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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation influences iron balance in the whole organism. A common clinical manifestation of these changes is anemia of chronic disease (ACD; also called anemia of inflammation). Inflammation reduces duodenal iron absorption and increases macrophage iron retention, resulting in low serum iron concentrations (hyposideremia). Despite the protection hyposideremia provides against proliferating microorganisms, this 'iron withholding' reduces the iron available to maturing red blood cells and eventually contributes to the development of anemia. Hepcidin antimicrobial peptide (Hamp) is a hepatic defensin-like peptide hormone that inhibits duodenal iron absorption and macrophage iron release. Hamp is part of the type II acute phase response and is thought to have a crucial regulatory role in sequestering iron in the context of ACD. Mice with deficiencies in the hemochromatosis gene product, Hfe, mounted a general inflammatory response after injection of lipopolysaccharide but lacked appropriate Hamp expression and did not develop hyposideremia. These data suggest a previously unidentified role for Hfe in innate immunity and ACD.
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PMID:An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice. 1509 34

The defensin-like circulatory peptide hepcidin is the iron-regulatory hormone that links innate immunity and iron metabolism. In response to inflammatory stimuli, the liver produces hepcidin: this antimicrobial peptide then limits the iron that is vital to invading pathogens, by decreasing iron release/transfer from enterocytes and macrophages and causing secondary hypoferremia. This may lead, however, to reduced iron availability for erythropoiesis and therefore to anemia (and anemia of chronic disease). When iron is scarce, the rate at which it is released into the bloodstream must be enhanced: indeed, iron starvation and hypoxia readily abrogate hepcidin expression. Conversely, if excess iron enters the circulation, hepcidin transcription is turned on and iron release from the intestine and macrophages abrogated. Circumstantial evidence indicates that the effect of circulatory iron on hepcidin requires functional HFE and hemojuvelin, two proteins of unknown function that have recently been linked to human hereditary hemochromatosis. In this disease it is likely that inadequate levels of circulating hepcidin lead to the uncontrolled release of iron from the intestine and macrophages, followed by tissue iron overload and organ damage. Given its role as the iron-regulatory hormone, the modulation of hepcidin activity using agonists or antagonists might offer new treatment opportunities in different human iron-dependent disorders.
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PMID:Mechanisms of disease: The role of hepcidin in iron homeostasis--implications for hemochromatosis and other disorders. 1626 43

Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Hepcidin could also act as an indicator of functional iron deficiency in these patients. Cross-sectional study was performed to assess hepcidin correlations with renal function, iron status, and hsCRP in patients with chronic renal failure on conservative treatment, on hemodialyses, and in kidney transplant recipients. Iron status, complete blood count, creatinine, albumin, lipids were assessed using standard laboratory methods. GFR was estimated using MDRD formula. Hepcidin and high sensitivity CRP were measured using commercially available kits. Ferritin and hepcidin were higher in hemodialyzed patients, kidney transplant recipients, and patients with chronic renal failure over controls. In patients with chronic renal failure, hepcidin correlated significantly with total protein, albumin, creatinine, and eGRF. In kidney transplant recipients, hepcidin correlated significantly in univariate analysis, with total protein, ferritin, time after transplantation, creatinine, eGRF and tended to correlate with cholesterol. In hemodialyzed patients hepcidin, correlated significantly with triglycerides, albumin, creatinine, urea, residual renal function, and hsCRP. In healthy volunteers, hepcidin was related to triglycerides and ferritin. Multiple regression analysis in hemodialyzed patients showed that hepcidin was independently related to creatinine, triglycerides, and residual renal function. Multiple regression analysis in kidney transplant recipients showed that hepcidin was independently related only to GFR and ferritin. Elevated hepcidin in all groups of patients studied may be due to low grade inflammation, frequently encountered in this population and mainly to impaired renal function.
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PMID:Hepcidin, iron status, and renal function in chronic renal failure, kidney transplantation, and hemodialysis. 1692 40

Hepcidin is a small, defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. We studied correlations of hepcidin concentrations with markers of iron status, erythropoietin therapy, and markers of inflammation among 130 kidney allograft recipients. In addition, we assessed the prevalence of anemia and its relation to hepcidin. Soluble receptor of transferrin (sTfR), high-sensitivity C-reactive protein (hsCRP), TNF-alpha, interleukin (IL)-6, prohepcidin, and hepcidin were measured using commercially available kits. According to the WHO definition, the prevalence of anemia was 28%. Among anemic recipients we found a significantly higher values of serum creatinine, serum prohepcidin, hepcidin, (hsCRP), TNF-alpha, IL-6, ferritin, and proteinuria in addition to more frequent use of rapamycin and significantly lower use of CSA with lower CSA concentrations, as well as lower cholesterol, hemoglobin, and estimated glomerular filtration rate (eGFR) (by the Modification of Diet in Renal Disease equation). Serum prohepcidin significantly correlated with creatinine, GFR, time after transplantation, albumin, hsCRP, IL-6, and TNF-alpha, whereas hepcidin-25 correlated with serum iron, ferritin, hsCRP, IL-6, hemoglobin, transferrin saturation (TSAT), creatinine, and GFR. Multiple regression analysis showed that prohepcidin was independently related only to GFR and ferritin. Upon multiple regression analysis, predictors of serum hepcidin were eGFR, ferritin, and hsCRP, explaining 79% of the variation of hepcidin values. In conclusion, the prevalence of anemia was relatively high among a population of kidney allograft recipients. The pathogenesis of anemia is mulitfactorial. Elevated hepcidin levels among kidney transplant recipients may be due to low-grade inflammation, which is frequently encountered in this population, and mainly to impaired renal function, but it did not seem to be a major pathogenetic factor for anemia in this population.
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PMID:A possible role of hepcidin in the pathogenesis of anemia among kidney allograft recipients. 1985 75

