Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.
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PMID:Inadequate erythroid response to hypoxia in cystic fibrosis. 673 32

Studies of ferrokinetics, iron status and serum erythropoietin levels were undertaken in 28 Asian patients on RDT as they appeared to be more anaemic and to have a poorer response to treatment than their Western counterparts. The main aetiological factor seemed to be inadequate bone marrow function which tended to be worst in those who had been on dialysis the longest. In addition it is possible that there was also a relative lack of erythropoietin. Dietary factors and iron deficiency were not important. The possible roles of a progressive accumulation of a toxic factor, or of relative underdialysis in patients who were profoundly uraemic prior to the institution of regular haemodialysis, are discussed.
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PMID:Studies on the anaemia of Asian patients with chronic renal failure undergoing regular haemodialysis. 707 23

Erythropoietin, a glycoprotein, is synthesized mainly in the kidney. With the destruction of renal tissue, erythropoietin production decreases; this is a major factor in the development of anemia in patients with renal failure. For about ten years now, recombinant human erythropoietin has been available for the treatment of renal anemia. All patients with renal insufficiency, independent of their plan for future renal replacement therapy, may benefit from erythropoietin. At what extent of anemia erythropoietin therapy should be started is still discussed and is certainly dependent on the degree of the patient's impairment by his anemia. Before beginning a therapy with erythropoietin, other forms of anemia observed in patients with renal failure, i.e. mainly iron deficiency, have to be excluded. A strict monitoring of hematocrit during treatment with erythropoietin is mandatory. Hypertension, seizures and cardiovascular complications have been observed with overdosing of erythropoietin. Special emphasis of this review is therefore put on the discussion of the dynamics of the erythropoietin-red cell system.
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PMID:[Erythropoietin, a milestone in the history of nephrology]. 748 78

Twenty-four premature infants, < 32 weeks gestational age, were randomly assigned in a double-blind, placebo-controlled trial to 6 weeks of treatment with either recombinant human erythropoietin (rHuEpo) 150 U/kg three times per week given sc (n = 12) or placebo (n = 12). The infants were fed a diet rich in protein (3.2 g/kg/day) and energy (130 kcal/kg/day) based on their own mother's milk fortified with bovine protein together with moderate iron supplementation (4 mg/kg/day). During the treatment (rHuEpo versus placebo) significant differences in mean (+/- SD) reticulocyte count (4.8 +/- 1.2 versus 2.7 +/- 1.4%; p < 0.01), mean packed red cell volume (PCV) (0.38 +/- 0.03 versus 0.34 +/- 0.04, p < 0.05) and mean haemoglobin concentration (12.6 +/- 1.1 versus 11.5 +/- 1.2 g/100 ml; p < 0.05) were found. Within the rHuEpo group, PCV and haemoglobin concentration remained unaltered from entry to 1 week after cessation of treatment whereas a significant decline was observed in the placebo group. No indications of iron deficiency were seen. We conclude that moderate doses of rHuEpo given to infants fed a diet rich in protein and energy are effective in ameliorating anaemia of prematurity. High iron supplementation does not seem to be essential for a significant erythropoietic response. No adverse effect attributable to rHuEpo was observed.
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PMID:Enhancement of erythropoiesis by erythropoietin, bovine protein and energy fortified mother's milk during anaemia of prematurity. 754 3

The precise cause of the anaemia that is commonly associated with severe pulmonary tuberculosis (PTB) has not been elucidated. The role of erythropoietin (Epo), the central hormone regulating red cell formation, still awaits clarification. We therefore determined serum Epo levels in patients with PTB; group 1, haemoglobin less than 110 g/L, group 2, haemoglobin greater than 110 g/L; group 3, controls, consisted of matched individuals with uncomplicated iron deficiency; group 4, healthy volunteers. Peripheral blood monocytes were obtained from patients with PTB and the controls, cultured, and the supernatant fluid (SNF) harvested. Tumour necrosis factor alpha (TNF alpha) levels were determined in the SNF, which were then added in various dilutions to a hepatocellular carcinoma cell line (HepG2) capable of regulated EPO synthesis in vitro. The influence of this cytokine was defined by the addition of specific neutralising anti-TNF alpha antibodies in this assay system. Patients in group 1 had significantly lower Epo levels (54 + 11 mU/mL) compared with those in group 3 (142 +/- 41 mU/mL) (p < 0.01). Monocyte supernatants from patients in the anaemic PTB group had markedly elevated TNF alpha levels and significantly suppressed Epo output by HepG2 cells in vitro (p < 0.01). This inhibition was consistently abrogated by anti-TNF alpha antibodies. Serum Epo levels were inappropriately low in untreated PTB patients when compared with corresponding haemoglobin levels in iron deficient controls. This blunted response could be ascribed to release of TNF alpha or other cytokines by activated monocytes.
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PMID:Blunted erythropoietin response to anaemia in tuberculosis. 758 43

Iron deficiency is common in hemodialysis patients, particularly if they are on recombinant human erythropoietin (rHuEPO) therapy. Ten anemic patients (hemoglobin concentration 89 +/- 2.2 g/l, mean +/- SEM) on hemodialysis with either storage (serum-ferritin < 60 mg/l) and/or functional (S-transferrin saturation < or = 17%) iron deficiency were followed for 5 weeks. During the first 3 weeks they were given 100 mg of iron dextran on 10 consecutive dialysis sessions. Half of the patients were concomitantly treated with rHuEPO. Iron therapy resulted in a rapid elevation in serum transferrin iron saturation from 11 +/- 1.5% to 80 +/- 7.2% (p < 0.0001), but it decreased to pre-treatment levels within 2 weeks after discontinuation of iron therapy. Serum ferritin concentration increased from 157 +/- 73 mg/l to 434 +/- 105 mg/l during iron therapy (p < 0.0001). In spite of this only 4 patients (2 rHuEPO treated) responded and had a hemoglobin increment > 10 g/l. In the whole group serum transferrin receptor (TfR) levels remained stable, but increased after the cessation of iron dextran only in the rHuEPO treated patients (p < 0.01). In the responders the TfR levels were higher during iron therapy than in the nonresponders (p < 0.02). In an attempt to explain the resistance to iron therapy, serum concentrations of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b (IL-1b) were also analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iron availability is transiently improved by intravenous iron medication in patients on chronic hemodialysis. 861 62

