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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of iron balance is of particular interest, especially iron absorption, cellular iron metabolism and transferrin-transferrin receptor in hematopoiesis. Recent advances in molecular and cell biology have helped to reveal the mysteries of cellular iron metabolism concerning mRNA encoding ferritin and transferrin receptor synthesis. The physiology of transferrin and transferrin receptor is applied in the evaluation of erythropoiesis, i.e., erythron transferrin uptake in ferrokinetics and measurement of serum transferrin receptor. In iron absorption, much of the key mechanism remains unknown. The importance of iron metabolism in human beings is discussed in traditional areas of iron deficiency and nutrition. Iron overload is a new clinical problem to be solved in hemochromatosis or in relation to ischemic heart disease.
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PMID:Overview of iron metabolism. 858 65

We determined the influence of undernutrition on blood soluble transferrin receptor (sTfR) concentrations, an indicator of iron deficiency, in 99 Zairean women (aged 16-45 y) without inflammation. They were recruited during a survey on iron deficiency in rural Bas-Zaire. sTfR was measured by enzyme immunoassay, and indicators of nutritional status [albumin, transthyretin (or prealbumin), and retinol binding protein] were measured by radial immunodiffusion. Undernutrition was diagnosed if the concentration of any one of the indicators was below normal: albumin < 35 g/L, transthyretin < 160 mg/L, and retinol binding protein < 30 mg/L. The sTfR concentration ranged from 1.89 to 19.1 mg/L (mean: 8.7 mg/L). Mean values for indicators of nutritional status, serum ferritin, and transferrin saturation were within the normal range for health subjects. Regardless of the iron status (iron sufficiency, anemia, or iron deficiency with or without anemia) and whether women were pregnant or nonpregnant, undernutrition did not significantly reduce sTfR concentrations. A higher percentage (80%) of iron-deficient women with two or three protein values below normal had sTfR concentrations > 8 mg/L (which are suggestive of iron-deficiency erythropoiesis) compared with iron-deficient women with no (72.7%) or one (66.7%) protein value below normal, anemic women (46-60%) and iron-sufficient women (18.2-36.8%). Results suggest that sTfR can be used as an indicator of iron deficiency in field studies without in-depth assessment of nutritional status. However, the effect of severe malnutrition on this index requires further investigation.
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PMID:Serum transferrin receptor concentrations in women with mild malnutrition. 859 25

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.
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PMID:Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. 863 55

The transmembrane protein, transferrin receptor (TfR), exists in serum as a soluble form that lacks cytoplasmic and transmembrane domains (residues 1-100). The level of soluble TfR in serum is a sensitive indicator of total erythropoiesis and iron deficiency. This study revealed that the major part of soluble TfR was saturated by transferrin (Tf) in serum, forming a stable complex which was more immunoreactive than intact TfR. Thus, we proposed that serum soluble TfR should be measured as the TfR-Tf complex (TRC), using prepared TRC for assay standardization. We developed a new assay for TRC, employing antibody-coated latex agglutination nephelometry (LA). Rapid and reproducible measurements were achieved using an automated analyzer. The values obtained by this LA assay were closely correlated with those obtained by conventional enzyme immunoassay (r = 0.967). The mean level of TRC in 179 adult healthy subjects was 1.62 mg/l. Patients with iron-deficient anemia showed significantly higher TRC levels than the healthy subjects.
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PMID:Soluble transferrin receptor-transferrin complex in serum: measurement by latex agglutination nephelometric immunoassay. 889 4

