sTfR Levels Research Articles

Effect of Qingshen Granules on inflammation/hepcidin axis and iron metabolism in patients with renal anemia: a single-center, randomized controlled trial

To evaluate the therapeutic effect of Qingshen Granules on renal anemia in patients with damp-heat syndrome and explore the mechanisms in light of inflammation/hepcidin axis and iron metabolism. Sixty patients with renal anemia and dampness-heat syndrome were randomized into control group (n=30) and treatment group (n=30). All the patients were given routine treatment, and the patients in the treatment group received additional treatment with Qingshen Granules (3 times a day). After 12 weeks of treatments, the patients were examined for changes in the integral value of TCM syndrome, serum creatinine (Scr), glomerular filtration rate (eGFR), hemoglobin (HGB), hematocrit (HCT), red blood cell (RBC) count, interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), ferritin, growth differentiation factor-15 (GDF-15), serum iron (SI), total iron binding capacity (TIBC), transferrin saturation (TAST), soluble transferrin receptor (sTfR) and ferritin levels. After the treatment, the scores of TCM syndrome were significantly improved in the treatment group and were better than those in the control group (P=0.000). Scr and eGFR were improved in both groups after the treatment. The levels of HGB, HCT and RBC were all improved in the two groups after treatment, and the improvements were more obvious in the treatment group (P=0.002, 0.002, and 0.017, respectively). The levels of IL-6, hs-CRP, hepcidine and GDF-15 were all lowered in the two groups after the treatment, and they were all significantly lower in the treatment group than in the control group (all P=0.000). The treatments increased the levels of SI and TAST in both of the groups, and compared with those in control group, the levels of TIBC, sTfR and ferritin were significantly lowered in the treatment group after the 12-week treatment (P=0.000). Qingshen granules can effectively improve renal anemia in patients with damp-heat syndrome possibly by improving iron metabolism through alleviation of inflammation and reduction of hepcidine level.

Analysis of the iron profile and the incidence of iron deficiency anemia in the third-trimester pregnant women in the coendemic areas of Bengkulu City, Indonesia

Pregnant women are at risk for iron deficiency anemia especially pregnant women in malaria-endemic areas. This study aimed to analyze the profile of iron in the third trimester pregnant women with iron deficiency anemia in co-endemic area of Bengkulu city. This study was cross-sectional study with a total sample of 66 pregnant women who met the inclusion criteria. Examination profile of iron in pregnant women is done by taking blood specimen through the vena cubity. Profile iron includes examination sTfR levels, hepcidin, transferrin were examined by ELISA. Determination of iron deficiency anemia is based on the results of Hb, serum iron and TIBC. The results showed 39.4% of pregnant women experience iron deficiency anemia. There is an average difference between hepcidin levels with the incidence of iron deficiency anemia (p-value 0.031). Based on binary logistic regression analysis profile iron with irondeficiency anemia in pregnant women, hepcidin levels are predictors factors on the incidence of iron deficiency anemia (p-value 0.000, 95% CI .296-.709).

Soluble Form of Transferrin Receptor as A Biomarker of Ineffective Erythropoiesis and Iron Overload in Pediatric Egyptian Patients with b-Thalassemia

AbstractBackground: Beta-thalassemias (b-thalassemias) are a group of inherited blood disorders caused by reduced or absent synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymp-tomatic individuals. Thalassemia is the commonest hereditary hemolytic anemia in Egypt. Iron overload is a major compli-cation of repeated blood transfusion in patients with thalassem-ia. Soluble Transferrin Receptor (sTfR), one of the main regulators of cellular iron homeostasis, is the truncated form of the tissue receptor.Aim of Study: This work was conducted to study the pathophysiology of iron overload in children with b-thalassemia intermedia and thalassemia major and explore the possible utility of Soluble Transferrin Receptor (sTfR) for the evaluation of iron overload and ineffective erythropoi-esis in pediatric Egyptian patients with s thalassemia major, b-thalassemia intermedia and comparing this with the controls.Patients and Methods: This study was conducted on sixty b-thalassemia patients (30 b-thalassemia major and 30 b-thalassemia intermedia) together with 30 age and sex matched controls. Patients were selected from the outpatient clinics of the Pediatric Hematology Unit and the Inpatients of Pediatric Department; Faculty of Medicine, Beni Suef University Hospital during the year 2017. Patients and control were subjected to clinical evaluation and complete blood count along with serum ferritin and sTfR levels by Enzyme-Linked Immunosorbent Assay (ELIZA) technique.Results: Both serum ferritin and sTfR levels were signif-icantly higher in patients compared with controls and in patients with thalassemia major compared with those with thalassemia intermedia. Serum ferritin and sTfR levels were significantly positively correlated with patients' age and with each other. Each of them was negatively correlated with age of disease onset, frequency of blood transfusions and with hemoglobin level.Conclusion: Serum levels of ferritin and soluble transferrin receptor were significantly higher in both thalassemic groups in comparison to control group.

