sTfR Concentrations Research Articles

Pro-inflammatory diet affects markers of iron metabolism in healthy older adults.

Inflammation and inadequate nutrition are common in older age and known to affect iron homeostasis. However, it is not known whether a pro-inflammatory diet affects iron status in older adults. We investigated the diet quality of healthy older adults considering markers of iron homeostasis and inflammation compared to a younger control. Serum markers of iron metabolism (iron, transferrin, ferritin, hepcidin, soluble transferrin receptor [sTfR]) and inflammation (interleukin-6 [IL-6], IL-10 high-sensitive C- reactive protein [hsCRP]) were quantified using immunosorbent assays. Insulin resistance was determined by calculating the homeostasis model assessment index (HOMA-IR). The Dietary Inflammatory Index® (DII) was computed based on dietary intake and inflammatory (ID) or less inflammatory diet (LID) groups were created by using median DII score specific to age group and sex. DII did not differ by age (p = 0.668, n = 80, F: 75 %, >65 years, n = 60, F: 72 %, ≤35 years). Iron and inflammation status were different between age groups in terms of higher transferrin saturation, sTfR, ferritin and IL-6 concentrations in the old (all p ≤ 0.001). Only in older adults, BMI, HOMA-IR, hsCRP, ferritin and hepcidin concentrations were significantly higher in ID compared to LID (all p < 0.01). In addition, a risk-factor adjusted regression analysis showed that ID was independently associated with higher ferritin and hepcidin concentrations in older adults. In older age, a pro-inflammatory diet is associated with systemic inflammation and disturbed iron homeostasis.

Assessment of serum soluble transferrin receptor in adult Egyptian aplastic anemia patients

Aplastic Anemia (AA) is one of the life-threatening bone marrow failure syndromes. One of the main pathologies of AA is reduced erythropoietic activity evidenced by decreased soluble transferrin receptor (sTfR) levels which results in minimal iron utilization and accumulation of iron in tissues in the form of ferritin. This study aimed to measure serum level of sTfR in adult AA patients and correlate it with the severity of the disease and the response to treatment. The study included 35 randomly selected AA patients recruited from the Hematology Department, aged from 17 to 66 years and 27 normal controls of matched age and sex. The level of sTfR was measured by using an enzyme linked immunoassay. The median level of sTfR was significantly lower in AA cases than in controls (17.9 nmol/l, ranged 9.87–30.42 nmol/l vs. 52.2 nmol/l; ranged 29.74–86.84 nmol/l, (p&lt;0.001). The concentration of sTfR was significantly lower in the Very Severe Aplastic Anemia (VSAA) patients in comparison to Severe Aplastic Anemia (SAA) 34.27 nmol/l (ranged 31.05 – 45.41 nmol/l) vs. 55.15 nmol/l (ranged 48.78–63.88 nmol/l), respectively, p= 0.004). The level of sTfR in responders to immunosuppressive treatment did not show any difference in comparison to non-responders [55.15 nmol/l (ranged 47.36 – 65.35 nmol/l) vs. 48.26 nmol/l (ranged 34.62 – 60.39 nmol/l), (p=0.808). In conclusion, sTfR level was significantly lower in AA cases than controls. The sTfR concentration expresses the erythropoietic activity in AA patients and can be an indicator of severity of bone marrow failure.

Novel loci and biomedical consequences of iron homoeostasis variation

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait expression, erythropoiesis, immune response and cellular trafficking. Mendelian randomisation of 292 disease outcomes in 1,492,717 participants revealed associations of iron-related loci and iron status with selected health outcomes across multiple domains. These associations were largely driven by HFE, which was associated with the largest iron variation. Our findings enhance understanding of iron homoeostasis and its biomedical consequences, suggesting that lifelong exposure to higher iron levels is likely associated with lower risk of anaemia-related disorders and higher risk of genitourinary, musculoskeletal, infectious and neoplastic diseases.

Association of Serum Soluble Transferrin Receptor Concentration With Markers of Inflammation: Analysis of 1001 Patients From a Tertiary Rheumatology Center.

