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1.
Toxicol Lett ; 318: 86-91, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669099

RESUMO

Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency.


Assuntos
Anemia Ferropriva/induzido quimicamente , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Duodeno/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepcidinas/metabolismo , Absorção Intestinal/efeitos dos fármacos , Ferro/sangue , Inibidores da Bomba de Prótons/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Anemia Ferropriva/sangue , Anemia Ferropriva/fisiopatologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Transporte de Cátions/metabolismo , Duodeno/metabolismo , Duodeno/fisiopatologia , Células Hep G2 , Hepatócitos/metabolismo , Antagonistas dos Receptores Histamínicos H2/toxicidade , Humanos , Ferro/deficiência , Masculino , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/genética
2.
Klin Lab Diagn ; 64(8): 477-480, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31479602

RESUMO

This research paper presents the results of a study of some indicators of iron metabolism in anaemia in pregnant women. The venous blood of 39 pregnant women with anaemia was examined. Serum ferritin, ferroportin and hepcidin were investigated for this purpose. The comparison group consisted of 19 pregnant women without anaemia. The haemoglobin concentration was measured by using «Mythic-18¼ haematological autoanalyzer. The concentrations of hepcidin and ferroportin were determined by using «Cloud-Clone Corp.¼ (USA), and ferritin concentrations were determined by using «Pishtaz teb¼ (Iran) reagents through enzyme-linked immunosorbent assay (ELISA) method. The study revealed a significant decrease in the level of ferritin, hepcidin and a significant increase in ferroportin level. A comprehensive definition of various indicators of iron metabolism provides important information not only for understanding the pathogenesis of iron deficiency anaemia in pregnant women but also for early diagnosis of the disease and the appointment of the correct treatment.


Assuntos
Anemia Ferropriva/sangue , Citocinas/sangue , Ferro/metabolismo , Complicações Hematológicas na Gravidez/sangue , Feminino , Ferritinas/sangue , Hepcidinas/sangue , Humanos , Gravidez
4.
Life Sci ; 234: 116787, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445028

RESUMO

Iron deficiency anemia (IDA) is a major worldwide public health problem. This is due to its prevalence among infants, children, adolescents, pregnant and reproductive age women. Ferrous sulfate (FeSO4) is the first line therapy for iron IDA. Unfortunately, it is reported that FeSO4 suffers from low absorption rate in the body and itself exhibits severe side effects. Herein, iron oxide magnetic nanoparticles-loaded liposomes (LMNPs) are prepared, characterized and evaluated as a treatment regimen for IDA in Wistar rats (as an animal model). Iron oxide magnetic nanoparticles (MNPs) are prepared and loaded into liposomes using the thin film hydration method. The size of the prepared formulations is in the range 10-100 nm, thus it can avoid the reticular endothelial system (RES), and increased their blood circulation time. For in vivo assessment, thirty-five Wistar rats are divided into 5 groups (n = 7): negative control group, positive control group, and three groups treated with different iron formulations (FeSO4, MNPs and LMNPs). Anemia is induced in the anemic groups by the bleeding method and then treatment started with different iron compounds administrated orally for 13 days. Hematological parameters are followed up during the treatment period. Results indicate that, in the LMNPs group, the hematological parameters turn to normal values and the histopathological structures of the liver, spleen and kidney remain normal. This proves that liposome increases the bioavailability of MNPs. In conclusion, LMNPs demonstrate superiority as a therapeutic regimen for the treatment of IDA among the tested iron formulations.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Ferrosos/administração & dosagem , Hematínicos/administração & dosagem , Lipossomos/química , Nanopartículas de Magnetita/química , Anemia Ferropriva/sangue , Animais , Disponibilidade Biológica , Feminino , Compostos Ferrosos/farmacocinética , Compostos Ferrosos/uso terapêutico , Hematínicos/farmacocinética , Hematínicos/uso terapêutico , Hemoglobinas/análise , Lipossomos/ultraestrutura , Nanopartículas de Magnetita/ultraestrutura , Ratos Wistar
5.
Ann Hematol ; 98(10): 2299-2302, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444663

