Serum Transferrin Concentrations Research Articles

Serum transferrin concentration: a new prognostic biomarker in heart failure with reduced ejection fraction

Abstract Introduction Iron deficiency (ID) is a common comorbidity in patients with reduced heart failure (HFrEF), and is associated with poor clinical status and outcomes, but there is not enough data investigating serum transferrin concentration (STC) as a biomarker HFrEF to predict prognosis and mortality. Purpose We investigated relationship between STC at admission and all-cause mortality during follow-up in HFrEF. Methods We reviewed the medical data of 420 patients hospitalised in our institution for HFrEF over a period of 18 months. Laboratory tests were performed on the first 24 hours of admission. Patients were divided into two groups according to STC, using the value of 199 μg/dl as the cut-off. This value was determined from the ROC analysis to be the value with the highest sensitivity and specificity. Then we analysed relationship between STC at admission and all-cause mortality during follow-up between the two groups, after adjustment of the various variables described in the literature. Results Of 420 patients with HFrEF, 18.6% had STC ≤ 199 μg/dl (group 1) and 81.4% had STC > 199 μg/dl (group 2) with no difference in age and sex distribution (p = 0.873 ; p = 0.304). Patients with low STC were more likely to be diabetic (70.5% vs 46.5% ; p < 0.001), have dyslipidemia (52.6% vs 33%; p = 0.002), and history of chronic renal failure (6.4% vs 2.0% ; p = 0.045). There was no relation between STC and NYHA class (p = 0.776), hospital stay (p = 0.491) nor EF (p = 0.146). Biologically, lower STC was significantly associated with higher serum ferritin (292.77 vs 198.17 ; p < 0.001), TSAT (68.30 vs 22.21 ; p = 0.020) and C-reactive protein (CRP) (124.91 vs 39.98 ; p = < 0.001), lower plasma B-type natriuretic peptide (BNP) (5798.32 vs 6449.97 ; p = 0.002), with no difference in haemoglobin level (p = 0.272) and estimated glomerular filtration rate (eGFR) (p = 0.260). The prevalence of iron deficiency by the ESC criteria was lower in those with low STC; ferritin < 100 μg/l (15.4% vs 29.2% ; p = 0.015) or TSAT < 20% (33.3% vs 51,8% ; p = 0.004). There was no difference between the two groups in term of NYHA class and EF at three months (p = 0.87, p = 0.108). However, all-cause mortality during follow-up was significantly associated with low STC (37.2% vs 17.0% ; p <0.001). (Figure 1) In multivariable analysis, all-cause mortality was independently associated with STC ≤ 199 μg/dl (HR 1.71; 95% CI : 1.08 ; 2.7 ; p = 0.02). This is the same finding for the ischaemic origin of HFrEF (HR 2.1 ; p = 0.001), therapeutic inertia during follow-up (HR 5.53 ; p <0.001) and EF < 36% (HR 1.03 ; p = 0.047) (Figure 2). Conclusion More data are required before the routine use of STC as a biomarker of prognosis in HFrEF, but it may represent a reliable and cost-effective option to predict mortality.FIGURE 1FIGURE 2

Iron-Status Indicators and HFE Gene Polymorphisms in Individuals with Amyotrophic Lateral Sclerosis: An Umbrella Review of Meta-analyses and Systematic Reviews.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Recent meta-analyses and systematic reviews suggest that HFE gene polymorphisms and iron-associated biomarkers may play a key role in the risk and occurrence of ALS. This umbrella study aimed to explore the roles of HFE gene polymorphisms and iron-associated biomarkers in individuals with ALS. A thorough search of three online scientific databases, namely Scopus, Web of Science, and PubMed, was conducted from their inception until September 13, 2024. The screening and selection processes were executed based on the PICO framework and eligibility criteria, followed by two independent reviewers. The Assessment of Multiple Systematic Reviews (AMSTAR)-2 and GRADE tools were utilized to assess the methodological quality and the certainty of evidence. Through an advanced search, 101 records were retrieved, of which eight meta-analyses and systematic reviews were selected for this umbrella review. A significant increase in iron concentrations was found in individuals with ALS compared to healthy controls (SMD, 0.26; 95% CI - 0.05, 0.57). Conversely, selected meta-analyses reported that serum transferrin concentrations in ALS patients were lower compared to healthy controls (SMD, - 0.15; 95% CI - 0.36, 0.05). Furthermore, mutations in H63D polymorphisms resulted in a 13% significant increase in the risk of ALS (OR, 1.13; 95% CI 1.05, 1.22). Our umbrella study of meta-analyses and systematic reviews reveals that individuals with ALS have lower serum concentrations of transferrin compared to healthy controls. Additionally, the H63D polymorphism in the HFE gene is associated with a slight increase in the risk of ALS. Future research should investigate broader aspects of iron-related biomarkers and HFE genes to elucidate their roles in ALS pathogenesis. Registration: Our umbrella study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42024559032 ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024559032 ).

Correlation between iron metabolism indicators and programmed death ligand 1 expression in advanced non-small cell lung cancer.