Soluble transferrin receptor (sTfR) is considered to be a useful biomarker for the diagnosis of iron deficiency, especially in the setting of inflammation, as it is thought to not be affected by inflammation. We analyzed the relationship between sTfR levels and inflammatory markers in patients with known or suspected inflammatory rheumatic disease (IRD). Blood samples of 1001 patients with known or suspected IRD referred to a tertiary rheumatology center were analyzed. Study participants were classified as patients with active IRD and patients with inactive IRD or without IRD. Correlation analyses were used to explore the relationship between sTfR levels and inflammatory markers (ie, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]). We applied multiple linear regression analysis to evaluate the predictive value of CRP levels for sTfR concentrations after adjustment for potential confounding factors. There were positive correlations between inflammatory markers (CRP, ESR) and serum sTfR levels (ρ 0.44, ρ 0.43, respectively; P < 0.001), exceeding the strength of correlation between inflammatory markers and the acute phase reactant ferritin (ρ 0.30, ρ 0.23, respectively; P < 0.001). Patients with active IRD demonstrated higher serum sTfR levels compared to patients with inactive or without IRD (mean 3.99 [SD 1.69] mg/L vs 3.31 [SD 1.57] mg/L; P < 0.001). After adjustment for potential confounding factors, CRP levels are predictive for serum sTfR concentrations (P < 0.001). The study provides evidence against the concept that sTfR is a biomarker not affected by inflammation.

Anaemia and iron deficiency associate with polymorphism TMPRSS6 rs855791 in Brazilian children attending day care centres.

Fe-deficiency anaemia is a major public health concern in children under 5 years of age. TMPRSS6 gene, encoding matriptase-2 protein, is implicated in Fe homoeostasis and has been associated with anaemia and Fe status in various populations. The aim of this cross-sectional study was to investigate the associations between the single nucleotide polymorphism (SNP) TMPRSS6 rs855791 and biomarkers of anaemia and Fe deficiency in Brazilian children attending day care centres. A total of 163 children aged 6-42 months were evaluated. Socio-economic, demographic, biochemical, haematological, immunological and genotype data were collected. Multiple logistic and linear regressions with hierarchical selection were used to assess the effects of independent variables on categorised outcomes and blood marker concentrations. Minor allele (T) frequency of rs855791 was 0·399. Each copy of the T allele was associated with a 4·49-fold increased risk of developing anaemia (P = 0·005) and a 4·23-fold increased risk of Fe deficiency assessed by serum soluble transferrin receptor (sTfR) (P < 0·001). The dose of the T allele was associated with an increase of 0·18 mg/l in sTfR concentrations and reductions of 1·41 fl and 0·52 pg in mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH), respectively. In conclusion, the T allele of SNP TMPRSS6 rs855791 was significantly associated with anaemia and Fe deficiency assessed by sTfR in Brazilian children attending day care centres. The effect was dose dependent, with each copy of the T allele being associated with lower MCV and MCH and higher concentrations of sTfR.

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.

Micronutrient Status During Pregnancy is Associated with Child Immune Status in Rural Bangladesh

BackgroundPoor immune function increases children’s risk of infection and mortality. Several maternal factors during pregnancy may affect infant immune function during the postnatal period. ObjectivesWe aimed to evaluate whether maternal micronutrients, stress, estriol, and immune status during the first or second trimester of pregnancy were associated with child immune status in the first two years after birth. MethodsWe conducted observational analyses within the water, sanitation, and hygiene (WASH) Benefits Bangladesh randomized controlled trial. We measured biomarkers in 575 pregnant women and postnatally in their children. Maternal biomarkers measured during the first and second trimester of pregnancy included nutrition status via vitamin D (25-hydroxy-D [25(OH)D]), ferritin, soluble transferrin receptor (sTfR), and retinol-binding protein (RBP); cortisol; estriol. Immune markers were assessed in pregnant women at enrollment and their children at ages 14 and 28 mo, including C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and 13 cytokines (including IFN-γ). We generated a standardized sum score of log-transformed cytokines. We analyzed IFN-γ individually because it is a critical immunoregulatory cytokine. All outcomes were prespecified. We used generalized additive models and reported the mean difference and 95% confidence intervals at the 25th and 75th percentiles of exposure distribution. ResultsAt child age 14 mo, concentrations of maternal RBP were inversely associated with the cytokine sum score in children (-0.34 adjusted difference between the 25th and 75th percentile [95% confidence interval -0.61, -0.07]), and maternal vitamin A deficiency was positively associated with the cytokine sum score in children (1.02 [0.13, 1.91]). At child age of 28 mo, maternal RBP was positively associated with IFN-γ in children (0.07 [0.01, 0.14]), whereas maternal vitamin A deficiency was negatively associated with child AGP (-0.07 [-0.13, -0.02]). Maternal iron deficiency was associated with higher AGP concentrations in children at age 14 mo (0.13 [0.04, 0.23]), and maternal sTfR concentrations were positively associated with child CRP concentrations at age 28 mo (0.18 [0, 0.36]). ConclusionMaternal deficiencies in vitamin A or iron during the first 2 trimesters of pregnancy may shape the trajectory of a child’s immune status.

