RESUMEN
BACKGROUND: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. METHODS: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). RESULTS: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. CONCLUSIONS: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.
Asunto(s)
Médula Ósea , Deferoxamina , Ferritinas , Sobrecarga de Hierro , Hierro , Hígado , Diálisis Renal , Humanos , Masculino , Femenino , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/metabolismo , Médula Ósea/metabolismo , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Ferritinas/sangre , Ferritinas/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/diagnóstico por imagen , Persona de Mediana Edad , Deferoxamina/uso terapéutico , Deferoxamina/administración & dosificación , Hierro/metabolismo , Anciano , Imagen por Resonancia Magnética , Estudios Prospectivos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/sangre , Factor-23 de Crecimiento de Fibroblastos , Hepcidinas/metabolismoRESUMEN
Hepcidin production is regulated by iron concentration, erythropoietic activity, and inflammation. There is no reference method for determining its levels, but results obtained through various methods strongly correlate and can be compared using recalibration equations. OBJECTIVE: To describe recalibrated serum hepcidin values at different percentiles in schoolchildren, considering age, sex, inflammatory processes, H. pylori infection, and iron status. METHODS: Secondary analysis of data incorporating information on inflammation, H. pylori infection, and iron status of 349 schoolchildren. Hepcidin analysis was performed using a competitive ELISA, and recalibrated hepcidin values were calculated using the inverse of the linear regression model equation obtained by van der Vorm et al. Results: Recalibrated hepcidin values were lower than non-calibrated values. In schoolchildren without infection/inflammation and without iron deficiency, recalibrated values at the 50th percentile (25th-75th) were 4.89 ng/mL (2.68-8.42). For schoolchildren without infection/inflammation but with iron deficiency, recalibrated values were 2.34 ng/mL (1.10-6.58), the lowest hepcidin values observed. The highest values were found in the group with infection/inflammation, regardless of iron deficiency status. CONCLUSIONS: Recalibrated hepcidin values were lower than non-calibrated values. The highest values were observed in schoolchildren with infectious or inflammatory processes, and the lowest values were observed in schoolchildren with iron deficiency but only in the absence of infectious or inflammatory processes. Using recalibrated hepcidin values allows comparison between data obtained using different analytical methods.
Asunto(s)
Hepcidinas , Inflamación , Humanos , Hepcidinas/sangre , Niño , Femenino , Masculino , México/epidemiología , Inflamación/sangre , Inflamación/epidemiología , Adolescente , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/epidemiología , Estado Nutricional , Hierro/sangre , Helicobacter pylori , Valores de ReferenciaRESUMEN
BACKGROUND/OBJECTIVES: Sickle cell anemia (SCA) is marked by hypoxia, inflammation, and secondary iron overload (IO), which potentially modulate hepcidin, the pivotal hormone governing iron homeostasis. The aim was to evaluate the iron incorporation in red blood cells (RBC) in SCA pediatric patients, considering the presence or absence of IO. SUBJECTS/METHODS: SCA children (n = 12; SCAtotal) ingested an oral stable iron isotope (57Fe) and iron incorporation in RBC was measured after 14 days. Patients with ≥1000 ng/mL serum ferritin were considered to present IO (SCAio+; n = 4) while the others were classified as being without IO (SCAio-; n = 8). Liver iron concentration (LIC) was determined by Magnetic Resonance Imaging (MRI) T2* method. RESULTS: The SCAio+ group had lower iron incorporation (mean ± SD: 0.166 ± 0.04 mg; 3.33 ± 0.757%) than SCAio- patients (0.746 ± 0.303 mg; 14.9 ± 6.05%) (p = 0.024). Hepcidin was not different between groups. Iron incorporation was inversely associated with serum ferritin level (SCAtotal group: r = -0.775, p = 0.041; SCAio- group: r = -0.982; p = 0.018) and sickle hemoglobin (HbS) presented positive correlation with iron incorporation (r = 0.991; p = 0.009) in SCAio- group. LIC was positively associated with ferritin (SCAtotal: r = 0.921; p = 0.026) and C reactive protein (SCAio+: r = 0.999; p = 0.020). CONCLUSION: SCAio+ group had lower iron incorporation in RBC than SCAio- group, suggesting that they may not need to reduce their intake of iron-rich food, as usually recommended. Conversely, a high percentage of HbS may indirectly exacerbate hypoxia and seems to increase iron incorporation in RBC. TRIAL REGISTRATION: This trial was registered at www.ensaiosclinicos.gov.br . Identifier RBR-4b7v8pt.
