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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of recombinant human erythropoietin (rhEPO) on erythropoiesis when given at different time intervals to healthy adults. 15 volunteers were randomly selected to receive rhEPO (2 x 300 U/kg) and parenteral iron (2 x 200mg) either within a 24 h or 72 h interval. Controls received parenteral iron only. Maximum EPO levels were found 24 h after the first intravenous injection (day 1) with a mean value of 364 and 390 U/l for the rhEPO-treated groups. When second rhEPO administration was after 72 h (group III), volunteers showed significantly higher absolute reticulocyte counts and a higher percentage of young RNA-rich reticulocytes (HFR ratio) over several days compared to those who received rhEPO within a 24 h interval (group II). Both rhEPO-treated groups showed an increase in the mean reticulocyte cell volume. Reticulocyte haemoglobin concentration was inversely correlated with the increasing cell size with a nadir on day 8. Reticulocyte haemoglobin content showed a significant decrease in group II after day 5. Serum ferritin levels showed an inverse pattern to the rate of erythropoiesis. After an initial rise, the serum ferritin decrease was most pronounced in group III. Contrary to previous reports with oral iron supplementation, functional iron deficiency was not seen during rhEPO stimulation, due to parenteral iron administration. Our data suggest that the time has interval between repeated administrations of rhEPO has an important influence on its pharmacodynamics. rhEPO given within an interval of 72 h was more effective in stimulating erythropoiesis than administration within 24 h interval for the same total dose.
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PMID:Optimal timing of repeated rh-erythropoietin administration improves its effectiveness in stimulating erythropoiesis in healthy volunteers. 860 88

It is known, that patients undergoing CAPD have less severe anaemia than those receiving hemodialysis (HD). In addition they require smaller doses of rHuEpo to control anaemia than HD pts. We have decided to compare plasma erythropoietin (pEpo) and iron reserves (IR) in these both groups of pts. 17 pts on CAPD and 50 pts on HD were diagnosed. 35% pts on CAPD and 52% pts on HD required permanent rHuEpo treatment to maintain hemoglobin (Hb) concentration above 9.5g/dl and Ht above 30%. Plasma EPO and ferritin levels were measured by enzymatic immunoassay. IR were estimated by formula: IR = 400x [ln (ferritin) - ln(50)]. Compared to CAPD, HD pts had higher IR (405 +/- 76 vs. 358 +/- 120 mg) but differences are not statistically significant. Plasma Epo level (geom. mean) was statistically significant higher p = 0.025 in HD pts compared to CAPD pts (8.68, range 2-53 vs. 5.21 range 2-15 mV/ml) Hb concentrations did not differ significantly between pts on CAPD and HD. CAPD pts controlled anaemia better than HD pts despite lower concentration of endogenous erythropoietin.
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PMID:[Comparison of the ability to control anemia in patients on hemodialysis and peritoneal dialysis considering iron reserves and plasma erythropoietin]. 875 36

We conducted a prospective study on 81 consecutive patients who had a kidney transplant with graft function for over 3 months to evaluate the prevalence of erythrocytosis following renal transplantation (PTE) and its potential risk factors. True PTE was defined as a RBC mass > 120% of the theoretical value allowing for sex, weight and height. 18 patients (22.2%) developed PTE (RBC mass = 157 +/- 21%) with no evidence of polycythemia vera (PV), or secondary polycythemia due to reduced arterial oxygen, kidney or hepatic tumors. PTE was more common in males (p = 0.041) and less common in patients treated with recombinant erythropoietin (rHEPO) prior to transplantation. 18 non-polycythemic patients (Hb 12.6 +/- 1.3 g/dl) matched for sex, age and renal function were used as case controls. Fewer PTE patients were transfused post-transplantation (p = 0.026). At the time of diagnosis, mean serum EPO was normal and similar to that of controls. PTE patients had lower serum ferritin (p = 0.005) and more commonly received iron supplementation when PTE occurred (p = 0.003). Other clinical factors did not differ significantly between the two groups. Two patients had a thrombotic event, 6 recovered spontaneously and 11 were successfully treated with angiotensin-converting enzyme inhibitors (ACEI). The normalization of Hb, hematocrit and RBC mass in ACEI treated patients was accompanied by a decline in serum EPO (p = 0.008). We conclude that true erythrocytosis is prevalent in cyclosporine-treated renal transplant patients. PTE seems to be an idiopathic erythrocytosis. Pretransplant rHEPO treatment may limit PTE by blunting the increased sensitivity of erythroid precursors to EPO and iron supplementation, which stimulates the development of PTE. ACEI treatment is effective and safe.
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PMID:Factors predisposing to post-renal transplant erythrocytosis. A prospective matched-pair control study. 912 2

