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1.
PLoS One ; 12(6): e0179608, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28662118

RESUMO

BACKGROUND: Optimal iron levels in patients on hemodialysis are currently unknown, and a higher level than that for the healthy population is usually set for such patients considering the use of erythropoiesis-stimulating agents or the occurrence of chronic inflammation. However, excessive iron causes oxidative stress and impairment of its utilization by cells. Therefore we investigated the relationship between hemoglobin (Hb) level and iron status in hemodialysis patients to identify the optimal iron levels for patients undergoing hemodialysis. METHODS: A total of 208 outpatients on maintenance hemodialysis were followed up between July 2006 and June 2007. Men accounted for 64.9% cases [mean age, 59.3 ± 13.1 years and median dialysis history, 7.7 (3.6-13.2) years], and diabetic nephropathy accounted for 25.0% cases. Hemoglobin level was measured twice a month and serum ferritin, serum iron, and total iron-binding capacity were measured once a month. The doses of recombinant human erythropoietin and low-dose iron supplement were adjusted to maintain a hemoglobin level of 10-11 g/dL, according to the guidelines of the Japanese Society for Dialysis Therapy. Hepcidin was measured at baseline. Using the mean values for 1-year period, the relationships among hemoglobin, serum ferritin levels, and transferrin saturation levels were investigated based on a receiver operating characteristic curve and a logistic regression model. In addition, the correlations among serum ferritin, transferrin saturation, and hepcidin levels were analyzed by Pearson product-moment correlation coefficient and linear regression model. RESULTS: By receiver operating characteristic curve, the cutoff point of serum ferritin and transferrin saturation levels with a hemoglobin ≥10 g/dL showed <90 ng/mL (sensitivity: 69.1%, specificity: 72.1%, p < 0.001) and ≥20% (sensitivity: 77.6%, specificity: 48.8%, p = 0.302). Upon logistic regression model analysis with a hemoglobin ≥10 g/dL as the endpoint, the analysis of odds ratios relative to a group with serum ferritin ≥90 ng/mL and transferrin saturation <20% revealed that the group with serum ferritin <90 ng/mL and transferrin saturation ≥20% had the highest ratio: 46.75 (95% confidence interval: 10.89-200.70, p < 0.001). In Pearson product-moment correlation coefficient, hepcidin showed a strong positive correlation with serum ferritin [r = 0.78 (95% confidence interval: 0.72-0.83, p < 0.001)] and a weak positive correlation with transferrin saturation [r = 0.18 (95% confidence interval: 0.04-0.31, p = 0.010)]. In the multivariable analyses of the linear regression model, a positive relationship was shown between hepcidin and serum ferritin [ß-coefficient of 0.30 (95% confidence interval: 0.27-0.34, p < 0.001)]; however, no relationship was shown with transferrin saturation [ß-coefficient of 0.09 (95% confidence interval: -0.31-0.49, p = 0.660)]. CONCLUSIONS: In this study, the iron status of serum ferritin <90 ng/mL and transferrin saturation ≥20% was optimal in hemodialysis patients receiving recombinant human erythropoietin for anemia therapy. This result indicates that the threshold values for the optimal iron status may be lower than those currently recommended in iron-level management guideline.


Assuntos
Ferritinas/sangue , Hemoglobinas/metabolismo , Diálise Renal , Transferrina/metabolismo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
Nephron Extra ; 4(1): 55-63, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24847351

RESUMO

BACKGROUND/AIMS: We examined whether regulation of hepcidin-25 by short- or long-acting recombinant human erythropoietin (rhEPO) is dependent on ferritin and predicts the response to rhEPO in hemodialysis (HD) patients. METHODS: Two studies with rhEPO were performed in 9 HD patients with a 2-year interval. Serum hepcidin-25 was measured at 0-18 h after intravenous epoetin-ß (EPO) or methoxy polyethylene glycol-epoetin-ß (PEG-EPO) administration and on days 3-7 after PEG-EPO. Hemoglobin (Hb), serum ferritin, transferrin, C-reactive protein (CRP), and interleukin (IL)-6 were analyzed before hepcidin measurement and 6 months after rhEPO. Based on the serum ferritin levels before hepcidin measurement, the patients in the two studies with EPO or PEG-EPO were combined into low (11; serum ferritin of <15.0 ng/ml) and high ferritin groups (7; serum ferritin of ≥15.0 ng/ml). The response of hepcidin-25 to rhEPO and the effect of rhEPO on anemia were compared between the groups. RESULTS: The serum hepcidin-25 levels rose at 6-9 h and returned to the baseline at 18 h after EPO. They rose at 6-9 h, returned to the baseline at 18 h, and decreased on day 5-7 after PEG-EPO. Serum hepcidin-25 levels were low (<5.0 ng/ml) in the low ferritin group, but rose at 6-9 h after rhEPO in the high ferritin group. Serum transferrin levels were similar, and CRP and IL-6 were normal in both groups. Hb tended to increase in the low ferritin group, but it significantly decreased in the high ferritin group after rhEPO. CONCLUSION: Regulation of hepcidin-25 by rhEPO may be dependent on ferritin, affecting the response to rhEPO in HD patients.