(Invited) Portable Iron Screening System for Point-of-Care Iron Status Determination

Women undergoing basic military training are particularly susceptible to iron deficiency (ID) and iron deficiency anemia (IDA). Symptoms of iron depletion, such as fatigue and reduced cognitive ability, have raised concerns over the effect of unchecked iron deficiencies on United States military preparedness. Therefore, screening recruits for iron status is vital to the health and safety of the people serving our country. Currently, there exists no robust point-of-care method for rapid iron status determination. Here we present a point-of-care iron status determination system, which can rapidly determine iron status based on a panel of markers. The methodology used for determination of iron status is based on immunosensor measurement from human plasma samples by means of impedance analysis. Antibodies respective to soluble transferrin receptor (sTfR), transferrin, and ferritin were linked to the electrode surface using dithiobis succinimidyl propionate (DSP). The transferrin sensor exhibited linear calibration curve for concentrations ranging from 0.5-5.5 mg/mL transferrin protein. With given linearity, the transferrin levels detected in all tested plasma samples were found to be 1.5 - 1.7 mg/mL respectively, that fall within expected normal reference ranges. The transferrin clinical threshold for ID and IDA is >4.0mg/mL. The sTfR sensor was capable of measuring sTfR in PBS between 0.1 and 3.2 mg/L. The clinical threshold for ID and IDA is >3.6 mg/L of sTfR. The sTfR levels detected in all tested plasma samples were found to be 1.8 - 4.4mg/L respectively. The concentrations measured by the developed sensors were in excellent agreement with ELISA. Further improvements will be performed with screen printed array gold electrodes for multiplex sensing of all the biomarkers. These sensors will be integrated into a cartridge, and along with electronic hardware and software for interpreting the results, will be a fully functional system for the rapid determination of ID and IDA.

Associations between iron status and insulin resistance in Chinese children and adolescents: findings from the China Health and Nutrition Survey.

Iron homeostasis abnormalities are associated with insulin resistance (IR), but studies on such associations in children and adolescents are limited and have contrasting results. The purpose of this study was to determine the associations between indicators of iron status and IR, and assesse if there are sex disparities in these associations. We selected data of 689 children and adolescents (367 boys and 322 girls) aged 6-18 years in the analysis. Serum ferritin, transferrin, and soluble transferrin receptor (sTfR) levels were determined. The level of glycated hemoglobin (HbA1c) was assessed using highperformance liquid chromatography. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to indicate the status of insulin resistance. Stepwise and multivariate logistic regression analyses were computed to evaluate associations between iron status and glucose parameters. The prevalence of IR (HOMAIR >3.16) and high HbA1c (HbA1c ≥5.7%) were 29.8% and 16.4%, respectively. Serum transferrin and sTfR were significant associated with HbA1c (p<0.001), while serum transferrin was associated with HOMA-IR (p<0.001). Furthermore, the highest transferrin concentrations were associated with higher risks of both HOMAIR and high HbA1c, while decreased sTfR concentrations were associated with a risk of higher HbA1c in both children and adolescents. Serum transferrin and sTfR were statistically significantly associated with glucose parameters, which may suggest that transferrin and sTfR levels should be taken into consideration when studying IR in both boys and girls.

The effect of donation activity dwarfs the effect of lifestyle, diet and targeted iron supplementation on blood donor iron stores.

The iron status of blood donors is a subject of concern for blood establishments. The Finnish Red Cross Blood Service addresses iron loss in blood donors by proposing systematic iron supplementation for demographic at-risk donor groups. We measured blood count, ferritin and soluble transferrin receptor (sTfR) and acquired lifestyle and health information from 2200 blood donors of the FinDonor 10000 cohort. We used modern data analysis methods to estimate iron status and factors affecting it with a special focus on the effects of the blood service’s iron supplementation policy. Low ferritin (< 15 μg/L), an indicator of low iron stores, was present in 20.6% of pre-menopausal women, 10.6% of post-menopausal women and 6% of men. Anemia co-occurred with iron deficiency more frequently in pre-menopausal women (21 out of 25 cases) than in men (3/6) or post-menopausal women (1/2). In multivariable regression analyses, lifestyle, dietary, and blood donation factors explained up to 38% of the variance in ferritin levels but only ~10% of the variance in sTfR levels. Days since previous donation were positively associated with ferritin levels in all groups while the number of donations during the past 2 years was negatively associated with ferritin levels in pre-menopausal women and men. FRCBS-provided iron supplementation was negatively associated with ferritin levels in men only. Relative importance analyses showed that donation activity accounted for most of the explained variance in ferritin levels while iron supplementation explained less than 1%. Variation in ferritin levels was not significantly associated with variation in self-reported health. Donation activity was the most important factor affecting blood donor iron levels, far ahead of e.g. red-meat consumption or iron supplementation. Importantly, self-reported health of donors with lower iron stores was not lower than self-reported health of donors with higher iron stores.