Familial juvenile nephronophthisis (NPH) is a hereditary form of chronic tubulointerstitial nephritis with onset in childhood. About one-third of patients develop anaemia before renal insufficiency. We investigated the pathogenetic mechanisms leading to anaemia by comparing 6 patients with NPH and 12 reference patients with other renal diseases. We studied their iron metabolism and measured transferrin receptor-ferritin ratios. There was no evidence for iron deficiency or haemolysis. The serum erythropoietin concentrations of the patients with NPH (12 +/- 2.3 U/I) were low compared with the 12 reference patients (25 +/- 18.9 U/I). In the 2 patients with NPH who were fully investigated, the pharmacokinetics of recombinant human erythropoietin appeared normal. Thus, anaemia in patients with NPH does not result from iron deficiency or correlate with impaired iron status. The mechanism underlying the anaemia of NPH appears to affect the function or regulation of the cells producing erythropoietin.
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PMID:Mechanism underlying early anaemia in children with familial juvenile nephronophthisis. 889 59

Iron deficiency anemia (IDA) is a major global problem. Early onset of iron deficiency in developing countries makes it imperative to identify iron deficiency in neonates. Most conventional laboratory parameters of iron status fail to distinguish neonates with iron deficient erythropoiesis. Serum transferrin receptor (STFR) levels are a recent sensitive measure of iron deficiency and the present study was carried out to evaluate the usefulness of cord serum transferrin receptors in identifying iron deficient erythropoiesis in neonates. A complete hemogram, red cell indices, iron profile: serum iron (SI), percent transferrin saturation (TS%) and serum ferritin (SF) was carried out in 100 full-term neonates and their mothers at parturition. Cord and maternal STFR levels were estimated using a sensitive enzyme-linked immunosorbent assay (ELISA) technique. Anemic women had a significantly lower SI, their TS% and high STFR levels suggesting that iron deficiency was responsible for the anemia. In the neonates of iron deficient mothers, cord SI, TS% and cord ferritin were not significantly different from those of neonates born to non-anemic mothers. Cord STFR level correlated well with hemoglobin (Hb) and laboratory parameters of iron status, and its level was significantly higher in neonates born to anemic mothers than in those born to non-anemic mothers. It was the only laboratory parameter to differentiate between neonates born to anemic and non-anemic mothers. Therefore, STFR is a sensitive index of iron status in neonates and identifies neonates with iron deficient erythropoiesis.
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PMID:Serum transferrin receptor levels in the evaluation of iron deficiency in the neonate. 931 6

Intestinal nonheme iron levels and mRNA levels of genes implicated in iron metabolism were measured in mice with altered iron metabolism [chronic (4 wk) and acute (4 days) dietary iron deficiency; iron overload and hypoxia] to investigate their role in the process and regulation of intestinal iron absorption. Mucosal nonheme iron levels were decreased by both chronic and acute iron deficiency and increased by iron overload but were not affected by hypoxia. There was evidence of a gradient of mucosal nonheme iron along the small intestine (duodenum, jejunum > ileum). There were also regional differences in H-ferritin (duodenum > ileum) and transferrin receptor (ileum > duodenum) mRNA levels. Iron overload produced a decrease in transferrin receptor (TfR) mRNA in the duodenum, with ferritin mRNA levels unaffected in both the duodenum and ileum. Chronic iron deficiency induced a twofold increase in TfR mRNA levels in both the duodenum and ileum, whereas H- and L-ferritin mRNA levels did not change significantly. The ratio of H- to L-ferritin mRNA decreased significantly during exposure to hypoxia; however, individual ferritin and TfR mRNA levels were not significantly altered. Calreticulin (mobilferrin), cysteine-rich intestinal protein, and H(+)-adenosinetriphosphatase mRNA levels were virtually unchanged in all models. A comparison with previously published data on changes in iron absorption leads us to conclude that 1) iron absorption can be altered independently of effects on transcripts of genes for iron-related proteins, and 2) it is not essential for iron absorption to be coordinated with regulation of mucosal iron metabolism.
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PMID:Expression of genes involved in iron metabolism in mouse intestine. 894 90