The authors compared the effect of recombinant human erythropoietin (rhEPO) in combination with iron with that of iron therapy only in the treatment of postpartum anaemia. Ninety patients (30 patients/group) received either rhEPO (300 U kg-1, i.v. or s.c., once) and iron (parenteral and oral), or iron therapy only. Erythropoiesis was assessed by haemoglobin and haematocrit increase, absolute reticulocyte counting and reticulocyte flow cytometry. Ferrokinetics was assessed by serum ferritin, transferrin and transferrin saturation measurements. There was no difference before therapy for baseline haematological values or iron status. Patients with endogenous EPO levels below 145 mU mL-1 had a significant benefit from intravenous rhEPO administration with highest haematocrit and haemoglobin levels 4 and 14 days after therapy. rhEPO-treated groups showed a higher absolute reticulocyte count 1 and 4 days after therapy and an elevated percentage of high fluorescent reticulocytes (HFRs). Parenteral iron therapy caused a significant increase of ferritin and transferrin saturation, while transferrin concentration decreased. Ferritin and transferrin levels were lowest after i.v. administration of rhEPO, 1 and 4 days after therapy. C-reactive protein concentration was highest in patients who underwent caesarean section until the end of the observation period. A single dose of rhEPO in combination with iron was more effective in treating postpartum anaemia than iron therapy only, in patients who had low EPO levels despite peripartal blood loss. Postpartum low endogenous EPO levels might be a consequence of inhibiting inflammatory cytokines that are released after spontaneous or operative deliveries.
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PMID:Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia. 890 21

Functional iron deficiency occurs when recombinant human erythropoietin (rHuEPO) accelerates erythropoiesis to an extent that the iron availability cannot meet the anticipated demand. Such a phenomenon will reduce the optimal response to rHuEPO. To estimate the iron needs of functional iron deficiency in hemodialysis patients on rHuEPO therapy, we utilized a mathematical method. Forty hemodialysis patients were examined in the study, and all had a baseline serum ferritin (SF) level > 100 microg/l. They were stratified into patients with a transferrin saturation (TfS) value > or = 25% (group I) and those below this value (group II). The treatment protocol consisted of rHuEPO therapy in the two groups for 6 months and iron supplement only in group II. The target hemoglobin level was 10.5 g/dl, and iron metabolism indices were analyzed prior to and following therapy. The results showed (1) in group I (n = 20) hemoglobin rose from 7.5 +/- 0.9 to 10.7 +/- 0.7 g/dl (p < 0.01) and the mean SF level declined from 1,583 +/- 997 to 968 +/- 664 mg (p < 0.01); (2) in group II (n = 20) hemoglobin also increased from 7.8 +/- 0.9 to 10.6 +/- 0.8 g/dl (p < 0.01) following iron supplement, while the SF rose from 183 +/- 70 to 326 +/- 125 mg (p < 0.01); (3) TfS was significantly elevated in group II following iron therapy (18.9 +/- 4.8 vs. 34.5 +/- 9.1%, p < 0.01), and (4) the nomogram showed a sensitivity of 80%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 83% in estimating the iron status before rHuEPO therapy. We conclude that SF levels reflect iron stores and that TfS < 25% is an index of functional iron deficiency. Iron supplementation is not necessary in patients with SF > 100 microg/l and TfS > or = 25%. It seems rational to provide intravenous iron in EPO-resistant patients with functional iron deficiency (SF > 100 microg/l, TfS < 25%). This paper illustrates the importance that accurate assessment of iron needs by a mathematical method would enhance treatment efficacy and avoid iron overload in hemodialysis patients on rHuEPO therapy.
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PMID:Mathematical approach for estimating iron needs in hemodialysis patients on erythropoietin therapy. 909 47