Evaluation of Iron Status in Patients of Chronic Kidney Disease - A study to assess the best Indicators Including Serum Transferrin Receptor Assay

Anemia is an early complication of chronic kidney disease (CKD). The iron deficiency is an important contributor, more so in the Pakistani population. As routine standalone iron tests do not accurately reflect the actual status in the complex environment of CKD, there is a need to study better indicators. Serum iron, ferritin, total iron-binding capacity (TIBC), and serum transferrin receptor (sTfR) levels were estimated in 100 primary iron deficiency anemia (IDA) patients (controls-Group 1) and 68 newly diagnosed CKD cases. The CKD patients were divided into two groups: Serum ferritin 100 μg/L (Group 3). The values of percentage saturation, log of ferritin (log_ferritin), and the ratio of sTfR to log ferritin (sTfR/log_f or sTfR index) were calculated. The CKD cases were further divided depending on ferritin cut-offs of 30, 50, 70, and 100 μg/L and statistically analyzed including ROC and AUC, to choose the best diagnostic parameter for accurate assessment of iron status in CKD cases. The mean serum ferritin was 11.34 μg/L, 28.70 μg/L, and 281.81 μg/L, and the mean sTfR was 2.34 μg/ml, 1.82 μg/ml, and 1.28 μg/ml in Groups 1, 2, and 3. Among all groups, the difference was found to be significant for serum iron, log_ferritin, and sTfR/log_f. The sTfR and sTfR/log_f showed good discrimination between IDA and Anemia of chronic disease in CKD cases, but sTfR/log_f gave the best discrimination at all cut-off levels of ferritin. At a ferritin cut-off of 50 μg/L, the sTfR/log_f value of 0.83 had a sensitivity of 93.5% and specificity of 95.45%, and at a ferritin cut-off 100 μg/L, the same value of 0.83 had a sensitivity of 95.5% and specificity of 86.5%. The ratio of sTfR/log_f is the best indicator for assessing iron status in CKD. Keywords: Anemia, chronic kidney disease, ferritin, transferrin receptor DOI : 10.7176/JMPB/57-03 Publication date : July 31 st 2019

Prevalence of anemia in patients with ankylosing spondylitis and peculiarities of hemopoiesis and ferrokinetics, depending on the degree of anemia

Anemic syndrome is a frequent complication of ankylosing spondylitis (AS), worsening the course of the disease and prognosis. The purpose of this work was to determine the frequency of anemia, relationship with age, sex and duration of the disease, as well as the peculiarities of hemopoiesis and ferrokinetics in patients with AS. 118 patients with AS and 26 controls were examined. Hematologic parameters were determined on the apparatus of ERMA PCE-210 (Japan), indicators of ferrokinetics were determined on a biochemical analyzer Humalyzer 2000 using sets in accordance with the instructions of the manufacturer. Statistical data was processed using the Microsoft Office Excel statistical software package. The probability of the results was estimated using Student's criteria (probable results were considered at p&lt;0.05) and Fischer's criterion. Analysis of data showed that anemia was detected in 28.8% of patients. In 79.4%, anemia was mild, and 20.6% had an average degree of severity. Anemia was detected in 68.8% of women and 22.5% of men. Anemia was observed in 52.9% of patients with a disease duration of up to 5 years. According to cytometric indices, it is normocytic anemia in 55.9%, microcytic it is in 26.5%, and only in 17.6% is macrocytic. In patients with moderate severity of anemia, serum iron levels, ferritin and coefficient of saturation of transferrin were significantly lower, compared with light, and total iron binding capacity (TIBC) and sTfR levels were higher, p&lt;0.05. Thus, among patients with SAR, anemia is detected in 28.8% of patients with predominantly mild degrees. Anemia is more often diagnosed in women than in men. There is no relationship between age and the occurrence of anemia. In debut disease, every second patient has anemic syndrome. According to the cytometric characteristic, anemia is a mild degree of normocytic, and anemia of middle degree is microcytic. Patients with microcytic anemia had the lowest levels of iron, ferritin, coefficient of saturation of transferrin, and the highest levels of TIBC and sTfR.

Iron deficiency, elevated erythropoietin, fibroblast growth factor 23, and mortality in the general population of the Netherlands: A cohort study.