RESUMO

Iron deficiency anemia (IDA) is often associated with mild to moderate thrombocytosis, and iron deficiency-associated thrombocytopenia (IDAT) is much more uncommon and often misdiagnosed as immune thrombocytopenia (ITP). To better describe the features of IDAT, we conducted a retrospective multicenter case-control study. We identified 10 patients (9 women) with a definite diagnosis IDAT, with a median age of 43.5 [range, 16-72] years and a median platelet count of 30.5 × 109/L [range, 21-80], and 7 patients with a possible diagnosis of IDAT. Bleeding manifestations were absent in all patients but one. All the patients recovered (platelet count ≥ 150 × 109/L) upon iron therapy ± red blood cell transfusion after a median time of 6 [4-39] days. When compared with 30 randomly newly diagnosed ITP patients matched on age, the baseline platelet count was significantly lower in ITP (median = 7 × 109/L [4-59], p < 0.001) whereas MPV was higher (10.5 fL [9,4-13,8] vs 8.2 fL, for IDAT p < 0.001). The median platelet count on day 7 was 337 × 109/L [113-1000] for IDAT cases vs 72 × 109/L [13-212] for ITP controls (p < 0.001). IDAT is potentially an under-recognized cause of thrombocytopenia that may be easily managed with iron therapy.


Assuntos
Anemia Ferropriva , Trombocitopenia , Adolescente , Adulto , Fatores Etários , Idoso , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/epidemiologia , Erros de Diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/etiologia , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia
6.
Int J Cardiovasc Imaging ; 35(9): 1619-1626, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31037476

RESUMO

There are few data on the effects of low hemoglobine levels on the left atrium (LA) in anemic patients. Our aim was to evaluate left atrial (LA) volume and functions in anemic patients using real time three-dimensional echocardiography (RT3DE) and also to investigate changes in variables of LA after the correction of anemia. In total, 55 iron-deficiency anemia patients without traditional cardiovascular (CV) risk factors and 30 age- and gender-matched controls were studied. Assessments included history, physical examination and echocardiography. Of the 55 patients with anemia enrolled, 50 (39 females and 11 males 40.3 years) were followed and underwent echocardiography after correction of the anemia. LA maximum volume (LAVmax), LA minimal volume (LAVmin), LAVmax index (LAVI), before atrial contraction volume (LAVpreA), LA total emptying fraction, LA active emptying volume were higher in anemic patients. LA passive emptying fraction was significantly lower in anemic patients. Following correction of anemia, LA volume and function parameters were observed to be significantly reduced. Moreover, significant increase was noted in LA passive emptying fraction. Correlation analysis was performed and a significant negative correlation was noted between the percentage change in hemoglobin level and percentage change in LAVI (r = - 0.382, p = 0.003). It was shown that volume and functions of LA are impaired in anemic patients. However impaired parameters were improved after correction of anemia. It may be thought that RT3DE LA parameters can be used as an important preclinical marker of disease pathogenesis before developing heart failure or atrial arrhythmia.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Função do Átrio Esquerdo , Ecocardiografia Tridimensional , Átrios do Coração/diagnóstico por imagem , Cardiopatias/diagnóstico por imagem , Hematínicos/uso terapêutico , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Anemia Ferropriva/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Átrios do Coração/fisiopatologia , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Resultado do Tratamento
7.
Heart Fail Clin ; 15(3): 359-369, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079694

RESUMO

Anemia and iron deficiency (ID) represent 2 prevalent, often interrelated, comorbidities in heart failure (HF). Both of them are significantly related to functional capacity and are undoubted predictors of poor prognosis in patients with HF. Although anemia and ID both have "global" detrimental effects, these 2 conditions are too often overlooked in cardiology daily clinical practice. The present review sought to summarize briefly the prevalence and the underlying pathophysiologic mechanisms of anemia and ID as regards HF severity (ie, exercise capacity) and prognosis.


Assuntos
Anemia Ferropriva/epidemiologia , Insuficiência Cardíaca/epidemiologia , Ferro/sangue , Anemia Ferropriva/sangue , Comorbidade , Saúde Global , Insuficiência Cardíaca/sangue , Humanos , Ferro/deficiência , Prevalência , Prognóstico
8.
Trials ; 20(1): 194, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947751

