Plasma Ferritin Concentrations Research Articles

High Ferritin and Low Total Iron-Binding Capacity in Plasma Predict All-Cause Mortality During the First 3 Years of Hemodialysis in Patients with End-Stage Chronic Kidney Disease.

To determine all-cause mortality rate and the predictive value of plasma ferritin and total iron-binding capacity (TIBC) concentrations for mortality during the first 3 years of hemodialysis in patients with end-stage chronic renal disease (ESRD). We conducted a study on 174 ESRD patients (estimated Glomerular Filtration Rate < 15 mL/min/1.73m2). The plasma TIBC level was quantified by the ELISA method in all patients at the time before hemodialysis. Based on TIBC concentration, patients were divided equally into 2 groups. Each group had 87 patients. Patients were initiated on hemodialysis, and patients who died from any cause during the first 3 years of hemodialysis were recorded. The all-cause mortality rate of ESRD patients in the first 3 years of maintenance hemodialysis was 22.9%. Plasma high hs-CRP, high ferritin, and low TIBC concentrations were independent factors associated with all-cause mortality in the patients. Plasma ferritin (cut-off value = 454.2 ng/L) and TIBC (cut-off value = 39.84 µmol/L) were predictors of all-cause mortality, AUC is: 0.772; 0.723, p < 0.001. Plasma ferritin and TIBC were good predictors of all-cause mortality in ESRD patients during the first 3 years of hemodialysis.

Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS)

BackgroundInflammatory subphenotypes have been identified in acute respiratory distress syndrome (ARDS). Hyperferritinaemia in sepsis is associated with hyperinflammation, worse clinical outcomes, and may predict benefit with immunomodulation. Our aim was...

Plasma CRP-hs and Ferritin Concentration Related to Kidney Injury in Adult Patients with Beta-Thalassemia: A Cross-Sectional Study in Vietnam

Background: Kidney injury (KI) is one of the complications of β-thalassemia patients. Objectives: To determine the rate of KI and its relationship with plasma ferritin and CRP-hs in β-thalassemia patients. Methods: A total of 142 patients diagnosed with β-thalassemia (58.5% minor, 17.6% intermedia, and 23.9% major) were included in our study. In all patients, we measured plasma ferritin, CRP-hs, urine albumin, and serum creatinine and calculated the urine albumin to creatinine ratio (uACR). Based on uACR, we divided the patients into 2 groups: with KI (n = 19, uACR ≥ 3.0 mg/mmol) and without KI (n = 123, uACR &lt; 0.3 mg/mmol). Results: The ratio of KI in β-thalassemia patients was 13.4%. The median concentrations of plasma ferritin and CRP-hs in the KI group were significantly higher than in the non-KI group (P &lt; 0.001). Plasma ferritin and CRP-hs were independent risk factors for KI (P &lt; 0.001). At a cut-off value of 2.35 mg/L, plasma CRP-hs had a predictive value for KI (AUC = 0.841, P &lt; 0.001). Similarly, plasma ferritin at the cut-off value of 2394.95 µg/L showed a predictive value for KI (AUC = 0.789, P &lt; 0.001). Conclusions: The rate of KI was low in adult patients with β-thalassemia. Plasma ferritin and CRP-hs had a good predictive value for KI in β-thalassemia patients.

Associations between higher plasma ferritin and hepcidin levels with liver stiffness in patients with type 2 diabetes: An exploratory study.