The dysregulation of iron metabolism is closely linked to the onset and progression of lung cancer. This study aimed to explore the association between iron metabolism indicators (serum iron, transferrin, ferritin) and the expression level of programmed death factor ligand 1 in primary lesions of advanced non-small cell lung cancer. A cohort of 62 patients, including 42 men and 20 women, was recruited from October 2022 to July 2023, all diagnosed with advanced non-small cell lung cancer, confirmed through radiographic imaging and histopathological analysis. Comprehensive clinical data (such as gender, age, familial lung cancer history, smoking history, pathological classification, clinical stage, etc.) and concentrations of fasting serum iron, transferrin, and ferritin were collected. Patients were categorized into PD-L1 negative (<1% expression) and programmed death ligand 1 (PD-L1) positive (≥1% expression) groups based on PD-L1 expression levels in tumor tissues. Subsequently, the correlation between levels of serum iron, transferrin, ferritin, and PD-L1 expression in advanced non-small cell lung cancer were examined. Patients in the PD-L1 positive group exhibited lower levels of peripheral serum iron and transferrin compared to those in the PD-L1 negative group (P<0.05). For patients exhibiting positive PD-L1 expression, a negative correlation was observed between PD-L1 expression and both serum iron and transferrin levels (r = -0.465, P=0.003; r = -0.447, P=0.005), and a positive correlation was noted between PD-L1 expression and ferritin levels (r=0.393, P=0.015). We conclude that in In patients with advanced non-small cell lung cancer, serum iron and transferrin levels can serve as partial predictors of PD-L1 expression; among those positive for PD-L1, a significant association exists between indicators of iron metabolism and PD-L1 expression.

Cohort-Based Reference Values for Serum Ferritin and Transferrin and Longitudinal Determinants of Iron Status in European Children Aged 3–15 Years

BackgroundReference values of ferritin and transferrin for European children do not exist. ObjectiveWe aimed to provide sex-, age-, and body mass index (BMI)-specific serum ferritin and transferrin reference percentiles of 3–15-y-old children based on cohort data and to investigate determinants of iron status. MethodsA total of 3390 ferritin and 3416 transferrin measurements from children residing in 8 European countries participating in the IDEFICS/I.Family cohort (https://www.isrctn.com/ISRCTN62310987) at baseline (W0) and 6 y later (W3) were used to estimate percentiles using the generalized additive model for location, scale and shape. Associations of serum ferritin and transferrin concentrations with total iron intake, total iron intake additionally adjusted for vitamin C intake, and iron from heme sources were investigated separately with adjustment for sex, age, country of residence, parental education, usual energy intake and BMI z-score in regression models using cross-sectional and longitudinal data. ResultsThe age-specific ferritin and transferrin 5th and 95th reference percentiles ranged from 10.9 to 81.1 μg/L and 2.23 to 3.56 g/L, respectively. A deficient iron status was observed in 3% of children at W0 and 7% of children and adolescents at W3, respectively. At both waves, a higher iron intake from heme sources was positively associated with serum ferritin {W0: β = 3.21 [95% confidence interval (CI): 0.71, 5.71]; W3: β = 4.48 [95% CI: 2.09, 6.87]}, that is, children consuming one mg more heme iron had a 3.21 and 4.48 μg/L higher ferritin concentration. Adherence to a mainly vegetarian diet was associated with a lower chance for sufficient serum ferritin cross-sectionally at W3 [odds ratio (OR) 0.40 (95% CI: 0.21, 0.81)] and longitudinally [OR 0.35 (95% CI: 0.15, 0.93)]. ConclusionsAge-, sex-, and BMI-specific reference percentiles of serum ferritin and transferrin concentrations based on cohort data are provided for European children aged 3–15 y and may be used in clinical practice.

Treatment of Congenital Hypotransferrinemia Patients with Human Apotransferrin Resolves Anemia and Reduces Iron Accumulation

