfR were progressively reduced. Although a higher prevalence of anemia and lower hemoglobin was observed with increased BF%, but there was no statistical difference. Women in the highest BF% group demonstrated a significantly higher risk of iron deficiency compared to those in the lowest BF% group. BF% should be given more attention, and women with high BF% should pay attention to iron deficiency.

Elevated Serum Levels of Soluble Transferrin Receptor Are Associated with an Increased Risk of Cardiovascular, Pulmonary, and Hematological Manifestations and a Decreased Risk of Neuropsychiatric Manifestations in Systemic Lupus Erythematosus Patients.

The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and the disease activity and organ manifestations in SLE patients. We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. The median serum levels of sTfR (p > 0.000001) and IL-4 (p < 0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p < 0.0001), a lower iron concentration (p = 0.008), a lower value of total iron-binding capacity (TIBC) (p = 0.03), and lower counts of RBC (p = 0.004), HCT (p = 0.0004), PLT (p = 0.04), neutrophil (p = 0.04), and lymphocyte (p < 0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p = 0.0005), HGB (p = 0.0001) and HCT (p = 0.008), and positively correlated with IL-4 (p = 0.01). Elevated serum sTfR > 2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71-464.78; p = 0.001), ischemic heart disease (OR: 3.25 95 CI 1.02-10.40; p = 0.04), lung manifestations (OR: 4.48 95 CI 1.44-13.94; p = 0.01), and hematological manifestations (OR: 2.07 95 CI 1.13-3.79; p = 0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22-0.80; p = 0.008). Serum IL-4 was negatively correlated with CRP (p = 0.003), and elevated serum IL-4 levels > 0.17 mg/L were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26-0.90; p = 0.02). In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study

BackgroundRoxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs).MethodsThis prospective cohort study enrolled PD patients with a mean hemoglobin level of 60–100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency.ResultsCompared with ESAs, roxadustat significantly decreased hepcidin level (difference, − 20.09 ng/mL; 95% CI, − 30.26 to − 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, − 7.87 nmol/L; 95% CI, − 12.11 to − 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study.ConclusionsCompared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients.Trial registration: This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231).Graphical abstract

Changes in Iron Status Biomarkers with Advancing Age According to Sex and Menopause: A Population-Based Study.

The risk of chronic diseases increases markedly with age and after menopause. An increase in bodily iron following menopause could contribute to this phenomenon of increased risk of chronic diseases. We aimed to investigate how various iron biomarkers change with advancing age, according to sex and menopausal status. We enrolled community-dwelling individuals with available information on ferritin, transferrin, iron, hepcidin, and soluble transferrin receptor levels from the Prevention of Renal and Vascular Endstage Disease study. The association of the iron biomarkers with age, sex, and menopausal status was investigated with linear regression models. Mean (SD) age of the 5222 individuals (2680 women [51.3%], among whom 907 [33.8%] were premenopausal, 529 [19.7%] perimenopausal, and 785 [29.3%] postmenopausal), was 53.4 (12.0) years. Iron biomarkers showed a constant increase in women throughout their life course, in some cases at older ages surpassing values in men who, in turn, showed consistently higher levels of iron status compared to women in most age categories. Ferritin, hepcidin, and transferrin saturation levels were 3.03, 2.92, and 1.08-fold (all p < 0.001) higher in postmenopausal women compared to premenopausal. We found that iron accumulates differently depending on sex, age, and menopausal status. An increased iron status was identified in women, especially during and after menopause.

Abstract P1159: Association Of Membrane Ferritin Transporter And Transferrin Receptor Plasma Levels With Coronary Atherosclerosis