Currently, there is no information about the association between circulating levels of ferritin and hepcidin and liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). We enrolled 153 patients with T2DM with no known liver diseases, who consecutively attended our diabetes outpatient service and who underwent liver ultrasonography and liver stiffness measurement (LSM) by vibration-controlled transient elastography (Fibroscan® for the non-invasive assessment of liver fibrosis). Plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. After stratification of patients by LSM tertiles [1st tertile median LSM: 3.6 (interquartile range: 3.3-4.0) kPa, 2nd tertile: 5.3 (4.9-5.9) kPa and 3rd tertile: 7.9 (6.7-9.4) kPa], we found that plasma ferritin and hepcidin concentrations increased across LSM tertiles [median ferritin: 68.7 (interquartile range: 25.1-147) vs. 85.8 (48.3-139) vs. 111 (59.3-203) μg/L, p = 0.021; median hepcidin: 2.5 (1.1-5.2) vs. 4.4 (2.5-7.3) vs. 4.1 (1.9-6.8) nmol/L, p = 0.032]. After adjustment for age, sex, diabetes duration, waist circumference, haemoglobin A1c, HOMA-insulin resistance score, triglycerides, haemoglobin, presence of hepatic steatosis on ultrasonography and patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genetic variant, higher plasma ferritin levels were associated with greater LSM values (adjusted-odds ratio 2.10, 95% confidence interval 1.23-3.57, p = 0.005). Higher plasma hepcidin levels were also associated with greater LSM values (adjusted-odds ratio 1.90, 95% confidence interval 1.15-3.13, p = 0.013). Higher levels of plasma ferritin and hepcidin were associated with greater NAFLD-related liver fibrosis (assessed by LSM) in patients with T2DM, even after adjustment for established cardiometabolic risk factors, diabetes-related variables and other potential confounders.

Relative validity of the Planetary Health Diet Index by comparison with usual nutrient intakes, plasma food consumption biomarkers, and adherence to the Mediterranean diet among European adolescents: the HELENA study.

The EAT-Lancet Commission proposed an evidence-based global reference diet to improve human health within planetary boundaries. Recently, the Planetary Health Diet Index (PHDI) was developed based on the EAT-Lancet recommendations and validated among Brazilian adults. However, the relative validity of the PHDI in adolescents has yet to be assessed. Thus, we aimed to evaluate the relative validity of the PHDI in European adolescents. We used cross-sectional data from 1804 adolescents (12.5-17.5years) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. The PHDI (0-150 points) was calculated based on dietary intake data from two non-consecutive 24-h dietary recalls. Associations between the PHDI and usual nutrient intakes, plasma food consumption biomarkers, and adherence to the Mediterranean diet were evaluated using multivariable-adjusted mixed-effects linear regression models. Higher PHDI score was associated with greater intakes of nutrients predominantly from plant-source foods, such as vegetable protein, vitamin E, and folate and with lower intake of nutrients predominately from animal-source foods, such as total and saturated fat, cholesterol, and animal protein. Furthermore, a higher PHDI score was also positively associated with plasma β-carotene, vitamin C, vitamin D, folate, and ferritin concentrations, while negatively associated with trans-fatty acids concentration. Moreover, higher PHDI was related to a greater adherence to the Mediterranean dietary pattern. The PHDI showed good relative validity among adolescents in the HELENA study. Hence, future research should assess adherence to the PHDI and long-term health outcomes.

Association of elevated mid-pregnancy maternal plasma ferritin concentrations and triglyceride concentrations with the risk of gestational diabetes mellitus: A prospective cohort study.

Ferritin levels are well known to be associated with gestational diabetes mellitus (GDM). However, the association of the combination of ferritin and triglyceride (TG) levels in early mid-pregnancy with GDM has not been studied in depth. We investigated the independent and combined relationships of plasma ferritin and TG concentrations with the risk of GDM as well as the mediation effect of TG on ferritin. We analysed 2071 pregnant women from the Tongji Maternal and Child Health Cohort who had their plasma ferritin and TG concentrations measured at 11-20weeks of gestation. Associations between ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Youden's index was calculated to find the cut-off values of ferritin and TG by ROC curve analysis. The mediation effect of the TG concentration on the ferritin level with GDM risk was explored by a mediation analysis. A total of 264 (12.3%) participants developed GDM. The median and IQR of ferritin was 53.9 (30.5-92.7) ng/mL. After adjusting for potential confounders, the relative risks (RRs) and 95% confidence intervals of GDM were 2.19 (1.42, 3.39) for ferritin and 2.02 (1.37, 2.97) for TG. The adjusted RR for combination was 2.40 (1.62, 3.55). Moreover, we found that the TG concentration mediated 15.0% of the total effect of the ferritin concentration on the risk of GDM. Women with a combination of both high plasma ferritin (˃55.7ng/mL) and high TG (˃1.9mmoL/L) were at the highest risk of GDM. Additionally, we have revealed for the first time that an elevated maternal TG concentration in early pregnancy mediates the relationship between ferritin concentration and GDM risk. This trial is registered at https://ClinicalTrials.gov as NCT03099837.