The transferrin receptor in serum provides a useful measure of tissue iron deficiency and the rate of erythropoiesis, whereas serum ferritin reflects the amount of storage iron in normal subjects. We studied the serum transferrin receptor and the transferrin receptor-ferritin ratio in 57 healthy prepubertal or early pubertal boys and followed them at 3-mo intervals for 24 mo to evaluate their iron status during puberty. The mean laboratory parameters changed as follows: Hb from 13.0 to 13.3 g/dL (p = 0.01), mean corpuscular volume from 85 to 84 fL (p = 0.0001), transferrin receptor from 6900 to 7200 micrograms/L (p = 0.03) ferritin from 36 to 23 micrograms/L (p = 0.0001), and transferrin receptor-ferritin ratio from 230 to 400 (p = 0.0001). At the start of the investigation, the serum transferrin receptor was elevated (> 9000 micrograms/l) or ferritin low (< = or 12 micrograms/L) in fewer than 2% of the boys. During the subsequent 2 y the proportion of boys with an elevated transferrin receptor or low ferritin value increased. The two parameters were simultaneously abnormal in none of the boys initially, but in about 3% of the boys 2 y later. The change in transferrin receptor-ferritin ratio was closely correlated with genital development. The proportion of elevated transferrin receptor-ferritin ratios increased 4.5-fold during the 2 y, indicating the high responsiveness of the ratio. At the end of the study, iron therapy was started to eliminate any iron deficiency. In response to the therapy, the mean transferrin receptor-ferritin ratio fell to 210 +/- 19, i.e. close to the level at the beginning of the study. The marked responses of the transferrin receptor and the receptor-ferritin ratio to iron therapy reflect the dependence of these parameters on iron status rather than on physiologic differences in the rate of erythropoiesis.
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PMID:Body iron stores decrease in boys during pubertal development: the transferrin receptor-ferritin ratio as an indicator of iron status. 902 43

The description by Ramsay in 1957 of a practical way of determining the total iron binding capacity of serum (a measure of transferrin concentration) provided a diagnostic test for both iron deficiency and iron overload. Since 1957 the introduction of the assay for serum ferritin (in 1972) has made it possible to assess the levels of storage iron in normal subjects and assays for free erythrocyte protoporphyrin and the circulating transferrin receptor methods to evaluate iron supply for erythropoiesis. In 1957 iron metabolism in man was already well understood but its evaluation relied on measurement of tissue iron concentrations and the use of radioisotopes of iron to measure rates of erythropoiesis. The evaluation can now be carried out using the various blood assays along with the measurement of haemoglobin concentration but interpretation of the measurements in disease still requires an understanding of the way in which these measures are influenced by pathological processes.
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PMID:The laboratory assessment of iron status--an update. 908 90

Ten patients, who received cadaveric kidneys, were followed for 24 wk with serial measurements of serum erythropoietin (S-Epo), transferrin receptor (S-TfR) and iron variables. The mean pretransplant creatinine clearance was 8.2 (range 0-22) ml/min and the mean haemoglobin (Hb) level was 99 +/- 18.6 (range 66-124) g/l. Nine patients demonstrated a gradual increase in S-Epo levels, which reached a peak, and was accompanied by a parallel increase in S-TfR levels with a median lag period of 3 wk between both peaks. Hb correction followed the S-TfR peak after a second lag period (median 7 wk). Elevated S-Epo and S-TfR did not result in correction of anaemia in 1 patient due to impaired graft function. Within 4 months, S-Epo levels reached the normal range while TfR levels were higher than normal. Follow-up of iron status demonstrated the development of iron deficiency in 5 patients, which was corrected spontaneously. Improvement in erythropoiesis after renal transplantation seems to occur by means of expansion of the erythroid marrow, as detected by increasing S-TfR levels, subsequent to a S-Epo peak. This expansion precedes Hb normalization. A nonuraemic environment is probably a prerequisite for the correction of anaemia but not for the increase in S-Epo or S-TfR levels. Iron deficiency may occur after transplantation due to an increase in iron utilization.
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PMID:Assessment of erythropoiesis following renal transplantation. 915 Jul 10


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