Ready-to-Use Therapeutic Foods Fail to Improve Vitamin A and Iron Status Meaningfully during Treatment for Severe Acute Malnutrition in 6–59-Month-old Cambodian Children

Severe acute malnutrition (SAM) remains a global health concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on micronutrient status during SAM treatment are almost nonexistent. The objective was to investigate the impact of RUTFs on the iron and vitamin A status of 6-59-month-old children receiving SAM treatment. Biomarkers of vitamin A status (retinol-binding protein, RBP), iron status (ferritin and soluble transferrin receptor, sTfR), and inflammation (C-reactive protein, CRP, and alpha-1 acid glycoprotein, AGP) were collected at admission and discharge (week 8) during an RUTF effectiveness trial. Vitamin A deficiency was defined as RBP <0.70 µmol/L, low body iron as body iron (BI) <0 mg/kg and deficient iron stores as ferritin <12 µg/L. Data were available for 110 and 75 children at admission and discharge, respectively. There was no significant difference in haemoglobin, ferritin, sTfR, BI or RBP concentrations between admission and discharge. At discharge, BI was 0.2 mg/kg lower, and there was a tendency towards a slightly lower RBP concentration, but the prevalence of vitamin A deficiency was low at admission and discharge (6% and 3%, respectively). The small impact of both RUTFs on improving vitamin A and iron status during SAM treatment calls for further research on the bioavailability of micronutrients to enhance the effectiveness of SAM treatment on micronutrient status.

Iron Status of a People Living with HIV in Sub-Saharan Africa Using a Multi-Criteria Approach Based on the Determination of Blood Ferritin, sTfR, CRP and sTfR-F Index

Background: The assessment of iron status using a single biomarker of iron metabolism is not enough sensitive and specific to reliably diagnose iron deficiency associated with multiple comorbidities. The objective of this study was to describe the iron status of people living with HIV in sub-Saharan Africa using a multi-criteria approach based on the determination of blood ferritin, sTfR, CRP and the calculation of sTfR-F index. Methods: This study was conducted using a retrospective panel of 933 sera/plasmas. We determined serum ferritin concentration, serum sTfR concentration, and C-reactive protein (CRP) by immunoturbidimetry for each subject. The sTfR-F index was determined by calculating the sTfR/log ferritin ratio. The statistical test used was Chi2. Results: Regardless of the inflammatory syndrome, we determined 3.80%, 30.29%, and 42.70% iron deficiency based on the separate interpretation of ferritin concentration, sTfR, and sTfR-F calculation, respectively. We used those biomarkers in addition to CRP in an algorithm for the diagnosis of iron deficiency. Subjects without inflammatory syndrome, had iron deficiency of 2.89% (n = 26). Taking into account the presence of an inflammatory syndrome, the frequency obtained was n = 88 (9.78%). Overall, iron deficiency was diagnosed in 114 (12.67%) patients when we used the diagnostic algorithm. Conclusion: The use of diagnostic algorithms combining several biomarkers of iron metabolism and taking into account the presence or absence of an inflammatory syndrome is a good approach to detect a large number of iron deficiencies in a population. Therefore, an assessment of the effectiveness of different diagnostic algorithms is necessary.

Association between iron deficiency and hospitalization rate in community-dwelling older adults: A 3-year prospective observational study of DO-HEALTH