BackgroundEmerging data in chronic kidney disease (CKD) patients suggest that iron deficiency and higher circulating levels of erythropoietin (EPO) stimulate the expression and concomitant cleavage of the osteocyte-derived, phosphate-regulating hormone fibroblast growth factor 23 (FGF23), a risk factor for premature mortality. To date, clinical implications of iron deficiency and high EPO levels in the general population, and the potential downstream role of FGF23, are unclear. Therefore, we aimed to determine the associations between iron deficiency and higher EPO levels with mortality, and the potential mediating role of FGF23, in a cohort of community-dwelling subjects.Methods and findingsWe analyzed 6,544 community-dwelling subjects (age 53 ± 12 years; 50% males) who participated in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study—a prospective population-based cohort study, of which we used the second survey (2001–2003)—and follow-up was performed for a median of 8 years. We measured circulating parameters of iron status, EPO levels, and plasma total FGF23 levels. Our primary outcome was all-cause mortality. In multivariable linear regression analyses, ferritin (ß = –0.43), transferrin saturation (TSAT) (ß = −0.17), hepcidin (ß = −0.36), soluble transferrin receptor (sTfR; ß = 0.33), and EPO (ß = 0.28) were associated with FGF23 level, independent of potential confounders. During median (interquartile range [IQR]) follow-up of 8.2 (7.7–8.8) years, 379 (6%) subjects died. In multivariable Cox regression analyses, lower levels of TSAT (hazard ratio [HR] per 1 standard deviation [SD], 0.84; 95% confidence interval [CI], 0.75–0.95; P = 0.004) and higher levels of sTfR (HR, 1.15; 95% CI 1.03–1.28; P = 0.01), EPO (HR, 1.17; 95% CI 1.05–1.29; P = 0.004), and FGF23 (HR, 1.20; 95% CI 1.10–1.32; P < 0.001) were each significantly associated with an increased risk of death, independent of potential confounders. Adjustment for FGF23 levels markedly attenuated the associations of TSAT (HR, 0.89; 95% CI 0.78–1.01; P = 0.06), sTfR (HR, 1.08; 95% CI 0.96–1.20; P = 0.19), and EPO (HR, 1.10; 95% CI 0.99–1.22; P = 0.08) with mortality. FGF23 remained associated with mortality (HR, 1.15; 95% CI 1.04–1.27; P = 0.008) after adjustment for TSAT, sTfR, and EPO levels. Mediation analysis indicated that FGF23 explained 31% of the association between TSAT and mortality; similarly, FGF23 explained 32% of the association between sTfR and mortality and 48% of the association between EPO and mortality (indirect effect P < 0.05 for all analyses). The main limitations of this study were the observational study design and the absence of data on intact FGF23 (iFGF23), precluding us from discerning whether the current results are attributable to an increase in iFGF23 or in C-terminal FGF23 fragments.Conclusions and relevanceIn this study, we found that functional iron deficiency and higher EPO levels were each associated with an increased risk of death in the general population. Our findings suggest that FGF23 could be involved in the association between functional iron deficiency and increased EPO levels and death. Investigation of strategies aimed at correcting iron deficiency and reducing FGF23 levels is warranted.

PS1299 SOLUBLE TRANSFERRIN RECEPTOR AND ITS FERRITIN INDEX IN COMPARISON WITH BIOCHEMICAL AND HEMATOLOGICAL PARAMETERS FOR THE DIFFERENTIATION OF ANEMIA STATES AND CORRELATION WITH IV IRON RESPONSE

Background:Soluble transferrin receptor (sTfR) increases in iron deficiency (ID), and is used as biomarker of tissue ID and bone marrow demand for iron. Iron‐deficient erythropoiesis is the most common cause of elevated sTfR. The sTfR is not significantly influenced by infection or inflammation and appears a useful marker in the differentiation of iron states in anemia. The sTfR/log10ferritin index (sTfR/logFerr) is directly proportional to the measurement of the functional and storage iron compartments and seems to fully assess body iron status. Hematological indices of hypochromia indicate impaired hemoglobin synthesis due to restricted iron delivery to erythrocyte precursors. Iron restriction to erythropoiesis is a common mechanism in iron deficiency anemia (IDA) and iron sequestration accompanying to some extent anemia of inflammation and chronic diseases (AICD). In combination with sTfR, hematological indices and other parameters of ID could provide evidence of increased bone marrow iron demand and iron‐restricted erythropoiesis (IRE), that may benefit from iv iron treatment, and help to avoid unnecessary iron therapy.Aims:The aim of this study was to assess correlation between sTfR and biochemical markers of iron status and hematological indices in patients with anemia states and low serum iron, referred to our Clinic for treatment, and to investigate the association of baseline sTfR and sTfR/logFerr index with iron response.Methods:Patients over 18 years were prospectively recruited and after clinical history and examination, blood tests including hematological indices and biochemical markers were performed. Diagnostic investigations and iv iron supplementation were prescribed as appropriate. Patients were classified as: iron deficiency anemia (IDA), anemia of inflammation and chronic disease (AICD), or the combined state of IRE with AICD (IRE/AICD) using clinical findings, traditional biochemical parameters and red cell indices. To determine the iron response, the full blood count was repeated at 7 and 14 days. Serum concentration of sTfR was measured via chemiluminescent immunoassay (Access1 sTfR immunoassay system, Beckman Coulter), a new routine parameter in our laboratory, and sTfR/logFerr index was calculated.Results:The sTfR immunoassay proved a good analytical reliability. The characteristics of the patients classified in the 3 types of anaemia are shown in a table. Numbers are given as median (10–90 percentiles).Soluble transferrin receptor concentrations and sTfR/logFerr correlated significantly with mean corpuscular hemoglobin (MCH). Level of sTfR was more than 2.1 mg/l (ULN) in 32 of 35 patients with IDA, in 12 of 16 patients with IRE/AICD, and in 7 of 30 patients with AICD. Calculated sTfR/logFerr was more than 2 in 31 of 35 patients with IDA and only in 3 of 16 patients with IRE/AICD and 1 patient with AICD. There were moderate correlations between sTfR and other anemia parameters (Hb, MCV, CHr, transferrin, TSAT), but low linear association with serum ferritin and no association with CRP was found. From 57 patients treated with iv iron, 37 responded (increase of Hb&gt;10 g/l by 2 weeks) and 20 failed to achieve an adequate increase of hemoglobin. There was correlation between iron response and sTfR and sTfR/logFerr index.Summary/Conclusion:A negative strong correlation exists between sTfR and MCH. The majority of patients had impaired hemoglobin synthesis and correspondingly high sTfR concentrations. The increased sTfR and sTfR/logFerr index correlated with subsequent iv iron response in the anemic patients and may provide help in their therapeutic management.image