Asunto(s)
Anemia de Células Falciformes , Eritrocitos , Ferritinas , Hepcidinas , Isótopos de Hierro , Sobrecarga de Hierro , Hierro , Humanos , Anemia de Células Falciformes/sangre , Proyectos Piloto , Eritrocitos/metabolismo , Niño , Masculino , Femenino , Ferritinas/sangre , Hierro/sangre , Hierro/metabolismo , Sobrecarga de Hierro/sangre , Adolescente , Hepcidinas/sangre , Hígado/metabolismoRESUMEN
PURPOSE: Iron absorption in sickle cell anemia (SCA) remains unclear and studies in adults with SCA are scarce. The aim of this study was to evaluate the iron absorption SCA adults and its association with iron status and hepcidin concentration. METHODS: SCA patients (n = 13; SCAtotal) and control participants (n = 10) ingested an oral stable iron isotope (57Fe). Iron absorption was measured by inductively coupled plasma mass spectrometry (ICP-MS) 14 days after isotope administration. Patients with ≥ 1000 ng/mL serum ferritin were considered to present iron overload (IO) (SCAio+; n = 3) and others classified without IO (SCAio-; n = 10). RESULTS: Iron absorption in the control group ranged from 0.3 to 26.5% (median = 0.9%), while it varied from 0.3 to 5.4% in SCAio+ (median = 0.5%) and from 0.3 to 64.2% in the SCAio- (median = 6.9%). Hepcidin median values were 14.1 ng/mL (3.0-31.9 ng/mL) in SCAio-, 6.2 ng/mL (3.3-7.8 ng/mL) in SCAio + and 6.2 ng/mL (0.6-9.3 ng/mL) in control. Iron absorption was associated with ferritin level (r = - 0.641; p = 0.018) and liver iron concentration (LIC; r = - 0.786; p = 0.036) in the SCAtotal group. CONCLUSION: Our data suggest that SCAio- individuals may be at risk of developing primary IO. Simultaneously, secondary IO may induce physiological adaptation, resulting in reduced iron absorption. Further studies evaluating intestinal iron absorption using larger sample sizes should be conducted to help establish a safe nutrition approach to be adopted and to ensure the security of food-fortifying public policies for these patients. TRIAL REGISTRATION: This trial was registered at www.ensaiosclinicos.gov.br (Identifier RBR-4b7v8pt).
Asunto(s)
Anemia de Células Falciformes , Hepcidinas , Absorción Intestinal , Isótopos de Hierro , Humanos , Anemia de Células Falciformes/sangre , Adulto , Masculino , Femenino , Isótopos de Hierro/farmacocinética , Hepcidinas/sangre , Adulto Joven , Ferritinas/sangre , Hierro/sangre , Hierro/farmacocinética , Hierro/metabolismo , Sobrecarga de Hierro , Hierro de la Dieta/farmacocinética , Hierro de la Dieta/administración & dosificación , Persona de Mediana Edad , Estado NutricionalRESUMEN
OBJECTIVES: This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity's inflammation biomarkers. DATA SOURCE: Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes. SUMMARY OF FINDINGS: Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin's quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity's inflammatory environment began to be published in 2008. CONCLUSIONS: Obesity's chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.