Introduction Congenital hypotransferrinemia is a very rare inherited and life-threatening disorder (MIM#209300) characterized by systemic iron overload and anemia. The deficiency of serum transferrin leads to inadequate iron supply to erythroid bone marrow, resulting in microcytic hypochromic anemia. This triggers hepcidin downregulation, causing increased iron absorption and production of non-transferrin bound iron (NTBI), leading to iron overload in various organs and tissues. Currently, there is no targeted therapy for this disease. Method In an open-label phase II/III study, four children (age 0-7 years) and one adult (20 years) with congenital hypotransferrinaemia were treated with purified plasma-fractionated human apotransferrin for nearly 10 years. All patients received an initial intravenous dose of 75 mg/kg every 8 weeks for 6 months, followed by 75 mg/kg every 4 weeks for additional 6 months, and in the subsequent years apotransferrin was administered every 4 weeks but the dose was adjusted to 75-150 mg/kg based on clinical judgement of physician according to patient condition. Prior to the start of the study two patients already received replacement therapy, i.e., human apotransferrin or plasma. Serum transferrin and serum iron were determined before every infusion. Primary objective was to investigate the effect of apotransferrin treatment on anemia and iron overload. Hemoglobin, hematocrit, and erythrocytes as markers of anemia were measured every 8 weeks. Iron overload was monitored by measuring serum ferritin every 8 weeks and yearly iron quantification in liver and heart through MRI. Labile Plasma Iron (LPI) was measured before and after infusion (starting after 2 years of treatment). The need for additional treatment for anemia or iron overload was defined as a secondary outcome. Safety and clinical tolerance were evaluated by adverse event surveillance and laboratory measurements. Results Baseline serum transferrin levels were significantly below the normal range in all patients (&amp;lt;10-189 mg/L; normal range: 1800-3500 mg/L). Treatment with human apotransferrin increased serum transferrin and serum iron levels in all patients. Fifteen minutes after the first infusion, transferrin levels ranged from 1340-2415 mg/L, but declined to values just above baseline before the next infusion (dosing interval 8 weeks). During the study period serum transferrin concentrations were affected by dose adjustments; however, trough levels of transferrin remained below the normal range throughout the study (range 200-800 mg/L). Despite subnormal trough levels, apotransferrin infusion led to rapid increase of hemoglobin (Figure 1), hematocrit, and erythrocyte levels up to normal values. The two patients who were already treated before the study, showed normal levels at baseline that were maintained. In all patients hematologic parameters remained stable throughout the study. Ferritin levels were elevated at baseline and decreased to normal ranges in 1.2 to 7.3 years, with a maximum decrease ranging from 82% to 97% of baseline. MRI examinations revealed liver iron overload at baseline which normalized in all patients after apotransferrin treatment, in most cases after 3 to 4 years (Figure 2). No myocardial iron overload was observed at baseline and during the follow-up. Pre-infusion LPI was found in all five patients, however in three patients the values were undetectable on most occasions. Immediately after infusion with apotransferrin, in none of the patients LPI was present anymore. Throughout the study no additional use of plasma/blood products or iron chelators was needed. Apotransferrin infusions were well tolerated. No serious adverse events were reported. No loss of clinical response to treatment was detected over time. Conclusion Treatment with human apotransferrin in patients with congenital hypotransferrinemia demonstrated good long-term clinical efficacy. Apotransferrin infusions increased hematopoiesis, reduced iron overload in organs, and eliminated the need for additional medication. The therapy was well-tolerated and showed good clinical safety. Human apotransferrin holds promise as the mainstay treatment option for congenital hypotransferrinemia.

The Effect of a Six-Week Nordic Walking Training Cycle on Oxidative Damage of Macromolecules and Iron Metabolism in Older Patients with Multiple Myeloma in Remission-Randomized Clinical Trial.

Multiple myeloma (MM) is an incurable hematologic malignancy originating from clonal plasma cell proliferation within the bone marrow, predominantly affecting older individuals. While anemia serves as a diagnostic criterion for MM, it often ameliorates upon achieving disease remission. Iron metabolism parameters have emerged as potential prognostic indicators in MM. Notably, physical exercise has been established to influence iron metabolism. This study aimed to assess alterations in serum iron, ferritin, and transferrin concentrations, as well as leukocyte gene expression, in MM patients undergoing a six-week cycle of Nordic walking training. Thirty patients divided into an exercise group (NW, n = 15, mean age 63.1 ± 8.4 years) and a control group (CG, n = 15, mean age: 63.5 ± 3.6 years) completed the study protocol. Blood samples were collected at baseline, after three and six weeks of training, and after nine weeks. Serum ferritin, transferrin, and iron concentrations were measured, along with the leukocyte expression of genes. Additionally, serum oxidative damage marker levels were determined. Following the Nordic walking training cycle, a declining trend in serum ferritin concentrations was observed. Intracellular mRNA levels of genes associated with iron metabolism were positively influenced by the training regimen, indicating the potential impact of this physical activity on gene expression and ferritin concentrations. Although positive trends were noted, extended training periods might be requisite for significant changes. To conclude, moderate-intensity exercise induces favorable shifts in the analyzed parameters among MM patients, potentially influencing disease progression. Consequently, Nordic walking training is a safe recommendation for MM patients, though sustained training beyond six weeks could be necessary for notable effects on iron metabolism factors.

Rusfertide for the treatment of iron overload in HFE-related haemochromatosis: an open-label, multicentre, proof-of-concept phase 2 trial

