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)

Resistance to recombinant human erythropoietin occurs in a small but important proportion of hemodialysis patients. This may be due to increased immune activation because pro-inflammatory cytokines inhibit erythropoiesis in vitro. Using FACScan flow cytometry, the proportion of PMA/ionomycin-stimulated T cells expressing cytokines ex vivo was compared in 18 poor responders to erythropoietin, 14 good responders to erythropoietin, and 14 normal controls. CD4(+) T cells from poor responders expressed more interferon-gamma (IFN-gamma; 19 +/- 6%) compared with good responders (11 +/- 6%, P < 0.001) and controls (12 +/- 6%, P < 0.01). Similarly, CD4+ T cells from poor responders expressed more tumor necrosis factor-alpha (TNF-alpha; poor responders: 51 +/- 19% versus good responders: 27 +/- 15% [P < 0.01] and controls: 30 +/- 19% [P < 0.01]). CD4+ expression of IL-10 was also enhanced (poor responders: 1.6 +/- 1.1% versus good responders: 0.7 +/- 0.6% [P < 0.05] and controls: 0.5 +/- 0.2% [P < 0.01]). Likewise, CD4+ expression of interleukin-13 (IL-13) was increased (poor responders: 4.4 +/- 4.2% versus good responders: 1.6 +/- 1.7% [P < 0.05] and controls: 1.6 +/- 1.5% [P < 0.05]). CD8+ T cells from poor responders also showed enhanced expression of cytokines. For IFN-gamma, poor responder expression was 48 +/- 20% compared with 31 +/- 17% (P < 0.05) for good responders and 23 +/- 15% (P < 0.01) for controls. TNF-alpha expression for poor responders was 41 +/- 21% versus 25 +/- 14% for good responders (P < 0.05) and 21 +/- 15% for controls (P < 0.01). IL-10 expression for poor responders was 2.0 +/- 1.2% (good responders: 0.7 +/- 0.6% [P < 0.01]; controls: 0.5 +/- 0.2% [P < 0.001]). These data indicate that T cells from poor responders are in an enhanced activation state possibly as a result of chronic inflammation. In the absence of any other cause (such as iron deficiency), the overproduction of cytokines may account for hyporesponsiveness to erythropoietic therapy in patients with renal failure.
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PMID:Increased expression of erythropoiesis inhibiting cytokines (IFN-gamma, TNF-alpha, IL-10, and IL-13) by T cells in patients exhibiting a poor response to erythropoietin therapy. 1281 37

In patients with renal anemia, iron therapy can be administered intermittently or regularly at a low dose. We performed a randomized clinical trial in pediatric patients with end-stage renal failure on hemodialysis and absolute or functional iron deficiency. The study group received maintenance iron therapy according to the ferritin serum levels and the control group received intermittent 10-weekly doses. Success was defined as stabilization of ferritin levels between 100 and 800 microg/l and transferrin saturation (TSAT) between 20% and 50%, in addition to an increase in the hemoglobin level. The major reason for exclusion was iron overload. The study group received 6 mg/kg per month of parenteral iron [95% confidence interval (CI) 3.3-8.8] and the control group 14.4 mg/kg per month (95% CI 12-16.8) ( P<0.001). After 4 months of treatment, ferritin levels increased to 66 microg/l (95% CI 69-200) in the study group and to 334 microg/l (95% CI 145-522) in the control group ( P=0.009). Maintenance therapy and intermittent weekly doses were successful in 73% and 38%, respectively. After 3 months of treatment, hemoglobin levels increased to 10 g/dl, with no difference between the groups. However, in the control group the increase in hemoglobin levels was unsustained, and 3 patients needed transfusion. Patients in the control group had a higher risk of iron overload than patients in the study group (70% vs. 19%). Thus, the regimen based on assessment of serum ferritin levels was more efficient than the intermittent regimen because it increased and maintained the hemoglobin levels with lower iron doses and a lower risk of iron overload.
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PMID:Intermittent versus maintenance iron therapy in children on hemodialysis: a randomized study. 1463 60