To define the etiology of anemia post-renal transplantation, we assessed hematologic parameters and EPO levels in 38 anemic and 16 non-anemic control renal transplant recipients (RTRs) with varying degrees of allograft function at periods > 3 months post-transplantation. Significant differences between the two groups were found for serum creatinine (Cr) 291.7 +/- 26.5 vs. 203.3 +/- 26.5 mumol/l, p < 0.01; iron 9.3 +/- 0.92 vs. 13.6 +/- 1.7 mumol/l, p < 0.05; and ferritin 345.5 +/- 90.8 vs. 91.1 +/- 18.5 micrograms/l, p < 0.01. Serum EPO levels were inappropriately low in anemic patients with no significant correlation between EPO and Cr or hematocrit (Hct) levels. Serum iron was the only predictive factor for anemia on regression analysis (p < 0.05). Ferritin levels did not correlate with serum iron or Hct, and may be falsely elevated in iron deficient RTRs. Iron deficiency, poor renal function and inappropriately low EPO levels are major contributors to the 12% of our outpatient renal transplant population who are anemic.
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PMID:Anemia following renal transplantation: erythropoietin response and iron deficiency. 926 20

Recombinant erythropoietin (rHuEPO) is well established in the management of anemia of chronic renal disease. However, a number of clinical issues, including the best laboratory indicators of an imminent marrow response to rHuEPO replacement, the ideal measurements to detect masked iron deficiency, and optimal methods of iron replacement, remain unanswered. To investigate these issues, studies were performed in anemic chronic hemodialysis patients. A number of standard hematologic measurements in addition to automated reticulocyte counts (Sysmex R-1000) and serum transferrin receptors (TfR) were obtained in these patients. A response to initiation of rHuEPO administration could be predicted if the serum TfR concentration was less than 6 mg/L (normal, 3.8 to 8.5 mg/L). In patients on rHuEPO, an imminent hemoglobin response to an increased rHuEPO dose could be predicted after 1 week based on a greater than 20% increase from baseline in the serum TfR or absolute reticulocyte count, with a sensitivity of 92%. In patients on rHuEPO replacement with serum ferritin levels greater than 30 microg/L, none of the panel of tests, including serum TfR, reliably detected masked iron deficiency. In a long-term study over 5 months in patients on a stable maintenance dose of EPO, a gradual decline in total body iron occurred, even in subjects with initial adequate iron stores, and despite taking 50 mg elemental iron daily as oral ferrous sulphate. The serum TfR is useful for predicting a hemoglobin response when initiating rHuEPO therapy, and combined with automated reticulocyte counting it is valuable for predicting a hemoglobin response when increasing the dose of rHuEPO. The serum TfR loses its specificity for detecting tissue iron deficiency in patients on maintenance rHuEPO therapy because of increased erythropoiesis, which itself raises serum TfR levels.
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PMID:Markers of masked iron deficiency and effectiveness of EPO therapy in chronic renal failure. 932 69

We measured pretreatment serum levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in 25 patients with myelodysplastic syndrome receiving recombinant human erythropoietin (rhEPO) at dosages up to 300 U/kg thrice weekly for 12 weeks. Both TNF-alpha and IL-1 beta levels were measured using commercially available enzyme-linked immunoassays. A complete response (CR) was defined as a rise in untransfused haemoglobin concentrations of at least 2 g/dl or a 100% decrease in RBC transfusion requirements over the treatment period; a partial response (PR) was an increase in untransfused haemoglobin values of 1-2 g/dl or a decrease in RBC transfusion requirements equal to or greater than 50%; no response (NR) was defined as a response less than a PR. After 12 weeks of rhEPO treatment, four patients showed a CR, five patients a PR, and 16 patients NR. Serum levels of both TNF-alpha (80.5 %/- 64.8 vs 8.1 +/- 4.2 ng/l, P < 0.001) and IL-1 beta (60.4 +/- 49.9 vs 8.9 +/- 4.7 ng/l, P < 0.001) were higher in MDS patients than in a group of 28 normal controls. Responders (CR + PR) showed significantly lower serum levels of TNF-alpha than non-responders (21.6 +/- 26.2 vs 106.3 +/- 60.8 ng/l, P < 0.001), whereas IL-1 beta concentrations between those who benefited from therapy and unresponsive cases were not significantly different (39.8 +/- 48.9 vs 73.4 +/- 48.2 ng/l, P = 0.120). It is noteworthy that TNF-alpha levels were within the normal range in all responsive patients but one, whereas all non-responders presented elevated cytokine concentrations. No relationship was found between TNF-alpha or IL-1 beta values and haemoglobin levels, transfusion requirement, serum EPO or ferritin concentrations. We conclude that pre-treatment TNF-alpha levels might help to select those MDS patients who are most likely to benefit from rhEPO treatment.
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PMID:Serum levels of tumour necrosis factor-alpha predict response to recombinant human erythropoietin in patients with myelodysplastic syndrome. 935 45

