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

The development of hypoproliferative anemia with generally normocytic red blood cells in most patients with chronic renal failure impairs the success of maintenance dialysis therapy, particularly hemodialysis. Anemia can be a complication of the hemodialysis procedure itself, with its associated blood losses and mild effect on oxygen transport functioning. However, the primary cause of anemia in the chronic dialysis patient is decreased erythropoiesis. The most important mechanism leading to decreased erythropoiesis involves the production of subnormal levels of erythropoietin (EPO). Insufficient nephric output of EPO or, possibly, suppression of the effect of EPO by uremic inhibitors may cause this decreased erythropoiesis. Other factors, such as iron deficiency, hyperparathyroidism, systemic infections, and aluminum toxicity may contribute to anemia in some patients. Increased hemolysis, a comparatively mild factor in the anemia of chronic dialysis patients, may be related to retention of protein metabolism products, hypersplenism, hypophosphatemia, drugs, or other conditions in affected patients. There are several traditional treatment options for anemia: transfusions; iron, vitamin B12, or folic acid supplementation when indicated; a change to peritoneal dialysis; parathyroidectomy; and administration of androgens. None of these treatments have proved satisfactory, and some, such as transfusions and androgen therapy, pose risks and have serious side effects. A comparatively new approach, administration of genetically engineered erythropoietin (r-HuEPO; EPOGEN, AMGEN inc, Thousand Oaks, CA), has been found effective in treating anemia in clinical trials. Patients have shown improved cardiac performance as well as enhanced quality of life, and hypertension appears to be the most serious side effect of r-HuEPO therapy.
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PMID:Overview of anemia associated with chronic renal disease: primary and secondary mechanisms. 264 18

The traditional options available for the correction of hemodialysis-related anemia are blood transfusions and androgen therapy to stimulate erythropoiesis. A new therapeutic option, recombinant human erythropoietin (r-HuEPO; EPOGEN, AMGEN Inc, Thousand Oaks, CA), is currently undergoing clinical trials. Each treatment alternative has certain attendant adverse effects. The adverse effects of transfusion include transmission of infections such as hepatitis or acquired immunodeficiency syndrome, iron overload, and sensitization to histocompatibility antigens. Androgen therapy can cause masculinization of women and children and, in some forms, is associated with a high incidence of abnormal liver function. Treatment with r-HuEPO has some potential adverse effects, including hypertension, thrombosis of arteriovenous fistulae, prolonged duration of dialysis, hyperkalemia, and iron deficiency. Gradual and careful introduction of r-HuEPO should prevent hypertension from becoming problematic.
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PMID:Adverse effects of therapy for the correction of anemia in hemodialysis patients. 264 19

Extensive testing has proven that recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) corrects the anemia of end-stage renal disease and eliminates the need for transfusions in virtually all patients. Patients whose hematocrit levels are less than 0.30 or who are transfusion dependent are candidates for therapy. A dosage of 50 to 150 U/kg body weight intravenously three times a week produces an increase in hematocrit by approximately 0.01 to 0.02 per week. Once the hematocrit reaches 0.30 the dose is adjusted so that a target hematocrit of 0.32 to 0.38 is maintained. Eighty percent of patients need maintenance doses of r-HuEPO of less than or equal to 150 U/kg; the other 20% of patients require larger doses. Reasons for poor responses include iron deficiency, inflammation due to surgery or infection, and osteitis fibrosa. Most patients require iron supplementation to prevent functional iron deficiency. BP increased in one third of patients, and in 3% seizures occurred during the initial phase of therapy, often associated with a sudden increase in BP. This hypertension can be controlled with medication. Increased dialyzer clotting may occur, which is prevented when heparin doses are adjusted, and dialyzer solute clearances may decrease slightly. Treatment with r-HuEPO does not elicit an antibody response. The mechanism of action of r-HuEPO is identical to that of natural erythropoietin, and therefore is an appropriate therapy for the long-term management of anemia in chronic renal failure.
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PMID:Guidelines for recombinant human erythropoietin therapy. 266 49