Objective: Given the potential role of iron in inflammation and atherosclerosis, we investigated the correlation between the plasma levels of membrane ferritin transporter (FPN) and soluble transferrin receptor (sTFR) with the severity of coronary artery stenosis (CAS). Methods: Clinical data of 85 patients admitted to our institution between August 2022 and December 2022 with suspected coronary artery disease (CAD) was utilized. Patients were stratified according to their coronary angiography results: CAD group (n=50) and control group (n=50). Patients with CAD were further divided depending on their use of statin: statin taking group (PSU, n=15) and non-statin taking group (NSU, n=35). The coronary Gensini score was used to assess the severity of CAS. Spearman’s regression analysis was used to correlate plasma FPN and sTFR concentrations with the severity of CAS. Results: Plasma sTFR [2,216.88 (1,922.42, 2479.01) ng/mL vs. 1,928.96 (1490.50, 2289.23) ng/mL] concentration was higher in patients with CAD, while HDL cholesterol [0.94 (0.84, 1.17) mmol/L vs. 1.14 (0.95, 1.38) mmol/L] and plasma FPN [0.71 (0.42, 2.71) ng/mL vs. 2.90 (1.32, 4.40) ng/mL] concentration was lower when compared to patients without CAD. The coronary Gensini score was positively correlated with plasma sTFR concentration (R s =0.24, p =0.045) and negatively correlated with plasma FPN concentration (R s =-0.28, p =0.021). Plasma FPN level [1.50 (0.52, 4.77) ng/mL VS 0.51 (0.28, 2.46) ng/mL, P=0.007] in PSU patients was higher than the NSU group. Levels of total cholesterol [3.71±0.28mmol/L VS 4.67±0.15mmol/L, P=0.002] and low-density lipoprotein [2.24±0.25mmol/L VS 2.96±0.10mmol/L, P=0.002] were significantly lower in the PSU group. Regression analysis indicates that low plasma FPN concentration is an independent risk factor for the development of CAD ( p =0.038). Conclusion: Our results suggest that sTFR and FPN concentrations are positively and negatively correlated respectively with the severity of CAS. Furthermore, regression analysis indicates that low plasma FPN concentration is an independent risk factor for the development of CAD. While our data provides some reference for evaluating the incidence and severity of CAD, future research is needed to verify our results.

Roxadustat alleviates the inflammatory status in patients receiving maintenance hemodialysis with erythropoiesis-stimulating agent resistance by increasing the short-chain fatty acids producing gut bacteria

BackgroundHypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have improved the treatment of renal anemia, especially in patients resistant to erythropoiesis-stimulating agents (ESAs). HIF facilitates maintain gut microbiota homeostasis, which plays an important role in inflammation and iron metabolism, which are in turn key factors affecting ESA resistance. The current study aimed to investigate the effects of roxadustat on inflammation and iron metabolism and on the gut microbiota in patients with ESA resistance.MethodsWe conducted a self-controlled, single-center study including 30 patients with ESA resistance undergoing maintenance hemodialysis. All patients received roxadustat without iron agents for renal anemia. Hemoglobin and inflammatory factors were monitored. Fecal samples were collected before and after 3 months’ administration and the gut microbiota were analyzed by 16S ribosomal RNA gene sequencing.ResultsHemoglobin levels increased after treatment with roxadustat for 3 months (P < 0.05). Gut microbiota diversity and abundance also changed, with increases in short-chain fatty acid (SCFA)-producing bacteria (Acidaminococcaceae, Butyricicoccus, Ruminococcus bicirculans, Ruminococcus bromii, Bifidobacterium dentium, Eubacterium hallii) (P < 0.05). Serum SCFA levels also increased (P < 0.05). Inflammatory factors, including interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, interferon-γ, and endotoxin gradually decreased (P < 0.05). Serum hepcidin, ferritin, and total and unsaturated iron-binding capacities decreased (P < 0.05), while soluble transferrin receptor levels increased at each time point (P < 0.05). There were no significant differences in serum iron and transferrin saturation at each time point. The abundance of Alistipes shahii was significantly negatively correlated with IL-6 and TNF-α (P < 0.05).ConclusionsRoxadustat alleviated renal anemia in patients with ESA resistance by decreasing inflammatory factors and hepcidin levels and improving iron utilization. These effects were at least partly mediated by improved diversity and abundance of SCFA-producing gut bacteria, probably via activation of HIF.

Association of Ferroptosis with Severity and Outcomes in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy: A Case-control Study.