Serum Soluble Transferrin Receptor-Ferritin Indices in Diagnosing and Differentiating Iron Deficiency Anemia from Anemia of Chronic Disease among Patients with Chronic Kidney Disease

Background: Anemia is common in patients with chronic kidney disease (CKD) and this is generally anemia of chronic disease (ACD), but iron deficiency anemia (IDA) is also common. Soluble transferrin receptor (sTfR) is a useful marker for IDA. Present study was undertaken to assess the utility of sTfR as a marker of IDA and to differentiate ACD from IDA in selected group of Bangladeshi patients with CKD.&#x0D; Methods: This cross-sectional study was conducted in the Department of Nephrology, BSMMU, Dhaka, Bangladesh from January 2013 to December 2014. Patients with anemia admitted in Nephrology Department, whether on hemodialysis or not and Medicine Department of BSMMU were taken for study. The study population was further divided into two groups; Group A, patients (30) who were having IDA and Group B, patients (40) with ACD and a control group was also selected. Data were collected by face to face interview and laboratory investigations with a self-administered questionnaire.&#x0D; Results: The mean age of the patients in Group A and Group B were 38.40±13.23 and 34.85±10.52 years respectively and male-female ratio were 0.5:1 and 1:0.5. Mean sTfR level was higher (4.81± 1.64 μg/ml) in patients with IDA than (2.89±1.40 μg/ml) in patients with ACD (p &lt;0.0001). Mean ferritin level was 599.59± 449.15μg/L in ACD patients whereas 101.23±119.42 in IDA patients (p&lt;0.0001). Total iron binding capacity (TIBC) was more in ACD patients with sTfRe”3μg/ml as compared to ACD patients with sTfR&lt;3μg/ml. Transferrin saturation (TSAT) level was significantly decreased in ACD patients with sTfRe”3μg/ml as compared to ACD patients with sTfR&lt;3μg/ml. sTfR and ferritin indices between group A (IDA) and group B (ACD) shows mean sTfR:logSF level was significantly (P&lt;0.001) high in group A (2.71±1.13) in comparison to group B (1.08±0.54). Mean log sTFR:SF was also significantly higher (P&lt;0.05) in group A (0.001±0.0008) compared to group B (0.013±0.012).&#x0D; Conclusion: sTfR level has a comparable ability to serum ferritin in diagnosing IDA and ACD. However, sTfR and serum ferritin alone cannot definitely exclude coexisting iron deficiency in ACD. Log sTfR/ ferritin index has role in identifying development of iron deficiency in ACD whereas sTfR/ log SF ratio can differentiate pure IDA from ACD with or without iron deficiency. Thus, it is important to estimate both serum sTfR and sTfRferritin indices to be able to differentiate pure IDA, ACD and ACD with co-existing iron deficiency thus providing a non-invasive alternative to bone marrow iron.&#x0D; Birdem Med J 2019; 9(2): 151-156

Iron metabolism and its association with dyslipidemia risk in children and adolescents: a cross-sectional study

BackgroundInformation on the association between iron metabolism and dyslipidaemia in children is limited. Thus, this study aims to evaluate the iron metabolic status of children with different body mass index (BMI) and to examine the association between iron metabolism and dyslipidaemia risk.MethodIn total, 1866 children and adolescents aged 7–18 were enrolled in this study, including 912 boys and 954 girls. In this cross-sectional study, parameters for anthropometry, lipids and iron metabolism including transferrin, soluble transferrin receptor (sTfR), ferritin and serum iron (SF) were evaluated. Data regarding demographic characteristics, diet, and physical activity were collected by self-reported questionnaires.ResultsThe prevalence of dyslipidaemia and iron deficiency in children and adolescents increased based on BMI categories (both P < 0.05) and were 58.3 and 8.9% in subjects with obesity, respectively. The lowest SF and the highest ferritin levels were observed in subjects who were obese (both P < 0.001). Subjects with dyslipidaemia had lower SF, transferrin and sTfR levels by different BMI categories, and those who were obese had higher ferritin levels (all P < 0.05). Most importantly, higher concentrations of transferrin and sTfR were related to lower dyslipidaemia risk (OR for transferrin: 0.49, 95% CI: 0.33–0.71; OR for sTfR: 0.68, 95% CI: 0.46–0.99).ConclusionsA downward trend in SF level by BMI categories and the highest ferritin level in subjects with obesity suggested that iron storage was associated with BMI in children and adolescents. Moreover, an inverse relationship was observed between transferrin and sTfR concentrations and dyslipidaemia risk in children with different BMI.

Erythropoiesis and Iron Homeostasis in Non-Transfusion-Dependent Thalassemia Patients with Extramedullary Hematopoiesis.