Plasma Ferritin Concentrations in the General Population: A Cross-Sectional Analysis of Anthropometric, Metabolic, and Dietary Correlates

BackgroundElevated concentrations of ferritin seem to be detrimental to human health while being quite common in the elderly. Data on dietary, anthropometric, and metabolic correlates of circulating ferritin levels in the elderly are scant. ObjectivesWe aimed to identify a dietary pattern, anthropometric, and metabolic traits associated with plasma ferritin status in an elderly cohort (n = 460, 57% male, age: 66 ± 12 y) from Northern Germany. MethodsPlasma ferritin levels were measured by immunoturbidimetry. Reduced rank regression (RRR) yielded a dietary pattern explaining 13% of the variation in circulating ferritin concentrations. Cross-sectional associations of anthropometric and metabolic traits with plasma ferritin concentrations were assessed using multivariable-adjusted linear regression analysis. Restricted cubic spline regression was used to identify nonlinear associations. ResultsThe RRR pattern was characterized by a high intake of potatoes, certain vegetables, beef, pork, processed meat, fats (frying and animal fat), and beer and a low intake of snacks, representing elements of the traditional German diet. BMI, waist circumference, and CRP were directly, HDL cholesterol inversely, and age nonlinearly associated with plasma ferritin concentrations (all P < 0.05). After additional adjustment for CRP, only the association of ferritin with age remained statistically significant. ConclusionHigher plasma ferritin concentrations were associated with a traditional German dietary pattern. The associations of ferritin with unfavorable anthropometric traits and low HDL cholesterol were rendered statistically nonsignificant upon additional adjustment for chronic systemic inflammation (measured as elevated biomarker of the measurement of inflammation (CRP)), suggesting that these associations were largely driven by the proinflammatory role of ferritin (an acute-phase reactant).

A Vegetarian Diet Rich in Soybean Products Compromises Iron Status in Young Students

The iron status of young Chinese Buddhist vegetarians (23 men and 32 women) and nonvegetarian students (20 men and 39 women from a medical college) was investigated by dietary assessment of iron intake and hematological measurement of biochemical indices including hemoglobin, plasma iron, transferrin, transferrin saturation and plasma ferritin. A characteristic of the vegetarian diet in this study was the replacement of meat by soybean products. Results of the dietary assessment showed that the average iron density of the diets ranged from 1.9 to 2.2 mg/MJ, with no difference between the vegetarian and nonvegetarian diets. Daily iron intake was similar in both vegetarian and nonvegetarian men. However, iron intake was significantly higher in female vegetarians than nonvegetarians, averaging 104 and 78% of the RDA, respectively. Results of blood analysis showed that, for both sexes, the median plasma ferritin concentration of the vegetarians (male 47 µg/L and female 12 µg/L) was about half the level of the nonvegetarians (male 91 µg/L and female 27 µg/L). Occurrence and risk of iron deficiency are more prevalent in vegetarians. Correlation between plasma ferritin concentration and years of vegetarian practice in vegetarian men was marginally significant (r = -0.38, P = 0.077). We conclude that a vegetarian diet that is rich in soybean products and restricted in animal foods is limited in bioavailable iron and is not adequate for maintaining iron balance in men and women.

Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or α1-Acid Glycoprotein

BackgroundFerritin and hepcidin are markers of iron status that typically increase during inflammation or infection. The postpartum period is a physiologically unique life stage in which the relations between these proteins and other markers of inflammation have not been extensively studied. ObjectiveWe aimed to determine whether 2 markers of inflammation [high-sensitivity C-reactive protein (CRP) and α1-acid glycoprotein (AGP)] were associated with ferritin or hepcidin in postpartum women in California. MethodsThis is a secondary analysis of a randomized controlled iron-intervention trial. Plasma CRP, AGP, ferritin, and hepcidin were analyzed at 2 and 17 wk postpartum in 114 lactating women. We examined Pearson correlation coefficients between all biomarkers at both time points and differences in mean values of ferritin and hepcidin between those with and without elevated CRP and/or AGP. ResultsAt 2 and 17 wk postpartum, 58% and 26% of women had CRP >5 mg/L and 78% and 29% had AGP >1 g/L, respectively. Neither CRP nor AGP was significantly correlated with ferritin (r = 0.07 and −0.06; n = 114 at 2 wk; −0.14 and −0.14; n = 95 at 17 wk) or hepcidin (r = 0.18 and −0.03 at 2 wk; −0.05 and −0.14 at 17 wk; P > 0.05 for all). At 2 wk, geometric mean plasma ferritin and hepcidin concentrations did not differ between women with and without elevated CRP or AGP (P > 0.5), but at 17 wk women with elevated CRP or AGP had lower mean (95% CI) ferritin and hepcidin than did women without either elevated CRP or AGP [ferritin: 30.3 ng/mL (23.4, 39.1 ng/mL) compared with 40.2 ng/mL (32.9, 49.2 ng/mL); P < 0.01; hepcidin: 44.3 ng/mL (32.3, 60.9 ng/mL) compared with 67.6 ng/mL (56.1, 81.5 ng/mL); P = 0.02]. ConclusionsLower ferritin and hepcidin among women with elevated CRP or AGP at 17 wk postpartum suggests that these markers of iron status react differently to physiologic immune activation than to pathologic inflammatory states.

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

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

The Relationship Between Ferritin and BMI is Mediated by Inflammation Among Women in Higher-Income Countries, But Not in Most Lower-Income Countries Nor Among Young Children: A Multi-Country Analysis

In the presence of inflammation, the serum or plasma ferritin concentration ("ferritin" hereafter) transiently increases, confounding its interpretation as an iron status marker. The extent to which adiposity-related inflammation may influence ferritin interpretation is uncertain. We describe relationships between weight status, inflammation, and ferritin among nonpregnant women of reproductive age (WRA; 15-49 years) and preschool-age children (PSC; 6-59 months) with normal weight to overweight or obesity (OWOB) in differing geographic settings. Cross-sectional data were separately analyzed from 18 surveys (WRA) and 25 surveys (PSC) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (in WRA) or BMI-for-age z-score (BAZ; in PSC), inflammatory biomarkers of C-reactive protein (CRP) and/or α-1-acid glycoprotein (AGP), ferritin by linear regression, and potential mediation by CRP and/or AGP in relationships between BMI or BAZ and ferritin with structural equation modeling. Regression and mediation models accounted for complex survey designs. Results were grouped by World Bank income classifications. In 5 of 6 surveys among WRA from upper-middle and high-income countries, ferritin was significantly positively associated with BMI, and this relationship was partially (or fully, in the United States) mediated by CRP and/or AGP. Mediation was present in 4 of 12 surveys for WRA in low- and lower-middle income countries. Among PSC, ferritin was positively associated with CRP and/or AGP in all surveys, but there were no significant CRP- or AGP-mediated relationships between ferritin and BAZ, except a negative relationship in the Philippines. Where having OWOB is common among WRA, measurements of inflammatory biomarkers and their uses in interpreting ferritin may improve iron status assessments. While these relationships were inconsistent among PSC, inflammation was common and should be measured to interpret iron status. Included Kenyan trial data are registered at clinicaltrials.gov as NCT01088958.

Efficacy of iron-folic acid treatment for reducing anemia prevalence and improving iron status in women of reproductive age: A one-year longitudinal study.