Ferroptosis, an iron-dependent form of cell death, is characterized by intracellular accumulation of iron and reactive oxygen species-induced lipid peroxidation. Animal experiments have shown the important roles of ferroptosis in ischemic stroke, but the evidence in human stroke is insufficient. This prospective study evaluated the associations between plasma ferroptosis biomarkers at hyperacute stage and long-term outcomes in patients with acute ischemic stroke undergoing endovascular thrombectomy (EVT). The plasma samples were collected immediately before and after EVT (T1 and T2) and at 24h (T3) for the 126 stroke patients and once for the 50 stroke-free control subjects. Compared with controls, stroke patients had higher 4-hydroxynonenal (4-HNE) levels at T1 and T2 while lower homocysteine and soluble transferrin receptor (sTfR) levels at T3. In stroke patients, higher National Institutes of Health Stroke Scale scores at admission were correlated with higher 4-HNE and lower sTfR levels. Lower Alberta Stroke Program Early CT (ASPECT) scores and larger infarct core volumes on CT perfusion before EVT were correlated with higher 4-HNE and homocysteine levels. After adjusting for significant parameters, homocysteine levels at T2 were significantly associated with poor functional outcome and mortality at 3 months. In the receiver operating characteristic (ROC) models, adding homocysteine levels at T2 and hemoglobin levels to the reference model for predicting poor functional outcome significantly increased the area under the ROC curve. In summary, this study provides evidence that ferroptosis is associated with stroke severity and outcomes in patients with acute ischemic stroke undergoing EVT.

Iron metabolism disorders of patients with chronic paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is caused by Paracoccidioides spp.; during infection, some host mechanisms limit the availability of iron, thereby reducing its reproduction. However, Paracoccidioides spp. can evade the immune defense and, even under limited iron conditions, use this mineral for growth and dissemination. This study evaluated the iron metabolism of 39 patients who were diagnosed with chronic PCM from 2013 to 2021. The forms of iron before treatment and at the time of clinical cure were evaluated based on the following: serum ferritin levels (storage iron); total iron-binding capacity (TIBC) and transferrin saturation (TSAT) level (transport iron); red blood cell (RBC), hemoglobin (Hb), hematocrit (HCT), and soluble transferrin receptor (sTfR) levels; and sTfR/log ferritin ratio (functional iron). The mean age of the patients was 54.5 years (±6.7 years). Most patients were men (97.4%), rural workers (92.1%), and smokers (84.6%); furthermore, most had moderate disease severity (66.7%). After achieving clinical cure, we observed that serum ferritin levels decreased, and parameters of functional iron increased. The extent of alteration in these parameters were more pronounced in severe cases than in to mild or moderate cases. Furthermore, moderate correlations were observed between C-reactive protein and the Hb (r = -0.500; p = 0.002), RBC (r = -0.461; p = 0.005), HCT (r = -0.514; p = 0.001), and iron levels (r = -0.491; p = 0.002). However, it is possible to infer that PCM interferes with functional and storage iron because improvements in these parameters after treatment as well as associations with disease severity were observed. PCM can lead to anemia of inflammation, which can be differentiated from iron deficiency anemia by a careful investigation of the iron form parameters.

Markers of Iron Metabolism and Outcomes in Patients with Heart Failure: A Systematic Review

Iron deficiency (ID) in conjunction with heart failure (HF) poses a challenge for clinicians and is associated with worse HF outcomes. Treatment of ID with IV iron supplementation for patients with HF has demonstrated benefits in quality of life (QoL) and HF-related hospitalizations. The aim of this systematic review was to summarize the evidence linking iron metabolism biomarkers with outcomes in patients with HF to assist in the optimal use of these biomarkers for patient selection. A systematic review of observational studies in English from 2010 to 2022 was conducted using PubMed, with keywords of "Heart Failure" and respective iron metabolism biomarkers ("Ferritin", "Hepcidin", "TSAT", "Serum Iron", and "Soluble Transferrin Receptor"). Studies pertaining to HF patients, with available quantitative data on serum iron metabolism biomarkers, and report of specific outcomes (mortality, hospitalization rates, functional capacity, QoL, and cardiovascular events) were included, irrespective of left ventricular ejection fraction (LVEF) or other HF characteristics. Clinical trials of iron supplementation and anemia treatment were removed. This systematic review was conducive to formal assessment of risk of bias via Newcastle-Ottawa Scale. Results were synthesized based on their respective adverse outcomes and iron metabolism biomarker(s). Initial and updated searches identified 508 unique titles once duplicates were removed. The final analysis included 26 studies: 58% focused on reduced LVEF; age range was 53-79 years; males composed 41-100% of the reported population. Statistically significant associations of ID were observed with all-cause mortality, HF hospitalization rates, functional capacity, and QoL. Increased risk for cerebrovascular events and acute renal injury have also been reported, but these findings were not consistent. Varying definitions of ID were utilized among the studies; however, most studies employed the current European Society of Cardiology criteria: serum ferritin < 100 ng/mL or the combination of ferritin between 100-299 ng/mL and transferrin saturation (TSAT) < 20%. Despite several iron metabolism biomarkers demonstrating strong association with several outcomes, TSAT better predicted all-cause mortality, as well as long-term risk for HF hospitalizations. Low ferritin was associated with short-term risk for HF hospitalizations, worsening functional capacity, poor QoL, and development of acute renal injury in acute HF. Elevated soluble transferrin receptor (sTfR) levels were associated with worse functional capacity and QoL. Finally, low serum iron was significantly associated with increased risk for cardiovascular events. Considering the lack of consistency among the iron metabolism biomarkers for association with adverse outcomes, it is important to incorporate additional biomarker data, beyond ferritin and TSAT, when assessing for ID in HF patients. These inconsistent associations question how best to define ID to ensure proper treatment. Further research, potentially tailored to specific HF phenotypes, is required to optimize patient selection for iron supplementation therapy and appropriate targets for iron stores replenishment.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Soluble Transferrin Receptor, Antioxidant Status and Cardiometabolic Risk in Apparently Healthy Individuals.

