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)

The treatment efficacy of erythropoietin (EPO) in end-stage renal disease (ESRD) can be limited by deficiencies of iron, folate, or vitamin B12, by hyperparathyroidism, or by aluminum intoxication. Since EPO costs are significant, this study attempted to determine the cost-effectiveness of performing a panel of screening tests for anemia before starting EPO. Anemia screening was performed prospectively in 48 new-onset ESRD patients at the Ralph H. Johnson Veterans Affairs Medical Center before EPO treatment was started. Serum iron, transferrin, folate, vitamin B12, parathyroid hormone, and aluminum levels were determined, and transferrin saturation (Tfsat) was calculated at the first dialysis session. At presentation for dialysis, the mean hematocrit was 0.264 +/- 0.036 and the mean blood urea nitrogen was 32 +/- 2 mmol/L. Eighteen patients (37.5%) had a serum iron level lower than 7 micromol/L, suggesting iron deficiency. Twenty-five patients (52%) had Tfsat less than 0.20, consistent with overt iron deficiency. No patient was found to be vitamin B12 deficient, to be aluminum intoxicated, or to have significant hyperparathyroidism. One patient had folate deficiency. A cost-effectiveness analysis was performed assuming that (1) EPO would be given at an average starting dose of 6,000 U/wk at a cost of $14/2,000 U of EPO; (2) that without screening 1 month would elapse before a poor response was identified; and (3) that the failure to treat aluminum intoxication and hyperparathyroidism or to replete iron, vitamin B12, or folate deficiency would significantly impair the response to EPO. The Tfsat screen had a cost-effectiveness ratio of 0.2019, saving approximately $5.00 in EPO use for each dollar of test administration. All other screens had cost-effectiveness ratios greater than 1.0, indicating that their testing costs exceeded dollar savings in EPO use. In conclusion, iron deficiency is common in anemic patients starting dialysis, but other causes of anemia are not. It is imperative that current clinical practices be influenced by cost-effectiveness considerations. Given the cost of laboratory screens, and the relative ineffectiveness of the other screens examined here to identify factors known to impair the response to EPO, anemia screening before initiating EPO therapy should be limited to tests to identify iron deficiency.
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PMID:A cost-effectiveness analysis of anemia screening before erythropoietin in patients with end-stage renal disease. 915 97

The influence of angiotensin-converting enzyme inhibitors (ACEIs) on recombinant human erythropoietin (rhEPO) maintenance doses in hemodialysis patients was studied. One hundred and eight chronic hemodialysis patients (55 males and 53 females, mean age 61.2+/-12.6 years) were investigated. The rhEPO maintenance doses in the ACEI-treated group (n = 49) were 101.7+/-51.7 U/kg/week and in the nontreated group (n = 59) 79.2+/-37.8 U/kg/week (p < 0.05). No difference was observed in hematocrit between the ACEI-treated and nontreated groups. In stepwise regression analysis, the parameters associated with increased rhEPO maintenance doses were female gender, ACEI administration, low total iron binding capacity, and low serum free carnitine levels. In conclusion, ACEI administration might reduce the response to rhEPO. In hemodialysis patients who need high-dose rhEPO to maintain the target hematocrit in the absence of iron deficiency, hyperparathyroidism, infection, malignancy, malnutrition, and aluminum toxicity, ACEI administration should be considered.
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PMID:Angiotensin-converting enzyme inhibitors are associated with the need for increased recombinant human erythropoietin maintenance doses in hemodialysis patients. Risks of Cardiac Disease in Dialysis Patients Study Group. 934 82

Anemia is the most common hematologic abnormality in patients with chronic renal failure. The reasons for anemia in chronic renal failure are many and include erythropoietin and iron deficiencies, inflammation, infection, aluminum toxicity, and hyperparathyroidism. Iron deficiency alone affects more than 50% of patients on dialysis, and the estimated iron loss for these patients is 1.5 to 3 grams per year. The use of erythropoietin has also uncovered iron deficiency in a multitude of patients. Iron and erythropoietin supplementation has often restored normal or near-normal levels of hematocrit in these patients and has therefore improved some of the symptoms classically connected with chronic renal failure, such as fatigue, cold intolerance, and mental sluggishness, among others. Resistance to erythropoietin is frequently observed in the maintenance care for dialysis patients, and the most common reason is iron deficiency. It is important to understand the physiology of renal anemia, erythropoiesis and iron metabolism in order to avoid mistakes and misconceptions in the management of iron in chronic dialysis patients. In this article, we review several mistakes, misconceptions, practices, and guidelines in iron supplementation therapy. We also review the physiology of anemia in renal disease and the importance of erythropoietin and iron in causing anemia and discuss recent Dialysis Outcomes Quality Initiative (DOQI) guidelines on the topic.
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PMID:The use of iron in patients on chronic dialysis: mistake and misconceptions. 956 79