Background Extramedullary hematopoiesis (EMH) is common in non-transfusion-dependent thalassemia (NTDT) patients. Clinical presentations of EMH vary as MRI screening is not feasible. Hence, serum biomarkers are used to predict the risk of EMH. Materials and Methods 52 NTDT patients, including 26 EMH (+) and 26 EMH (-), together with 26 healthy controls, were enrolled in this case-control study from 2013 to 2016. EMH was confirmed by computed tomography or MRI. Demographic, transfusion, genetic, laboratory, and liver iron concentration (LIC) data, as well as clinical complications, were analyzed. Results EMH (+) patients had significantly higher serum ferritin (SF), growth differentiation factor 15 (GDF15), and erythropoietin (EPO) levels compared with EMH (-) patients and controls. The levels of erythroferrone (ERFE), hepcidin, and sTfR did not differ significantly between EMH (+) and EMH (-) patients (p>0.05). In NTDT patients, serum ERFE was not related to SF, LIC, hepcidin, sTfR, EPO, GDF15, and Hb levels. GDF15, EPO concentrations, and GDF15 to sTfR and GDF15 to EPO ratios are able to determine the presence of EMH with considerable sensitivity and specificity. Conclusions GDF15, EPO, and GDF15 to EPO and GDF15 to sTfR ratios are potential biomarkers for the early prediction of NTDT in patients who are at risk for EMH.

Cognitive function observation and clinical features of 100 cases of elderly patients with non-alcoholic fatty liver disease

Objective To observe the changes of cognitive function, clinical characteristics and hippocampal structure in elderly patients with non-alcoholic fatty liver disease (NAFLD). Methods From December 2014 to June 2016, at Department of Geriatrics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 169 elderly hospitalized patients who underwent health checkups were enrolled and divided into NAFLD group and non-NAFLD group. The clinical data of two groups were collected, and the Montreal cognitive assessment scale (MoCA) was used for cognitive function assessment. The serum level of soluble transferrin receptor (sTfR) was detected, the liver-spleen ratio was measured and hippocampal proton magnetic resonance spectroscopy (1H-MRS) was performed. T test and linear regression analysis were used for statistical analysis. Results Among the 169 elderly patients, 100 were NAFLD and 69 were non-NAFLD. The body mass index(BMI) and waist-to-hip ratio(WHR)of patients in NAFLD group were (25.9±3.4) kg/m2 and 1.03±0.13, respectively, which were higher than those in non-NAFLD group ((24.2±3.7) kg/m2 and 0.95±0.06), and the differences were statistically significant (t=-2.714 and -3.605, both P<0.01). MoCA score of the patients in NAFLD group was 20.1±5.8, which was lower than that in non-NAFLD group (22.1±4.4), and the difference was statistically significant(t=2.154, P=0.033). The serum sTfR level and liver-spleen computed tomography(CT) ratio of NAFLD group were (8.78±4.31) mg/L and 0.97±0.12, respectively, which were lower than those of non-NAFLD group ((12.66±3.93) mg/L and 1.19±0.15), and the differences were statistically significant(t=3.765 and 6.142, both P<0.01). The CT ratio of liver to spleen (β=7.597, 95% confidence interval(CI): 2.938 to 12.935) and sTfR (β= 0.552, 95%CI: 0.304 to 0.787) were positively correlated with cognitive function in elderly patients (both P<0.01). The height of right hippocampus of NAFLD group was (0.410±0.074) mm, which was lower than that of non-NAFLD group ((0.453±0.086) mm), and the difference was statistically significant (t=2.078, P=0.042). Conclusion Cognitive impairment in elderly NAFLD patients is closely related to iron load and liver fat. Key words: Cognition; Non-alcoholic fatty liver disease; Soluble transferrin receptor; Proton magnetic resonance spectroscopy

Effect of intense physical exercise on hepcidin levels and selected parameters of iron metabolism in two different trial of training

Summary Research question The aim of the study was to analyse changes in selected pro-inflammatory cytokines and parameters of iron metabolism, observed after an intense ergometric test conducted during two different phases of a yearly training cycle. Research methods The study included a group of elite rowers (n = 15). During each of the analysed training phases, the athletes were subjected to a 2000-m ergometric exercise test. Results and findings Irrespective of the training phase, similar levels of IL-6, hepcidin and sTfR were found in blood samples collected immediately after the ergometric tests. In contrast, post-exercise levels of Fe, TNF-α and CK were significantly higher in material collected after the test conducted during the competitive phase of a yearly training cycle. This study of elite rowers showed that physical exercise may stimulate changes in the pro-inflammatory profile of blood serum, via the influence on TNF-α levels. This effect is modulated by a number of training-related factors that acted prior to the ergometric test, such as exercise frequency and intensity. Implications Therefore, post-training adaptation to physical exercise is not always sufficient, which may result in the impairment of the immune response and thus negatively affect iron metabolism.