Body iron excess appears to be related to insulin resistance and cardiometabolic risk and increased oxidative stress might be involved in this relationship. Very few studies have described the association between soluble transferrin receptor (sTfR) levels and cardiometabolic risk in the general population or antioxidant status. There were 239 subjects (20-65 years old) included in this cross-sectional study. Linear regressions adjusting for BMI, menopausal status, insulin resistance (HOMA-IR), physical inactivity, alcohol intake and subclinical/chronic inflammation were used to describe the association between sTfR, total antioxidant capacity (TAC), and measures of cardio-metabolic risk. sTfR levels were positively associated with TAC in men (βeta [95% confidence interval ]: 0.31 [0.14 to 0.48]) and women (βeta = 0.24 [0.07 to 0.40]) in non-adjusted and adjusted models (p &lt; 0.05). In men, sTfR levels were inversely associated with waist circumference (βeta [95% confidence interval]: -1.12 [-2.30 to -0.22]) and fasting glucose (-2.7 (-4.82 to -0.57), and positively with LDL cholesterol (12.41 (6.08 to 18.57) before and after adjustments for confounding variables. LDL cholesterol had a significant and positive association with TAC in non-adjusted and adjusted models in men (p &lt; 0.05). sTfR levels are significantly associated with antioxidant status and a few specific cardio-metabolic risk variables, independently of covariates that included serum ferritin and hepcidin. This might imply that iron biomarkers in regard to cardiometabolic risk reflect physiological contexts other than iron metabolism.

Effect of hemoglobin extracted from Tegillarca granosa on iron deficiency anemia in mice

Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world. This study was aimed to evaluate the therapeutic effects of hemoglobin from Tegillarca granosa (T. granosa) on IDA in mice. Mice were randomly divided into five groups: a normal control group, an anemia model group, a positive (FeSO4) control group, a low-dose and high-dose hemoglobin groups. After 4-week iron supplements administration, it was observed that hemoglobin at 2.0 mg iron/kg body weight had better restorative effective on IDA mice than that of FeSO4 with regard to routine blood parameters and serum biochemical indicators. Meanwhile, the IDA-caused alterations of organ coefficients and liver morphology were ameliorated in mice after hemoglobin supplementation in a dose-dependent manner. Further correlation analysis of indicators showed that serum ferritin (iron storage protein) and soluble transferrin receptor (cellular iron uptake membrane glycoprotein) were susceptible to iron deficiency, indicating possibledisorder of iron metabolism caused by IDA. And levels of serum ferritin and soluble transferrin receptor were restored after administration of hemoglobin. These findings confirmed the safety and effectiveness of T. granosa derived hemoglobin in alleviating IDA in mice, suggesting its great potential as an alternative for iron supplementation.

Formulation and Effect of Iron Fortified Instant Bose Corn on Addressing Anemia among Adolescent Girls in Kupang, Indonesia.