RESUMO

BACKGROUND: Intravenous (IV) iron is frequently used to treat iron deficiency/anemia in patients who are unable to tolerate oral iron or the oral iron is not sufficient toreplete iron requirements. However, safety concerns regarding the potential increase in oxidative stress and other adverse effects persist and it remains unclear whether all iron preparations are equivalent. Indeed, the comparative risk of adverse events with IV iron preparations has not been extensively assessed. We hypothesize that IV iron leads to changes in oxidative stress, endothelial function, and potential renal damage depending on the iron formulation (related to the generation of "free" or catalytic labile iron) and this may result in more tubular and glomerular injury manifested as increased proteinuria and raised neutrophil gelatinase-associated lipocalin (NGAL) levels in patients with chronic kidney disease (CKD). METHODS: IRON-CKD is a prospective, open-label, explorative, randomized, single-center study designed to compare the safety and efficacy of three parenteral iron preparations: low-molecular-weight iron dextran-Cosmofer, iron sucrose-Venofer, and iron isomaltoside-Monofer. The study includes 40 adults who have established CKD stages 3-5 and serum ferritin (SF) of less than 200 µg/L or transferrin saturation (TS) of less than 20% (or both); they were randomly assigned in a 1:1:1:1 ratio to 200 mg iron dextran, 200 mg iron sucrose, 200 mg iron isomaltoside, or 1000 mg iron isomaltoside. After randomization, participants undergo baseline assessments and then an iron infusion. Each participant is followed up at 2 h, day 1, week 1, and months 1 and 3. At each follow-up visit, patients undergo clinical review, measurement of pulse wave velocity (PWV), blood tests for renal function, and collection of serum/plasma samples for oxidative stress and inflammatory markers. The primary outcomes are measures of oxidative stress, inflammatory markers, and markers of acute renal injury in comparison with baseline measures of each iron preparation and between each of the iron preparations. Secondary objectives include effects on hematinic profiles and hemoglobin concentrations, changes in arterial stiffness, incidence of significant side effects, and change in patients' quality of life. RESULTS: Between October 2015 and April 2018, 521 individuals were identified as potential participants; 216 were contacted, 56 expressed an interest, 49 attended a screening visit, and 40 were confirmed to meet the eligibility criteria and were randomly assigned. The mean age was 58.3 (standard error of the mean 4.4) years, and 23 (58%) were male. All patients were white and English-speaking. The mean SF was 66.6 µg/L, TS was 21.2%, and hemoglobin was 121.6 g/L at randomization for the whole group. The mean estimated glomerular filtration rate was 27.8 mL/min, the urinary protein/creatinine ratio was 104.3 mg/mmol, and CRP was 6.65 mg/L. DISCUSSION: IRON-CKD will provide important information on the short-term effects of three preparations of IV iron in CKD patients with biochemical functional or absolute iron deficiency on measures of oxidative stress, inflammation, endothelial function, and renal injury. TRIAL REGISTRATION: European Clinical Trials Database (EudraCT) number 2010-020452-64 .


Assuntos
Lesão Renal Aguda/induzido quimicamente , Anemia Ferropriva/tratamento farmacológico , Dissacarídeos/administração & dosagem , Compostos Férricos/administração & dosagem , Óxido de Ferro Sacarado/administração & dosagem , Hematínicos/efeitos adversos , Complexo Ferro-Dextran/administração & dosagem , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal Crônica/complicações , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/urina , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Anemia Ferropriva/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Dissacarídeos/efeitos adversos , Inglaterra , Feminino , Compostos Férricos/efeitos adversos , Óxido de Ferro Sacarado/efeitos adversos , Hematínicos/administração & dosagem , Hemoglobinas/metabolismo , Humanos , Mediadores da Inflamação/sangue , Infusões Intravenosas , Complexo Ferro-Dextran/efeitos adversos , Rim/metabolismo , Rim/patologia , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteinúria/induzido quimicamente , Proteinúria/urina , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Fatores de Tempo , Resultado do Tratamento
9.
Dis Markers ; 2019: 4864370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984307

RESUMO

Background: Influence of TMPRSS6 A736V and HFE (C282Y and H63D) polymorphisms on serum hepcidin-25 levels and iron status parameters in end-stage renal disease (ESRD) patients stratified according to gender has not been previously investigated. In addition, we aimed to evaluate the diagnostic accuracy of the parameters to separate iron-deficiency anemia (IDA) from anemia of chronic disease. Materials and Methods: Iron status parameters and genetic analysis were performed in 126 ESRD patients and in 31 IDA patients as the control group. Results: ESRD patients had significantly higher ferritin and hepcidin-25 (<0.001) relative to IDA patients. Cut-off values with the best diagnostic accuracy were found for hepcidin ≥9.32 ng/mL, ferritin ≥48.2 µg/L, transferrin saturation ≥16.8%, and MCV ≥81 fL. Interaction between gender and HFE haplotypes for the hepcidin-25 and ferritin levels in ESRD patients (p = 0.005, partial eta squared = 0.09; p = 0.027, partial eta squared = 0.06, respectively) was found. Serum transferrin was influenced by the combined effect of gender and TMPRSS6 A736V polymorphism in ESRD patients (p = 0.002, partial eta squared = 0.07). Conclusion: Our findings could contribute to the further investigation of mechanisms involved in the pathophysiology and important gender-related involvement of the TMPRSS6 and HFE polymorphisms on anemia in ESRD patients.