Classic iron deficiency (ID) does not represent a challenge for the laboratory and physicians. The anemia that accompanies infection, inflammation, and cancer, commonly termed anemia of chronic disease (ACD), features apparently normal or increased iron stores. However, 20% of these patients have iron-restricted erythropoiesis (functional ID), an imbalance between the iron requirements of the erythroid marrow and the actual iron supply. Functional ID leads to a reduction in red cell hemoglobiniza-tion, causing hypochromic microcytic anemia. The diagnosis of functional ID in real time is based on measuring the hemoglobin content of reticulocytes. An examination of the biochemical markers of iron metabolism demonstrates weaknesses in the diagnosis of functional ID. We developed a diagnostic plot for the assessment of iron status in ACD and the detection of advancing ID in patients with ID, ACD, and the combined state of functional ID and ACD. The plot indicates the correlation between a marker of the iron supply for erythropoiesis (ie, the ratio of the soluble transferrin receptor value to the logarithm of the ferritin value) and the reticulocyte hemoglobin content and functions as a marker of iron demand. The diagnostic plot shows good selectivity for assessing the iron status of disease-specific anemias such as classic ID, end-stage renal failure, cancer-related anemia, and the anemia of infection and inflammation. The therapeutic implications of the diagnostic plot are to differentiate patients who should be administered oral iron supplements, recombinant human erythropoietin (r-HuEPO), or a combination of r-HuEPO and iron. The response of erythropoiesis to r-HuEPO depends on the iron supply and the proliferation of erythropoiesis. The lack of an increase or a decrease in reticulocyte hemoglobin levels indicates a nonresponder to r-HuEPO or functional ID.
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PMID:Anemia of chronic disease: pathophysiology and laboratory diagnosis. 1579 May 48

The restless legs syndrome (RLS) is a sensorimotor disorder characterised by an intense urge to move the legs and sometimes also other parts of the body, and accompanied by a marked sense of discomfort or pain in the affected body parts. This urge has a circadian pattern - it is most pronounced in the evening or during the night. RLS symptoms are relieved by movement. The pathophysiology of RLS is related to dopamine transmission insufficiency, low iron storage in substantia nigra neurons, and spinal cord dysfunction. RLS is idiopathic or secondary (usually associated with iron deficiency, end-stage renal failure, pregnancy and spinal lesions). One half of the patients with idiopathic RLS have positive family history of RLS. RLS is curable, though the choice of therapy and proper dosage titration may take a long time, and though the therapy may sometimes have to be changed owing to augmentation. The most important pharmacologic treatment used in RLS includes L-DOPA, dopamine agonists, opiates, anticonvulsants and benzodiazepines. Therapy improves significantly the condition in long-term at least in 80% of RLS patients.
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PMID:Restless legs syndrome in 2004. 1582 31

In patients with renal failure, severe anemia and associated fatigue, cognitive and sexual dysfunctions have a significant impact on the quality of life. Anemia also represents an important etiological factor in the development of left ventricular hypertrophy. An inadequate production of a glycoprotein hormone, erythropoietin (EPO), is the major cause of anemia in presence of a reduction in the glomerular filtration rate. EPO is the primary regulator of the growth and survival of the erythroid progenitor. The treatment of anemia in chronic renal failure has been revolutionized by the introduction of recombinant human EPO. The vast majority of patients responds very well to treatment, although 5-10% of patients shows some resistance to EPO, the most common cause of which is iron deficiency. Several studies have recently been started in order to investigate the effects of preventing renal anemia from ever developing in uremic patients. The hemoglobin concentration target in pre-dialysis and dialysis patients is the subject of continuous re-assessment.
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PMID:Anemia and erythropoietin treatment in chronic kidney diseases. 1594 19

Restless legs syndrome (RLS) is a poorly understood sensory-motor neurological disorder whose prevalence in Caucasian populations ranges from 10% to 15%. The patient reports unpleasant sensations in the lower limbs with dysesthesia resulting in an urge to move the legs. The symptoms occur during periods of inactivity, increasing in the evening and at night. Moving the legs provides relief. In 80% of cases, polysomnography shows periodic leg movements during sleep. Patients with idiopathic RLS often report similar symptoms in family members. Secondary RLS may be due to medications, diabetes mellitus, renal failure, iron deficiency, neurological disorders, or rheumatoid arthritis. In secondary RLS, the management rests on treatment of the cause. Symptomatic treatment is warranted in patients with moderate-to-severe symptoms that adversely affect the quality of life. Dopaminergic agents are tried first. When they fail or induce adverse effects, weak opioids, benzodiazepines, anticonvulsants or, if needed, strong opioids, may be used.
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PMID:Is restless legs syndrome underrecognized? Current management. 1621 71

The anaemia associated with chronic renal failure is multi-factorial. Although a relative erythropoietin deficiency is a major factor, it has also been recognized in recent times that uraemia is a chronic inflammatory state, and thus patients with renal failure also develop anaemia due to mechanisms associated with chronic inflammation. Thus, patients with chronic renal failure have activation of various immune cells, both monocytes and T-cells. These mononuclear cells have also been shown to release pro-inflammatory cytokines such as IL-1, IL-6, TNF-alfa and interferon gamma. These cytokines, particularly TNF-alfa and interferon gamma, are known to cause significant suppression of erythropoiesis. The exact molecular mechanism for this effect is not yet clear, but interferon gamma is an important stimulator of apoptosis in various cell types, including erythroid progenitor cells. This effect may be potentiated by other cytokines such as TNF-alfa, and this might then antagonise the anti-apoptotic action of erythropoietin on erythroid progenitors cells, thus reducing responsiveness to exogenous erythropoietic therapy. Chronic renal failure is also associated with increased hepcidin production which may also exacerbate the anaemia by inducing a functional iron deficiency in such patients.
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PMID:Hyporesponsiveness to erythropoietic therapy due to chronic inflammation. 1628 56