Hepcidin and diabetes are independently related with soluble transferrin receptor levels in chronic dialysis patients

Background: Soluble transferrin receptor (sTfR) is a biomarker of erythropoiesis, which is often impaired in dialysis patients. The aim of our study was to evaluate sTfR levels in chronically dialyzed patients and assess potential determinants of its levels.Methods: We performed a cross-sectional study by evaluating 246 end-stage renal disease patients undergoing dialysis and 32 healthy controls. Circulating levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, hepcidin, sTfR, growth differentiation factor 15 (GDF15), and traditional iron metabolism markers were measured, as well as hemogram parameters. Clinical data was obtained from all patients.Results: Compared to controls, patients presented similar values of sTfR, reticulocytes and reticulocyte production index (RPI), and significantly higher levels of IL-6, CRP, ferritin, hepcidin, TNF-α, and GDF15. Iron, transferrin, hemoglobin levels, erythrocyte count, mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) values were significantly lower in dialysis group. Within patients, sTfR values were higher in diabetic patients and were positively and significantly correlated with reticulocytes and erythrocytes, RPI, and therapeutic doses of erythropoiesis stimulating agents (ESA) and intravenous iron; and inversely and significantly correlated with circulating iron, ferritin, transferrin saturation, hepcidin, MCH, and MCHC. In multiple linear regression analysis, ESA dose, RPI, serum iron, diabetes, and hepcidin levels were independently associated with sTfR levels in dialysis patients and, thus, with erythropoiesis.Conclusion: Our data suggest that, besides RPI and ESA dose, diabetes and hepcidin are closely related to erythropoiesis in dialysis patients. The influence of diabetes on sTfR levels deserves further investigation.

Alterations in the Iron Homeostasis Network of Hepatocytes Caused by Hepatitis B Virus.

It is unclear whether hepatitis B virus (HBV) itself causes iron metabolism disorder in patients with chronic hepatitis B (CHB). In this study, we investigated the effect of HBV on iron metabolism at the clinical and cellular levels to determine the pathogenesis of CHB. We enrolled 41 CHB patients and 20 healthy controls (HCs) in a retrospective study. Parameters of iron status included serum iron (SI), ferritin (SF), transferrin (TRF), soluble transferrin receptor (sTfR), transferrin saturation (TS), total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC), and hepcidin. Liver function indicators included serum alanine transaminase (ALT) and albumin. Furthermore, we investigated the correlations between iron markers and liver function indicators. Finally, the alterations in SF, TRF, transferrin receptor (TfR), and hepcidin expression were detected by RT-PCR, western blot, and cell immunofluorescence after HepG2 cells and Huh7 cells were transfected with the pSM2-HBV plasmid. We also measured these alterations between HepG2 cells and HepG2.215 cells. The significance of differences was analyzed by SPSS version 17.0. Compared with healthy controls, the CHB patients were more likely to have lower levels of serum hepcidin, TRF, sTfR, TIBC, and UIBC and higher levels of SI, SF, and TS (p < 0.05, all). In CHB patients, the levels of SI and SF correlated positively with ALT concentrations, and the serum hepcidin concentrations correlated positively with albumin concentrations (p < 0.05, all). The expression levels of ferritin, transferrin, and hepcidin mRNA and protein were significantly higher in HepG2.215 cells than in HepG2 cells, while expression levels of TfR were lower. The alterations in these iron markers in HepG2 and Huh7 cells that were transfected with pSM2-HBV plasmid were consistent with those in HepG2.215 cells. Serum iron markers tended to be abnormal in CHB patients. In hepatocytes, HBV promoted the expression of ferritin, transferrin, and hepcidin, while it inhibited the expression of TfR.

Anemia of Chronic Disease: Key Mechanisms of Pathogenesis in Patients with Malignancies and Feasible Classification Approaches

Aim. To study the effect of hepcidin, soluble transferrin receptor (sTfR), and cytokines on iron metabolism and occurrence of anemia in patients with malignancies and to propose, on this basis, a draft classification of anemia of chronic disease (ACD) based on the major pathogenic factor. Materials &amp; Methods. The trial included 63 patients with malignancies of stage II/IV: 41 patients with anemia (34 men, 7 women, mean age 67.1 ± 9.9 years), 22 patients without anemia (17 men, 5 women, mean age 60.2 ± 14.9 years). Comparative analysis was based on the values of iron metabolism, C-reactive protein (CRP), hepcidin, sTfR, as well as pro-inflammatory (interleukin-6 [IL-6], tumour necrosis factor α [TNF-α]) and anti-inflammatory (IL-10) cytokines in solid malignancy patients with and without anemia. The correlation analysis between IL-6, IL-10, TNF-α, hepcidin, sTfR, and blood count was performed. Results. Compared with the control group patients with anemia show lower levels of iron concentration, total iron-binding capacity (TIBC), and percent transferrin saturation (TSAT), as well as higher level of CRP, hepcidin, sTfR, IL-6, IL-10, and TNF-α (p &lt; 0.05). IL-6 (r = -0.58), TNF-α (r = -0.32), and hepcidin (r = -0.57) proved to negatively affect erythrocyte level. A negative correlation was established between hemoglobin concentration and IL-6 (r = -0.57), IL-10 (r = -0.64), TNF-α (r = -0.65), hepcidin (r = -0.3), and sTfR (r = -0.57). A correlation was identified between concentrations of hepcidin and IL-6 (r = 0.58), IL-10 (r = 0.33), TNF-α (r = -0.4), as well as between concentrations of sTfR and IL-10 (r = 0.58), TNF-α (r = -0.53). A relationship was identified between IL-6 concentration and iron status (r = -0.38), TIBC (r = -0.56), TSAT (r = -0.31), ferritin (г = 0.56), transferrin (r = -0.72), CRP (r = 0.86) as well as between concentrations of IL-10 and iron (r = -0.63), TSAT (r = -0.67), transferrin (r = -0.7), ferritin (r = 0.55), CRP (r = 0.65), TIBC (r = -0.71). A correlation between the levels of TNF-α and TIBC (r = -0.36), transferrin (r = -0.5) was confirmed. Conclusion. The paper deals with multi-factorial pathogenesis of anemia in patients with malignancies. Most important factors are iron deficiency and erythropoietic disorder. A draft ACD classification based on the major pathogenic factor of anemia (ACD with dominating iron deficiency, ACD with impaired regulatory mechanism of erythropoiesis, and ACD with insufficient erythropoietin production) is proposed.