Hereditary haemochromatosis protein (HFE)-related haemochromatosis, an inherited iron overload disorder caused by insufficient hepcidin production, results in excessive iron absorption and tissue and organ injury, and is treated with first-line therapeutic phlebotomy. We aimed to investigate the efficacy and safety of rusfertide, a peptidic mimetic of hepcidin, in patients with HFE-related haemochromatosis. This open-label, multicentre, proof-of-concept phase 2 trial was done across nine academic and community centres in the USA and Canada. Adults (aged ≥18 years) with HFE-related haemochromatosis on a stable therapeutic phlebotomy regimen (maintenance phase) for at least 6 months before screening and who had a phlebotomy frequency of at least 0·25 per month (eg, at least three phlebotomies in 12 months or at least four phlebotomies in 15 months) and less than one phlebotomy per month, with serum ferritin of less than 300 ng/mL and haemoglobin of more than 11·5 g/dL, were eligible. Patients initiated 24 weeks of subcutaneous rusfertide treatment within 7 days of a scheduled phlebotomy at 10 mg once weekly. Rusfertide doses and dosing schedules could be adjusted to maintain serum transferrin iron saturation (TSAT) at less than 40%. During rusfertide treatment, investigators were to consider the need for phlebotomy when the serum ferritin and TSAT values exceeded the patient's individual pre-phlebotomy serum ferritin and TSAT values. No primary endpoint or testing hierarchy was prespecified. Prespecified efficacy endpoints included the change in the frequency of phlebotomies; the proportion of patients achieving phlebotomy independence; change in serum iron, TSAT, serum transferrin, serum ferritin, and liver iron concentration (LIC) as measured by MRI; and treatment-emergent adverse events (TEAEs). The key efficacy analyses for phlebotomy rate and LIC were conducted by use of paired t tests in the intention-to-treat population, defined as all patients who received any study drug and who had pretreatment and at least one post-dose measurement. We included all participants who received at least one dose of rusfertide in the safety analyses. This trial is closed and completed and is registered with ClinicalTrials.gov, NCT04202965. Between March 11, 2020, and April 23, 2021, 28 patients were screened and 16 (ten [63%] men and six [38%] women) were enrolled. 16 were included in analyses of phlebotomy endpoints and 14 for the LIC endpoint. 12 (75%) patients completed 24 weeks of treatment. The mean number of phlebotomies was significantly reduced during the 24-week rusfertide treatment (0·06 phlebotomies [95% CI -0·07 to 0·20]) compared with 24 weeks pre-study (2·31 phlebotomies [95% CI 1·77 to 2·85]; p<0·0001). 15 (94%) of 16 patients were phlebotomy-free during the treatment period. Mean LIC in the 14 patients in the intention-to-treat population was 1·4 mg iron per g dry liver weight (95% CI 1·0 to 1·8) at screening and 1·1 mg iron per g dry liver weight (95% CI 0·9 to 1·3) at the end of treatment (p=0·068). Mean TSAT was 45·3% (95% CI 33·2 to 57·3) at screening, 36·7% (24·2 to 49·2) after the pretreatment phlebotomy, 21·8% (15·8 to 27·9) 24 h after the first dose of rusfertide, 40·4% (27·1 to 53·8) at the end of treatment, and 32·6% (25·0 to 40·1) over the treatment duration. Mean serum iron was 24·6 μmol/L (95% CI 18·6 to 30·6), 20·1 μmol/L (14·8 to 25·3), 11·9 μmol/L (9·2 to 14·7), 22·5 μmol/L (15·9 to 29·1), and 19·0 μmol/L (15·3 to 22·6) at these same timepoints, respectively. Mean serum ferritin was 83·3 μg/L (52·2 to 114.4), 65·5 μg/L (32·1 to 98·9), 62·8 μg/L (33·8 to 91·9), 150·0 μg/L (86·6 to 213.3), and 94·3 μg/L (54·9 to 133.6) at these same timepoints, respectively. There were only minor changes in serum transferrin concentration. 12 (75%) patients had at least one TEAE, the most common of which was injection site pain (five [31%] patients). All TEAEs were mild or moderate in severity, except for a serious adverse event of pancreatic adenocarcinoma, which was considered severe and unrelated to treatment and was pre-existing and diagnosed 21 days after starting rusfertide treatment. Rusfertide prevents iron re-accumulation in the absence of phlebotomies and could be a viable therapeutic option for selected patients with haemochromatosis. Protagonist Therapeutics.

Influence of serum transferrin concentration on diagnostic criteria for iron deficiency in chronic heart failure.

Transferrin saturation (TSAT), a marker of iron deficiency, reflects both serum concentrations of iron (SIC) and transferrin (STC). TSAT is susceptible to changes in each of these biomarkers. Little is known about determinants of STC and its influence on TSAT and mortality in patients with heart failure. Accordingly, we studied the relationship of STC to clinical characteristics, to markers of iron deficiency and inflammation and to mortality in chronic heart failure (CHF). Prospective cohort of patients with CHF attending a clinic serving a large local population. A total of 4422 patients were included (median age 75 (68-82) years; 40% women; 32% with left ventricular ejection fraction ≤40%). STC≤2.3g/L (lowest quartile) was associated with older age, lower SIC and haemoglobin and higher high-sensitivity C-reactive protein, ferritin and N-terminal pro-brain natriuretic peptide compared with those with STC>2.3g/L. In the lowest STC quartile, 624 (52%) patients had SIC ≤13μmol/L, of whom 38% had TSAT ≥20%. For patients in the highest STC quartile, TSAT was <20% when SIC was >13μmol/L in 185 (17%) patients. STC correlated inversely with ferritin (r=-0.52) and high-sensitivity C-reactive protein (r=-0.17) and directly with albumin (r=0.29); all P<0.001. In models adjusted for age, N-terminal pro-brain natriuretic peptide and haemoglobin, both higher SIC (hazard ratio 0.87 [95% CI: 0.81-0.95]) and STC (hazard ratio 0.82 [95% CI: 0.73-0.91]) were associated with lower mortality. SIC was more strongly associated with both anaemia and mortality than either STC or TSAT. Many patients with CHF and a low STC have low SIC even when TSAT is >20% and serum ferritin >100μg/L; such patients have a high prevalence of anaemia and a poor prognosis and might have iron deficiency but are currently excluded from clinical trials of iron repletion.