This study aimed to develop Fe-fortified instant Bose corn (IBC), a traditional Timorese food, as a strategy to address anemia among adolescent girls in Kupang, Indonesia. Instant corn and cowpea grits were made to shorten the preparation time with various times of soaking (IBC1=10 min; IBC2=15 min; IBC3=20 min) to select the best formula. The selected IBC was then fortified with NaFeEDTA·3H2O and nutrient content was evaluated. In the intervention study, a pre-post controlled trial was applied to 40 anemic adolescent girls aged 16∼19 years. Subjects with severe anemia (Hb=8.5∼10.4 g/dL) received the fortified selected IBC, whereas those with moderate anemia (Hb=10.5∼11.5 g/dL) received the unfortified selected IBC. A total of 100 g IBC were provided three times/week for 2 months. The hemoglobin and soluble transferrin receptor (sTfR) levels were measured at baseline and endline, respectively. IBC3 produced the highest acceptance level as compared to other formulas. The fortified IBC3 met 127.4% recommended dietary allowances for iron. Moreover, both fortified and unfortified IBC3 significantly increased the hemoglobin levels of adolescent girls with the higher improvement found in the group of fortified IBC3 (1.73±1.21 g/dL; P<0.05). However, the beneficial effects of the fortified IBC3 could not be observed on sTfR levels. Since the effect on Hb levels was significant with less effect, the intervention of IBC3 for only 2 months did not adequate to improve sTfR levels. Nevertheless, this study suggests that Fe-fortified IBC may be effective in preventing anemia among adolescent girls in Kupang, Indonesia.

Serum Soluble Transferrin Receptor and Transferrin Levels among Regular Blood Donors

Background: The study evaluated the effects of regular blood donation on serum transferrin and soluble transferrin receptor levels at Wenchi Methodist Hospital. Methods: This was a hospital-based cross-sectional study conducted at the Medical Laboratory Department of the Wenchi Methodist Hospital in the Bono Region of Ghana. A total of eighty-nine (89) venous blood samples from apparently healthy blood donors were analyzed. Complete blood count parameters were analyzed using an automated haematology analyzer and serum transferrin and transferrin receptor using ELISA. The data were analyzed using SPSS version 22.0. Results: Haemoglobin (p&lt;0.001) and HCT (p=0.004) were significantly lower among the regular blood donors compared with the first-time donors. Regular blood donors had relatively higher serum transferrin (p&lt;0.001) and soluble transferrin receptor levels (p&lt;0.001). A negative correlation was observed between Hb and serum transferrin (r=-0.552, p&lt;0.001), as well as Hb and serum soluble transferrin receptor (r=-0.552, p&lt;0.001). Remunerated donors had lower Hb (p=0.001) and HCT% (p=0.001) but a higher transferrin receptor (p=0.041) than non-remunerated donors. Conclusion: Regular blood donors had relatively lower erythrocyte parameters but higher serum transferrin and soluble transferrin receptors, indicating a possible reduction in serum iron and iron stores. Moderate negative correlations exist between Hb and both transferrin and soluble transferrin receptors. Again, remunerated donors had lower erythrocyte parameters but higher transferrin and soluble transferrin receptors than non-remunerated donors. Periodic assessment of iron parameters among regular blood donors is recommended. A future longitudinal study to assess the entire iron profile of regular blood donors is recommended. Doi: 10.28991/SciMedJ-2022-04-03-01 Full Text: PDF

Iron Deficiency and Incident Infections among Community-Dwelling Adults Age 70 Years and Older: Results from the DO-HEALTH Study.

To assess if baseline iron deficiency, with or without anemia, is associated with incident infections over 3 years among community-dwelling older adults. Prospective secondary analysis of DO-HEALTH, a 3-year randomized, double-blind controlled trial. 2157 community-dwelling adults age 70+ from 5 European countries with good cognitive function and mobility and no major health events in the 5 years prior to enrollment Measurements: Incident infections, their severity and type were recorded every 3 months throughout the 3-year follow-up. Iron deficiency was defined as soluble transferrin receptor (sTfR) levels > 28.1 nmol/l and anemia as hemoglobin levels < 120 g/l for women and 130 g/l for men. We applied negative binomial mixed effects regression models with random effects for countries, and controlling for treatment allocation, age, sex, body mass index, polypharmacy, number of comorbidities, smoking status, living situation, alcohol intake, frailty status, and physical activity levels. A pre-defined stratified analysis was performed to explore if the associations between iron deficiency and infections were consistent by baseline anemia status. In total, 2141 participants were included in the analyses (mean age 74.9 years, 61.5% of women, 26.8% with iron deficiency). Across all participants, baseline iron deficiency was not associated with incident overall infections, but was associated with a 63% greater rate of incident severe infections requiring hospitalization (incidence rate ratio [IRR] 1.63, 95% Confidence Interval [CI] 1.11-2.41, p=0.01). This association was more pronounced among the 2000 participants who did not have anemia at baseline (IRR=1.80, 95% CI 1.20-2.69, p=0.005). Based on this prospective study among generally healthy European community-dwelling older adults, iron deficiency was not associated with the incidence rate of overall infections but may increase the incidence of severe infections. Intervention studies are needed to prove the causality of this observation.