BackgroundIron deficiency (ID) is associated with negative health outcomes in older adults. However, data on the impact of ID on the number of hospitalizations and length of hospital stay (LOS) is lacking. ObjectiveTo explore the associations between baseline ID and the number of hospitalizations and between baseline ID and at least one LOS ≥5 days in community-dwelling older adults. MethodsThis is a secondary observational analysis of a randomized controlled trial including 2157 community-dwelling adults aged ≥70 years without major diseases at baseline. The main exposure was defined as ID (soluble transferrin receptor [sTfR] concentrations >28.1 nmol/L) at baseline. The primary outcome was the number of hospitalizations over a 3-year follow-up. The secondary outcome was having at least one LOS ≥5 days over the study period among individuals with one or more hospitalizations. Interaction between ID and anemia (hemoglobin <130 g/L for men and <120 g/L for women) was also investigated. ResultsBaseline sTfR concentration was determined in 2141 participants (median age 74.0 years). At 3 year, 1497 hospitalizations were reported with an incidence rate of hospitalization of 0.26 per person-year (95% CI: 0.24, 0.28). Overall, baseline ID was associated with a 24% increased incidence rate of hospitalization (incidence rate ratio: 1.24; 95% CI: 1.05, 1.45) over 3 years. This association was independent of anemia status at baseline since the interaction between ID and anemia at baseline was not significant. Moreover, ID was not significantly associated with having a LOS ≥5 days (OR: 1.40; 95% CI: 1.00, 1.97) among participants with at least one hospitalization over 3 years. ConclusionsID is associated with increased hospitalization rate and not associated with LOS ≥5 days among generally healthy older adults. Efforts to minimize ID in older adults may improve overall health and optimize healthcare costs.

Associations between serum soluble transferrin receptor and the prevalence of cancers.

As increasing experimental evidence suggests that iron metabolism play crucial roles in cancer and non-cancer conditions, there is a lack of data on serum soluble transferrin receptor (sTfR), a promising marker representing unmet cellular iron demands, between cancer risk from epidemiological studies. Here, we aimed to evaluate the predictive value of sTfR and cancer prevalence. We analyzed on 5,480 adult participants from 2015 to 2018 National Health and Nutrition Examination Survey (NHANES). Spearman correlation analysis was performed to investigate the correlations between sTfR and other characteristics. To identify the associations between sTfR and the prevalence of cancers, stratified multivariable logistic regression models, subgroup and sensitivity analyses were also performed. In tertile analyses, participants in the highest level of sTfR were significantly associated with increased prevalence of total cancers [odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.15-2.02] as compared with those at the lowest tertile. Each unit increment in ln-transformed sTfR concentration was shown to be associated with 39% increased risks of total cancers. Similar associations were found in males rather than females. Further subgroup and sensitivity analyses indicated that, in continuous and tertile analyses, sTfR was more closely associated with male- and female-specific cancers of prostate and testis (2.35: 1.03-5.40; 2.03: 1.00-4.09; respectively), and breast, cervix, ovary and uterus (1.92: 1.11-3.35; 1.66: 1.02-2.69; respectively). Our findings suggested that elevated level of sTfR was associated with the prevalence of cancers, especially in sex-specific cancers. In order to better determine them, further research in humans will be required.

Iron Status and Homeostasis Across 2 Competitive Seasons in NCAA Division I Collegiate Cross-Country Runners Residing at Low Altitude.

Inflammatory cytokines including interleukin-6 can upregulate hepcidin and decrease iron absorption. Endurance exercise is associated with transient increases in cytokines, which may alter the risk of iron deficiency (ID). This study examined whether chronic elevations in basal levels of cytokines and hepcidin were associated with ID in highly trained runners. Fifty-four collegiate runners (26 males and 28 females) living at ∼1625m were recruited from an NCAA Division I cross-country team for this prospective cohort study. Over 2 seasons, fasted, preexercise blood draws were performed in the morning 4 times per season and were analyzed for hemoglobin concentration, ferritin, soluble transferrin receptor (sTfR), hepcidin, and 10 cytokines. Stages of ID were defined using ferritin, sTfR, and hemoglobin concentration. During the study, a registered dietician provided all runners with iron supplements using athletic department-created guidelines. Fifty-seven percent of females and 35% of males exhibited stage 2 ID (ferritin <20ng/mL or sTfR >29.5nmol/L) at least once. Cytokines, ferritin, and sTfR exhibited changes through the 2years, but changes in cytokines were not associated with alterations in hepcidin, ferritin, or sTfR. In males and females, lower ferritin was associated with lower hepcidin (both P < .0001). One female exhibited higher hepcidin and lower iron stores compared with other individuals, suggesting a different etiology of ID. ID is common in highly trained collegiate runners. In general, the high prevalence of ID in this population is not associated with alterations in basal hepcidin or cytokine levels.

Iron Deficiency and Blood Donation: Links, Risks and Management.