Assuntos
Anemia Ferropriva/genética , Proteína da Hemocromatose/genética , Hepcidinas/sangue , Falência Renal Crônica/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/genética , Adulto , Idoso , Anemia Ferropriva/sangue , Feminino , Ferritinas/sangue , Humanos , Ferro/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Transferrina/análise
10.
Perm J ; 232019.
Artigo em Inglês | MEDLINE | ID: mdl-30939262

RESUMO

BACKGROUND: Optimizing preoperative anemia is a required component of the Joint Commission Patient Blood Management Certification and an important component of Enhanced Recovery After Surgery. OBJECTIVE: To describe a preoperative anemia protocol developed and implemented at the Kaiser Permanente San Jose Medical Center in California to facilitate preoperative identification and treatment of anemia. METHODS: The protocol included all operations at risk of causing substantial blood loss. It excluded emergent operations and those for which the patient had a normal last hemoglobin value within the prior 12 months unless newly developed anemia was suspected. Eligible patients were screened for laboratory evaluation, and those with anemia were treated for reversible causes. Consistency was ensured by physician, staff, and patient education, and by use of electronic health records. Administration of intravenous iron and erythropoietin and consultation with specialists were expedited as part of a management algorithm. RESULTS: Among 510 patients enrolled during 1 year, 442 (87%) received anemia screening laboratory tests. Half of those with laboratory results were eligible for further optimization: 207 had anemia and 21 had iron deficiency without anemia. Among the 228 patients eligible for optimization, 189 (83%) had anemia addressed preoperatively. Of 129 patients with iron deficiency anemia, 102 (79%) received intravenous iron preoperatively, with a mean preoperative increase in hemoglobin level by 0.98 g/dL (n = 79). CONCLUSION: Integration of specialty services, optimization of technology, and consistency across practitioners were crucial for successful implementation and sustainability of a preoperative anemia protocol developed to expedite and enhance best practices.


Assuntos
Anemia Ferropriva/diagnóstico , Anemia Ferropriva/terapia , Prestação Integrada de Cuidados de Saúde/métodos , Eritropoetina/uso terapêutico , Ferro/uso terapêutico , Cuidados Pré-Operatórios/métodos , Anemia Ferropriva/sangue , Eritropoetina/sangue , Estudos de Viabilidade , Feminino , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Oligoelementos/uso terapêutico
11.
Nutrients ; 11(4)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010126

RESUMO

Multiple common variants in transmembrane protease serine 6 (TMPRSS6) were associated with the plasma iron concentration in genome-wide association studies, but their effect in young children where anemia and iron deficiency (ID) were prevalent has not been reported, particularly taking account of iron intake. This study aims to investigate whether TMPRSS6 SNPs (rs855791 and rs4820268) and iron intake are associated with a low iron and hemoglobin concentration in under-two-year-old children. The study analyzed the baseline of a randomized trial (NUPICO, ClinicalTrials.gov NCT01504633) in East Lombok, Indonesia. Children aged 6-17 months (n = 121) were included in this study. The multiple linear regressions showed that TMPRSS6 decreased serum ferritin (SF) by 4.50 g/L per copy minor allele (A) of rs855791 (p = 0.08) and by 5.00 µg/L per copy minor allele (G) of rs4820268 (p = 0.044). There were no associations between rs855791 and rs4820268 with soluble transferrin receptor (sTfR) and hemoglobin (Hb) concentration (rs855791; p = 0.38 and p = 0.13, rs4820268; p = 0.17 and p = 0.33). The finding suggests the need for further studies to explore whether the nutrient recommendation for iron should be based on genetic characteristics, particularly for children who have mutation in TMPRSS6.


Assuntos
Anemia Ferropriva/genética , Grupo com Ancestrais do Continente Asiático/genética , Dieta , Genótipo , Ferro/sangue , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/genética , Alelos , Anemia Ferropriva/sangue , Feminino , Ferritinas/sangue , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hemoglobinas/metabolismo , Humanos , Indonésia , Lactente , Ferro/administração & dosagem , Ferro/deficiência , Modelos Lineares , Masculino , Mutação , Necessidades Nutricionais , Estado Nutricional , Receptores da Transferrina/sangue , Transferrina/metabolismo
12.
Int J Lab Hematol ; 41(3): 418-423, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30938931