Anemia control has hitherto been through prophylaxis with weekly iron folic acid (IFA) in Indian women of reproductive age (WRA). Recently, a more precise approach has been proposed, that uses a 'screen and treat with IFA' approach for anemic WRA, combined with continued prophylactic IFA in non-anemic WRA. The efficacy of this approach was assessed in Indian WRA, along with changes in iron status biomarkers. Young WRA (n=470), aged 17-21y, were screened for their venous blood hemoglobin (Hb) and treated with IFA for 90 days according to their grade of anemia, or if non-anemic, administered prophylactic IFA, per Indian policy guidelines, and then followed-up for an additional 9-months. Their Hb, plasma ferritin (PF), transferrin receptor, hepcidin and C-reactive protein concentrations were measured at baseline, during treatment and further follow-up. Anemia was diagnosed using Hb (<12g/dL) and iron deficiency (ID) using PF (<15μg/L) cut-offs after adjustment for inflammation. Co-existence of anemia and ID was labelled iron deficiency anemia (IDA). At baseline, in the whole group anemia, ID and IDA prevalence was 69.6%, 68.7% and 62.4%, respectively. At 90 days, IFA treatment or prophylaxis significantly reduced anemia by 40 percentage points (pp), from 69.6% at baseline to 29.8%; ID by 47.3 pp, and IDA by 48 pp. Moreover, significant treatment effects persisted at 365 days of follow-up. The 'screen and treat with IFA' approach is efficacious in reducing the prevalence of anemia in general among WRA, with persistent and significant effects after 9 months of follow-up. CTRI No:2019/02/017806, http://ctri.nic.in/.

Association between maternal plasma ferritin concentration, iron supplement use, and the risk of gestational diabetes: a prospective cohort study

The association between iron supplementation and gestational diabetes mellitus (GDM) is still inconclusive, and this association has not been extensively studied in relation to plasma ferritin in the early second trimester. We aimed to prospectively examine the independent and combined associations of plasma ferritin concentrations and iron supplement use with GDM. We studied 2117 women from the Tongji Maternal and Child Health Cohort in Wuhan, China. Plasma ferritin around 16weeks' gestation was measured by ELISA kits and information on iron supplement use was collected by questionnaires. GDM was diagnosed by a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks' gestation. A log-Poisson regression model was used to estimate the RR of GDM associated with plasma ferritin and iron supplementation. The median and IQR of plasma ferritin was 52.1 (29.6-89.9) ng/mL, and 863 (40.8%) participants reported use of iron supplements during the second trimester. A total of 219 (10.3%) participants developed GDM. Adjusted RRs (95% CIs) for GDM across increasing quartiles of plasma ferritin were 1.00 (reference), 2.14 (1.37, 3.34), 2.03 (1.30, 3.19), and 2.72 (1.76, 4.21), respectively. After adjustment, supplemental iron ≥60 mg/d during the second trimester was associated with an increased risk of GDM compared with nonusers (RR: 1.37; 95% CI: 1.02, 1.84). Both elevated plasma ferritin concentrations in the early second trimester and use of ≥60 mg/d of supplemental iron during pregnancy are independently associated with increased risk of GDM. Further clinical trials with precision nutrition approaches considering both baseline iron status and supplement use are needed to evaluate the benefits and risks of iron supplementation during pregnancy.

Iron overload and iron chelating agent exposure in anemia-associated outer retinal degeneration: a case report and review of the literature

BackgroundDeferoxamine retinopathy is the informally designated term used to describe a characteristic pattern of outer retinal degeneration in iron-overloaded chronic anemia patients who are treated with deferoxamine. We hypothesize that insufficiently treated iron overloading and not only deferoxamine is the cause of the retinal degeneration. Our case report is based on exposure histories of two anemia patients and literature review.Case presentationBoth anemia patients presented with bilateral visual loss secondary to photoreceptor and retinal pigment epithelium degeneration. Chart review showed that visual loss came after a year-long slow, and rather monotonous rise in plasma ferritin concentrations, with no obvious relation to iron chelator exposure. In one patient, the onset of symptomatic visual loss came after a bout of fever followed by two additional febrile episodes, all accompanied by plasma ferritin spikes. Adjustment of iron chelation therapy did not improve visual function. Experimental studies clearly show that both systemic and intraocular exposure to iron ions can induce retinal degeneration.ConclusionThe available evidence indicates that retinal degeneration in chronic anemia patients treated by deferoxamine is cause by insufficient iron chelation, not by deferoxamine. The actual role of iron chelating agents may be to promote a long enough survival to allow the slow development of retinal siderosis.

Serum or plasma ferritin concentration as an index of iron deficiency and overload.

Serum or plasma ferritin concentration as an index of iron deficiency and overload.

Secretion of von Willebrand Factor and Suppression of ADAMTS-13 Activity by Markedly High Concentration of Ferritin.