Ferritin as proinflamatory biomarker of iron metabolism in tuberculosis patients (review)

Traditional methods of tuberculosis (TB) diagnosis, including sputum microscopy and culture for Mycobacterium tuberculosis detection, are time-consuming or have unsatisfactory sensitivity. However, early diagnosis of TB with high accuracy and sensitivity is very important for disease outcomes and prevention. Therefore, there is an urgent need for new TB diagnostic methods based on TB-associated biomarkers, with rapid availability of results that do not require sputum analysis, are inexpensive, and have high sensitivity and specificity. Objective — to study the mechanisms of ferritin participation in the pathogenesis of tuberculosis basing on the literature data. Materials and methods. 242 literature sources were found in the PubMed system by the query «Ferritin AND Tuberculosis» and 40 of them were selected for further detailed study. Results and discussion. Studies have shown that serum iron and transferrin concentrations are lower and ferritin levels are higher in patients with TB compared to those without TB. These deviations in the concentration of ferritin and transferrin usually normalize after treatment. Lower transferrin levels are associated with both early and late TB progression, and higher ferritin and hepcidin levels are associated with a higher risk of early TB progression in TB contacts. In addition, the status of biomarkers of iron metabolism can be used as an indicator of treatment failure (low ferritin) and mortality (high ferritin). Finally, low levels of transferrin and serum iron, as well as high ferritin concentrations in HIV-infected patients predict an increased risk of TB disease and relapse. Conclusions. Iron metabolism between M. tuberculosis and the host organism is closely related and plays an important role in the pathogenesis of tuberculosis. Parameters of iron metabolism are promising markers of both the course and effectiveness of tuberculosis treatment. In particular, changes in the level of ferritin can be predictors of both the ineffectiveness of tuberculosis treatment and mortality from this disease, so the prognostic value of this marker requires further detailed study.

Long-COVID sequelae are associated with oxidative stress in hemodialysis patients

pathophysiology of long-COVID sequelae in the general population of SARS-CoV-2-infected patients has been shown to be strongly influenced by oxidative stress. However, the potential role of oxidative stress in the development of long-COVID sequelae in hemodialysis patients (HD) has never been investigated.&#x0D; The present study aimed to evaluate the oxidative status of HD patients 3.5 months after SARS-CoV-2 infection in relation to the presence of long-COVID sequelae and the severity of the acute phase COVID-19.&#x0D; Methods. This cross-sectional cohort study included 63 HD patients with a median age of 55 (43-62.5) years and a dialysis vintage of 42 (25-73) months who had been infected with COVID-19 at least 3 months before recruitment. Patients were divided into two groups according to the occurrence of long-COVID sequelae: Group 1 included 31 (49.2%) HD patients with sequelae, while Group 2 included 32 (50.8%) fully recovered individuals. At 3.5 (3.2-4.6) months after the acute phase of COVID-19, malondialdehyde (MDA) and erythrocyte levels (MDAe), sulfhydryl groups (SH -groups), serum catalase activity, transferrin, and ceruloplasmin were measured. A comparison of the obtained data was performed using the Student’s test or the Mann-Whitney test according to the data distribution. A correlation was evaluated with the Spearman test.&#x0D; Results. HD patients with persistent long-COVID sequelae had significantly higher concentrations of MDAs (p = 0.002), MDAe (p = 0.0006), and CTs (p = 0.02), and lower serum levels of SH-groups (p = 0.03) and ceruloplasmin (p = 0.03) compared with Group 2. The concentration of most studied indicators of pro- and antioxidant status did not depend on the severity of the acute phase COVID-19, and only catalase activity was statistically significantly related to the need for hospitalization (r = 0.59; p = 0.001), oxygen support (r = 0.44; p = 0.02), and the percentage of lung injury according to computed tomography (p = 0.03). Although the serum concentration of transferrin did not differ between the studied groups, the individual analysis showed that its value was statistically higher in HD patients with severe COVID-19 even 3.5 months after infection (p &lt; 0.0001).&#x0D; Conclusions. Long-term COVID-19 sequelae in HD patients are associated with oxidative stress. High levels of catalase activity and serum transferrin 3.5 months after COVID-19 may be a consequence of the severe course of the acute phase of the disease. The obtained data suggest that the use of antioxidants may be one of the possible strategies to treat the long-term consequences of COVID in HD patients.&#x0D;

A nomogram based on iron metabolism can help identify apathy in patients with Parkinson's disease.