RESUMO

INTRODUCTION: Haemoglobin (Hb) levels are used to assess eligibility for blood donation but are not correlated with iron status. The percentage of hypochromic red cells (%Hypo-He) has been suggested as a useful screening parameter for iron deficiency. The aim of this study was to determine the cut-off level and accuracy of %Hypo-He screening among blood donors. MATERIALS AND METHODS: A total of 170 blood donors were recruited into the study. Blood donors were classified into three groups: normal, latent iron deficiency and iron deficiency anaemia based on their Hb, serum ferritin and transferrin saturation (TSAT) levels. The diagnostic performance of %Hypo-He was evaluated with a validation group comprising 160 blood donors. RESULTS: Receiver operating characteristic (ROC) curve analysis showed that %Hypo-He is an excellent parameter for detecting iron deficiency, with an area under the curve (AUC) of 0.906, a confidence interval (CI) of 0.854-0.957 at a cut-off of 0.6%, and 74.51% sensitivity and 88.24% specificity. A moderate negative correlation between %Hypo-He and TSAT (ρ = -0.576 [P < 0.001]) and a strong negative correlation between %Hypo-He and serum ferritin (ρ = -0.703 [P < 0.001]) were found. A cut-off value of 0.6% was applied to the validation group and showed 82.9% sensitivity and 96% specificity. CONCLUSION: %Hypo-He with a cut-off value of 0.6% is a potential parameter with high sensitivity and specificity for evaluating iron status among blood donors. This parameter is suitable for screening because its measurement has a faster turnaround time than biochemical markers.


Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Doadores de Sangue , Eritrócitos/metabolismo , Eritrócitos/patologia , Ferro/metabolismo , Anemia Ferropriva/epidemiologia , Biomarcadores , Estudos Transversais , Índices de Eritrócitos , Feminino , Humanos , Ferro/sangue , Malásia/epidemiologia , Masculino , Programas de Rastreamento , Curva ROC , Sensibilidade e Especificidade
13.
BMC Public Health ; 19(1): 397, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975203

RESUMO

BACKGROUND: Iron deficiency is the most prevalent nutrient deficiency and the most common cause of anaemia worldwide. Because of the increased iron requirements during pregnancy, iron deficiency can lead to maternal anaemia and reduced newborn iron stores. We examined the proportion and risk factors of iron deficiency among pregnant women in a developed Asian country. METHODS: Within a prospective cohort in Singapore, 985 Asian women were assessed for iron status at 26-28 weeks' gestation, with plasma ferritin and soluble transferrin receptor (sTfR) measurements. Iron status was determined according to plasma ferritin concentrations at ≥30 µg/L (iron sufficiency), 15 to < 30 µg/L (modest iron depletion) and < 15 µg/L (severe iron depletion). Multivariable ordinal logistic regression was used to analyze risk factors for modest and severe iron depletion. RESULTS: The median (25-75th percentile) plasma ferritin concentration was 24.2 (19.9-30.6) µg/L. Overall, 660 (67.0%) and 67 (6.8%) women had modest and severe iron depletion, respectively. Higher plasma sTfR was observed in women with severe iron depletion than among those with iron sufficiency (median 17.6 versus 15.5 nmol/L; p < 0.001). Age < 25 years (odds ratio 2.36; 95% confidence interval 1.15-4.84), Malay (2.05; 1.30-3.24) and Indian (1.98; 1.14-3.44) ethnicities (versus Chinese), university qualification (1.64; 1.13-2.38), multiparity (1.73; 1.23-2.44) and lack of iron-containing supplementation (3.37; 1.25-8.53) were associated with increased odds of modest and severe iron depletion. CONCLUSIONS: Nearly three-quarters of Singaporean women were iron deficient in the early third trimester of pregnancy. These results suggest universal screening and supplementation of at-risk pregnancies may be evaluated as a preventive strategy. TRIAL REGISTRATION: NCT01174875 . Registered 1 July 2010 (retrospectively registered).


Assuntos
Anemia Ferropriva/epidemiologia , Ferritinas/sangue , Ferro na Dieta/administração & dosagem , Complicações Hematológicas na Gravidez/epidemiologia , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Ferro/sangue , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Receptores da Transferrina/sangue , Fatores de Risco , Singapura , Adulto Jovem
15.
EBioMedicine ; 42: 504-510, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30885726