Asunto(s)
Anemia Ferropénica , Deficiencias de Hierro , Obesidad Infantil , Adolescente , Niño , Humanos , Obesidad Infantil/complicaciones , Hepcidinas , Interleucina-6 , Índice de Masa Corporal , Hierro , Inflamación , Biomarcadores , Anemia Ferropénica/complicaciones , Anemia Ferropénica/epidemiologíaRESUMEN
PURPOSE: The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations. METHODS: We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60 min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB). RESULTS: Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (ß: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (ß: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (ß: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (ß: - 11.16; 95% CI: - 18.52, - 3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner. CONCLUSIONS: LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans. TRIAL REGISTRATION: The study was retrospectively registered in clinicaltrials.gov (April 2023). CLINICALTRIALS: gov Identifier: NCT05815641.
Asunto(s)
Ghrelina , Hambre , Masculino , Femenino , Humanos , Hambre/fisiología , Hepcidinas , Apetito , Obesidad , SensaciónRESUMEN
EBV and Helicobacter pylori (H. pylori) cause highly prevalent persistent infections as early as in childhood. Both pathogens are associated with gastric carcinogenesis. H. pylori interferes with iron metabolism, enhancing the synthesis of acute-phase proteins hepcidin, C-reactive protein (CRP), and α-1 glycoprotein (AGP), but we do not know whether EBV does the same. In this study, we correlated the EBV antibody levels and the serum levels of hepcidin, CRP, and AGP in 145 children from boarding schools in Mexico City. We found that children IgG positive to EBV antigens (VCA, EBNA1, and EA) presented hepcidin, AGP, and CRP levels higher than uninfected children. Hepcidin and AGP remained high in children solely infected with EBV, while CRP was only significantly high in coinfected children. We observed positive correlations between hepcidin and EBV IgG antibodies (p < 0.5). Using the TCGA gastric cancer database, we also observed an association between EBV and hepcidin upregulation. The TCGA database also allowed us to analyze the two important pathways controlling hepcidin expression, BMP−SMAD and IL-1ß/IL-6. We observed only the IL-1ß/IL-6-dependent inflammatory pathway being significantly associated with EBV infection. We showed here for the first time an association between EBV and enhanced levels of hepcidin. Further studies should consider EBV when evaluating iron metabolism and anemia, and whether in the long run this is an important mechanism of undernourishment and EBV gastric carcinogenesis.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Helicobacter pylori , Neoplasias Gástricas , Niño , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/metabolismo , Helicobacter pylori/metabolismo , Hepcidinas/metabolismo , Herpesvirus Humano 4 , Inmunoglobulina G/metabolismo , Interleucina-6/metabolismo , Hierro/metabolismo , Neoplasias Gástricas/etiologíaRESUMEN
IMPORTANCE: Since the beginning of the COVID-19 pandemic, numerous metabolic alterations have been observed in individuals with this disease. It is known that SARS-CoV-2 can mimic the action of hepcidin, altering intracellular iron metabolism, but gaps remain in the understanding of possible outcomes in other pathways involved in the iron cycle. OBJECTIVE: To profile iron, ferritin and hepcidin levels and transferrin receptor gene expression in patients diagnosed with COVID-19 between June 2020 and September 2020. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study that evaluated iron metabolism markers in 427 participants, 218 with COVID-19 and 209 without the disease. EXPOSURES: The primary exposure was positive diagnose to COVID-19 in general population of Santo André and São Bernardo cities. The positive and negative diagnose were determinate through RT-qPCR. MAIN OUTCOMES AND MEASURES: Devido a evidências de alterações do ciclo do ferro em pacientes diagnosticados com COVID-19 e devido a corregulação entre hepcidina e receptor de transferrina, uma análise da expressão gênica deste último, poderia trazer insights sobre o estado de ferro celular. A hipótese foi confirmada, mostrando aumento da expressão de receptor de transferrina concomitante com redução do nível de hepcidina circulante. RESULTS: Serum iron presented lower values in individuals diagnosed with COVID-19, whereas serum ferritin presented much higher values in infected patients. Elderly subjects had lower serum iron levels and higher ferritin levels, and men with COVID-19 had higher ferritin values than women. Serum hepcidin was lower in the COVID-19 patient group and transferrin receptor gene expression was higher in the infected patient group compared to controls. CONCLUSIONS AND RELEVANCE: COVID-19 causes changes in several iron cycle pathways, with iron and ferritin levels being markers that reflect the state and evolution of infection, as well as the prognosis of the disease. The increased expression of the transferrin receptor gene suggests increased iron internalization and the mimicry of hepcidin action by SARS-CoV-2, reduces iron export via ferroportin, which would explain the low circulating levels of iron by intracellular trapping.