The need for a renewable source of erythropoietin to treat the anaemia of chronic renal failure was first recognized in the 1960s, but cloning and expression of the human gene was not achieved until 1983. Clinical testing of recombinant human erythropoietin (r-HuEPO) began in 1985, leading to the first licence as a therapeutic agent in 1988. The first clinical trials showed that an intravenous dose requirement of about 200 IU/kg/week would increase haemoglobin concentrations to 10-12g/dl in >90% of haemodialysis patients. Subcutaneous administration has subsequently been found to be effective, and may allow lower maintenance doses. It is now the route of choice in Europe, but not the USA. The best marker of benefit of the introduction of r-HuEPO is the reduction in need for regular blood transfusions. A marked improvement in anaemia-related symptoms has been clearly demonstrated. The most important factor in optimizing the response to r-HuEPO is iron supply. The marrow should be stimulated slowly, to allow mobilization of iron stores. Functional or absolute iron deficiency should be pre-empted by regular iron supplementation. It is also important to recognize resistant states induced by inflammation and bleeding, and to exclude severe hyperparathyroidism, aluminium overload and other haematological diseases. The most important adverse events associated with r-HuEPO are increased blood pressure and a possible increased risk of access failure. These are, however, challenges to improve practice, not reasons to avoid the use of r-HuEPO.
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PMID:Recombinant human erythropoietin: 10 years of clinical experience. 956 83

Optimizing the use of recombinant human erythropoietin (r-HuEPO) involves choosing an appropriate dose regimen and target haemoglobin level, addressing factors that inhibit response, and considering appropriate adjuvant therapy. Subcutaneous administration of r-HuEPO two or three times weekly is optimal for most patients. Early detection and treatment of iron deficiency is mandatory. Measurement of the percentage of hypochromic red blood cells is a reliable marker of functional iron deficiency, and the treatment of choice is intravenous iron. Other factors that can affect the response to r-HuEPO include blood loss (sometimes occult), infection, inflammation, hyperparathyroidism with marrow fibrosis, aluminium toxicity, vitamin B12/folate deficiency, haemolysis, bone marrow disorders, haemoglobinopathies, under-dialysis and possibly angiotensin-converting enzyme inhibitors. These factors should be identified and corrected where possible. Ascorbic acid, vitamin D, folic acid, carnitine, other cytokines and growth factors have all been shown to augment the response to r-HuEPO in some patients. Further research is required before any of these adjuvant therapies can be incorporated into routine clinical practice. With regard to target haemoglobin value, the current practice is to aim for a level of 10-12 g/dl, but it may be argued that a higher target would achieve greater benefits in terms of physical performance, quality of life, and possibly cardiac morbidity and mortality. International multicentre trials are currently in progress to address this issue, as are studies on other substances that may be able to stimulate erythropoiesis.
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PMID:Meeting the challenges of a new millennium: optimizing the use of recombinant human erythropoietin. 1048 48

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.
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PMID:Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients. 991 69

Erythropoietin (EPO) treatment dramatically changes the life of a child with end-stage renal disease. The administration of recombinant human (rHu)EPO is beneficial and safe in the predialysis period, during hemodialysis or peritoneal dialysis, and after renal transplantation. The goal of hemoglobin correction should be the level at which normal quality of life is possible without adverse events: in children this is usually 10-11 g/dl. rHuEPO is administered once to twice a week subcutaneously to children before dialysis, during peritoneal dialysis, and after transplantation. There is no real benefit of intraperitoneal administration. In children on hemodialysis two to three times a week IV administration is preferred. Among the many reasons for non-response to rHuEPO, iron deficiency (absolute or functional), infections, and hyperparathyroidism are the most common in the pediatric renal patient. Hypertension is the most-frequent side effect of rHuEPO treatment and needs careful monitoring. Iron should be supplemented orally or IV. No significant beneficial effect of rHuEPO on growth has been demonstrated. However, the association with recombinant human growth hormone therapy is not detrimental in children.
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PMID:Erythropoietin treatment in children with renal failure. 1065 38