Apathy is common in Parkinson's disease (PD) but difficult to identify. Growing evidence suggests that abnormal iron metabolism is associated with apathy in PD. We aimed to investigate the clinical features and iron metabolism of apathetic patients with PD, and construct a nomogram for predicting apathy in PD. Data of 201 patients with PD were analyzed. Demographic data, Apathy Scale (AS) assessments, and serum iron metabolism parameters were obtained. Spearman correlations were used to assess relationships between AS scores and iron metabolism parameters, separately for male and female patients. Additionally, a nomograph for detecting apathetic patients with PD was built based on the results of logistic regression analysis. The serum transferrin (TRF, p < 0.0024) concentration and total iron binding capacity (TIBC, p < 0.0024) were lower in the apathetic group after Bonferroni correction, and they were negatively associated with AS scores in male participants with PD (TRF, r = -0.27, p = 0.010; TIBC, r = -0.259, p = 0.014). The nomogram was developed by incorporating the following five parameters: age, sex, serum iron concentration, TIBC and Hamilton Depression Rating Scale (HAMD) scores, which showed good discrimination and calibration, with a consistency index of 0.799 (95% confidence interval = 0.732-0.865). Abnormal iron metabolism may contribute to apathy in PD, especially among men. TIBC levels in combination with HAMD scores can be effectively used for the prediction of apathetic patients with PD.

Peripheral Iron Metabolism is Associated with Leg Movements on Polysomnography but Not with the Severity of Restless Legs Syndrome or Its Impact on Patients.

PurposeThis study investigated the associations of peripheral iron status with different manifestations of restless legs syndrome (RLS), including leg movements (LMs) on polysomnography (PSG), disease severity, and impact on patients.Patients and MethodsIn this cross-sectional study, 108 patients with RLS were enrolled at Sir Run Run Shaw Hospital’s Center for Sleep Medicine. Demographic information, disease characteristics, RLS severity, and impact on patients were assessed through a semi-structured questionnaire. Peripheral iron indicators [serum ferritin, iron, and transferrin concentrations; unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC); transferrin saturation (TSAT)] were measured following PSG to assess sleep stages, respiratory events, microarousals and LM parameters. Data from patients with and without ferritin concentration < 50 µg/L were compared in crude analyses, and Spearman correlations of other iron indicators with RLS data were examined. An ordinal logistic regression model was used to adjust for age, sex, body mass index, years of education, age at the time of RLS onset, prior treatment (yes/no), C-reactive protein (CRP)/hemoglobin level, total sleep time and apnea-hypopnea index.ResultsMultivariate analysis showed that periodic LMs during sleep (PLMS) and other LM parameters were significantly associated with a ferritin concentration < 50 µg/L, UIBC, TIBC, and serum transferrin concentration, but not serum iron or TSAT. By contrast, the severity and impact of RLS were not associated with a ferritin concentration < 50 µg/L or other peripheral iron indicators in the multivariate model.ConclusionIn this study, peripheral iron status was associated mainly with motor components (LMs on PSG) rather than sensory components (severity and impact of RLS) after adequately controlling for potential confounders, such as CRP and hemoglobin levels. Commonly used peripheral iron metabolism indicators may therefore not be ideal biomarkers of RLS severity or impact on patients.

Appropriate Method of TIBC Estimation in Reference to Serum Transferrin Levels.

Background The currently available various methods of estimation of total iron binding capacity (TIBC) show marked variation in reference range. Although serum transferrin (TF) level is a sensitive indicator of iron status, its measurement requires immunoassay equipment which may not be available in many routine biochemistry laboratories. So, this study was planned to find the most appropriate method to estimate TIBC. Objectives This study aimed to compare different methods of TIBC estimation and to corelate the TIBC values obtained by different methods with serum TF concentration. Material and Methods This analytical cross-sectional study was performed in the clinical chemistry laboratory of the Biochemistry Department of Medical College Baroda & SSG Hospital, Vadodara, Gujarat, on 250 leftover serum samples destined to be discarded. In all these samples, serum TIBC was estimated by direct method, indirect method, as well as calculated method (iron + unsaturated iron binding capacity [UIBC]) along with the measurement of serum TF level. Statistical Analysis Among the different methods, repeated analysis of variance (ANOVA) analysis and Bland-Altman plot were used to find out significance of difference. Correlation coefficients were found between different methods of TIBC estimation and serum TF levels. Results The means of TIBC by calculated, indirect, and direct methods were 344.51, 342.23, and 378.24 µg/dL, respectively. The mean of serum TF was 295.3 mg/dL. There was statistically significant difference between TIBC by direct and indirect methods and between direct and calculated methods. There was a strong positive correlation between TIBC by direct method and serum TF ( r = 0.888, p < 0.0001), but there was moderate correlation between TIBC by indirect method and serum TF ( r = 0.748, p < 0.04), and between TIBC by calculated method and serum TF ( r = 0.725, p < 0.05). Conclusion Among different methods of estimation of TIBC, direct method is more reliable in reference to serum TF levels.

Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease.