Hyperferritinemia is associated with poor outcomes in critically ill patients with sepsis, hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndromes (MAS) and coronavirus disease 19 (COVID-19). Autopsies of hyperferritinemic patients that succumbed to either sepsis, HLH, MAS or COVID-19 have revealed disseminated microvascular thromboses with von Willebrand factor (VWF)-, platelets-, and/or fibrin-rich microthrombi. It is unknown whether high plasma ferritin concentration actively promotes microvascular thrombosis, or merely serves as a prognostic biomarker in these patients. Here, we show that secretion of VWF from human umbilical vein endothelial cells (HUVEC) is significantly enhanced by 100,000 ng/ml of recombinant ferritin heavy chain protein (FHC). Ferritin fraction that was isolated by size exclusion chromatography from the plasma of critically ill HLH patients promoted VWF secretion from HUVEC, compared to similar fraction from non-critically ill control plasma. Furthermore, recombinant FHC moderately suppressed the activity of VWF cleaving metalloprotease ADAMTS-13. These observations suggest that a state of marked hyperferritinemia could promote thrombosis and organ injury by inducing endothelial VWF secretion and reducing the ADAMTS-13 activity.

Skeletal muscle ferritin abundance is tightly related to plasma ferritin concentration in adults with obesity.

What is the central question of this study? Obesity is associated with complex perturbations to iron homeostasis: is plasma ferritin concentration (a biomarker of whole-body iron stores) related to the abundance of ferritin (the key tissue iron storage protein) in skeletal muscle in adults with obesity? What is the main finding and its importance? Plasma ferritin concentration was tightly correlated with the abundance of ferritin in skeletal muscle, and this relationship persisted when accounting for sex, age, body mass index and plasma C-reactive protein concentration. Our findings suggest that skeletal muscle may be an important iron store. Obesity is associated with complex perturbations to whole-body and tissue iron homeostasis. Recent evidence suggests a potentially important influence of iron storage in skeletal muscle on whole-body iron homeostasis, but this association is not clearly resolved. The primary aim of this study was to assess the relationship between whole-body and skeletal muscle iron stores by measuring the abundance of the key iron storage (ferritin) and import (transferrin receptor) proteins in skeletal muscle, as well as markers of whole-body iron homeostasis in men (n=19) and women (n=43) with obesity. Plasma ferritin concentration (a marker of whole-body iron stores) was highly correlated with muscle ferritin abundance (r=0.77, P=2×10-13 ) and negatively associated with muscle transferrin receptor abundance (r=-0.76, P=1×10-12 ). These relationships persisted when accounting for sex, age, BMI and plasma C-reactive protein concentration. In parallel with higher whole-body iron stores in our male versus female participants, men had 2.2-fold higher muscle ferritin abundance (P=1×10-4 ) compared with women. In accordance with lower muscle iron storage, women had 2.7-fold higher transferrin receptor abundance (P=7×10-10 ) compared with men. We conclude that muscle iron storage and import proteins are tightly and independently related to plasma ferritin concentration in adults with obesity, suggesting that skeletal muscle may be an underappreciated iron store.

Plasma Iron Indices in Pregnant Women Referred to the University of Abuja Teaching Hospital, Nigeria

Background and Aims: Iron Deficiency (ID) is a common obstetric problem and nutritional disorder that occurs mostly in developing countries. Hence, nutritional studies are required every few years to determine the necessary healthcare interventions for pregnant women. This cross-sectional study evaluated the plasma iron, ferritin, transferrin, total iron-binding capacity (TIBC), and unsaturated iron-binding capacity (UIBC) levels of pregnant women referred to the University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria.&#x0D; Materials and Methods: Blood samples were collected from 58 non-pregnant women, 22 pregnant women in the first trimester, 52 in second, and 44 in the third trimester. The plasma ferritin concentration of these samples was measured by chemiluminescence assay, while the plasma transferrin, TIBC, and iron concentrations were measured by enzyme-linked immunosorbent assay. Plasma ferritin levels &lt;15μg/L were considered ID.&#x0D; Results: The overall prevalence of ID in pregnant women was 33.1%. However, the prevalence of ID was 29.3%, 22.7%, 34.6%, and 36.4% among non-pregnant women, women in the first trimester, second and third trimester, respectively. The mean±SEM iron levels were significantly higher among pregnant women compared to non-pregnant women (p=0.004). There was no significant difference in the mean±SEM of plasma ferritin, transferrin and TIBC concentrations between pregnant and non-pregnant women (p&gt;0.05). Nevertheless, the mean±SEM plasma iron, ferritin, and UIBC significantly differed across the gestational ages of pregnant women (p&lt;0.05).&#x0D; Conclusions: This study revealed a high prevalence of ID during pregnancy, which increases with the trimester of affected women. Healthcare interventional measures that can address ID are recommended.

