Serum sTfR Research Articles

Clinical Usefulness of the serum-Soluble Transferrin Receptor in Iron Dysregulation Associated with long-Term Hemodialysis

Background: Soluble transferrin receptor (sTfR) was reported to be a valuable diagnostic marker for iron dysregulation (ID). Hepcidin, which is a key regulator of iron metabolism, has been shown to have increased values in patients undergoing hemodialysis (HD). Either treatment with erythropoietin stimulating agent（ESA） or iron repletion therapy（IRT）had been reported to induce controversial effect on serum levels between sTfR and hepcidin. Thus, we measured serum levels both of sTfR and hepcidin in 97 HD patients and investigated the clinical value of these measures. Methods: We used a commercial enzyme-linked immunosorbent assay kit to measure serum levels both of hepcidin and sTfR. Results: Although serum sTfR levels did not clearly increase, both sTfR levels and its index value correlated with the saturation of transferrin, erythropoietin-stimulating agent dosage, and erythropoietin resistance index (ERI). In addition, a strong negative correlation was found for sTfR and log serum hepcidin values. Conclusions: Serum sTfR levels and the sTfR index were acceptable markers for iron dysregulation (ID) and ERI even in patients undergoing HD whose serum levels of hepcidin increased.

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.

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

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

Correlation of sTfR, Hemoglobin, Serum Iron, and eGFR in Pre-dialysis CKD Patients at Sanglah Hospital

Patients with CKD usually have chronic inflammation and impaired antioxidant systems, which worsen with the degree of renal impairment. Anemia is one of the major complications in pre-dialysis CKD patients Examination of iron status that is commonly done today such as serum iron parameters, ferritin, and transferrin saturation is still influenced by the inflammatory process. As an alternative to assessing iron status, the soluble transferrin receptor (sTfR) is not affected by chronic disease or inflammation. The purpose of this study was to determine the correlation of sTfR, hemoglobin, serum iron, and estimation of glomerular filtration rate (eGFR) in pre-dialysis CKD patients. This research was conducted from February to June 2022 at the Nephrology Outpatient Clinic and Clinical Pathology Laboratory of Sanglah Hospital, Denpasar. This research is an observational analytic study with a cross-sectional study design. The research subjects involved were 61 pre-dialysis CKD patients who met the inclusion and exclusion criteria. The results showed that the research subjects consisted of 54.1% male and 45.9% female. The results of the Spearman correlation test showed a weak significant negative correlation between sTfR levels and serum iron in pre-dialysis CKD patients (r = -0.264; p=0.040), but no significant correlation with hemoglobin (r = -0.116; p=0.372) and eGFR ((r = 0.134; p=0.302). This study showed a significant correlation indicating that an increase in serum sTfR levels would affect a decrease in serum iron, so it could be considered as a marker for the management of iron deficiency anemia in CKD.

Effects of continuous renal replacement therapy on inflammation-related anemia, iron metabolism and prognosis in sepsis patients with acute kidney injury.

This study aims to evaluate the effect of continuous renal replacement therapy (CRRT) on inflammation-related anemia, iron metabolism, and the prognosis in sepsis patients with acute kidney injury (AKI). Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups. The clinical and laboratory data on days 1, 3 and 7 after intensive care unit (ICU) admission were collected. The serum interleukin (IL)-6, hepcidin, erythropoietin, ferritin, and soluble transferrin receptor (sTfR) were determined by enzyme-linked immunosorbent assay. The Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were recorded. Data were analyzed using Pearson's Chi-square test or Fisher's exact test (categorical variables), and Mann-Whitney U-test or t-test (continuous variables). The hemoglobin and serum erythropoietin levels did not significantly differ between the CRRT and control groups though gradually decreased within the first week of ICU admission. On days 3 and 7, the serum IL-6, hepcidin, ferritin, and red blood cell distribution width significantly decreased in the CRRT group compared to the control group (all P<0.05). On day 7, the serum iron was significantly elevated in the CRRT group compared to the control group (P<0.05). However, the serum sTfR did not significantly differ between the groups over time. In addition, the SOFA scores were significantly lower in the CRRT group compared to the control group on day 7. The 28-day mortality did not significantly differ between the control and CRRT groups (38.0% vs. 28.2%, P=0.332) . CRRT might have beneficial effects on the improvement in inflammation-related iron metabolism and disease severity during the first week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.

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.

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

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

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.