Iron deficiency frequently complicates both acute and chronic phases of recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) therapy for dialysis-associated anemia. During acute correction of anemia, iron needed for new hemoglobin production may outstrip available body iron stores. During maintenance r-HuEPO therapy, blood lost both through the dialysis process and the uremic predisposition to gastrointestinal bleeding promotes ongoing negative iron balance. Failure to recognize and treat iron deficiency may lead to impaired efficacy of r-HuEPO in the anemic patient by converting the anemia associated with chronic renal failure to the anemia associated with iron deficiency. The risk of iron deficiency is assessed by weighing available iron stores, as reflected by the level of serum ferritin, against anticipated iron needs for new hemoglobin synthesis, as measured by the difference between the current and target hemoglobin. Using this approach, body iron reserves can be determined, iron deficits predicted, and appropriate iron replacement therapy planned. Once patients are identified as being at risk for iron deficiency, they are treated prophylactically with oral iron supplements. Parenteral iron therapy is reserved for those at greatest risk for iron deficiency during acute r-HuEPO treatment and those intolerant or unresponsive to oral iron supplements during chronic r-HuEPO treatment. Although no dose-response relationship has been observed in the restoration of iron balance with oral iron supplements, those taking supplements show distinctly higher projected iron stores and daily iron balance than those not given supplements.
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PMID:Iron deficiency in patients with dialysis-associated anemia during erythropoietin replacement therapy: strategies for assessment and management. 266 82

Recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) has proven to be an effective agent in treating the anemia of chronic renal failure. Of patients enrolled in recent phase III trials in the United States, 97% have responded with near normalization of hematocrit within 12 weeks of therapy. Small numbers of patients, however, may exhibit sluggish or minimal responsiveness to treatment. In these patients, loss of responsiveness due to red cell substrate depletion (in particular, iron deficiency) or underlying inflammatory disease may occur at any time during the treatment calendar, whether at induction of therapy or during maintenance treatment. Primary unresponsiveness at initiation of treatment may also result from such potentially reversible abnormalities as aluminum intoxication, poorly controlled hyperparathyroidism, and, possibly, severe azotemia. These abnormalities can be investigated in a systemic fashion and frequently corrected so that successful treatment can resume.
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PMID:Resistance to recombinant human erythropoietin therapy: a real clinical entity? 266 85

Erythropoietin is produced mainly by the kidneys and stimulates erythropoiesis in the bone marrow. Chronic renal failure is characterized by anemia, which is principally caused by erythropoietin deficiency. Recombinant human erythropoietin (r-hEPO) corrects the anemia of chronic renal disease and improves patient well-being, exercise tolerance, and cognitive function. The clinical pharmacology, efficacy, safety, and tolerance of r-hEPO are presented. Four major studies attest to r-hEPO's efficacy in the treatment of anemia of chronic renal disease and document potential toxicities of hypertension, iron deficiency, thrombosis, and bone pain. Careful attention to the extent of correction of the hematocrit, increased heparinization during hemodialysis therapy, and compliance with dietary restrictions may minimize the incidence and severity of adverse reactions. Resistance to r-hEPO may be due to iron deficiency, aluminum toxicity, or inflammation, including infection. Potential future uses of r-hEPO include the treatment of various other anemias, such as those seen in sickle cell anemia, rheumatoid arthritis, and autologous blood donation. Controlled clinical studies in these areas have not been reported.
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PMID:Recombinant human erythropoietin. 266 69

The chemistry, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, dosage and administration, and formulary considerations of epoetin are described. Erythropoietin, a glycoprotein hormone primarily synthesized in the kidney, is the chief regulator of red blood cell production. Erythropoietin concentrations increase in response to a hypoxic state, resulting in increased red blood cell formation, accelerated hemoglobin production, and premature movement of reticulocytes into the circulation. The human gene responsible for the production of erythropoietin recently was cloned, and the recombinant product--epoetin--has been made available through mass production. The apparent volume of distribution of i.v. epoetin approximates the assumed plasma volume both in healthy volunteers and in patients with chronic renal failure. Little is known about the metabolism and route of elimination of epoetin and erythropoietin. Epoetin recently was approved by the FDA for treatment of anemia associated with chronic renal failure. Clinical trials in patients receiving hemodialysis or peritoneal dialysis and in predialysis patients with renal dysfunction demonstrate epoetin's efficacy. Other potential indications include augmentation of blood production in patients enrolled in autologous blood donation programs and treatment of anemias associated with rheumatoid arthritis, sickle cell disease, acquired immunodeficiency syndrome, cancer, and premature birth. The most frequent adverse effect associated with epoetin therapy is the worsening or development of hypertension. Other adverse effects include thrombocytosis, hyperkalemia, rise in serum urea concentration, iron deficiency, and flu-like symptoms. No drug interactions with epoetin have been reported in humans. The recommended starting epoetin dosage in patients with chronic renal failure is 50-100 IU/kg three times weekly. Epoetin is available only as an injection for i.v. or s.c. administration. Epoetin provides a new therapeutic approach to the treatment of anemia associated with chronic renal failure in hemodialysis, peritoneal dialysis, and predialysis patients. Benefits of epoetin therapy include reduced need for blood transfusions, the amelioration of anemic symptoms, and an improved quality of life.
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PMID:Epoetin: human recombinant erythropoietin. 268 Feb 41