In historical studies erythropoietin stimulated bone marrow was shown to produce less stable, macrocytic, "stress erythrocytes". Recent work from our lab suggests that erythropoietin serves as both a growth factor and as a survival factor. To investigate the effects of recombinant human erythropoietin (rHuEPO) on development of red blood cell size of these longer lived erythrocytes, rHuEPO in 50-150 U/kg/dose was administered to patients with the anemia of chronic renal failure (CRF). Mean corpuscular volume (MCV) was determined at control, short term (n = 117, avg. 53 d), intermediate term (n = 73, avg. 136 d) and at long term (n = 66, avg. 221d) for effects of rHuEPO. Statistical evaluation at these time points was made comparing all patients to themselves as their own controls and using contingency tables for distribution of RBC size change. MCV at both short term (p = .02) and intermediate-term (p < .01) was decreased; there was no change (p = .71) at the long term. Analysis of distribution showed a significant (p < .01) trend toward microcytosis at short- and intermediate terms. This decrease of MCV and trend toward microcytosis is consistent with iron deficiency secondary to the early, rapid increase in bone marrow iron utilization and early increased reticulocytosis. Previous reports from our laboratory coupled with data presented in this report refute earlier findings that rHuEPO creates a "stress" mechanism producing less stable macrocytes.
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PMID:The effects of recombinant human erythropoietin on mean corpuscular volume in patients with the anemia of chronic renal failure. 760 80

Administration of recombinant human erythropoietin (r-HuEPO) in uraemic pre-dialysis patients is both effective and safe. The benefits are similar to those in dialysis patients: a marked increase in subjective wellbeing and ability to perform physical work. There is a strong argument for treating on the basis of anaemic symptoms, rather than on absolute haematocrit or haemoglobin. Some 30-40% of r-HuEPO-treated pre-dialysis patients may need initiation of, or an increase in, antihypertensive therapy. Provided blood pressure is carefully controlled, r-HuEPO does not appear to accelerate the progression of renal failure, and there is preliminary evidence that it may even delay the need for dialysis in children and possibly in adults. Subcutaneous self-administration is convenient for most pre-dialysis patients; once weekly administration can yield effective results and may enhance patient compliance. As in dialysis patients, detection and correction of iron deficiency play an essential role in maximizing the success of r-HuEPO administration. For most pre-dialysis patients, oral iron administration is convenient, and absorption is satisfactory.
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PMID:Starting r-HuEPO in chronic renal failure: when, why, and how? 764 5

The most common cause of limited response to recombinant human erythropoietin (r-HuEPO) is unrecognized, mild-to-moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Iron stores in patients with chronic renal failure (CRF) are often depleted through gastrointestinal bleeding, blood loss during haemodialysis, and blood sampling. Mobilization of iron stores may be inadequate, especially during rapid haemoglobin regeneration. Aluminium overload may also interfere with gastrointestinal and cellular iron uptake. Overt or unrecognized infection or inflammation is another common cause of hyporesponsiveness, and is a consequence of increased blood concentrations of cytokines such as tumour necrosis factor (TNF), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma), which suppress erythrocyte stem-cell proliferation. Less common causes include severe secondary hyperparathyroidism and myeloma (during chemotherapy). Response to r-HuEPO can be best predicted by baseline fibrinogen (a marker of subclinical inflammation); baseline transferrin receptor (sTfR) concentrations (a marker of functional iron deficiency); and sTfR increment after 2 weeks (a marker of early change in erythropoietic activity).
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PMID:R-HuEPO hyporesponsiveness--who and why? 764 9

Inadequate iron supply is probably the most common and most easily treated cause of sub-optimal response to recombinant human erythropoietin (r-HuEPO). A low ferritin value is a reliable indicator of iron deficiency, provided that patients are in equilibrium (e.g. without infection, bleeding, vitamin or folate deficiency). Normal or high ferritin values do not necessarily preclude iron deficiency. Transferrin saturation is not always a reliable indicator of iron deficiency. The measure which best reflects iron supply to the erythron is the percentage of hypochromic red cells. Iron supplementation should be targeted at keeping serum ferritin > 100 micrograms/l, transferrin saturation > 20%, and hypochromic red cells < 10%. Iron status should be monitored monthly for the first few months after initiation of r-HuEPO, and thereafter at 2-3 month intervals. For haemodialysis patients, who have a very high rate of iron loss, i.v. iron administration is preferable and may also be appropriate for patients on continuous ambulatory haemodialysis (CAPD) and pre-dialysis patients. Recent studies with i.v. iron supplementation have shown no difference between the s.c. and i.v. routes of administration of r-HuEPO. Both the i.v. and the s.c. route are appropriate for patients on haemodialysis, whereas patients on CAPD or pre-dialysis patients should receive s.c. r-HuEPO. The optimum frequency of s.c. administration in the vast majority of patients is 2-3 times weekly. For a small number of patients, once weekly s.c. administration may be suitable. When satisfactory haemoglobin values are reached, the dose of r-HuEPO should be titrated down gradually. It should not be stopped abruptly unless there are life-threatening complications.
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PMID:How to get the best out of r-HuEPO. 764 13


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