Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate storage iron deficiency and iron-deficient erythropoiesis we determined, in a cross-sectional study of 95 patients mainly including end-stage renal disease patients (ESRD) with (32) and without rh-EPO therapy (55), the following parameters: hemoglobin, mean corpuscular red cell volume, ferritin, transferrin saturation (TS), zinc protoporphyrin (ZPP) and soluble transferrin receptor (TfR). In the dialysis group the percentage of positive samples with each marker of tissue iron supply defined as TS < 20%, ZPP > 40 mumol/mol Heme and TfR > 3.05 microgram/ml was as follows: TS 43.7% and 32.2% at a diagnostic threshold level of < 16%, ZPP 33.3% and TfR 17.2%. Manifest storage iron deficiency defined as ferritin < 30 ng/ml was observed in 5.7% of the samples while the mean ferritin concentration of the rh-Epo treated dialysis patients was 509.3 ng/ml compared to 262.5 ng/ml in the group without rh-EPO therapy. These data reflect a generous iron substitution in our series taking a TS < 20% as an intervention criterion. Looking at the different results of the three markers the best correspondence was found between ZPP and TfR resulting in a weak positive correlation (+0.64). In conclusion, we found quite different results with different assays when evaluating endogenous iron availability in our series of mainly ESRD patients in a cross-sectional study. Because a gold-standard is not defined further firm conclusions cannot be drawn from this type of study. The adequacy of the different parameters of iron metabolism including threshold levels and, consequently, the decision and route of iron substitution deserve an evaluation in a longitudinal study to characterize the best marker or marker combination in this setting.
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PMID:Transferrin receptor assay and zinc protoporphyrin as markers of iron-deficient erythropoiesis in end-stage renal disease patients. 954 1

Recombinant human erythropoietin (EPO; epoetin) has been shown to be effective in improving anemia in a proportion of cancer patients. The response rate is approximately 60%, but varies considerably according to baseline hematocrit and transfusion needs, as well as the response criteria used. Response is not greatly influenced by the type of tumor, except in situations of major marrow involvement and limited residual hematopoiesis, or in the presence of specific mechanisms of anemia, such as hemolysis, splenomegaly, bleeding, hemodilution, or ineffective erythropoiesis. Stem cell damage by previous therapy as well as marrow suppression by current intensive chemotherapy can impair response. Besides its intensity, the type of chemotherapy may not be critical, although patients undergoing platinum-based chemotherapy may respond faster than those receiving non-platinum regimens. Complications, such as infections, bleeding, or nutritional deficiencies, may have a major negative impact on outcome. An important response-limiting factor is functional iron deficiency (ie, an imbalance between iron needs in the erythropoietic marrow and iron supply), which depends on the level of iron stores and its rate of mobilization. Functional iron deficiency is best monitored by the percentage of hypochromic red blood cells, and oral or intravenous iron supplements should be given when this percentage increases above 10%. All these factors explain why the response rate to epoetin is only approximately 60%. Therefore, it would be interesting to develop models that could help predict response to epoetin to help select the most appropriate cancer patients for this therapy. Few baseline parameters have been shown to be highly predictive of response in patients with solid tumors, although most studies in patients with myeloma or lymphoma have indicated that patients with a low baseline serum EPO level will respond better. Early changes after 2 to 4 weeks of treatment are also of great interest. Among these early changes, increments of soluble transferrin receptor, reticulocytes, and hemoglobin, as well as the persistence of elevated ferritin or EPO levels, have all shown some predictive value. Combination of baseline serum EPO and the 2-week increment of soluble transferrin receptor or hemoglobin may provide the best prediction of response.
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PMID:Prediction of response to optimize outcome of treatment with erythropoietin. 967 27

Transferrin receptor is a key protein for the cellular uptake of transferrin iron. The highest number of transferrin receptors is on the surface of erythroblasts. The released iron is used for hemoglobinosynthesis. Regulation occurs at mRNA level depending on the intracellular iron concentration. The synthesis of ferritin and transferrin receptor are regulated in an opposite manner. Serum transferrin receptor is a truncated monomeric form of the cellular receptor. Most of the circulating receptors come from erythroid marrow precursors. Its level mirrors the total tissue receptor mass, it depends on the rate of erythropoiesis and on the iron status. Serum transferrin receptor is easily measured by Elisa methods but the lack of standardization triggers large differences in the results. Unlike ferritin, the concentration of serum transferrin receptors is unaffected in inflammatory diseases, infections, malignancies or cytolysis. In these conditions its measurement is particularly valuable for assessing an associated iron deficiency. It is a very useful tool for the diagnosis of different causes of anemia. In chronic renal failure serum transferrin receptor can predict whether patients will respond to rHu EPO therapy.
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PMID:[The transferrin receptor: its role in iron metabolism and its diagnosis utility]. 992 Sep 62