RESUMO

BACKGROUND: Iron deficiency (ID) and anaemia are major health concerns, particularly in young children. Screening for ID based on haemoglobin (Hb) concentration alone has been shown to lack sensitivity and specificity. The American Academy of Pediatrics (AAP) recommends soluble transferrin receptor (sTfR) as a promising approach to screen for iron deficiency. However, in most settings, assessment of iron status requires access to centralized laboratories. There is an urgent need for rapid, sensitive, and affordable diagnostics for sTfR at the point-of-care. METHODS: An immunochromatographic assay-based point-of-care screening device was developed for rapid quantification of sTfR from a drop of serum within a few minutes. Performance optimization of the assay was done in sTfR-spiked buffer and commercially available sTfR calibrator, followed by a small-scale proof-of-concept validation with archived serum samples. FINDINGS: On preliminary testing with archived serum samples and comparison with Ramco ELISA, a correlation of 0.93 (P < 0.0001) was observed, demonstrating its potential for point-of-care assessment of iron status. INTERPRETATION: The analytical performance of the point-of-care sTfR screening device indicates the potential for application in home-use test kits and field settings, especially in low- and middle-income settings. An added advantage of sTfR quantification in combination with our previously reported serum ferritin diagnostics is in integration of Cook's equation as a quantitative and minimally-invasive indicator of total body iron stores. FUND: Thrasher Research Fund (Early Career Award #13379), NIH R03 EB 023190, NSF grant #1343058, and Nutrition International (project #10-8007-CORNE-01).


Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Testes Imediatos , Receptores da Transferrina/sangue , Testes Diagnósticos de Rotina/instrumentação , Testes Diagnósticos de Rotina/métodos , Humanos , Nanotecnologia , Fitas Reagentes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
Pak J Pharm Sci ; 32(1): 75-79, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30772793

RESUMO

Iron deficiency anemia (IDA) during pregnancy, although associated with disturbances of hematological parameters, is now also considered as a source of oxidative stress (OS). Present study aims to detect any alteration in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes activity in pregnant women with IDA. Levels of GSH-Px and SOD were measured in 156 anemic, pregnant women and compared with similar levels in 20 non anemic, pregnant women. Activity of SOD was found to be reduced in the anemic group when compared with the control group. We found a non- significant increase in GSH-Px activities in the anemic group. These findings could be explained in terms of OS under hypoxic condition which preserves the activity of GSH-Px with a decrease activity of SOD. A positive association was seen between IDA during pregnancy and OS with results suggesting that, apart from the deficiency of iron, some other factors are also associated for the increased OS seen during pregnancy.


Assuntos
Anemia Ferropriva/enzimologia , Glutationa Peroxidase/sangue , Estresse Oxidativo , Complicações Hematológicas na Gravidez/enzimologia , Superóxido Dismutase/sangue , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico
17.
Kardiol Pol ; 77(3): 347-354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740644

RESUMO

BACKGROUND: We believe that there is a physiological link between intracellular iron status (assessed by soluble transferrin receptor [sTfR]) and efficiency of energy production/consumption (assessed by lactate, a product of anaerobic cell metabolism), which may further impact the outcome of patients with acute heart failure (AHF). AIM: To examine if elevated levels of lactate (> 2 mmol/L) accompanied by unmet cellular iron requirements (defined as sTfR > 1.59 mg/L) identify AHF patients with an unfavourable outcome. METHODS: The study is a single-centre, retrospective analysis of AHF patients in whom lactate and iron status were assessed on admission. The endpoint of the study was one-year mortality. RESULTS: The study population consisted of 89 patients at a mean age of 65 ± 13 years. Mean systolic blood pressure and creatinine level were 135 ± 36 mmHg and 1.3 ± 0.6 mg/dL, respectively, and median [25th-75th quartiles] lactate level on admission was 2.0 [1.6-2.6] mmol/L. In 17 (19%) patients, both lactate and sTfR were below the cut-off values (group 1). In 38 (43%) individuals one of the markers was elevated (group 2) and in the remaining 34 (38%) patients both markers were above the predefined cut-off values (group 3). There was no difference in clinical and laboratory characteristics between the groups. During one-year follow-up 23 (26%) patients died. Mortality risk in group 3 was higher compared to the rest of the population (hazard ratio 5.6, 95% confidence interval 2.2-14, p = 0.0003), even after adjustments for well-defined prognostic factors. CONCLUSIONS: Patients with unmet iron cell requirements and hyperlactataemia on admission have significantly higher mortality risk compared to individuals without those pathologies.