3.
Nutrients ; 7(1): 103-18, 2014 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-25551249

RESUMO

The benefit of oral iron therapy (OIT) and factors predictive of OIT response are not established in hemodialysis (HD) patients with iron deficiency anemia (IDA). We examined the values of hepcidin-25, mean corpuscular volume (MCV), and ferritin as predictors of OIT response. Oral ferrous fumarate (50 mg/day, 8 weeks) was given to 51 HD patients with IDA (hemoglobin (Hb) < 12 g/dL, ferritin < 100 ng/mL) treated with an erythropoietin activator. Sixteen patients were responders (improvement of Hb (ΔHb) ≥ 2 g/dL) and 35 were non-responders (ΔHb < 2g/dL). Baseline Hb, MCV, serum hepcidin-25, ferritin, iron parameters, and C-reactive protein (CRP) before and ΔHb after OIT were compared between groups. Hepcidin-25, MCV, ferritin, and transferrin saturation were lower in the responders than in the non-responders. Hepcidin-25 positively correlated with ferritin. Hepcidin-25, MCV, and ferritin positively correlated with baseline Hb and negatively correlated with ΔHb. Despite normal CRP levels in all patients, CRP correlated positively with hepcidin-25 and ferritin. Stepwise multiple linear regression analysis and receiver operating characteristics curve analysis revealed that hepcidin-25, MCV, and ferritin could predict OIT response. We conclude that hepcidin-25, MCV, and ferritin could be useful markers of iron storage status and may help predict OIT response in HD patients.


Assuntos
Suplementos Nutricionais , Índices de Eritrócitos/fisiologia , Ferritinas/sangue , Hepcidinas/sangue , Ferro da Dieta/administração & dosagem , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/sangue , Anemia Ferropriva/tratamento farmacológico , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Eritropoetina/uso terapêutico , Feminino , Compostos Ferrosos/administração & dosagem , Hemoglobinas/metabolismo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade
4.
Am J Nephrol ; 40(6): 561-70, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25592750

RESUMO

BACKGROUND: The optimal level of serum ferritin (s-ft) for anemia control and good survival in hemodialysis (HD) patients remains unclear. A 10-year survey was performed to clarify the appropriate quantities of s-ft and investigate the relationships among s-ft, transferrin saturation (TSAT), and mortality in HD patients. METHODS: HD outpatients (n = 125) treated with erythropoiesis-stimulating agents (ESA) were followed for 10 years. The ESA and low-dose iron supplement dosages were adjusted to maintain the hemoglobin (Hb) at 10-11 g/dl, according to Japanese guidelines. The Kaplan-Meier method, log-rank tests, and the Cox proportional hazards model were used for performing the statistical analyses. The interactions among the Hb, s-ft, and TSAT were analyzed using a multiple linear regression model. Patients with TSAT ≥20% were classified according to the s-ft cutoff values: group 1 (s-ft <30 ng/ml); group 2 (s-ft 30-80 ng/ml); group 3 (s-ft >80 ng/ml); TSAT <20% was a predictor of poor outcome. RESULTS: The survival rate in group 2 was significantly higher than that in other groups (p = 0.013), and the Cox proportional hazards model analysis showed a good effect of low levels of s-ft on patients' survival. The multiple linear regression model showed a strong effect of s-ft on the Hb (log [s-ft], ß-coefficient -0.45: 95% confidence interval -0.65 to -0.26, p < 0.001). CONCLUSION: This study revealed that low levels of s-ft have a beneficial effect on the outcome of HD patients receiving ESA. Thus, the optimal s-ft level might be lower than that established previously for these patients.