The invention of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia was a hallmark in the care of patients with renal insufficiency. Recently published guidelines (European Best Practice Guidelines, NKF-DOQI) have set the target haemoglobin to be reached by treatment with rHuEpo to >11 g/dl. Normalizing haemoglobin levels may reduce morbidity and mortality and improve quality of life in haemodialysis patients. During long-term treatment, most patients will not respond adequately to therapy with rHuEpo alone. The most important confounding factor, limiting the effectiveness of rHuEpo, is absolute or functional iron deficiency, which is now recognized and treated in many dialysis units. However, there are several other adjuvant treatment options which may help to optimize the response to treatment with rHuEpo. A weekly dose of 2-3 mg of folic acid and 100-150 mg of vitamin B6 is recommended for haemodialysis patients on rHuEpo therapy. The addition of 0.25 mg/month of vitamin B12 may be necessary in selected patients. Vitamin C (1-1.5 g/week) was shown to overcome functional iron deficiency in patients with high ferritin levels. The potential increase of oxidative stress induced by intravenous iron therapy may be blunted by concomitant administration of vitamin E (1200 IU). There is clear evidence from the literature that treatment of secondary hyperparathyroidism by vitamin D improves erythropoiesis. The most recently discovered biological effects of rHuEpo include the induction of several genes in endothelial cells as well as a role for erythropoietin in the outcome of plasmodium infection. A new erythropoietin-like molecule is novel erythropoiesis stimulating protein (NESP), which is as effective and safe as rHuEpo, with the potential advantage of less frequent dosing.
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PMID:Novel aspects of erythropoietin response in renal failure patients. 1150 83

The introduction of recombinant human erythropoietin (rh-Epo, epoetin) as a treatment for the anaemia of renal failure has transformed the management of this condition. Nevertheless, a significant number of patients fail to respond. There are many different possible causes of inadequate response to epoetin. Iron deficiency, whether absolute or functional, is considered to be the most important, and it is widely accepted that maintaining adequate iron levels reduces rh-Epo dosage requirement and improves efficacy in haemodialysis patients. Infection and inflammation have been shown to influence responsiveness to rh-Epo by disrupting iron metabolism and eliciting the release of cytokines that inhibit erythropoiesis. Another factor for consideration is severe hyperparathyroidism, which can lead to a reduced number of responsive erythroid progenitor cells. Inadequate dialysis can also negatively impact on rh-Epo therapy, and aluminium overload interferes with iron metabolism and reduces the efficacy of rh-Epo. Deficiencies in vitamin B(12), folic acid and potentially vitamin C can all reduce the efficacy of treatment with rh-Epo. Optimizing patient response to rh-Epo therapy, therefore, requires consideration of many factors, some well established and others that are more controversial, and the list continues to grow with the identification of new factors.
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PMID:Hyporesponsiveness to recombinant human erythropoietin. 1159 Feb 53

Hyperparathyroidism is usually listed among the possible reasons for impaired response to recombinant human erythropoietin (rHuEPO) in patients with renal disease. However, its relevance in the context of other causes of renal anaemia, and the mechanisms by which it may worsen anaemia, are not entirely clear. Possible pathogenic links between anaemia and parathyroid hormone (PTH) include reduced erythropoiesis due to calcitrol deficiency, and direct or indirect effects of PTH on erythropoietin release, red blood cell (RBC) production, survival, and loss. Studies of these mechanisms have produced disparate results, possibly because secondary hyperparathyroidism may have only a relatively minor role in anaemia that may be masked by the confounding effects of other factors with greater impact. Variations in medical treatment or study methodology may also have affected study results. Severe parathyroid overfunction may contribute to the severity of anaemia in uraemic patients and diminish rHuEPO responsiveness in a minority of patients. However, overall, the importance of hyperparathyroidism appears to be minor compared with other factors such as iron deficiency or inflammation.
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PMID:Role of secondary hyperparathyroidism in erythropoietin resistance of chronic renal failure patients. 1209 4


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