Increased Serum Soluble Transferrin Receptor Levels Were Associated With High Prevalence of Cardiovascular Diseases: Insights From the National Health and Nutrition Examination Survey 2017-2018.

Background: Iron deficiency is common in cardiovascular diseases (CVD), e.g., heart failure and coronary heart disease. Soluble transferrin receptor (sTfR) is a promising marker representing unmet cellular iron demands. However, whether higher serum sTfR is associated with increased risk of CVDs needs further investigation. Methods: In the present cross-sectional study, we analyzed data of 4,867 adult participants of the National Health and Nutrition Examination Survey (NHANES) 2017–2018. Linear regression models were employed to identify possible correlations between sTfR and other characteristics. The association between sTfR and CVDs was assessed with univariable and multivariable logistics regression models. Results: The prevalence of CVDs was 9.5% among participants, and higher sTfR levels were found in participants with CVDs (p < 0.001). Linear regression models revealed positive associations between sTfR and age, body mass index, systolic blood pressure, glycated hemoglobulin A1c, and insulin resistance (all p < 0.001). In the multivariable logistics regression model, the adjusted odds ratio of sTfR for CVDs was 2.05 (per 1 log2 mg/L, 95% confidence interval: 1.03∼4.05, p = 0.046). Further subgroup analysis identified the associations of sTfR and CVDs were only significant in participants ≥60 years old, or with hypertension (all p < 0.05). Conclusion: Our study demonstrated that increased serum sTfR levels were associated with a high prevalence of cardiovascular diseases.

The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment.

Background and objectives: Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Materials and methods: Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. Results: MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients’ 2-year survival. Conclusions: Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.

Effects of Iron and Vitamin A Levels on Pregnant Women and Birth Outcomes: Complex Relationships Untangled Using a Birth Cohort Study in Uganda

IntroductionWomen and infants are among the most vulnerable groups for micronutrient deficiencies. Pregnancy micronutrient status can affect birth outcomes and subsequent infants’ growth.MethodsWe determined the relationship between maternal iron and vitamin A status at delivery using several biomarkers (ferritin, soluble transferrin receptor [sTFR], body iron stores [BIS], hemoglobin and retinol binding protein [RBP]) and birth outcomes (body weight, Z-scores, head circumference, small-for-gestational-age and preterm birth) in rural Uganda. We investigated women who had serum results at the point of delivery and paired them to their infants at birth (n = 1244). We employed multivariable linear and logistic regression, adjusting for clustering at the subcounty level to determine the relationship between maternal micronutrients and birth outcomes.ResultsAfter adjusting for relevant factors, we found that maternal iron status (ferritin and BIS) and anemia (hemoglobin) were not significantly associated with the assessed birth outcomes. However, there was a significant association between serum sTFR and preterm births (AOR: 0.67; 95% CI 0.48–0.94). For Vitamin A, we observed a significant positive association between RBP and length-for-age (LAZ) at birth (β = 0.12, p < 0.030).DiscussionThese findings indicate that the relationship between maternal iron status and birth outcomes needs to be further investigated, because depending on the biomarker used the associations were either in favor of an adverse birth outcome or not significant. Additionally, they confirm that higher maternal RBP levels could be beneficial for birth outcomes.Clinicaltrials.gov as NCT04233944.

Study on the Effect of Combination of Prednisone and Vitamin D in the Treatment of Primary Nephrotic Syndrome in Children.

Objective To study the effect of prednisone combined with vitamin D in the treatment of primary nephrotic syndrome in children. Method 73 cases of primary nephrotic syndrome admitted to the nephrology department of our hospital were randomly selected and retrospectively analyzed. 36 cases were treated with prednisone as the control group, and 37 cases were treated with prednisone combined with vitamin D as the observation group. The efficacy was compared after 3 months of continuous treatment. Result After 3 months of treatment, the blood calcium of the observation group was higher than that of the control group, PTH was lower than that of the control group, and 25-(OH)2D3 and 1,25-(OH)2D3 were higher than those of the control group (P < 0.05). After 1, 2, and 3 months of treatment in the observation group, Scr and 24-h urine protein quantification were lower than those in the control group and eGFR was higher than that in the control group (P < 0.05). CD4+ and CD4+/CD8+ were lower in the observation group than in the control group after 3 months of treatment (P < 0.05). The serum sTfR and TGF-β1 levels were lower in the observation group than in the control group after 3 months of treatment (P < 0.05). The total effective rate of the observation group was 83.78% after 3 months of combined treatment with prednisone and vitamin D, which was significantly higher than the total effective rate of the control group of 61.11% (P < 0.05). The incidence of nausea and vomiting, heartburn, headache, dry cough, hypercalcemia, and constipation during treatment in the observation group was not statistically different from that in the control group (P > 0.05). Conclusion Combined treatment of primary nephrotic syndrome in children with prednisone and vitamin D can more significantly improve the level of clinical indicators, improve renal function and immune function, and obtain more satisfactory efficacy, without significantly affecting the safety of treatment.