The purpose of this review is to raise awareness about the frequently underappreciated association of blood donation with iron deficiency, and to describe methods for its prevention and management. Blood donors cannot expect any health benefits from the donation but have justified expectations of no harm. Iron deficiency without anemia (IDWA) and iron deficiency anemia (IDA) are common consequences of regular blood donation, and this activity is the most important factor affecting iron status in regular blood donors. Awareness of blood donation as a primary cause of sideropenia is surprisingly low among physicians. Blood donation screening identifies potential donors with IDA but is frequently inadequate to detect IDWA. For the assessment of body iron stores, plasma or serum ferritin, transferrin saturation (TSAT) and soluble transferrin receptors (sTfR) concentrations are the most widely used biochemical markers, although the percentage of hypochromic mature erythrocytes and the hemoglobin content of reticulocytes are also useful. IDWA can be prevented by limiting the total volume of blood collected, by iron deficiency screening and deferral of sideropenic donors, by prolonging the interdonation intervals, and by iron supplementation between donations. IDWA tends to be more prevalent in younger people, females, and high-intensity donors. A potentially effective strategy to address sideropenia in blood donors is serum ferritin testing, but this may lead to a higher rate of deferral. Most regular blood donors cannot replenish their iron deficit by an iron-rich diet alone and will benefit from low-dose oral iron administration with various commercially available products post-donation, a well-tolerated strategy. However, valid concerns exist regarding the possibility of worsening the iron overload in donors with undiagnosed hemochromatosis or masking the symptoms of a clinically important gastrointestinal hemorrhage or other underlying medical condition. Finally, educational efforts should be intensified to improve the awareness of blood donation as a primary cause of iron deficiency among physicians of all specialties.

Study of Serum Ferritin, Zinc, and Copper Levels in Children With Helicobacter pylori Gastritis and the Effect of the Treatment.

This study aimed to assess serum iron, zinc, and copper in symptomatic children with Helicobacter pylori infection, to correlate their serum levels with the degree of gastritis, and to evaluate the effect of H. pylori treatment on their levels. This study was carried out on 70 children with upper gastrointestinal tract symptoms. H. pylori infection was diagnosed by the H. pylori antigen test in the stool and histopathologic findings during upper gastrointestinal endoscopy. Patients were divided into 2 groups; H. pylori -positive and H. pylori -negative groups. Hemoglobin, serum ferritin, transferrin (sTfR), zinc, and copper were assessed in all included children. The hemoglobin level, serum ferritin, and zinc were significantly lower in H. pylori -positive patients compared to H. pylori -negative patients. However, the serum copper level was comparable between the 2 groups. After treatment, the hemoglobin level, serum ferritin, and serum zinc significantly increased in H. pylori -positive patients, especially in those who responded to treatment compared to their levels before treatment. There was a significant negative correlation between the severity of histopathologic abnormalities and hemoglobin level, serum ferritin, and zinc levels, but a significant positive relation with sTfR concentrations in H. pylori -positive patients. H. pylori -infected children had low serum ferritin and zinc levels but high sTfR level with no effect on serum copper levels. After treatment, hemoglobin, serum ferritin, and zinc levels significantly improved in H. pylori -positive patients. Gastric histologic findings correlated significantly with hemoglobin, serum ferritin, zinc, and sTfR levels.

Role of Soluble Transferrin Receptor in Diagnostic Work Up for The Assessment of Iron Status and Iron Deficiency