Patients with chronic kidney disease (CKD) develop anemia largely because of inappropriately low erythropoietin (EPO) production and insufficient iron available to erythroid precursors. In four phase 3, randomized, open‐label, clinical trials in dialysis‐dependent and non–dialysis‐dependent patients with CKD and anemia, the hypoxia‐inducible factor prolyl hydroxylase inhibitor, vadadustat, was noninferior to the erythropoiesis‐stimulating agent, darbepoetin alfa, in increasing and maintaining target hemoglobin concentrations. In these trials, vadadustat increased the concentrations of serum EPO, the numbers of circulating erythrocytes, and the numbers of circulating reticulocytes. Achieved hemoglobin concentrations were similar in patients treated with either vadadustat or darbepoetin alfa, but compared with patients receiving darbepoetin alfa, those receiving vadadustat had erythrocytes with increased mean corpuscular volume and mean corpuscular hemoglobin, while the red cell distribution width was decreased. Increased serum transferrin concentrations, as measured by total iron‐binding capacity, combined with stable serum iron concentrations, resulted in decreased transferrin saturation in patients randomized to vadadustat compared with patients randomized to darbepoetin alfa. The decreases in transferrin saturation were associated with relatively greater declines in serum hepcidin and ferritin in patients receiving vadadustat compared with those receiving darbepoetin alfa. These results for serum transferrin saturation, hepcidin, ferritin, and erythrocyte indices were consistent with improved iron availability in the patients receiving vadadustat. Thus, overall, vadadustat had beneficial effects on three aspects of erythropoiesis in patients with anemia associated with CKD: increased endogenous EPO production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation.

RELATIONSHIP OF CHANGES IN HEMATOLOGICAL AND BIOCHEMICAL INDICATORS OF PERIPHERAL BLOOD WITH THE TRANSFERRIN CONCENTRATION AND CD71+ LYMPHOCYTE COUNT

Transferrin is an essential component of cell growth and metabolic processes that require iron. An increase in the expression of transferrin receptors on lymphocytes ensures their differentiation, maturation and activation of proliferation. It was of interest to study the relationship between the level of transferrin in the peripheral blood and the level of lymphocytes with the receptor to it.&#x0D; Purpose. To determine the nature of changes in hematological and biochemical parameters of peripheral blood based on the concentration of transferrin and the count of lymphocytes expressing the transferrin receptor CD71+.&#x0D; Materials and methods. a survey of 100 people aged 20 to 40 years living in the city of Arkhangelsk was carried out. Leukograms were carried out using a XS-1000i hematology analyzer (Sysmex). Enzyme immunoassay was used to measure cytokine concentrations. CD71 lymphocyte counts were carried out by flow cytometry (Epixs XL). A biochemical analyzer (STAT FAX 3300) was used to measure biochemical blood parameters. Analyses of the number of lymphocytes expressing the transferrin receptor and the concentration of transferrin in the blood serum were performed. The number of CD71+ lymphocytes within the physiological norm (less than 0.3 × 109 cells/L) and those with increased CD71+ levels (more than 0.5 × 109 cells/L) was identified. Within each group, subgroups with a normal and high transferrin content were identified.&#x0D; Results. It was found that an increase in the concentration of transferrin in the blood is associated with a decrease in the circulation of lymphocytes with the CD71+ receptor and a decrease in the coefficient of transferrin saturation with iron. This situation may be associated with an increased risk of secondary immunodeficiency. Against the background of increased concentrations of transferrin and an increase in the circulation of CD71+ lymphocytes, the concentration of lactate increases, which reflects an increase in the processes of tissue hypoxia.&#x0D; Conclusion. High concentrations of transferrin in the peripheral blood against the background of a decrease in the saturation of transferrin with iron and an increase in tissue hypoxia increase the risk of developing chronic inflammatory processes and may be associated with the formation of secondary immunodeficiency.

A STUDY ON SERUM IRON, TRANSFERRIN AND FERRITIN LEVELS IN NEPHROTIC SYNDROME PATIENTS AT HUE UNIVERSITY OF MEDICINE AND PHARMACY HOSPITAL

Background: The prolonged and excessive loss of protein through urine in nephrotic syndrome patients decreases blood protein and leads to other changes such as dyslipidemia, disorders of blood components, hematopoiesis…., if the blood albumin level decreases continuously, the more obvious these disorders, the serum iron, transferrin and ferritin levels will be changing. The aim of the study was to determine the concentrations of serum iron, transferrin, ferritin in nephrotic syndrome patients and the relation between these parameters. Materials and methods: Descriptive cross-sectional studies of 68 patients with the diagnosis of nephrotic syndrome and without renal failure. Results: The mean concentration of serum iron was 8.9 μmol/L, with the low level was 30.9%. While the serum transferrin which was lower than normal was 100% and the mean concentration was 0.68 mmol/L. The mean concentration of serum ferritin was 610.3 pmol/L, and its high level was 67.6%. Conclusions: Concentration of serum ferritin was elevated and inversely correlated with serum iron and transferrin concentrations. Key words: iron, transferrin, ferritin, nephrotic syndrome

Study on Relationship between Serum Iron, Transferrin and Ferritin With Proteinuria in Adult Nephrotic Syndrome Patients in Vietnam

Background: the loss of proteinuria in nephrotic syndrome (NS) patients reduces serum albumin and leads to many other changes such as dyslipidemia, disorders of blood clotting, disorders of hematopoietic components. The more and longer the loss of proteinuria occurs, the more pronounced these disorders are iron, transferrin and ferritin in serum. The objectives: Study the relationship between serum iron, transferrin and ferritin levels and proteinuria in NS patients. Subjects and Research Methods: randomized and controlled selection of 68 patients with NS in adults and without kidney failure; research according to the cross-descriptive method. Results: serum iron and transferrin levels in patients with NS are inversely correlated with proteinuria, with the following equations: y = -0.0633x + 9.531, R² = 0.0105 and y = -0.0041x + 0.725, R² = 0.0182; serum ferritin concentration positively correlated with proteinuria, with the equation y = 2.7432x + 583.65, R² = 0.0017.Conclusion: in NS serum iron and transferrin concentrations are inversely correlated with proteinuria, while serum ferritin is positively correlated with proteinuria.