MO789SERUM SOLUBLE TRANSFERRIN RECEPTOR IS A PROMISING MARKER OF IRON DEFICIENCY ANEMIA IN PREVALENT HEMODIALYSIS PATIENTS

Abstract Background and Aims End stage renal disease (ESRD) is chronic inflammatory condition which affects iron parameters. Serum soluble transferrin receptor (sTfR) is a reliable indicator for assessing iron status in inflammatory conditions. This study evaluates the usefulness of serum sTfR in iron deficiency anemia detection in prevalent hemodialysis patients. Method This case-control study included 40 ESRD patients on conventional hemodialysis with CRP&amp;gt;10, 40 ESRD patients with CRP&amp;lt;10 and 8 apparently healthy controls. Serum sTfR was measured for all patients and controls. Results STFRs predicts iron deficiency anemia in prevalent hemodialysis patients at cut off value 12.5 mg/l with area under curve 0.949, sensitivity 88.75, specificity 100, PPV 100% and NPV 47.1%. The prevalence of STFRs in patients with CRP&amp;lt;10 was 85%, while in patients with CRP&amp;gt;10 was 92.5% (P-value 0.288). Patients who have elevated STFRs have risk 1.22 times to have iron deficiency anemia if CRP &amp;lt;10 (odds ratio: 1.22) and 3.14 times if CRP&amp;gt;10 (odds ratio: 3.14). There was significant difference on comparing patients with CRP&amp;lt;10, CRP&amp;gt;10 and control as regard haemoglobin and STFR with P-value 0.0001 and 0.0001 respectively. Post Hoc analysis showed significant difference between the patients with CRP&amp;lt;10 and control also in patients with CRP&amp;gt;10 and control as regard haemoglobin and STFR (p value &amp;lt;0.0001). on comparing patients with CRP&amp;lt;10 with patients with CRP&amp;gt;10 there was significant difference in STFRs p value 0.0001 despite no significant difference in haemoglobin (p value 0.642) and classic iron markers (s.iron, TIBC, TSAT) with p value 0.701, 0.192, 0.382 respectively. Serum STFRs was negatively correlated with s.iron and Kt\v in patients with CRP &amp;lt;10 (r -0.372, P-value 0.018) and (r-0.416, p value 0.008) respectively. Conclusion Serum soluble transferrin receptor is a highly sensitive and specific marker of iron deficiency anemia in hemodialysis patients especially with high CRP level.

Serum soluble transferrin receptor levels are independently associated with homeostasis model assessment of insulin resistance in adolescent girls.

Markers of iron homeostasis are related to insulin resistance (IR) in adults. However, studies in children and adolescents are scarce and show contradictory results. The aim was to evaluate the potential relationship between iron status markers and IR. Additionally, no previous study has explored the mutual effect of biomarkers of iron homeostasis and inflammation (i.e. high sensitivity C-reactive protein (hsCRP)), and adipokines (i.e. retinol-binding protein 4 (RBP4)) on IR in the cohort of adolescent girls. A total of 60 girls age between 16 and 19 years were included in the study. Serum levels of ferritin, transferrin, soluble transferrin receptor (sTfR), hsCRP, and RBP4 were measured by immunonephelometry. Homeostasis model assessment of insulin resistance (HOMA-IR) and iron homeostasis indexes were calculated. Univariate and multivariate binary logistic regression analysis were used to investigate the possible independent associations of the examined biomarkers. Principal component analysis was used to examine their mutual effect on HOMA-IR in the studied girls. Ferritin, sTfR, hsCRP and RBP4 were significant predictors for higher HOMA-IR in univariate analysis (p = 0.020, p = 0.009, p = 0.007, p = 0.003, respectively). Multivariate regression analysis after adjustment for waist circumference (WC) showed that serum sTfR levels remained positively associated with higher HOMA-IR (p = 0.044). Factorial analysis revealed that the obesity-inflammation related factor (i.e., WC and hsCRP) and adipokine-acute phase protein related factor (i.e., RBP4 and ferritin) showed significant differences between HOMA-IR < 2.5 and HOMA-IR ≥ 2.5. Serum sTfR levels are independently associated with HOMA-IR, whereas higher serum ferritin levels together with higher RBP4 are related to higher HOMA-IR in adolescent girls.