Hepcidin is a recently recognized defensin-like peptide, which is considered to be the central regulator of iron metabolism. Hepcidin decreases the expression of iron transporting molecules. Hepcidin reduces gastrointestinal iron absorption, iron release from the macrophages, and hence it decreases serum iron levels. Clarification of hepcidin role in iron homeostasis could provide an explanation to anemia of inflammation and chronic diseases. At start of our work there was no commercially available method for measuring urine hepcidin levels. The aim of our study was to develop an easily achievable, reliable quantification method for the determination of urine hepcidin levels in human, in addition to examine a possible association of hepcidin with neonatal iron homeostasis. According to the sequence of native, human hepcidin we have synthesized peptide derivatives from which 1-7 peptide derivatives might be suitable representatives of the 25-amino-acid form of hepcidin in immune adsorption method. We presented a novel laser-desorption mass spectrometry based semi-quantitative, reproducible method for measuring hepcidin concentration in human urine first using the synthesized peptide derivative acetyl-1-25 peptide as hepcidin related internal standard. We described an easy and quickly achievable solid-phase extraction method which is suitable for purification of urine and concentration of hepcidin. In our study we have first measured serum prohepcidin and urine hepcidin in healthy human newborns. Serum prohepcidin levels showed no significant changes, however, urine hepcidin levels increased significantly during the first postnatal days. Serum prohepcidin and urine hepcidin levels showed no significant association in healthy human newborns. Associations have been demonstrated between cord blood prohepcidin values and mean corpuscular hemoglobin concentration as well as between urine hepcidin levels and serum iron and total iron binding capacity values. We have demonstrated that neonates with detectable non-protein-bound iron levels in cord blood were presented with lower prohepcidin concentrations. In summary, our results suggest a possible link between hepcidin and early iron adaptation of newborn's, however, further investigations should be done to elucidate this issue.
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PMID:[Role of iron metabolism-regulator hepcidin in perinatal iron homeostasis]. 2006 Dec 65

Iron is the fourth most common element in the Earth's crust and is crucial for life. Over the last few years, our understanding of iron metabolism has dramatically increased due to the discovery of hepcidin, which is produced by hepatocytes and modulated in response to anemia, hypoxia and inflammation. It has been found that anemia upregulates lipocalin 2 (NGAL; neutrophil gelatinase-associated lipocalin) in the liver and serum. The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin and NGAL in iron metabolism and its regulation, particularly in kidney disease. Elevated NGAL a few days after insult is a possible preventive or protective mechanism limiting renal injury. NGAL is an innate antibacterial factor as well as hepcidin. NGAL binds siderophores, thereby preventing iron uptake by bacteria. Hepcidin, an antibacterial defensin, prevents iron absorption from the gut and iron release from macrophages, leading to hypoferremia and anemia. Both proteins sequester iron, but by different mechanisms. However, these proteins involved in iron metabolism do not seem to be independently related. Taking into account the antimicrobial moieties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure.
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PMID:Neutrophil gelatinase-associated lipocalin and hepcidin: what do they have in common and is there a potential interaction? 2050 37

Hepcidin, a small defensin-like peptide produced by hepatocytes, is modulated in response to anemia, hypoxia, or inflammation. We studied hepcidin correlations with markers of iron status and of inflammation among 134 prevalent recipients of heart allografts (OHT). In addition, we assessed the prevalence of anemia and its relation to hepcidin. Soluble transferrin (sTfR), interleukin (IL)-6, cystatin C, and hepcidin receptors were measured using commercially available kits. According to the World Health Organization definition, the prevalence of anemia was 40%. Anemic OHT showed significantly higher values of serum creatinine, cystatin C, hepcidin, IL-6, ferritin, soluble transferrin receptor, NT-proBNP, everolimus treatment, and significantly lower quantities of cholesterol, low-density lipoprotein, ejection fraction, hemoglobin, erythrocyte count, and estimated glomerular filtration rate (GFR) (Modification of Diet in Renal Disease, CKD-EPI). Hepcidin correlated with total iron binding capacity, ferritin, IL-6, hemoglobin, erythrocyte count, cystatin C, NT-proBNP, creatinine, and GFR. Multiple regression analysis showed hepcidin to be independently related only to ferritin, explaining 76% of the variation in hepcidin. The prevalence of anemia is relatively great among the population of heart allograft recipients. In these patients the pathogenesis of anemia is multifactorial. Elevated hepcidin levels in heart transplant recipients may be due to low-grade inflammation, which is frequently encountered in this population, as well as probably to impaired renal function, but it does not seem to be a major pathogenic factor for anemia among this population.
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PMID:A possible role of hepcidin in the pathogenesis of anemia in heart allograft recipients. 2062 May 27