Background: Iron deficiency anaemia (IDA) is the most frequent form of anaemia in human population. For diagnosing IDA usually conventional laboratory tests such as serum iron, serum ferritin and transferrin saturation are used. However, both ferritin and transferrin proteins are markedly influenced by inflammation, behaving as acute-phase reactants and making it difficult to diagnosis iron-deficiency anemia (IDA) when it is combined with any inflammatory condition. Soluble transferrin receptor (sTfR) is a truncated extracellular form of the membrane transferrin receptor produced by proteolysis. Concentrations of serum sTfR are related to iron status and erythropoiesis in the body. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes.&#x0D; Aim: The aim of this study is to evaluate the significance of soluble transferrin receptors in diagnostic work up of iron deficiency.&#x0D; Materials and Methods: It was a prospective observational study carried out from June 2021 to November 2021 at the Department of Haematology and Biochemistry of Armed Forces Institute of Pathology (AFIP), Dhaka Cantonment. A total of 50 blood sample were collected and subjected to diagnose as microcytic hypochromic anaemia through complete blood count (CBC) and peripheral blood film (PBF). Then serum iron profile and serum sTfR was done by automated analyzer to evaluate differentials of microcytic hypochromic anaemia.&#x0D; Results: Among 50 cases 5 (10%) were male and 45 (90%) were female. Most of the patients were between 31-40 years age group (34%). Out of 50 patients 42 (84%) showed mild anaemia,6 (12%) showed moderately anaemia and 2(4%) showed severely anaemia according to reference range. Then serum iron profile was done. Among 50 samples 37 (74 %) had low serum iron, 18 (36 %) had high TIBC and 45 (90%) had low serum ferritin in comparison with reference range. Also this study revealed high serum sTfR than normal in 48 (96%) patients. While evaluating the frequency of sTfR level in perspective of both male and female anaemic patients, p-value was found &lt; 0.0001 which was statistically significant.&#x0D; Conclusion: This study demonstrates that sTfR level in conjunction with other biochemical markers of iron deficiency anaemia is very useful in evaluating iron status. Serum sTfR is a new diagnostic tool for evaluating of iron deficiency anemia when it is associated with other inflammatory condition.

Adjusting Iron Biomarkers for Inflammation in Pregnant Women: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) Project

ObjectivesAccurate assessment of iron deficiency during pregnancy is essential for program planning and interventions. We aimed to examine the relationship between serum ferritin (SF) and soluble transferrin receptor (sTfR) and inflammation and examine the impact of inflammation on the prevalence of iron deficiency in a large multi-country analysis.MethodsBiomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project provided 17 pregnancy datasets (n = 14,077) from 15 countries including at least one iron (serum ferritin, SF; soluble transferrin receptor, sTfR) and inflammation biomarker (C-reactive protein, CRP or α-1-acid glycoprotein, AGP). Spearman rank correlations between CRP or AGP and iron biomarkers (SF, sTfR) were examined. We report unadjusted and adjusted prevalence of iron deficiency, using the BRINDA regression correction approach to adjust for inflammation on behalf of the BRINDA Pregnancy Workgroup.ResultsFerritin concentrations were positively correlated with CRP in 6 out of 14 surveys (ρ from 0.65 in Mexico, P < 0.0001 to 0.06 in Vietnam, P < 0.05) and AGP in 8 out of 9 surveys (correlation coefficients (ρ) ranging from 0.41, in Guatemala to 0.19 in Pakistan, P < 0.0001). Among the 8 datasets with both CRP and AGP, adjustment for both AGP and CRP increased the estimated prevalence of iron deficiency (ferritin < 15 μg/L) by a median of 18.8 percentage points (pp) compared to 15.6 pp for AGP alone and 10.5 pp for CRP alone. sTfR concentrations were positively correlated with AGP in 4 out of 12 surveys (ρ ranging from 0.36 in Vietnam to 0.09 in Pakistan, P < 0. 01) and positively associated with CRP in 4 out of 10 surveys (ρ ranging from 0.20 in Vietnam to 0.07 in US and Ghana, P < 0.05).ConclusionsFailing to adjust for inflammation during pregnancy appears to underestimate iron deficiency using serum ferritin during pregnancy. Given the weak and inconsistent association between sTfR and inflammation, adjustment of sTfR biomarkers during pregnancy does not appear warranted at this time.Funding SourcesBill & Melinda Gates Foundation, Centers for Disease Control and Prevention, Eunice Kennedy Shriver National Institute of Child Health and Human Development, HarvestPlus, and the United States Agency for International Development.

Prevalence of postpartum anaemia and iron deficiency by serum ferritin, soluble transferrin receptor and total body iron, and associations with ethnicity and clinical factors: a Norwegian population-based cohort study.