Augmentation of gamma-gene synthesis by using recombinant human erythropoietin (r-Hu-EPO) represents a new approach to the therapy of beta-thalassemia. A prospective study was conducted in 26 transfusion-dependent beta-thalassemia major patients. r-Hu-EPO (Eprex/Cilag, Switzerland) was given to the patients at an initial dose of 500 IU/kg s.c. 3 times a week for at least 2 months during which no transfusion was applied. A sustained hemoglobin (Hb) level greater than 8 g/dl was considered as a response to EPO treatment. In the patients whose Hb levels remained under 8 g/dl or did not increase in comparison to pretreatment levels within 4 weeks, the dose of r-Hu-EPO was increased to 1,000 IU/kg 3 times a week and applied for another 4 weeks. Only 16 cases also received oral iron supplementation. The whole blood and reticulocyte counts, the biochemical tests including BUN, creatinine, AST, ALT, alkaline phosphatase and ferritin were done and the percentages of HbF and F cells were analyzed regularly. At the end of the 2nd month, 6 cases qualified to continue with the trial. At the end of the 6th month, r-Hu-EPO therapy was ceased in 3 cases of the 6 since their Hb levels had decreased below 7 g/dl. Only 3 cases (11.5%) continued with the r-Hu-EPO therapy without transfusion for up to 12 months. In conclusion, r-Hu-EPO may be useful in some selected transfusion-dependent patients with beta-thalassemia major. Selection criteria should include a mild beta-genotype of coinheritance of alpha-thalassemia, splenectomy and pretreatment reticulocyte response of the patients as well as the patients' compliance.
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PMID:Recombinant erythropoietin trial in children with transfusion-dependent homozygous beta-thalassemia. 940 97

EPO treatment rapidly corrects anemia in patients with end-stage renal failure treated with hemodialysis, as long as sufficient iron is available. Absolute and relative (to demand) iron deficiency blunts the erythropoietic response and parenteral iron is frequently required during the course of therapy to restore EPO efficacy. Since the optimum time course of iron administration to restore EPO response in the short term is unknown, we compared three protocols of i.v. iron dextran administration in apparent functionally iron-deficient HD patients on oral iron therapy (hemoglobin < 10.0 g/dl plus ferritin < 100 micrograms/l and/or transferrin saturation < 20%). Intravenous iron (Imferon; Fisons Pty Ltd.) was given either as a single 600 mg dose (n = 15, Group I) or in divided doses of 100 mg administered on 6 successive dialyses (n = 14, Group II) or weekly for 6 weeks (n = 14, Group III). Response was monitored for 8 weeks. No adverse effects were observed. Collectively, mean hemoglobin increased (p < 0.01) by 0.4-0.5 g/dl plateauing at 4 weeks (between group comparison, p = 0.92). Mean ferritin concentrations changed with time (p < 0.01), peaking at 2 weeks in Groups I and II and at 4 weeks in Group III. Mean transferrin saturation levels also increased during the study (p < 0.001). The between group comparisons for the trends in iron indices were significant (p < 0.01 and 0.05 respectively). As there were no clinically significant differences in hemoglobin response at 4 weeks, single dose iron infusion would seem to be the most expedient in the short term, however frequent small doses are similarly effective.
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PMID:Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO). 949 Dec 86


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