Study on Changes of the Concentration of Some Indicators of the Serum Iron Test in Patients with Nephrotic Syndromein Vietnam

Background: In nephrotic syndrome (NS), the excessive and prolonged loss of protein in the urine reducesalbumin blood and leads to many other changes such as dyslipidemia, blood clotting disorders, and disordersof hematopoietic components. In NS, the more persistent and persistent decrease in albumin in the blood, themore apparent these disorders, including disorders of iron, transferrin and ferritin in serum. The objectivesof the study were to: Determine serum iron, transferrin and ferritin concentrations and Investigate therelationship between iron, transferrin and ferritin concentrations and serum albumin in NS patients.Methodology: Cross-sectional descriptive research method. Convenient and controlled sample selectionof 68 NS patients without kidney failure, aged 16 years and over, hospitalized for treatment at InternalDepartment of Hue University of Medicine and Pharmacy Hospital, Vietnam.Results: The average serum iron concentration is 8.9 µmol/L, of which at low level, the rate is 30.9%; In100% of cases, the serum transferrin concentration is lower than normal, the average concentration is 0.68mmol/L; the average elevation of ferritin in serum was 610.3 pmol/L, of which at high level accounted for67.6% (46 patients). Serum albumin concentrations are positively correlated with iron and transferrin, butnegatively with serum ferritin.Conclusion: In NS, the serum ferritin concentration is elevated and inversely correlated with the serum iron,transferrin, and albumin concentration.

The Association between Serum Oxidative Stress Indexes and Pathogenesis of Parkinson's Disease in the Northwest of Iran.

Background:Parkinson’s disease (PD) is a prevalent neurodegenerative disorder. Oxidative stress is a main modulator in the advancement of PD. This investigation aimed to evaluate the relations between serum trace elements, vitamin C, ferritin, transferrin, Nitrite Oxide (NOx) and Peroxynitrite (PrN) concentrations and clinical parameters in patients with PD.Methods:Serum concentrations of variables were measured in 75 PD patients and 75 healthy subjects from Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran between Feb 2016 and Sep 2018. Receiver Operating Characteristic (ROC) analysis was performed to examine incremental diagnostic value of vitamin C, NOx, and PrN in the study groups.Results:Mean serum NOx (35.81±5.16 vs. 11.27±3.59 mol/L, P<0.001) and PrN (15.78±4.23 vs. 9.62±4.57 mol/L, P= 0.004) were markedly higher in patient group versus healthy individuals. Significant differences were also observed in the serum levels of vitamin C (P<0.001), copper (Cu) (P<0.001), Iron (Fe) (P=0.003), and Zinc (Zn) (P<0.001) between patients with PD and healthy subjects. Nevertheless, the serum levels of Se (P=0.515), ferritin (P=0.103), and transferrin (P=0.372) were not statistically significant between the study groups. ROC analysis has revealed a diagnostic ability of serum vitamin C levels for PD with an area under ROC curve of ≥0.7 (P<0.05) and relatively high sensitivity and specificity.Conclusion:Serum levels of NOx and PrN are significantly higher in patients with PD. In additions, serum vitamin C levels have a diagnostic value as a biomarker. Further studies are required with larger sample size to provide more detailed information about the cognitive profile of participants and the outcome measures.

Nonalcoholic Steatohepatitis Modifies Serum Iron-Related Variables in Patients with Morbid Obesity.

Nonalcoholic steatohepatitis (NASH) is frequently associated with severe obesity. The liver is the principal storage repository for iron, and the excessive accumulation of this metal may promote hepatic inflammation. Laparoscopic sleeve gastrectomy (LSG) results in weight loss and improvement in comorbidities such as NASH. The aim of this study was to assess the specific NASH-related changes in iron metabolism and to investigate whether these changes are reversed by LSG. We included 150 patients with morbid obesity who provided 12-h fasting blood samples immediately before LSG together with an intraoperative wedge-liver biopsy. Thirty-eight patients with NASH underwent a second blood extraction 12 months postsurgery. Serum samples were collected from a control group comprising 50 healthy volunteers. We found significantly higher serum iron and transferrin concentrations in patients with NASH along with the highest degrees of steatosis, fibrosis, hepatocellular ballooning, and lobular inflammation. However, we did not find any significant accumulation of iron in the hepatic biopsies. Presurgery serum iron concentrations were lower in the patient group than in the control group and increased 1 year postsurgery. Serum ferritin levels showed changes in the opposite direction. We did not observe any significant change in serum transferrin concentrations. These changes were reversed by LSG. We conclude that alterations in serum iron-related variables are related to the severity of NASH in patients with morbid obesity, and these alterations are reversed by LSG. We also found that severe forms of NASH can be found in the absence of increased iron stores.