Asunto(s)
COVID-19 , Transferrina , Masculino , Humanos , Femenino , Anciano , Transferrina/análisis , Hepcidinas , Estudios Transversales , Pandemias , SARS-CoV-2 , Hierro/metabolismo , Ferritinas , Receptores de Transferrina , HomeostasisRESUMEN
The stomach-derived octanoylated peptide ghrelin was discovered in 1999 and recognized as an endogenous agonist of the growth hormone secretagogue receptor (GHSR). Subsequently, ghrelin has been shown to play key roles in controlling not only growth hormone secretion, but also a variety of other physiological functions including, but not limited to, food intake, reward-related behaviors, glucose homeostasis and gastrointestinal tract motility. Importantly, a non-acylated form of ghrelin, desacyl-ghrelin, can also be detected in biological samples. Desacyl-ghrelin, however, does not bind to GHSR at physiological levels, and its physiological role has remained less well-characterized than that of ghrelin. Ghrelin and desacyl-ghrelin are currently referred to in the literature using many different terms, highlighting the need for a consistent nomenclature. The variability of terms used to designate ghrelin can lead not only to confusion, but also to miscommunication, especially for those who are less familiar with the ghrelin literature. Thus, we conducted a survey among experts who have contributed to the ghrelin literature aiming to identify whether a consensus may be reached. Based on the results of this consensus, we propose using the terms "ghrelin" and "desacyl-ghrelin" to refer to the hormone itself and its non-acylated form, respectively. Based on the results of this consensus, we further propose using the terms "GHSR" for the receptor, and "LEAP2" for liver-expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist.
Asunto(s)
Hepcidinas , Receptores de Ghrelina , Receptores de Ghrelina/metabolismo , Agonismo Inverso de Drogas , ConsensoRESUMEN
Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg-1·day-1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.
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Diabetes Mellitus Experimental , Sobrecarga de Hierro , Ratas , Masculino , Animales , Hepcidinas/metabolismo , Hierro/metabolismo , Capsaicina/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratas Wistar , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/metabolismo , Riñón/metabolismo , BiomarcadoresRESUMEN
BACKGROUND: Hepcidin is a protein that regulates the metabolism of iron. In addition, a high iron load can cause insulin resistance and subsequent diabetes. OBJECTIVE: To investigate the association between hepcidin levels and glucose, insulin, lipids, HOMA-IR, and inflammatory markers, C reactive protein (CRP), ferritin, Lp (a), and leucocytes, in indigenous school children living at 4000 m above sea level. Data were collected cross-sectionally from the four schools in San Antonio de los Cobres (SAC). BMI, glucose, insulin, lipids, CRP, hemoglobin, leucocytes, iron, ferritin, transferrin, and hepcidin levels were obtained. RESULTS: Three hundred and seventy-six children (170 males) aged 9.6 ± 2.3 y were included. Fifty-five(15.2 %) children were underweight, 28 (7.4 %) overweight and 10 (2.7 %) obese. Univariate analysis showed a significant inverse correlation between hepcidin and glucose (r = -0.14) and HOMA-IR (r = -0.30). Furthermore, hepcidin was found to be directly and significantly correlated with Lp(a) (r = 0.18), leucocytes (r = 0.24,) CRP (r = 0.32), and ferritin (r = 0.32). Multiple linear regression analysis indicated that hepcidin was significantly and inversely associated with glucose and BMI and directly with Lp(a), CRP, leucocytes, and ferritin; adjusted for age and gender (R2 0.26). CONCLUSION: In this study, which included indigenous children living at high altitudes (4000 m), hepcidin was significantly and inversely associated with glucose and BMI and directly associated with inflammatory markers such as CRP, Lp(a), leucocytes, and ferritin, suggesting that hepcidin could be a reliable marker of future type 2 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hepcidinas , Niño , Masculino , Humanos , Hepcidinas/metabolismo , Altitud , Biomarcadores , Ferritinas , Proteína C-Reactiva/metabolismo , Insulina/metabolismo , Glucosa , Hierro/metabolismo , LípidosRESUMEN
Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations of MINDI variables with maternal anemia, elevated serum transferrin receptor (sTfR), low serum iron, hepcidin, ferritin, and infant weight-for-age (WAZ), length-for-age (LAZ), and head-circumference-for-age (HCAZ) Z-scores in 99 mother-infant dyads. A bootstrapping resampling procedure preselected covariates for inclusion in multivariable regressions models from chronic maternal infections and nutritional status [folate, vitamins A, D, retinol-binding protein (RBP), insulin-growth factor-1 (IGF-1)] and inflammation [C-reactive protein (CRP), cytokines, platelet indices] indicators. Anemia was prevalent (53.5%) but underestimated due to widespread low plasma volume (<2.2 L, 79.9%) and was associated with indicators of malnutrition [lower IGF-1, body mass index (BMI), vitamin D, and intake of green/leafy vegetables], but not inflammation. Higher CRP was associated with lower serum iron, and higher hepcidin and ferritin, whereas maternal platelets were associated with lower HCAZ (ß = −0.22), WAZ (ß = −0.17), and LAZ (ß = −0.17). Higher LAZ was also associated with maternal serum vitamin D (ß = 0.23), whereas maternal iron supplementation lowered LAZ (ß = −0.22). Assessment of iron status in this MINDI cohort is complex and supplementation strategies must consider consequences for both the mother and the infant.
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Anemia Ferropénica , Anemia , Desnutrición , Anemia Ferropénica/epidemiología , Antropometría , Proteína C-Reactiva/metabolismo , Estudios Transversales , Femenino , Ferritinas , Hepcidinas , Humanos , Lactante , Inflamación , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hierro , Lactancia , Nutrientes , Vitamina DRESUMEN
INTRODUCTION: Although hyperferritinemia may reflect the inflammatory status of patients with non-alcoholic fatty liver disease (NAFLD), approximately 33% of hyperferritinemia cases reflect real hepatic iron overload. AIM: To evaluate a non-invasive method for assessing mild iron overload in patients with NAFLD using 3T magnetic resonance imaging (MRI) relaxometry, serum hepcidin, and the expression of ferritin subunits. METHODS: This cross-sectional study assessed patients with biopsy-proven NAFLD. MRI relaxometry was performed using a 3T scanner in all patients, and the results were compared with iron content determined by liver biopsy. Ferritin, hepcidin, and ferritin subunits were assessed and classified according to ferritin levels and to siderosis identified by liver biopsy. RESULTS: A total of 67 patients with NAFLD were included in the study. MRI revealed mild iron overload in all patients (sensitivity, 73.5%; specificity, 70%). For mild (grade 1) siderosis, the transverse relaxation rate (R2*) threshold was 58.9 s-1 and the mean value was 72.5 s-1 (SD, 33.9), while for grades 2/3 it was 88.2 s-1 (SD, 31.9) (p < 0.001). The hepcidin threshold for siderosis was > 30.2 ng/mL (sensitivity, 87%; specificity, 82%). Ferritin H and ferritin L subunits were expressed similarly in patients with NAFLD, regardless of siderosis. There were no significant differences in laboratory test results between the groups, including glucose parameters and liver function tests. CONCLUSIONS: MRI relaxometry and serum hepcidin accurately assessed mild iron overload in patients with dysmetabolic iron overload syndrome.
