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)

This multicentre study in 142 transfusion-dependent patients with chronic renal failure maintained by haemodialysis was performed to establish the appropriate dose regimen of rHuEpo and define its long-term safety profile. Only one of 132 patients eligible for efficacy analysis did not achieve the haemoglobin target of greater than or equal to 10 g/dl; this particular patient had folate deficiency and overt hyperparathyroidism. Regular blood transfusions were no longer necessary in any patients, however five patients needed blood transfusions only once, not due to rHuEpo failure: two for iron deficiency and three for intercurrent disease. In parallel with the haemoglobin increase a statistically significant improvement in quality of life scores was observed. The weekly dose required to maintain median haemoglobin between 10 and 10.5 g/dl for 1 year (n = 79) was 200-225 U/kg, applied as two or three i.v. injections. Mean serum ferritin decreased from 1900 to 1300 ng/ml and transferrin saturation from 60% to 30%; this feature was associated with statistically significant decrease of pre-study elevated liver enzymes. The treatment had no untoward effect on the outcome of renal transplantation (n = 24). Of the 56 patients who experienced hypertensive episodes during rHuEpo therapy, 47 had a history of hypertension and nine had not. The patient incidence during the first 3 months was 28.9% and fell markedly to 4% after 1 year. Only two hypertensive episodes could not be controlled and the patients dropped out. Seizures occurred in 11 patients, most of them during early treatment; annualised incidence during the first 3 months was 7.78 per year vs 2.07 per year for seizures beyond 3 months treatment. Clinical presentation, patients' history, haemoglobin pattern, BP recordings, brain scan, and EEG indicated that the pathophysiology is multifactorial, with emphasis on rate of haemoglobin increase. Therefore a smooth haemoglobin increase rate, induced by a conservative starting dose regimen (50 U/kg thrice weekly) is recommended, to allow the circulation to adapt to changes in haematocrit/viscosity and O2 delivery. The majority of the observed adverse reactions were related to rHuEpo's therapeutic effect, i.e. increase the haematocrit. The side-effects are therefore largely predictable and can be successfully managed.
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PMID:Treatment of transfusion-dependent anaemia of chronic renal failure with recombinant human erythropoietin. A European multicentre study in 142 patients to define dose regimen and safety profile. 179 95

The efficacy of recombinant human erythropoietin in correcting the anemia of the uraemic patient has been thoroughly confirmed. Iron deficiency, aluminum intoxication, severe hyperparathyroidism and infections are some of the main factors limiting patients' response to the drug. Worsening or de novo formation of arterial hypertension generally makes it necessary to diminish the degree of correction of anaemia. It is commonly accepted that anaemia should be only partially corrected and that the target haemoglobin level should be defined patient by patient.
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PMID:[Factors limiting the correction of anemia with recombinant human erythropoietin]. 181 32

The absence of any response to the administration of recombinant human erythropoietin (rHuEpo) is exceptional in uremic patients with anemia. Initial "nonresponders" generally respond to higher doses of the hormone. However, a small number of patients may remain unresponsive. The most common cause of limited response is mild to moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Another common cause of resistance is the presence of an overt or, more often, an unrecognized inflammatory state, including acute or chronic infection. Marked aluminum overload and severe hyperparathyroidism also have been shown to induce resistance in at least some patients. Other factors may contribute to the severity of anemia and hence increase rHuEpo requirements, such as acute or chronic hemolytic conditions or blood loss, folate deficiency, hemoglobinopathies, and still poorly defined uremic toxins. In patients who show a resistance to the effect of the recombinant hormone, these should be sought and eliminated, if possible.
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PMID:Modulating factors in the hematopoietic response to erythropoietin. 192 86

The administration of recombinant human erythropoietin (rHuEPO) to anemic hemodialysis patients is usually followed by a rapid increase in hemoglobin. Initial 'nonresponders' may either respond to higher doses of rHuEPO or rarely may remain totally unresponsive. Schematically, one can distinguish between a state of relative and absolute resistance to the action of the hormone. The most common causes of resistance are iron deficiency, aluminium overload, episodes of infection or other inflammatory processes, probably severe hyperparathyroidism, acute or chronic hemolytic conditions, acute or chronic blood loss, folate deficiency, and hemoglobinopathies in exceptional instances. Antibody formation against rHuEPO or marrow fibrosis secondary to rHuEPO treatment can be discarded as potential causes of resistance.
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PMID:Resistance to recombinant human erythropoietin in hemodialysis patients. 226 Jun 16