Anaemia is a frequent complication of diabetic nephropathy. It has only recently been recognised that in diabetic patients anaemia is seen not only in preterminal renal failure, but also frequently in patients with only minor derangement of renal function. At any level of glomerular filtration rate (GFR) anaemia is more frequent and severe in diabetic compared to nondiabetic patients. A major cause of anaemia is an inappropriate response of erythropoietin to anaemia. Additional factors are iron deficiency and iatrogenic factors, e.g. ACE inhibitor treatment. When serum creatinine is still normal, the erythropoietin concentration is predictive of more rapid loss of glomerular function. When serum creatinine is elevated, the haemoglobin values are predictive of the rate of progression. It is currently under investigation whether reversal of anaemia attenuates the rate of progression. Because most of the late complications of diabetes (retinopathy, neuropathy, heart disease, peripheral arterial disease) involve ischaemic tissue damage, it would be intuitively plausible that treatment with human recombinant erythropoietin should be beneficial, but definite evidence for this hypothesis is currently not available.
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PMID:Diabetic nephropathy and anaemia. 1628 61

Over a 2-month period, 200 type 1 diabetic patients attending a paediatric diabetic clinic in Cairo, Egypt were screened for anaemia and other complications of diabetes. The mean age was 11.2 years and the mean duration of diabetes was 4.0 years. Anaemia was diagnosed in 75 patients (37.5%) overall: 45 had microcytic hypochromic anaemia, 18 normocytic normochromic and 12 macrocytic hyperchromic. Of the 75, 41 patients (54.7%) had iron deficiency, 14 (18.7%) had folate deficiency and 14 (18.7%) had thalassaemia minor. Three patients (4%) had coeliac disease, and 18 patients (24%) had parasitic infections. None of the patients had hypothyroidism, renal failure or vitamin B12 deficiency.
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PMID:Prevalence and type of anaemia in young Egyptian patients with type 1 diabetes mellitus. 1676 66

A normocytic normochromic anemia is one of the first signs of renal failure. Since anemia increases morbidity and mortality, its elimination is one of the essential objectives of the treatment. Human recombinant erythropoietin (rHuEPO) has changed the therapeutical approach to anemia. The aim of the present study was to compare efficacy of anemia correction in peritoneal dialysis patients depending on treatment and dialysis modality. The study is the retrospective analysis of 64 patients who presented to our Clinic in 2003. Eighteen (28.13%) patients were treated with rHuEPO, 14 (28%) underwent continuous ambulatory peritoneal dialysis (CAPD), 2 (100%)--automated peritoneal dialysis (APD) and 2 (33.3%)--intermittent peritoneal dialysis (IPD). Mean hemoglobin level was 98.6 +/- 17.82 g/l in patients treated with rHuEPO versus 98.81 +/- 15.14 g/l in patients without rHuEPO treatment. Erythropoietin requirements were 3392.85 +/- 1211.77 IU/week All patients received iron supplementation during rHuEPO therapy. Mean serum ferritin levels were 463.41 +/- 360 ug/l. Transferrin saturation (TSAT) was 0.35 +/- 0.16%. No difference of serum iron and TSAT levels was found between CAPD and IPD patients. The degree of anemia significantly differed between CAPD and IPD patients. A total of 17.11% of PD patients were given blood transfusions, most frequently during the first three months after the onset of dialysis. Our conclusion is that the number of patients receiving rHuEPO should be increased, as 50% of our patients should be substituted, while only 28% are being treated. As 50% of patients receiving rHuEPO failed to reach target Hgb levels, higher EPO doses should be considered. Iron stores should be continuously monitored, particularly in patients receiving rHuEPO, since iron deficiency is an important problem for patients undergoing peritoneal dialysis, especially during erythropoietin therapy. Oral iron supplementation is satisfactory in the majority of patients, and iron-gluconate is absorbed better than iron-sulphate. If required, intra-venous iron bolus is safe and efficient. Continuous peritoneal dialysis treatment improves blood count more effectively compared to intermittent procedures, as hemoglobin levels are significantly higher in patients with comparable iron stores. Peritoneal dialysis is particularly efficient in improving the blood count in diabetics, since no significant difference of anemia between patients affected by diabetes mellitus and the others could be found in our study.
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PMID:[Anemia in peritoneal dialysis patients]. 1691 54


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