High soluble transferrin receptor in patients with heart failure: a measure of iron deficiency and a strong predictor of mortality.

Iron deficiency (ID) is frequent in heart failure (HF), linked with exercise intolerance and poor prognosis. Intravenous iron repletion improves clinical status in HF patients with left ventricular ejection fraction (LVEF) ≤45%. However, uncertainty exists about the accuracy of serum biomarkers in diagnosing ID. The aims of this study were (i) to identify the iron biomarker with the greatest accuracy for the diagnosis of ID in bone marrow in patients with ischaemic HF, and (ii) to establish the prevalence of ID using this biomarker and its prognostic value in HF patients. Bone marrow was stained for iron in 30 patients with ischaemic HF with LVEF ≤45% and 10 healthy controls, and ID was diagnosed for 0-1 grades (Gale scale). A total of 791 patients with HF with LVEF ≤45% were prospectively followed up for 3 years. Serum ferritin, transferrin saturation, soluble transferrin receptor (sTfR) were assessed as iron biomarkers. Most patients with HF (n=25, 83%) had ID in bone marrow, but none of the controls (P < 0.001). Serum sTfR had the best accuracy in predicting ID in bone marrow (area under the curve 0.920, 95% confidence interval 0.761-0.987, for cut-off 1.25 mg/L sensitivity 84%, specificity 100%). Serum sTfR was ≥1.25 mg/L in 47% of HF patients, in 56% and 46% of anaemics and non-anaemics, respectively (P < 0.05). The reclassification methods revealed that serum sTfR significantly added the prognostic value to the baseline prognostic model, and to the greater extent than plasma N-terminal pro B-type natriuretic peptide. Based on internal derivation and validation procedures, serum sTfR ≥1.41 mg/L was the optimal threshold for predicting 3-year mortality, independent of other established variables. High serum sTfR accurately reflects depleted iron stores in bone marrow in patients with HF, and identifies those with a high 3-year mortality.

AB0720 SOLUBLE TRANSFERRIN RECEPTOR IN DIAGNOSIS OF IRON DEFICIENCY ANEMIA IN PATIENTS WITH SPONDYLOARTHRITIS

Background:Anemia is a frequent hematological disorder in patients with rheumatic diseases. The main pathogenetic variants of anemia are anemia of chronic disease (ACD), iron deficiency anemia (IDA), and anemia of chronic disease with iron deficiency (ACD/IDA). The presence of systemic inflammation hinders to diagnose absolute iron deficiency, because standard tests of iron status are affected by it. Soluble transferrin receptors (sTfR) measurement and the calculation of the sTfR/ log ferritin index (sTfR index) are recommended, but data about diagnostically significant levels of these indicators in patients with spondyloarthritis (SpA) is currently limited.Objectives:To assess the diagnostic significance of sTfR and the sTfR index for detecting absolute iron deficiency in patients with SpA and anemia.Methods:Complete blood count, standart iron metabolism parameters, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were evaluated in 68 patients with SpA. Serum concentration of sTfR was measured with enzyme-linked immunosorbent assay (ELISA) using sTfR ELISA kit («Monobind Inc.», USA). The sTfR index was calculated by the formula sTfR/log10ferritin. Anemia was defined using the World Health Organization criteria. Depending on the serum ferritin concentration, transferrin saturation, and CRP level, ACD, IDA, or combined anemia (ACD/IDA) were diagnosed. Disease activity was determined by the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score based on CRP) scales. Receiver operating characteristic (ROC) analysis was performed with MedCalc.Results:Anemia was found in 48 of 68 (70,6%) SpA patients. 16 (33,3%) patients had ACD and 32 (66,7%) had ACD/IDA. Hemoglobin level in ACD was 118 [112; 123] g/L, in ACD/IDA – 110 [106; 120] g/L, in non-anemic patients – 133 [129; 145] g/L (p&lt;0.001 for all groups). CRP and ESR values were higher in ACD compared to ACD/IDA patients (31.5 [20.3; 46.4] mg/L and 27.0 [16.0; 35.5] mm/h versus 9.8 [5.6; 16.9] mg/L and 15.5 [12.0; 22.5] mm/h, respectively [p=0.00 and p=0.038]). No statistically significant difference was found between all groups in BASDAI and ASDAS-CRP scores.ACD/IDA patients had significant increases in serum sTfR levels (1.7 [1.4; 2.2] mg/L) compared to ACD (1.5 [1.1; 1.7] mg/L, p=0,04) and to non-anemic patients (1,3 [1,1; 1,6] mg/L, p=0,003). The sTfR index was significantly higher in ACD/IDA (0.93 [0.82; 1.24]) compared to patients with ACD (0.64 [0.48; 0.75], p&lt;0.001) and without anemia (0.67 [0.56; 0.81], p&lt;0.001).The areas under the curves (AUCs) for distinguishing between ACD/IDA and ACD were 0.85 for sTfR index (p&lt;0,001), 0.72 for sTfR (p&lt;0,001). The sTfR index (cutoff &gt;0.83) and sTfR (cutoff &gt;1.39 mg/L) had sensitivities of 75% and 53%, and specificities of 83% and 81%, respectively.Conclusion:According to obtained data, serum concentration of sTfR &gt;1.39 mg/L and the sTfR index &gt;0.83 point to the presence of iron deficiency component in the structure of anemic syndrome in patients with SpA.