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

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

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

Recombinant human erythropoietin (EPO) is an effective and safe therapy for correction of anemia in end-stage renal disease (ESRD). Clinical trials reported to date suggest that EPO improves anemia in over 90% of hemodialysis patients with anemia (Eschbach 1989). Factors which have been identified that appear to inhibit the effectiveness of EPO are infection [Muirhead N et al. 1990], iron deficiency, hyperparathyroidism, aluminium excess [Casati 1991] and persistent GIT bleeding. The development of reticulocytosis in response to EPO in the absence of a rise in hematocrit should alert the clinician to the possibility of either hemolysis or occult blood loss. We present a case in which, despite the development of a reticulocytosis of 5% in response to EPO and the absence of hemolysis, we had difficulty in identifying the presumed source of blood loss.
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PMID:Chronic occult intra-alveolar hemorrhage: a rare cause of failure to respond to erythropoietin. 800 33

Recombinant human erythropoietin (rHuEpo) has been shown to be effective in correcting the anemia of chronic renal failure, but the dose needed may be variable. The reason for this variation is not known, but several factors could be involved, such as iron deficiency, inflammation, aluminum intoxication, hyperparathyroidism, blood losses, or marrow dysfunction. Treatment with rHuEpo was given intravenously thrice weekly after hemodialysis to 64 consecutive unselected patients with the anemia of chronic renal failure. The starting dose was 50 U/kg/dose, which was increased to 75 and 100 U/kg/dose if no response was observed after 1 and 2 months of treatment. After a minimum follow-up of 6 months, response was evaluated as early (hematocrit [Hct] > or = 30% before 3 months) or late (Hct > or = 30% after 3 months) response, or failure (target Hct not attained). We examined the value of various laboratory parameters (baseline values and early changes) as predictors of response to rHuEpo. The best prediction by pretreatment parameters only was obtained with baseline serum transferrin receptor (TfR) (< or > or = 3,500 ng/mL) and fibrinogen (< or > or = 4 g/L): 100% response rate when both parameters were low, versus only 29% when they were both high, and versus 67% when one was low and the other high. When the 2-week TfR increment was greater than 20%, the response rate was 96%. When TfR increment was less than 20%, the response rate was 100% when baseline TfR and fibrinogen were low, 12% when fibrinogen was elevated, and 62% when fibrinogen was low but baseline TfR high. The predictive value of baseline TfR and fibrinogen and of the 2-week increment of TfR was confirmed by life table analysis and stepwise discriminant analysis. Major reasons for failure or late response were identified and included subclinical inflammation, iron deficiency, functional iron deficiency, marrow disorders, hemolysis, bleeding, and low Epo dose. We conclude that response to rHuEpo can be predicted early by pretreatment fibrinogen and TfR, together with early changes of TfR levels. These prognostic factors illustrate the importance of the early erythropoietic response, subclinical inflammation, and functional iron deficiency. Early recognition of a low probability of response in a given patient could help identify and correct specific causes of treatment failure to hasten clinical improvement and avoid prolonged ineffective use of an expensive medication.
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PMID:Early prediction of response to recombinant human erythropoietin in patients with the anemia of renal failure by serum transferrin receptor and fibrinogen. 840 Feb 53

The discovery of recombinant human erythropoietin has enabled treatment of anaemia in patients whose anaemia was primarily caused by the lack of erythropoietin. This agent was most widely used in the treatment of anaemia in chronic renal failure patients. Non-regulated hypertension is considered to be the only absolute contraindication for recombinant human erythropoietin application, but thrombocytosis, predisposition to thromboses of arterio-venous fistulae, and convulsions are regarded as relative contraindications. Recombinant human erythropoietin may be administered intravenously, but the subcutaneous route is considered more rational. The treatment is initiated by low doses with gradual dose increase, what enables gradual anaemia correction and prevents the appearance of adverse effects. Haemoglobin level of around 100 g/l is considered the target haemoglobin level. The majority of patients respond well to treatment by human recombinant erythropoietin and the absence of anaemia improvement may be the result of iron deficiency, occult haemorrhages, chronic infection, inadequate dialysis, secondary hyperparathyroidism, aluminium intoxication. Anaemia improvement during the treatment with recombinant erythropoietin leads to the improvement of function of most organs and the quality of life in general as well as avoidance of blood transfusions and their adverse effects. The most frequent adverse effect of recombinant erythropoietin is the development of iron deficiency or hypertension aggravation.
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PMID:[Treatment of anemia in patients with chronic renal insufficiency with recombinant human erythropoietin]. 910 27


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