Assuntos
Anemia Ferropriva/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Ácido Láctico/sangue , Doença Aguda , Adulto , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores da Transferrina/metabolismo , Estudos Retrospectivos , Fatores de Risco , Volume Sistólico/fisiologia
18.
Clin Nephrol ; 91(4): 237-245, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802204

RESUMO

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing dialysis often require intravenous iron for iron deficiency anemia (IDA). MATERIALS AND METHODS: The Ferumoxytol for Anemia of CKD Trial (FACT), a randomized, multicenter, open-label, phase 4 study, compared the long-term safety and efficacy of ferumoxytol with iron sucrose for the treatment of IDA in patients with CKD undergoing hemodialysis. Patients with IDA and CKD undergoing hemodialysis were randomized 2:1 to ferumoxytol 1.02 g (2 × 510 mg) or iron sucrose 1.0 g (10 × 100 mg) for a 5-week treatment period (TP). Over 11 months, patients underwent additional 5-week TPs whenever IDA (hemoglobin < 11.5 g/dL and transferrin saturation < 30%) was detected. The primary efficacy endpoint was mean change in hemoglobin from baseline to week 5 for each TP. Adverse events were recorded during the study. RESULTS: Overall, 293 patients received ferumoxytol (n = 196) or iron sucrose (n = 97). Ferumoxytol was noninferior to iron sucrose regarding hemoglobin change from baseline to week 5. The mean change in hemoglobin in the ferumoxytol and iron sucrose groups was 0.5 and 0.4 g/dL, respectively, in TP 1 (least-squares mean difference, 0.13; 95% confidence interval, -0.11 to 0.36) and 0.6 and 0.3 g/dL, respectively, in TP 2 (0.30; 0.06 - 0.55). Treatment-related and serious adverse events were similar in both groups; no new safety signals emerged. CONCLUSION: Long-term administration of ferumoxytol has noninferior efficacy and a similar safety profile to iron sucrose when used to treat IDA in patients with CKD undergoing hemodialysis.
.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Óxido de Ferro Sacarado/uso terapêutico , Óxido Ferroso-Férrico/uso terapêutico , Hematínicos/uso terapêutico , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Feminino , Óxido de Ferro Sacarado/efeitos adversos , Óxido Ferroso-Férrico/efeitos adversos , Hematínicos/efeitos adversos , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/complicações , Adulto Jovem
19.
Nutrients ; 11(2)2019 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-30781529

RESUMO

Serum ferritin concentration is the preferred biomarker to assess population iron status in the absence of inflammation. Interpretation of this biomarker is complicated in populations with a high burden of infection, however, because inflammation increases serum ferritin concentration independently of iron status. We aimed to compare estimates of iron status of Kenyan pregnant women, with circulating ferritin concentrations adjusted for inflammation using newly proposed methods by the BRINDA project, or using previously proposed adjustment methods. We re-analyzed data from pregnant Kenyan women living in a rural area where malaria is highly endemic (n = 470) or in an urban area (n = 402). As proposed by the BRINDA group, we adjusted individual ferritin concentration by internal regression for circulating concentrations of C-reactive protein (CRP) and α1-acid glycoprotein (AGP). Other adjustment methods comprised: (a) arithmetic correction factors based on CRP or AGP; (b) exclusion of subjects with inflammation (CRP >5 mg/L or AGP >1 g/L); and (c) higher ferritin cut-off value (<30 µg/L). We additionally adjusted for Plasmodium infection as appropriate. Lastly, we assessed iron status without adjustment for inflammation. All correction methods increased prevalence of iron deficiency compared to the unadjusted estimates. This increase was more pronounced with the internal regression correction method. The iron deficiency prevalence estimate increased from 53% to 87% in rural Kisumu study and from 30% to 41% in the urban Nairobi study after adjusting for inflammation (CRP and AGP) using the BRINDA internal regression method. When we corrected for both inflammation and Plasmodium infection using the regression correction, it resulted in lower prevalence estimates compared to uninfected women. Application of linear regression methods to adjust circulating ferritin concentration for inflammation leads to markedly decreased point estimates for ferritin concentration and increased estimates for the prevalence of iron deficiency in pregnancy.


Assuntos
Anemia Ferropriva/epidemiologia , Ferritinas/sangue , Inflamação/sangue , Ferro/deficiência , Complicações na Gravidez/epidemiologia , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/etiologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Quênia/epidemiologia , Malária/sangue , Malária/complicações , Malária/epidemiologia , Estado Nutricional , Orosomucoide/análise , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/etiologia , Prevalência , Análise de Regressão , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto Jovem
20.
Cochrane Database Syst Rev ; 2: CD007857, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30790278