Low Serum Soluble Transferrin Receptor Levels Are Associated with Poor Prognosis in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Iron metabolism disorder is closely related to acute-on-chronic liver failure (ACLF). This study was conducted to analyze the serum levels of soluble transferrin receptor (sTfR) in hepatitis B virus (HBV)-related ACLF and to evaluate the predictive value of sTfR for the short-term prognosis of HBV-ACLF. A total of 359 patients, including 139 with HBV-ACLF, 103 with chronic hepatitis B (CHB), and 117 healthy controls (HCs), participated in this study. We measured serum levels of ferritin, transferrin, and sTfR using nephelometry and performed data analysis using SPSS software. Ferritin levels were significantly higher in HBV-ACLF patients (both P < 0.001), while transferrin and sTfR were significantly lower (all P < 0.001) than in patients with CHB and HCs. Spearman correlation analysis demonstrated that serum sTfR significantly correlated with the alanine aminotransferase (ALT) (r = -0.366, P<0.001), aspartate aminotransferase (AST) (r = -0.322, P < 0.001), total bilirubin (TBIL) (r = -0.222, P = 0.009), alpha fetoprotein (AFP) (r = 0.329, P < 0.001), prothrombin time-international normalization ratio (PT-INR) (r = -0.428, P < 0.001), and model for end-stage liver disease (MELD) (r = -0.459, P < 0.001). Nonsurviving HBV-ACLF patients who died within 30 days had much lower serum sTfR levels than surviving patients (P < 0.001). Logistic regression analysis showed that decreased serum sTfR levels were independently associated with 30-day mortality in patients with HBV-ACLF (P = 0.003). Receiver operating characteristic (ROC) curve analysis for predicting 30-day mortality showed that the area under the curve (AUC) for serum sTfR was 0.813 (95% CI: 0.738-0.874, P < 0.001). This was similar to that of the MELD score (AUC = 0.812, 95% CI: 0.737-0.873, P < 0.001). Serum sTfR combined with MELD score significantly improved the predictive capacity for 30-day mortality in patients with HBV-ACLF (AUC = 0.871, 95% CI: 0.803-0.922, P < 0.001). Kaplan-Meier analysis revealed that the overall cumulative 30-day mortality rate was significantly higher in patients with serum sTfR levels ≤ 0.55 mg/L compared to those with serum sTfR levels > 0.55 mg/L (P < 0.001).

Iron and iron-related proteins in COVID-19.

COVID-19 can cause detrimental effects on health. Vaccines have helped in reducing disease severity and transmission but their long-term effects on health and effectiveness against future viral variants remain unknown. COVID-19 pathogenesis involves alteration in iron homeostasis. Thus, a contextual understanding of iron-related parameters would be very valuable for disease prognosis and therapeutics.Accordingly, we reviewed the status of iron and iron-related proteins in COVID-19. Iron-associated alterations in COVID-19 reported hitherto include anemia of inflammation, low levels of serum iron (hypoferremia), transferrin and transferrin saturation, and high levels of serum ferritin (hyperferritinemia), hepcidin, lipocalin-2, catalytic iron, and soluble transferrin receptor (in ICU patients). Hemoglobin levels can be low or normal, and compromised hemoglobin function has been proposed. Membrane-bound transferrin receptor may facilitate viral entry, so it acts as a potential target for antiviral therapy. Lactoferrin can provide natural defense by preventing viral entry and/or inhibiting viral replication. Serum iron and ferritin levels can predict COVID-19-related hospitalization, severity, and mortality. Serum hepcidin and ferritin/transferrin ratio can predict COVID-19 severity. Here, serum levels of these iron-related parameters are provided, caveats of iron chelation for therapy are discussed and the interplay of these iron-related parameters in COVID-19 is explained.This synopsis is crucial as it clearly presents the iron picture of COVID-19. The information may assist in disease prognosis and/or in formulating iron-related adjunctive strategies that can help reduce infection/inflammation and better manage COVID-19 caused by future variants. Indeed, the current picture will augment as more is revealed about these iron-related parameters in COVID-19.