Hepcidin is a small defensin-like peptide produced in the liver in response to anemia, hypoxia, or inflammation. In addition to its anti-microbial properties, it has also been found to be a key regulator of iron utilization, providing increased understanding of why chronic kidney disease patients absorb iron poorly from the gut and also why many hemodialysis patients develop functional iron deficiency in the presence of inflammation. Hepcidin synthesis is upregulated in uremia, as in other inflammatory states. The ability to measure hepcidin in biologic fluids has stimulated interest in the potential applicability of this measurement as a more informative marker of iron status than the traditional iron indices such as serum ferritin and transferrin saturation. Until recently, however, the assays for measuring hepcidin have lacked precision, accuracy, and internal validation. Over the last few years, however, several assays have become available that address these limitations. Broadly speaking, these can be divided into radioimmunoassays, ELISAs, and mass spectrometry methods. The purpose of this review is to outline the various assays available at the present time, to critique their advantages and limitations, and to report comparative data in patients with chronic kidney disease. A concern with the immunoassays is that they detect more than biologically active hepcidin-25. Mass spectrometric assays are specific for hepcidin-25 but are labor intensive and require more costly and sophisticated instrumentation. Thus, although mass spectrometry is more accurate, it is less practical for routine clinical use at the present time.
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PMID:Current status of the measurement of blood hepcidin levels in chronic kidney disease. 2072 18

The production by hepatocytes of hepcidin, a small defensin-like peptide, is modulated in response to anemia, hypoxia, or inflammation. We studied hepcidin as a marker of iron status (serum iron, ferritin, and soluble receptor of transferrin [sTfR], and as a marker of inflammation among 170 prevalent kidney transplantation (KT) patients and 168 prevalent orthotopic heart transplant (OHT) patients. In addition, we assessed the prevalence of anemia and its relation to measurements of hepcidin, sTfR, and high-sensitivity C-reactive protein, using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Prevalence of anemia was 37% in KT patients and 34% in OHT patients according to the World Health Organisation (WHO) definition. Anemic KT patients displayed significantly higher values of serum creatinine, hepcidin, hsCRP, ferritin, and proteinuria associated with greater use of mTOR and significantly lower CSA therapy. The hemoglobin and estimated glomerular filtration rate (eGFR). Upon multiple regression analysis eGFR, ferritin, and hsCRP independently predicted hepcidin levels, explaining 78% of the variation in hepcidin. Anemic OHT patients showed significantly lower GFR, red blood cell (RBC), and hemoglobin values and significantly higher creatinine and NT-proBNP content. Upon multiple regression analysis the predictors of serum hepcidin were eGFR and ferritin, which explained 68% of the variation in hepcidin. The prevalence of anemia is relatively high and not adequately treated (mainly due to reimbursement regulations) among heart and kidney allograft recipients. In conclusion, elevated hepcidin levels in heart and kidney transplant recipients suggest subclinical inflammation and impaired kidney function.
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PMID:Anemia in heart and kidney allograft recipients: is there a role for hepcidin? 2116 77

Hepcidin is a small defensin-like peptide produced primarily by hepatocytes, but also by other cells, including macrophages. In addition to hepcidin's antimicrobial properties, it is the main regulator of iron metabolism and controls both the amount of dietary iron absorbed in the duodenum and the iron release by reticuloendothelial cells. Hepcidin expression is upregulated by a variety of stimuli, including inflammation and iron overload, and downregulated by anemia, hypoxia, and iron deficiency. Chronic kidney disease (CKD) is associated with increased serum hepcidin levels, and the increased levels may contribute to the development and severity of anemia and to resistance to erythropoiesis-stimulating agents (ESAs). Elevated serum hepcidin levels contribute to the dysregulation of iron homeostasis in CKD patients. Although parenteral iron supplementation can bypass some of the iron-blocking effects of hepcidin in CKD patients with anemia, and free iron and iron stores increase as a result, the anemia is only partially corrected, and the ESA dose requirements remain significantly higher than needed for physiological replacement. Treatment with agents that lower serum hepcidin levels or inhibit its actions may be an effective strategy for restoring normal iron homeostasis and improving anemia in CKD patients. The aim of this article was to review the regulation of hepcidin levels and the role of hepcidin in CKD-related anemia, and to discuss hepcidin's potential as a clinical biomarker and several investigational treatments designed to lower serum hepcidin levels.
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PMID:Hepcidin is a potential regulator of iron status in chronic kidney disease. 2337 86


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