RESUMO

BACKGROUND: The anaemia seen in chronic kidney disease (CKD) may be exacerbated by iron deficiency. Iron can be provided through different routes, with advantages and drawbacks of each route. It remains unclear whether the potential harms and additional costs of intravenous (IV) compared with oral iron are justified. This is an update of a review first published in 2012. OBJECTIVES: To determine the benefits and harms of IV iron supplementation compared with oral iron for anaemia in adults and children with CKD, including participants on dialysis, with kidney transplants and CKD not requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 7 December 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in which IV and oral routes of iron administration were compared in adults and children with CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias, and extracted data. Results were reported as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) was used or standardised mean difference (SMD) if different scales had been used. Statistical analyses were performed using the random-effects model. Subgroup analysis and univariate meta-regression were performed to investigate between study differences. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: We included 39 studies (3852 participants), 11 of which were added in this update. A low risk of bias was attributed to 20 (51%) studies for sequence generation, 14 (36%) studies for allocation concealment, 22 (56%) studies for attrition bias and 20 (51%) for selective outcome reporting. All studies were at a high risk of performance bias. However, all studies were considered at low risk of detection bias because the primary outcome in all studies was laboratory-based and unlikely to be influenced by lack of blinding.There is insufficient evidence to suggest that IV iron compared with oral iron makes any difference to death (all causes) (11 studies, 1952 participants: RR 1.12, 95% CI 0.64, 1.94) (absolute effect: 33 participants per 1000 with IV iron versus 31 per 1000 with oral iron), the number of participants needing to start dialysis (4 studies, 743 participants: RR 0.81, 95% CI 0.41, 1.61) or the number needing blood transfusions (5 studies, 774 participants: RR 0.86, 95% CI 0.55, 1.34) (absolute effect: 87 per 1,000 with IV iron versus 101 per 1,000 with oral iron). These analyses were assessed as having low certainty evidence. It is uncertain whether IV iron compared with oral iron reduces cardiovascular death because the certainty of this evidence was very low (3 studies, 206 participants: RR 1.71, 95% CI 0.41 to 7.18). Quality of life was reported in five studies with four reporting no difference between treatment groups and one reporting improvement in participants treated with IV iron.IV iron compared with oral iron may increase the numbers of participants, who experience allergic reactions or hypotension (15 studies, 2607 participants: RR 3.56, 95% CI 1.88 to 6.74) (absolute harm: 24 per 1000 with IV iron versus 7 per 1000) but may reduce the number of participants with all gastrointestinal adverse effects (14 studies, 1986 participants: RR 0.47, 95% CI 0.33 to 0.66) (absolute benefit: 150 per 1000 with IV iron versus 319 per 1000). These analyses were assessed as having low certainty evidence.IV iron compared with oral iron may increase the number of participants who achieve target haemoglobin (13 studies, 2206 participants: RR 1.71, 95% CI 1.43 to 2.04) (absolute benefit: 542 participants per 1,000 with IV iron versus 317 per 1000 with oral iron), increased haemoglobin (31 studies, 3373 participants: MD 0.72 g/dL, 95% CI 0.39 to 1.05); ferritin (33 studies, 3389 participants: MD 224.84 µg/L, 95% CI 165.85 to 283.83) and transferrin saturation (27 studies, 3089 participants: MD 7.69%, 95% CI 5.10 to 10.28), and may reduce the dose required of erythropoietin-stimulating agents (ESAs) (11 studies, 522 participants: SMD -0.72, 95% CI -1.12 to -0.31) while making little or no difference to glomerular filtration rate (8 studies, 1052 participants: 0.83 mL/min, 95% CI -0.79 to 2.44). All analyses were assessed as having low certainty evidence. There were moderate to high degrees of heterogeneity in these analyses but in meta-regression, definite reasons for this could not be determined. AUTHORS' CONCLUSIONS: The included studies provide low certainty evidence that IV iron compared with oral iron increases haemoglobin, ferritin and transferrin levels in CKD participants, increases the number of participants who achieve target haemoglobin and reduces ESA requirements. However, there is insufficient evidence to determine whether IV iron compared with oral iron influences death (all causes), cardiovascular death and quality of life though most studies reported only short periods of follow-up. Adverse effects were reported in only 50% of included studies. We therefore suggest that further studies that focus on patient-centred outcomes with longer follow-up periods are needed to determine if the use of IV iron is justified on the basis of reductions in ESA dose and cost, improvements in patient quality of life, and with few serious adverse effects.


Assuntos
Anemia Ferropriva/terapia , Compostos de Ferro/administração & dosagem , Falência Renal Crônica/complicações , Administração Oral , Adulto , Anemia Ferropriva/sangue , Transfusão de Sangue/estatística & dados numéricos , Causas de Morte , Criança , Ferritinas/sangue , Hemoglobina A/metabolismo , Humanos , Injeções Intravenosas , Compostos de Ferro/efeitos adversos , Falência Renal Crônica/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Transferrina/metabolismo
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