This article, based on our own studies and those of others, presents evidence to show that the anemia of chronic renal failure in the predialysis period is, to a significant extent, caused by iron deficiency and can be improved in most cases by the administration of intravenous (i.v.) but not oral iron. We estimate that in approximately 30% of all predialysis patients with anemia, a target hematocrit (Hct) of 35% can be reached and maintained by giving i.v. iron alone without exceeding currently acceptable limits of serum ferritin (500 microg/liter) or the percentage of iron saturation (40%). If, in addition, subcutaneous erythropoietin (EPO-usually in only low doses-is added, the combination has an additive effect on the Hct response, and almost all anemic predialysis patients can reach and maintain the target Hct of 35% over a one-year period. Therefore, the advantage of maintaining adequate iron stores with i.v. iron is that if EPO is needed, lower doses will be required to achieve the target Hct than if EPO were used alone. This not only avoids the high cost of EPO therapy but also its associated side-effects, especially hypertension. Using Venofer, a ferric hydroxide sucrose complex, as our i.v. iron supplement, we have seen no anaphylactic reactions in over 20,000 infusions over a four-year period in 360 hemodialysis, 123 predialysis, and 58 peritoneal dialysis patients.
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PMID:Intravenous iron for the treatment of predialysis anemia. 1008 91

Iron deficiency is the most frequently encountered cause of suboptimal response to recombinant human erythropoietin (rHuEPO). Carefully assessing iron status is of paramount importance in chronic renal failure patients prior to or during rHuEPO therapy. Because there is great need for iron in the EPO-stimulated erythroid progenitors, it is essential that serum ferritin and transferrin saturation levels should be maintained over 300 microg/liter and 30%, respectively. Investigators have shown that oral iron is unlikely to keep pace with the iron demand for an optimal rHuEPO response in uremics. Therefore, patients with iron deficiency will always require intravenous iron therapy. The early and prompt iron supplementation can lead to reductions in rHuEPO dose and hence cost. After the iron deficiency has been corrected or excluded, we must remember all of the possible causes of hyporesponsiveness in every rHuEPO-treated patient. As dose requirements vary, it is not clear which dose of rHuEPO causes this hyporesponsiveness. However, if the patient with iron repletion does not respond well after the induction period, the major causes blunting the response to rHuEPO should be investigated. Most factors are reversible and remediable, except resistant anemia associated with hemoglobinopathy or bone marrow fibrosis, which requires a further increase in the rHuEPO dose. By means of early detection and correction of the possible causes, the goal of increasing therapeutic efficacy can be achieved. Iron overload may lead to an enhanced risk for infection, cardiovascular complication, and cancer. Over-treatment with iron should be avoided in dialysis patients, despite the fact that the safe upper limit of serum ferritin to avoid iron overload is not clearly defined. On the other hand, functional iron deficiency may develop even when serum ferritin levels are increased. Controversy remains as to whether intravenous iron therapy can overcome this form of hyporesponsiveness in iron-overloaded patients. Moreover, a treatment option of iron supplementation is not warranted in these patients, as the potential hazards of iron overload will be worsened. We demonstrated that the mean hematocrit significantly increased from 25.1+/-0.9% to 31+/-1.2% after eight weeks of intravenous ascorbate therapy (300 mg three times a week) in 12 hemodialysis patients with serum ferritin levels of more than 500 microg/liter. The enhanced erythropoiesis paralleled with a rise in transferrin saturation (27.8+/-2.5% vs. 44.8+/-9.5%, P < 0.05) and reductions in erythrocyte zinc protoporphyrin (130+/-32 vs. 72+/-19 micromol/mol heme, P < 0.05) and monthly rHuEPO dose (24.2+/-4.5 vs. 16.8+/-3.4 x 10(3) units, P < 0.05) at the end of study. It is speculated that ascorbate supplementation not only facilitates the iron release from storage sites and its delivery to hematopoietic tissues, but also increases iron utilization in erythroid cells. Our study provides a more complete understanding of the pathogenesis of iron overload-related anemia and the development of an adjuvant therapy, intravenous ascorbic acid, to the existing treatments.
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PMID:Erythropoietin hyporesponsiveness: from iron deficiency to iron overload. 1008 94

