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)

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

Treatment of anemia in children with end-stage renal disease (ESRD) has been greatly facilitated by the introduction of recombinant human erythropoietin (rHuEPO). A major limiting factor in the treatment of renal anemia is sufficient iron supplementation. Eight children (aged 10-17 years) receiving hemodialysis were treated with intravenous iron (1 mg/kg per week) for 3 months. Hemoglobin (Hb), hematocrit (Hct), and serum ferritin levels were measured regularly. The mean Hct increased from 25% to 30%, the mean Hb increased from 7. 8 g/dl to 9.2 g/dl, and the mean ferritin level from 200 to 395 mg/dl. The mean EPO dosage could be tapered from 6,500 IU to 6,150 IU. No adverse side-effects were noted. Hence, in this uncontrolled study intravenous iron was an effective treatment for iron deficiency during rHuEPO therapy in children with ESRD on hemodialysis.
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PMID:Intravenous iron treatment of renal anemia in children on hemodialysis. 1046 May 5

In most chronic disease conditions, the systemic inflammatory response and its mediators play an essential pathogenic role. Protein calorie malnutrition, a prominent feature of end-stage renal disease (ESRD), also develops, largely as a consequence of the systemic inflammatory response. ESRD (uremia), dialysis, systemic metabolic acidosis, and infections activate the systemic inflammatory response. Elevations in C-reactive protein and depressions of serum albumin below 4 g/dL are found in more than 50% of ESRD patients undergoing dialysis. In many patients receiving dialysis, the impact of this acute-phase response on measures of iron metabolism limits the ability to diagnose iron deficiency. Furthermore, there are risks to iron administration, although data linking iron overload to risk of infection in dialysis patients is suggestive, not definitive. It seems reasonable to hypothesize that the greatest risk of iron administration is in patents who are already infected, and the greater risk would be to raise the serum iron level and transferrin saturation precipitously. The total-dose infusion method, which provides all iron required to correct deficiency in 1 dose, is more likely to produce side effects and rapidly raise serum iron levels and transferrin saturation. The use of low-dose intravenous iron supplementation (10 to 20 mg per dialysis treatment or 100 mg every second week) avoids iron overtreatment and should reduce adverse events. In ESRD patients receiving dialysis, the importance of the systemic inflammatory response in the development of protein calorie malnutrition, the impact of the acute-phase response on iron nutriture, and the response to erythropoietin therapy must be considered to achieve an understanding of the altered responses to nutritional therapy in this setting.
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PMID:The systemic inflammatory response and its impact on iron nutriture in end-stage renal disease. 1051 74

Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease (ESRD) patients. Functional iron deficiency occurs with serum ferritin >500 ng/ml and/or transferrin saturation (TSAT) of 20 to 30%. This study examines the effects of a maintenance intravenous iron dextran (ivID) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30% (control group) to those of 30 to 50% (study group) for a period of 6 mo. Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period, during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30% and baseline levels of hemoglobin of 9.5 to 12.0 g/dl. After the run-in period, 19 patients randomized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo. Twenty-three patients randomized to the study group received four to six loading doses of ivID, 100 mg each, over a 2-wk period to achieve a TSAT >30% followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50% for 6 mo. Both regimens were effective in maintaining targeted hemoglobin levels. Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the rhEPO dose needed to maintain prestudy hemoglobin levels. Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml. Epoetin dose requirements for the study group decreased by the third month and remained 40% lower than for the control group, resulting in an overall cost savings in managing the anemia. Secondary indicators of iron-deficient erythropoiesis were also assessed. Zinc protoporphyrin did not change in either group. Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg. It is concluded that maintenance of TSAT between 30 and 50% reduces rhEPO requirements significantly over a 6-mo period.
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PMID:Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients. 1070 77

Anemia is an important cause of morbidity, and may be associated with increased mortality in patients with end-stage renal disease (ESRD) receiving dialysis. Therapy with recombinant human erythropoietin (rHuEPO) has revolutionized the care of ESRD patients, but this is a costly medication and concerns have been expressed about whether the outcome, as measured by achieved hematocrit (Hct), could be improved. The number and proportion of ESRD patients receiving rHuEPO increased steadily from 1995 to 1998, as did the dose of rHuEPO per patient. The amount of intravenous iron administered to patients increased markedly over the study period. The patients' mean hematocrit also rose, but proportionally less over the study period. The increase in both the amounts of payments per patient for rHuEPO, and the number of patients receiving rHuEPO over this time has resulted in a marked increase in the total costs to Medicare for this therapy. We suggest that a combination of payment regulations, provider financial opportunities and disincentives, and patient resistance to the effects of rHuEPO, as a result of both iron deficiency and inflammation, largely explain the findings.
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PMID:Trends in erythropoietin therapy in the U.S. dialysis population: 1995 to 1998. 1092 35

Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with its use. We analyzed data from Fresenius Medical Care North America (FMCNA) clinical variance reports to determine the incidence of suspected iron dextran-related adverse drug events (ADEs) and associated patient characteristics, dialysis practice patterns, and outcomes. We used a case-cohort study design, comparing individuals who experienced suspected ADEs with the overall FMCNA population. Among 841,252 IV iron dextran administrations from October 1998 through March 1999, there were 165 reported suspected ADEs, corresponding to an overall rate of 0.000196%, or approximately 20 per 100,000 doses. Forty-three patients (26%) required an independent emergency department evaluation, 18 patients (11%) required hospitalization, and 1 patient (0.6%) died. Dyspnea (43%), hypotension (23%), and neurological symptoms (23%) were the most common major ADEs; nausea (34%), vomiting (23%), flushing (27%), and pruritus (25%) were the most common other ADEs. ADEs were 8.1-fold more common among patients administered Dexferrum (American Regent Laboratories, Inc, Shirley, NY) compared with those administered InFed (Watson Pharmaceuticals, Phoenix, AZ). In summary, serious adverse reactions to IV iron dextran are rare in clinical practice. The risk appears to depend on the specific formulation of IV iron dextran. Otherwise, iron dextran-related ADEs are difficult to predict.
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PMID:Suspected iron dextran-related adverse drug events in hemodialysis patients. 1127 88

The strong association between anemia and cardiovascular complications among patients with end-stage renal disease suggests that anemia during chronic renal insufficiency (CRI) may also have important consequences. We performed a retrospective cohort study to identify factors associated with severe anemia (hematocrit [Hct] < 30%) and examine anemia management practices in CRI. The CRI cohort was composed of 604 adult patients with elevated serum creatinine levels. There was a direct correlation between predicted glomerular filtration rate and Hct (r = 0.49) and an inverse correlation between serum creatinine level and Hct (r = -0.37). Anemia was noted early in CRI; 45% of patients with serum creatinine levels of 2 mg/dL or less had an Hct less than 36%, and 8% had an Hct less than 30%. During the course of the study, mean Hct decreased from 35.1% +/- 5.6% to 31.8% +/- 5.6%. Iron studies were obtained in only 19% of patients, and among these, the prevalence of iron deficiency (transferrin saturation < 20%) was 54%. Only 30% and 26% of patients were administered recombinant human erythropoietin (rHuEPO) and iron, respectively. Multivariate analyses showed that diabetes as the cause of renal disease, greater serum creatinine level, and having a single nephrology visit were associated with greater odds for the presence of anemia. A lower Hct and having a single nephrology visit were associated with greater odds for rHuEPO use. These results show that anemia begins early in the course of CRI, and management of anemia is suboptimal, even among patients under the care of nephrologists. Educational programs to optimize anemia management among patients with CRI are needed.
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PMID:Anemia: an early complication of chronic renal insufficiency. 1157 84

With the widespread use of recombinant erythropoietin (EPO) for patients with end-stage renal disease (ESRD), management of iron deficiency is an ongoing issue for the renal team. Effective iron replacement and maintenance play a vital role in efficient use of EPO. For hemodialysis patients, intravenous (i.v.) iron has proven convenient and, as an ancillary drug outside of the composite rate, generates profits for dialysis facilities. Improvements in the vehicle with which i.v. iron is administered have led to a reduction in severe or fatal reactions common with iron dextran products. Oral iron has had a spotty track record as an effective therapy for dialysis patients. Compliance has been hindered by patient discomfort when taking oral iron. Patients on peritoneal dialysis and those with chronic kidney disease remain good candidates for oral iron because of convenience, and oral formulas could prove more effective even in the hemodialysis patient population if they were better tolerated and better absorbed, and if using them would not place an economic burden on the patient and/or an economic hardship on the facility. In a capitated/bundled payment environment, oral iron may become a blessing rather than a curse for facilities that need to find more economic ways of providing services. Heme-iron, now undergoing clinical studies, may be a reliable replacement for i.v. iron in that scenario.
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PMID:The biological and economic value of oral organic iron in maintenance dialysis. 1190 60

Our knowledge of erythropoiesis and iron in renal disease is limited. The accepted view of the control of erythropoiesis was founded on observations made in a variety of disorders, but the control mechanism in healthy individuals may not be quite the same. Evidence suggests that mechanisms other than erythropoietic stimulation may play a role in increased red blood cell production. Measuring erythropoiesis is complex. The quantitative reticulocyte count is probably the closest practical assessment of erythropoietic activity we can achieve, yet there is very little correlation between circulating erythropoietin level and reticulocyte count in normal and near normal subjects. Oxygen transport in humans depends entirely upon iron. In renal disease, the failure of the erythropoietin positive feedback mechanism can be readily and directly remedied; recombinant human erythropoietin therapy can replace the missing erythropoietin, but this will be negated if iron supply to the erythroid marrow falls short of demand. Measurement of iron stores is also complex. The use of serum ferritin concentration as a direct quantitative estimate of iron in the stores is not advisable, and in practice we have not found the transferrin receptor assay to be useful in identifying patients who require iron therapy. Use of percentage hypochromia as a measure of iron deficiency is complicated by the fact that hypochromic cells are not exclusively a consequence of functional iron deficiency. There are clearly lessons still to be learned in this field and there is much that we do not yet understand about the control of erythropoiesis and iron metabolism in humans.
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PMID:Iron and erythropoietin in renal disease. 1209 2

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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