Fourteen nondialyzed patients with chronic renal insufficiency (serum creatinine 265 to 972 mumol/L [3.0 to 11.0 mg/dL]) and severe anemia (hematocrit less than 30%) were randomized to receive either recombinant human erythropoietin (r-HuEPO) or a placebo subcutaneously thrice weekly for 12 weeks or until reaching a hematocrit of 38% to 40%. Anemia was significantly ameliorated in the treated patients. No acceleration in the progression of renal failure (1/serum creatinine v time) or change in serum potassium was noted for either the placebo or treated group over the 12-week period. Six of seven treated patients had a significant decrease in serum ferritin and percent transferrin saturation (plasma iron/total iron-binding capacity). This resulted in functional iron deficiency and the requirement for iron supplementation. The average systolic and diastolic blood pressure did not differ significantly between the two groups of patients during the study. Quality of life was improved in all r-HuEPO-treated patients but not in those in the placebo group. This study demonstrates the safety and efficacy of r-HuEPO in the correction of anemia in predialysis patients without adverse effects on renal function over a 12-week period. Improved patient well-being as a result of the correction of anemia resulted in one patient refusing appropriate initiation of dialysis therapy.
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PMID:The use of recombinant human erythropoietin in the correction of anemia in predialysis patients and its effect on renal function: a double-blind, placebo-controlled trial. 268 5

The characteristics and uses of epoetin alfa (recombinant human erythropoietin) are described, and the issues associated with its use are discussed. The use of epoetin alfa was recently approved by FDA for the treatment of anemia associated with end-stage renal disease. Epoetin alfa acts on burst-forming and colony-stimulating units in the blood to raise hemoglobin and hematocrit levels, thus correcting the patient's anemia. It has a relatively short half-life and may be given either i.v. or s.c. Doses vary and must be adjusted according to the individual patient response. Clinical trials have involved doses ranging from 15 to 500 units/kg three times per week. Treatment causes a dose-related rise in the hematocrit, with subsequent improvement in the quality of life of dialysis patients. Adverse effects include hypertension, iron deficiency, and thrombocytosis. Additional research indicates that epoetin alfa may be effective in the correction of other uncomplicated anemias, such as those related to antineoplastic therapy. Issues facing hospital pharmacists and other health-care professionals include cost (the estimated cost of therapy is $4000 to $8000 per patient per year), appropriate use and potential misuse, use and reimbursement for indications not included in FDA-approved labeling, and restriction to particular prescribers. Because epoetin alfa does not produce therapeutic effects for at least 7 to 14 days, it is an ideal agent for formulary restriction. Epoetin alfa, like other products of biotechnology, will have substantial impact, both therapeutic and economic, on the practice of pharmacy. Hospital pharmacists need to be aware of these new therapies so that they may act quickly and decisively when issues associated with their use arise.
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PMID:Recombinant human erythropoietin. 269 Jun 6

Adequate body iron stores are crucial to assuring rapid and complete response to recombinant human erythropoietin (rHuEPO). In the present study, markers of iron storage were examined in 27 patients with normochromic, normocytic anemia undergoing acute rHuEPO (150 to 300 U/kg t.i.w.) treatment for anemia. We calculated projected iron needed for new hemoglobin synthesis from the difference between initial and target hemoglobin concentrations, initial iron reserves available from initial serum ferritin levels, and net projected surplus or deficit from the difference between needs and reserves. Of 22 patients predicted to develop iron deficiency (mean projected deficit 268 +/- 70 mg), 20 developed evidence of exhausted iron stores (transferrin %sat less than 16 or ferritin less than 30 micrograms/liter) before reaching target hemoglobin; two predicted to become deficient (projected deficit less than 100 mg) did not; and all five predicted to avoid iron deficiency (mean projected surplus 177 +/- 20 mg) remained iron replete. During acute rHuEPO therapy net body iron balance remained neutral in patients receiving no iron supplements and increased 5 mg/kg in patients prescribed oral ferrous sulfate. However, in patients given iron dextran i.v. less than 60% of elemental iron administered became measurable as iron stores or usable for hemoglobin synthesis.
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PMID:Iron status in patients receiving erythropoietin for dialysis-associated anemia. 270 74


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