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

Recombinant human erythropoietin (rhEPO), which increases red cell mass, is one of the most abused substances in sport. Abuse is currently undetectable by the only direct routine method, immunoassay, since blood and urine rhEPO are immunologically indistinguishable from endogenous EPO. Elevated EPO levels are only detectable several days after rhEPO administration. Indirect parameters have therefore been introduced, primarily the haematocrit level, but also markers of functional iron deficiency during or after rhEPO administration (hypochromic red cells and reticulocytes, serum transferrin receptors, ferritin levels) and, in the urine, fibrin degradation products. Although iron status indices have yielded promising results, athletes are currently banned solely on the basis of their haematocrit. Yet various factors can cause false positive haematocrit results with potentially fatal consequences to athletes' careers. Until new direct assays such as liquid chromatography-mass spectrometry have been evaluated and introduced, efforts must be directed at using a battery of tests to increase the sensitivity and specificity and reduce the number of false positives and false negatives.
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PMID:Erythropoietin test methods. 1093 16

Anemia of prematurity is a hyporegenerative anemia usually appearing after the second week, reaching highest intensity in the second month of life. It's normocytic and normochromic with low reticulocyte count. It has been attributed to EPO deficiency. The low EPO levels detected in premature infants and the proper response to synthetic erythropoietin suggested that EPO administration in premature of < or =32 weeks gestational age could be of benefit trying to maintain or increase the hematocrit levels. Protocols of EPO administration to premature babies should always be considered as EPO+Fe, keeping ferritin levels over 100 ng/ml. Failures to EPO+Fe treatment in very small premature babies, measured as no decrease in the need of blood transfusions, may be due to the amount of blood looses that should be restricted.
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PMID:Anaemia of prematurity: treatment with erythropoietin. 1175 36

We present the results on Anaemia Management in Fresenius Medical Care Spain dialysis centres as reported by EuCliD (European Clinical Database), evaluating a population of 4,426 patients treated in Spain during the year 2001. To analyse the erythropoietin dose and the haemoglobin levels we divided the population in two groups according to the time with dialysis treatment: patients treated less than six months and patients between six months, and four years on therapy. We compared our results with the evidence based recommendations Guidelines: the European Best Practice Guidelines (EBPG) and the US National Kidney Foundation (NKF-K/DOQI). We also compared our results with those presented by the ESAM2 on 2,618 patients on dialysis in Spain carried out in the second half of the year 2000. We observed that 70% of the population reaches an haemoglobin value higher that 11 g/dl, with a mean erythropoietin (rHu-EPO) dose of 111.9 Ul/kg weight/week (n = 3,700; SD 74.9). However, for those patients on treatment for less than six months, the mean Haemoglobin only reaches 10.65 g/dl (n = 222; SD 1.4). The rHu-EPO was administrated subcutaneously in 70.2% of the patients. About the iron therapy, 86% of the patients received iron treatment and the administration route was intravenous in 93% of the population. The ferritin levels were below 100 micrograms/dl in 10% of the patients and 26.4% showed a transferrin saturation index (TSAT) below 20%. The erythropoieting resistance index (ERI), as rHu-EPO/haemoglobin, has been used to evaluate the response to rHu-Epo, according to different variables. It was observed that the following factors lead to a higher rHu-EPO resistance: intravenous rHu-EPO as administration route, the presence of hypoalbuminemia, increase of protein C reactive, Transferrin saturation below 20% and starting dialysis during the last six months.
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PMID:[Anemia management in haemodialysis. EuCliD database in Spain]. 1251 89

We showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status with regard to erythrocytopoiesis in chronic dialysis status. The mean CHr level was 32.3 +/- 2.2 pg in dialysis patients and CHr was significantly correlated with the conventional parameters of iron deficiency. We aimed to utilize the measurement of CHr levels to monitor iron status in clinical practice. We measured CHr, iron parameters, and the intrinsic EPO concentration in non-dialysis CRF patients to clarify the alterations in CHr levels that occur as renal anemia progresses. CRF patients who visited our out-patient clinic (n = 189) were included in the study. Iron deficiency was defined by the transferrin saturation and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA). The mean CHr value of the non-dialysis patients (creatinine clearance less than 70 ml/min) was 32.7 pg, which did not differ significantly from that of the dialysis patients. Significant correlations were found between CHr and TSAT (r = 0.032, p < 0.0177), unlike the correlation with intrinsic EPO levels. Overall, 11% of the patients were diagnosed as having iron deficiency. There was a positive correlation between CHr and serum creatinine levels. Non-dialysis CRF patients treated with rHuEPO at the dose of 24,000 U/month showed different CHr levels compared with other patients (less than 24,000 U/month). It is possible that rHuEPO treatment in non-dialysis patients affects iron dynamics. In conclusion, CHr is an easily measurable and reliable marker of iron status in non-dialysis CRF patients. Moreover, the CHr level was also sensitive to iron alternations in non-dialysis CRF patients under rHuEPO treatment. Accordingly, if long-acting EPO is available for non-dialysis CRF patients, the CHr value is likely to be indicative of the need for iron supplementation.
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PMID:[Measuring the content of reticulocyte hemoglobin (CHr) in predialysis chronic renal failure (CRF) patients]. 1450 18


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