Analytical evaluation of three soluble transferrin receptor measurement systems for diagnosis of iron deficiency anemia: A retrospective study.

BackgroundSoluble transferrin receptor (sTfR) is a promising indicator of iron deficiency anemia (IDA). Here, we investigated the application value of sTfR assays based on three different methods for the diagnosis of IDA.MethodsThe sTfR concentrations in two groups of patient specimens with high‐level and low‐level sTfR concentrations and in quality control materials were measured four times a day for five consecutive days to evaluate the precision of the three methods. We selected patients with IDA, anemia of chronic disease (ACD), or chronic diseases with iron deficiency anemia (CIDA), and apparently healthy subjects, and measured the serum sTfR concentrations in all subjects using the three different methods. The cutoff points for an IDA diagnosis using the three assays and their corresponding clinical sensitivities and specificities were calculated by receiver operating characteristic analysis.ResultsFor the diagnosis of IDA, the cutoff points of sTfR measured by the chemiluminescent, immunoturbidimetric, and immunonephelometric assays were 2.91, 6.70, and 2.48 mg/L, respectively. The corresponding sensitivities were 85.59%, 85.59%, and 85.59%, the specificities were 91.47%, 90.31%, and 90.70%, and area under the curve was 0.943, 0.944, and 0.936, respectively. The sTfR concentrations measured by the different methods were significantly higher in the IDA and CIDA groups than in the other two groups (P < .05).ConclusionsThe sTfR based on the three different measurement methods presented promising analytical performances and met the clinical requirements for sensitivity and specificity. However, the different measurement methods had markedly different cutoff points for IDA diagnosis, which should be critically considered in clinical practice.

Markers of iron status, blood pressure and incident hypertension among Chinese adults

Background and aimsThe evidence on the relationship between markers of iron, blood pressure and hypertension are limited and inconsistent. This prospective cohort study aimed to investigate the relationship of serum ferritin (SF), transferrin, soluble transferrin receptor (sTFR) and haemoglobin on blood pressure and incident hypertension in the China Health and Nutrition Survey (CHNS) study. Methods and resultsWe studied 8337 adults aged 18 years old or above from CHNS in 2009 to investigate the association of markers of iron and blood pressure (BP). Among them, 4509 non-hypertensive participants who completed follow up were included to investigate the association of markers of iron and hypertension development. Linear regression model was used to assess the association between markers of iron and BP. Cox regression model was used to examine the association of markers of iron and hypertension development. SF and serum sTFR concentration had a non-significant effect on incident hypertension. Transferrin and haemoglobin concentrations were positively associated with incident hypertension. Compared to the participants with the lowest tertile of transferrin, those with the highest tertile had a higher risk of developing hypertension [HR: 1.26, 95% CI (1.04, 1.53), P = 0.017]. Similarly, participants with the highest tertile of haemoglobin had a significantly higher risk of incident hypertension [HR: 1.27, 95% CI (1.01, 1.59), P = 0.038]. ConclusionThe current study found that haemoglobin and transferrin levels were positively associated with blood pressure and incident hypertension. Further research in different ethnic groups is required to confirm the association of the full range of markers of iron with BP and incident hypertension.

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

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