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Hiperferritinemia , Sobrecarga de Hierro , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Siderosis , Estudios Transversales , Ferritinas , Hepcidinas , Humanos , Sobrecarga de Hierro/diagnóstico por imagen , Sobrecarga de Hierro/etiología , Hígado/patología , Síndrome Metabólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Siderosis/metabolismo , Siderosis/patologíaAsunto(s)
Anemia Ferropénica , Desnutrición , Biomarcadores , Hepcidinas , Humanos , Hierro , Desnutrición/complicacionesRESUMEN
Abstract Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.
Asunto(s)
Humanos , Masculino , Femenino , Trastornos del Metabolismo del Hierro , Hemocromatosis/diagnóstico , Hemocromatosis/terapia , Flebotomía , Sobrecarga de Hierro , Hepcidinas/deficiencia , Proteína de la HemocromatosisRESUMEN
OBJECTIVES: To evaluate whether extremely preterm infants regulate iron status via hepcidin. STUDY DESIGN: In this retrospective analysis of infants from the Preterm Epo Neuroprotection (PENUT) Trial, urine hepcidin (Uhep) normalized to creatinine (Uhep/UCr) was evaluated among infants randomized to erythropoietin (Epo) or placebo. RESULTS: The correlation (r) between Uhep/UCr and serum markers of iron status (ferritin and zinc protoporphyrin-to-heme ratio [ZnPP/H]) and iron dose was assessed. A total of 243 urine samples from 76 infants born at 24-276/7 weeks gestation were analyzed. The median Uhep/UCr concentration was 0.3, 1.3, 0.4, and 0.1 ng/mg at baseline, 2 weeks, 4 weeks, and 12 weeks, respectively, in placebo-treated infants. The median Uhep/UCr value in Epo-treated infants were not significantly different, with the exception of the value at the 2-week time point (median Uhep/UCr, 0.1 ng/mg; P < .001). A significant association was seen between Uhep/UCr and ferritin at 2 weeks (r = 0.63; P < .001) and at 4 weeks (r = 0.41; P = .01) and between Uhep/UCr and ZnPP/H at 2 weeks (r = -0.49; P = .002). CONCLUSIONS: Uhep/UCr values correlate with serum iron markers. Uhep/UCr values vary over time and are affected by treatment with Epo, suggesting that extremely preterm neonates can regulate hepcidin and therefore their iron status. Uhep is suppressed in extremely preterm neonates, particularly those treated with Epo.
Asunto(s)
Creatinina/orina , Eritropoyetina/administración & dosificación , Hepcidinas/orina , Recien Nacido Extremadamente Prematuro/metabolismo , Hierro/metabolismo , Biomarcadores/sangre , Ferritinas/sangre , Hemo , Humanos , Lactante , Recién Nacido , Protoporfirinas/sangre , Estudios RetrospectivosRESUMEN
The effects of an adequate supply of vitamin A and iron, in comparison with diets low or absent in vitamin A and low in iron, on the mRNA expression of some biomarkers of iron homeostasis as hepcidin (Hamp), transferrin receptor-1 (Tfrc), iron regulatory protein-2 (Ireb2) and ferritin (Fth1) in rats were investigated. 35 male Wistar rats were randomly divided into 5 dietary groups: control, sufficient in iron and insufficient in vitamin A (FesvAi), sufficient in iron and depleted in vitamin A (FesvAd), insufficient in iron and sufficient in vitamin A (FeivAs) and insufficient in both iron and vitamin A (FeivAi). After 6 weeks rats showed no significant effects of variations in vitamin A on the expression of Hamp relative to the control group (FesvAi: 1.37-fold; FesvAd: 1.22-fold); however, iron deficiency showed significant reduction on it relative to the control group (FeivAs: 71.4-fold, P = 0.0004; FeivAi: 16.1-fold, P = 0.0008). Vitamin A deficiency (FesvAd) affects expression of Fth1 independent of low dietary iron in spleen (0.29-fold, P = 0.002) and duodenum (5.15-fold, P = 0.02). Variations of dietary iron and vitamin A showed significant effects relative to the control group for expression of Tfrc in spleen (FesvAd: 0.18-fold, P = 0.01; FeivAs: 0.24-fold, P < 0.0001; FeivAi: 0.42-fold, P = 0.014), Ireb2 in spleen (FeivAs: 3.7-fold, P < 0.0001; FeivAi: 2.9-fold, P < 0.0001) and Ireb2 in duodenum (FeivAs: 2.68-fold, P = 0.012; FeivAi: 2.60-fold, P = 0.014). These results show that vitamin A and iron must be supplied together to regulate some of the main biomarkers of iron metabolism as a strategy to reduce prevalence of iron deficiency anemia.