Worldwide, there are limited data on the prevalence of postpartum anaemia and iron status. The aims of the present study were to assess the prevalence of anaemia and iron deficiency (ID) by three iron indicators 14 weeks postpartum, their relations to haemoglobin (Hb) and associations with ethnicity and clinical factors in a multi-ethnic population. We conducted a population-based cohort study of 573 women followed from early pregnancy. The prevalence of postpartum anaemia (Hb <12·0 g/dl) was 25 %. ID prevalence varied from 39 % by serum ferritin (SF <15 μg/l), to 19 % by soluble transferrin receptor (sTfR >4·4 mg/l) and 22 % by total body iron (TBI < 0 mg/kg). The mean Hb concentration was 12·8 g/dl in women with no ID, 12·6 g/dl in those with ID by SF only and 11·6 g/dl in those with ID by SF, sTfR and TBI. ID by sTfR and TBI defined by the current threshold values probably identified a more severe iron-deficient population compared with ID assessed by SF. Compared with Western Europeans, the prevalence of anaemia was at least the double in ethnic minorities (26-40 % v. 14 %; P < 0·01-0·05), and the prevalence of ID by sTfR and TBI, but not of ID by SF < 15 μg/l, was significantly higher in some minority groups. After adjustment for covariates, only South Asians had lower Hb and higher sTfR concentration. Insufficient iron intake, gestational anaemia or ID, and postpartum haemorrhage were associated with lower postpartum Hb concentration and poorer iron status.

Iron deficiency is an independent risk factor of increased myocardial energy expenditure in chronic heart failure patients

Chronic heart failure (CHF) is a major public health burden and is associated with high morbidity, mortality, and cost. Recent studies demonstrated iron metabolism and myocardial energy metabolism were altered in CHF patients. In this study, we aimed to analyze the effects and correlations of iron metabolism on myocardial energy metabolism in CHF. One hundred and thirty patients with CHF [age: 66.2±11.5 years, males: 58.5% and New York Heart Association (NYHA) class (II/III/IV): 67/43/20] were included. Serum concentrations of ferritin, transferrin saturation (Tsat), and soluble transferrin receptor (sTfR) were quantified as the indexes of iron metabolism, and echocardiography was used to assess myocardial energy expenditure (MEE) levels. Iron deficiency (ID) was defined as ferritin <100 or 100-300 µg/L with Tsat <20%. Patients with CHF were divided into two groups based on iron status. The prevalence of ID in CHF was 36.9%, and increased with the severity of CHF, reaching 80.0% in those with NYHA class IV (NYHA class II/III/IV: 17.9% vs. 46.5% vs. 80.0%, P=0.000). The demographic characteristics [age, sex, body mass index (BMI), blood pressure, and heart rate] and hemoglobin (HGB) concentrations in two groups were similar (all P>0.05). MEE was significantly higher in the ID group (92.7±23.0 vs. 65.6±20.8 cal/min, P=0.000), while NYHA classes II and III was significantly higher in the ID group (71.6±16.4 vs. 60.3±14.8 cal/min, P=0.022; 88.9±10.4 vs. 69.1±20.1 cal/min, P=0.000). In univariable linear regression models, the presence of ID, higher NYHA class, increased N-terminal pro-B-type natriuretic peptide (NT-proBNP), sTfR, left ventricular internal diastolic diameter (LVIDd), as well as reduced ferritin, Tsat levels, and lower left ventricular ejection fraction (LVEF) were associated with elevated MEE levels (all P<0.05). In multivariable regression models, the presence of ID, reduced Tsat. and increased sTfR remained independent predictors of elevated MEE levels after adjustment for all variables that showed a significant association with MEE (all P<0.05). The prevalence of ID is high in CHF and is associated with the severity of cardiac dysfunction. The presence of ID as well as reduced Tsat and increased sTfR concentrations are associated with elevated MEE levels in CHF.

Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: a US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study

Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin thresholds of less than 12 μg/L for children and less than 15 μg/L for women, which were developed on the basis of expert opinion, to define iron deficiency. We aimed to derive new physiologically based serum ferritin concentration thresholds for iron deficiency in healthy young children and non-pregnant women using data from the US National Health and Nutrition Examination Survey (NHANES). In this serial cross-sectional study, we examined the relationship of serum ferritin with two independent indicators of iron-deficient erythropoiesis, haemoglobin and soluble transferrin receptor (sTfR), in children (12-59 months) and non-pregnant women (15-49 years) using cross-sectional NHANES data from 2003-06, 2007-10, and 2015-18. NHANES is a US national stratified multistage probability sample that includes a household interview followed by a standardised physical examination in a mobile examination centre. We excluded individuals with missing serum ferritin, sTfR, haemoglobin, or white blood cell counts measurements; non-pregnant women with missing C-reactive protein (CRP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) data were also excluded. In addition, individuals with infection (white blood cell counts >10·0×109/L) and non-pregnant women with possible liver disease (ALT >70 IU/L or AST >70 IU/L) and inflammation (CRP >5·0 mg/L) were excluded. We examined distributions of haemoglobin and sTfR with serum ferritin and used restricted cubic spline regression models to determine serum ferritin thresholds for iron-deficient erythropoiesis. 5964 children and 10 462 non-pregnant women had physical examinations and were screened for inclusion in the study, of whom 2569 (43·1%) children and 7498 (71·7%) non-pregnant women were included. At lower serum ferritin concentrations, median haemoglobin concentration decreased as sTfR concentration increased, with each varying in a curvilinear manner. Using restricted cubic spline plateau points to determine the onset of iron-deficient erythropoiesis, the serum ferritin thresholds identified by haemoglobin and sTfR concentrations were not different. For children, the haemoglobin identified serum ferritin threshold was 19·9 μg/L (95% CI 18·8-22·6) and the sTfR identified serum ferritin threshold was 20·0 μg/L (19·4-20·9; p=0·89). For women the haemoglobin identified serum ferritin threshold was 25·2 μg/L (24·2-26·2) and the sTfR identified serum ferritin threshold was 24·0 μg/L (23·3-24·6; p=0·05). The association between two independent indicators of iron-deficient erythropoiesis, haemoglobin and sTfR, identified serum ferritin concentration thresholds of about 20 μg/L for children and 25 μg/L for non-pregnant women, providing physiological evidence of potential new thresholds for consideration when determining the prevalence and distribution of iron deficiency in populations. In healthy children and non-pregnant women, physiologically based thresholds for iron deficiency might be more clinically and epidemiologically relevant than those based on expert opinion. Validation of this physiologically based approach in non-US populations might help the international harmonisation of serum ferritin thresholds for iron deficiency. None.

Evaluation of One Egg per Day on Iron and Anemia Status Among Young Malawian Children: A Randomized Controlled Trial

ObjectivesYoung children with complementary feeding diets that lack diversity and have low micronutrient density are at risk of iron deficiency anemia. Our objectives were to determine the impact of supplementing diets with 1 egg/day on: (1) plasma ferritin, soluble transferrin receptor (sTfR), and hemoglobin (Hb) concentrations; and (2) the prevalence of iron deficiency (ID), anemia, and iron deficiency anemia (IDA). MethodsChildren age 6–9mo in the Mangochi District of Malawi were individually randomized to receive 1 egg/day for 6mo (n = 331) or continue their usual diet (n = 329). Venous blood samples were collected at enrollment and a 6mo follow-up by assessors masked to group assignment. Plasma ferritin, sTfR, c-reactive protein (CRP), and α1-acid glycoprotein (AGP) were assessed using ELISA and hemoglobin was measured using Hemocue analyzers. Ferritin and sTfR were corrected for inflammation using CRP and AGP in linear regression models. Ferritin, sTfR, and hemoglobin concentrations were compared between groups using linear regression models, adjusting for baseline values. The prevalence ratios (PR) of ID (fer < 12μg/L, sTfR >8.3mg/L, or total body iron< 0mg/kg), anemia (Hb< 11g/dL), and IDA (Hb < 11g/dL and ID) were compared between egg and control groups using binomial or Poisson regression models. ResultsA total of 585 children were included in this analysis (Egg: n = 286; Control: n = 299). At enrollment, the prevalence of anemia and IDA was 61% and 55%. At the 6mo follow-up, there was no difference between groups in inflammation-adjusted ferritin (geometric mean [95% CI]; Egg: 6.52μg/L [5.98,7.10]; Control: 6.82 [6.27, 7.42]) or sTfR (Egg: 11.34mg/L [10.92,11.78]; Control: 11.46 [11.04,11.89]) concentrations. There was also no difference in mean hemoglobin concentration between groups (mean [95%CI]; Egg: 11.0g/L [10.8,11.1]; Control:11.1 [11.0,11.3]). Overall, 43% of children had anemia, 89% had ID, and 40% had IDA. No group-level differences were observed in the prevalence of anemia [PR: 1.15 (95% CI: 0.96, 1.38)], ID [PR: 0.99 (0.94, 1.05)], or IDA [PR: 1.12 (0.92, 1.36)]. ConclusionsIron and anemia indices did not differ between the egg intervention group and control group. Other interventions are needed to address the high prevalence of iron deficiency and anemia among young, Malawian children. Funding SourcesBill & Melinda Gates Foundation.