A Pharmacologic "Stress Test" for Assessing Select Antioxidant Defenses in Patients with CKD.

Oxidative stress is a hallmark and mediator of CKD. Diminished antioxidant defenses are thought to be partly responsible. However, there is currently no way to prospectively assess antioxidant defenses in humans. Tin protoporphyrin (SnPP) induces mild, transient oxidant stress in mice, triggering increased expression of select antioxidant proteins (e.g., heme oxygenase 1 [HO-1], NAD[P]H dehydrogenase [quinone] 1 [NQO1], ferritin, p21). Hence, we tested the hypothesis that SnPP can also variably increase these proteins in humans and can thus serve as a pharmacologic "stress test" for gauging gene responsiveness and antioxidant reserves. , setting, participants, & measurementsA total of 18 healthy volunteers and 24 participants with stage 3 CKD (n=12; eGFR 30-59 ml/min per 1.73 m2) or stage 4 CKD (n=12; eGFR 15-29 ml/min per 1.73 m2) were injected once with SnPP (9, 27, or 90 mg). Plasma and/or urinary antioxidant proteins were measured at baseline and for up to 4 days post-SnPP dosing. Kidney safety was gauged by serial measurements of BUN, creatinine, eGFR, albuminuria, and four urinary AKI biomarkers (kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, cystatin C, and N-acetyl glucosaminidase). Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (r=-0.85 to -0.95). All four proteins manifested statistically significant dose- and time-dependent elevations after SnPP injection. However, marked intersubject differences were observed. p21 responses to high-dose SnPP and HO-1 responses to low-dose SnPP were significantly suppressed in participants with CKD versus healthy volunteers. SnPP was well tolerated by all participants, and no evidence of nephrotoxicity was observed. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.

EP19 Hyperferritinaemia causes in a UK district general hospital

Abstract Background Hyperferritinaemia has multiple causes including iron overload, liver disease, and systemic inflammation either in the context of infection, autoimmunity, or malignancy. Marked hyperferritinaemia has been used to aid diagnosis of rare autoimmune conditions such as adult onset Still’s disease. Methods Patients with plasma ferritin concentrations over 3000 μg/L from 7 April 2014 until 30 August 2019 (just over 5 years) in a district general hospital were identified. Those without sufficient documentation to identify the likely causes of hyperferritinaemia were excluded. Included patients (n = 283) were grouped according to maximum ferritin concentration, and likely causes of hyperferritinaemia from the following list were classified as follows: Infection; solid organ malignancy; haematological malignancy, autoimmune disease; transfusion dependence; liver disease, renal failure, haemolytic anaemia. Results The most common causes of hyperferritinaemia were infection (31%), solid organ malignancy, (28%), haematological malignancy (23%), and liver disease (22%). Peak ferritin concentration did not appear to be strongly associated with the factors that caused it. To explore the diagnostic utility of ferritin to distinguish autoimmune processes, infection, malignancy, and liver disease, an association between these factors and maximum ferritin concentration was tested for using Fisher’s exact test. No statistically significant association was found (p = 0.8967). Conclusion We found no association between maximum ferritin concentration and the causes thereof, however this study does not elucidate the diagnostic utility of hyperferritinaemia since most of the patients studied had established diagnoses before their hyperferritinaemia was identified. Hyperferritinaemia appears to be a marker of severe disease, in that most of the patients studied had died by the time of data collection. Disclosures T. Fieldman None. L. Stimson None. S. Zeb None. S. Alderson None. M. Lloyd None.