Asunto(s)
Anemia Ferropénica , Hepcidinas , Animales , Biomarcadores , Hepcidinas/genética , Hepcidinas/metabolismo , Hepcidinas/farmacología , Homeostasis , Hormonas/farmacología , Hierro/metabolismo , Hierro de la Dieta , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Vitamina A/farmacologíaRESUMEN
Anemia in older adults is a growing public health issue in Mexico; however, its etiology remains largely unknown. Vitamin A deficiency (VAD) and vitamin D deficiency (VDD) have been implicated in the development of anemia, though by different mechanisms. The aim of this study is to analyze the etiology of anemia and anemia-related factors in older Mexican adults. This is a cross-sectional study of 803 older adults from the southern region of Mexico in 2015. The anemia etiologies analyzed were chronic kidney disease (CKD), nutritional deficiencies (ND), anemia of inflammation (AI), anemia of multiple causes (AMC) and unexplained anemia (UEA). VAD was considered to be s-retinol ≤ 20 µg/dL, and VDD if 25(OH)D < 50 nmol/L. IL-6 and hepcidin were also measured. Multinomial regression models were generated and adjusted for confounders. Anemia was present in 35.7% of OA, independent of sex. UEA, CKD, AI and ND were confirmed in 45%, 29.3%, 14.6% and 7% of older adults with anemia, respectively. Hepcidin and log IL-6 were associated with AI (p < 0.05) and CKD (p < 0.001). VAD was associated with AI (p < 0.001), and VDD with ND and AMC (p < 0.05). Log-IL6 was associated with UEA (p < 0.001). In conclusion, anemia in older adults has an inflammatory component. VAD was associated to AI and VDD with ND and AMC.
Asunto(s)
Anemia/etiología , Hepcidinas/sangre , Desnutrición/sangre , Vitamina A/sangre , Vitamina D/análogos & derivados , Anciano , Anciano de 80 o más Años , Causalidad , Estudios Transversales , Femenino , Humanos , Inflamación/sangre , Inflamación/complicaciones , Interleucina-6/sangre , Masculino , Desnutrición/complicaciones , Desnutrición/epidemiología , México/epidemiología , Persona de Mediana Edad , Análisis de Regresión , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/complicaciones , Deficiencia de Vitamina A/epidemiología , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
OBJECTIVE: This study evaluates the association of serum retinol, hepcidin levels, and anemia in children. METHODS: This cross-sectional study included 312 children, ages 6 to 59 mo, from Rio de Janeiro, Brazil. The association between hepcidin and retinol levels, hematologic parameters, and body mass index (BMI) was analyzed using a generalized linear model with and without adjustment for C-reactive protein (CRP) level. Logistic regression analysis was used to test anemia as an outcome and serum retinol level as a predictive variable using the odds ratio (OR) function. RESULTS: Anemia was present in 14.6% of the children, 5.8% presented iron deficiency anemia, and 9.6% had vitamin A deficiency. The increase in serum retinol levels reduced the chances of anemia (OR = 0.13; confidence interval = 0.29-0.59). When CRP level was not adjusted for in the multiple regression analyses, retinol, ferritin levels, and BMI/age were predictors of serum hepcidin levels (ß = -3.36, 0.14, 1.02, respectively; P = 0.032). Accordingly, serum retinol levels were inversely associated with CRP levels (ß = -0.025 and P < 0.001). CONCLUSIONS: The association between serum retinol and hepcidin levels in children ages 6 to 59 mo seems to be dependent on inflammation. Taken together, the results reinforce the need for the development of further studies to better understand the relationship between vitamin A and anemia of inflammation.