Assuntos
Anemia/sangue , Ferritinas/sangue , Hemoglobinas/metabolismo , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Transferrina/metabolismo , Adulto , Idoso , Causas de Morte , Suplementos Nutricionais , Feminino , Hematínicos/administração & dosagem , Humanos , Ferro/administração & dosagem , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/sangue , Estudos Retrospectivos , Taxa de Sobrevida
5.
Clin J Am Soc Nephrol ; 8(6): 969-78, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23599410

RESUMO

BACKGROUND AND OBJECTIVES: A 1-year multicenter prospective randomized controlled study was conducted on the effects of vitamin E-bonded polysulfone dialyzers on erythropoiesis-stimulating agent response in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Major inclusion criteria were use of high-flux polysulfone dialyzers with 50-70 ml/min ß2-microglobulin clearance over 3 months, transferrin saturation over 20%, same erythropoiesis-stimulating agent for over 3 months, and hemoglobin at 10-12 g/dl. Hemodialysis patients were placed in four interventional groups: two hemoglobin ranges (10.0-10.9 or 11.0-11.9 g/dl) and two dialyzers. Patients were randomly assigned by central registration to a vitamin E-bonded polysulfone dialyzers or polysulfone control group. Primary end point was relative erythropoiesis resistance index at baseline between groups at 12 months. Erythropoiesis resistance index was defined as total weekly erythropoiesis-stimulating agent dose divided by hemoglobin. RESULTS: There were no statistically significant differences in age or sex. There was no significant difference in relative erythropoiesis resistance index between vitamin E-bonded polysulfone dialyzers and control groups at 12 months (vitamin E-bonded polysulfone dialyzers: 1.1, control: 1.3). The vitamin E-bonded polysulfone dialyzers group showed better relative erythropoiesis resistance index than the control group at 11.0-11.9 g/dl hemoglobin (vitamin E-bonded polysulfone dialyzers: 1.0, control: 1.4 at 12 months, significant difference) but no difference at 10.0-10.9 g/dl hemoglobin. CONCLUSIONS: The overall relative erythropoiesis resistance index showed no difference between the vitamin E-bonded polysulfone dialyzers and control groups, although the change in relative erythropoiesis resistance index differed according to hemoglobin level.


Assuntos
Antioxidantes/administração & dosagem , Materiais Revestidos Biocompatíveis , Eritropoese/efeitos dos fármacos , Hematínicos/uso terapêutico , Membranas Artificiais , Polímeros , Diálise Renal/instrumentação , Insuficiência Renal Crônica/terapia , Sulfonas , Vitamina E/administração & dosagem , Idoso , Análise de Variância , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Feminino , Hemoglobinas/metabolismo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Fatores de Tempo , Resultado do Tratamento
8.
Haematologia (Budap) ; 32(3): 225-38, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12611483

RESUMO

Serum soluble transferrin receptor (sTfR) has been reported to be higher in patients with iron deficiency or with elevated erythropoiesis. In the present study, serum sTfR was measured in various anemic diseases and their clinical significance was examined in a multi-institutional joint study. Serum sTfRs in patients with the following anemic diseases were markedly higher than those in normal healthy adults: non-treated iron deficiency anemia (IDA) (9.13 +/- 7.04 mg/l, n = 52, p < 0.0001), anemia of chronic disorders (ACD) (3.45 +/- 1.38 mg/l, n = 20, p < 0.0001), hemolytic anemia (HA) (5.57 +/- 3.26 mg/l, n = 17, p < 0.0001), and myelodysplastic syndrome (MDS) (4.03 +/- 2.83 mg/l, n = 20, p < 0.0001). There were significant differences between IDA and ACD (p < 0.0001), between aplastic anemia (AA) (1.58 +/- 1.26 mg/l, n = 16) and MDS (p < 0.001), and between AA and MDS with refractory anemia (MDS-RA) (4.16 +/- 3.40 mg/l, n = 9) (p < 0.02). In patients with chronic renal failure (CRF), serum sTfR levels and serum sTfR/log serum ferritin ratios (sTfR/F index) were compared in the two classified groups according to Muirhead's criteria, as IDA and non-IDA groups with or without recombinant human erythropoietin (rHuEPO) treatment. Significantly high levels of both serum sTfR (p < 0.0001) and the sTfR/F index (p < 0.0001) were observed in IDA without rHuEPO treatment. Especially in CRF with rHuEPO treatment, the sTfR/F index showed marked elevation in the IDA group (p < 0.0001) compared with serum sTfR (p < 0.001), indicating more diagnostic efficacy of the sTfR/F index for CRF with IDA. In conclusion, the serum sTfR concentration is a useful diagnostic tool for discrimination between IDA and ACD, and between AA and MDS-RA, and for the detection of iron deficiency in CRF patients in the Japanese population.


Assuntos
Anemia/diagnóstico , Receptores da Transferrina/sangue , Adulto , Fatores Etários , Anemia/sangue , Anemia Hemolítica/sangue , Anemia Hemolítica/diagnóstico , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Eritropoetina/farmacologia , Eritropoetina/uso terapêutico , Feminino , Ferritinas/sangue , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/diagnóstico , Kit de Reagentes para Diagnóstico , Proteínas Recombinantes , Insuficiência Renal/sangue , Fatores Sexuais , Solubilidade
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