Evaluation of Iron Status in Patients of Chronic Kidney Disease - A Study to Assess the Best Indicators Including Serum Transferrin Receptor Assay.

Anemia is an early complication of chronic kidney disease (CKD). The iron deficiency is an important contributor, more so in the Indian population. As routine standalone iron tests do not accurately reflect the actual status in the complex environment of CKD, there is a need to study better indicators. Serum iron, ferritin, total iron-binding capacity (TIBC), and serum transferrin receptor (sTfR) levels were estimated in 100 primary iron deficiency anemia (IDA) patients (controls-Group 1) and 68 newly diagnosed CKD cases. The CKD patients were divided into two groups: Serum ferritin <=100 μg/L (Group 2) and >100 μg/L (Group 3). The values of percentage saturation, log of ferritin (log_ferritin), and the ratio of sTfR to log ferritin (sTfR/log_f or sTfR index) were calculated. The CKD cases were further divided depending on ferritin cut-offs of 30, 50, 70, and 100 μg/L and statistically analyzed including ROC and AUC, to choose the best diagnostic parameter for accurate assessment of iron status in CKD cases. The mean serum ferritin was 11.34 μg/L, 28.70 μg/L, and 281.81 μg/L, and the mean sTfR was 2.34 μg/ml, 1.82 μg/ml, and 1.28 μg/ml in Groups 1, 2, and 3. Among all groups, the difference was found to be significant for serum iron, log_ferritin, and sTfR/log_f. The sTfR and sTfR/log_f showed good discrimination between IDA and Anemia of chronic disease in CKD cases, but sTfR/log_f gave the best discrimination at all cut-off levels of ferritin. At a ferritin cut-off of 50 μg/L, the sTfR/log_f value of 0.83 had a sensitivity of 93.5% and specificity of 95.45%, and at a ferritin cut-off 100 μg/L, the same value of 0.83 had a sensitivity of 95.5% and specificity of 86.5%. The ratio of sTfR/log_f is the best indicator for assessing iron status in CKD.

Expression Changes of Serum Transferrin Receptor and Its Mechanism in Children with Acute Leukemia

To investigate the expression changes of serum transferrin receptor（sTFR） and its related mechanism in children with acute leukemia（AL）. Forty-six children with acute leukemia treated in our hospital from June 2016 to June 2017 were selected and enrolled in the AL group, 40 healthy children were enrolled in the control group. The related clinical data were recorded, including age, sex and CNSL level. RNA interference technology was used to silence TFR genes of KG-1a and TCHu147 cells, MTT method and flow cytometry were used to analyze the effect of TFR gene on proliferation and cell cycle of KG-1a cells and TCHu147 cells. Western blot was used to detect the level of cyclin related to leukemic cells after siRNA interference. The level of sTFR in AL patients was significantly higher than that of healthy people (P<0.05). The mRNA and protein expression levels of TFR in peripheral blood leukemic cells were all higher than those in healthy people (P<0.05). The level of sTFR closely related to the white blood cell（WBC） count, the proportion and absolute number of leukemic cells, hepcidin（Hepc） level, and risk grade in AL patients (P<0.05). The proliferation ability of KG-1a and TCHu147 cells after TFR siRNA interference was significantly inhibited (P<0.05). Fow cytometry showed that after the TFR siRNA interference, the ratio of KG-1a and TCHu147 cells in G0/G1 phase was 62.51%±5.39% and 63.37%±4.27%, respectively, which increased significantly as compared with the blank and negative control group (P<0.05); the ratio of KG-1a and TCHu147 in G2/M phase was 5.74%±1.34% and 7.37%±1.56%, respectively, which significantly decreased as compared with the blank control and the negative control group (P<0.05). The peripheral blood leukemic cells of AL patients can synthesize more TFR protein, lead into the increase of sTFR level. It can effectively interfere the division of leukemia cells by downregulating the expression of TFR gene.