Hepcidin‐25/erythroferrone ratio predicts improvement of anaemia in haemodialysis patients treated with ferric citrate hydrate

Hara, Masaki; Nakamura, Yuya; Suzuki, Haruo; Asao, Rin; Nakamura, Masayuki; Nishida, Kazumasa; Kenmotsu, Sachiyo; Inagaki, Masumi; Tsuji, Mayumi; Kiuchi, Yuji; Ohsawa, Isao; Goto, Yoshikazu; Gotoh, Hiromichi

doi:10.1111/nep.13495

Cited by 9 publications

(8 citation statements)

References 18 publications

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“…As shown in Fig 3A, the levels of iron, hepcidin and ERFE plus the three ratio indicators (HE, EE and EH) were markedly associated with the pregnancy status. In parallel to our findings, the increased HE ratio has been used to predict the relief of anaemia in haemodialysis patients following ferric citrate hydrate, 49 pinpointing its scientific value in disease diagnosis. Therefore, it would be of great interest to evaluate the significance of these indicators in differentiating spontaneous abortion in early pregnancy.…”

Section: Resultssupporting

confidence: 76%

“…More recently, the placental iron deficiency index, calculated as the ratio of the placental FPN protein‐to‐the placental TFR1, has been developed as a sensitive surrogate in recognizing iron deficiency on the maternal‐fetal interface, particularly in mothers with disordered iron homeostasis 16 . Collectively, the combination of more than one parameter would be more potent for predicting the occurrence and progression of diseases, consistent with reports by previous studies 30,49,51,52 . Thus, we here developed a ratio of serum hepcidin and ERFE for the prediction of spontaneous abortion.…”

Section: Resultssupporting

confidence: 74%

“…16 Collectively, the combination of more than one parameter would be more potent for predicting the occurrence and progression of diseases, consistent with reports by previous studies. 30,49,51,52 Thus, we here developed a ratio of serum hepcidin and ERFE for the prediction of spontaneous abortion.…”

Section: Correlation Determination Of Eh Ee and He Ratios With Spontaneous Abortionmentioning

confidence: 99%

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Disordered serum erythroferrone and hepcidin levels as indicators of the spontaneous abortion occurrence during early pregnancy in humans

Wei

Liu

et al. 2020

Br J Haematol

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Summary Spontaneous abortion is a common, detrimental outcome of pregnancy, and can be induced by a variety of factors, including pathophysiological conditions and socioeconomic circumstances. Despite numerous studies examining the aetiology of spontaneous abortion, there is limited understanding of the disordered iron transportation between mother and fetus through the placenta. Recently, erythroferrone (ERFE) was recognized as a novel negative regulator of hepcidin that can elevate nutritional iron absorption and macrophagic iron egress for enhanced erythropoiesis. However, its diagnostic significance in different disease conditions associated with iron remains poorly understood. In the current study, we discovered disordered maternal iron homeostasis in women who had spontaneous abortions during early pregnancy, as characterized by increased serum iron and hepcidin levels, and conversely, reduced serum ERFE levels, compared to healthy control individuals and women with normal pregnancy. Comprehensive statistical analyses revealed the correlation between different variables and pregnancy status, signifying the pronounced diagnostic value of an increased ratio of serum hepcidin and ERFE (HE ratio) in recognizing adverse pregnancy status. In contrast to previous non‐selective discrete surrogates, such as iron, hepcidin and ferritin, the HE ratio may otherwise stand for a novel and more representative hallmark for early spontaneous abortion.

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Section: Resultssupporting

confidence: 76%

Section: Resultssupporting

confidence: 74%

Section: Correlation Determination Of Eh Ee and He Ratios With Spontaneous Abortionmentioning

confidence: 99%

See 1 more Smart Citation

Disordered serum erythroferrone and hepcidin levels as indicators of the spontaneous abortion occurrence during early pregnancy in humans

Wei

Liu

et al. 2020

Br J Haematol

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“…In the cross-sectional cohort, we observed a strong positive association between serum EPO and ERFE, consistent with the known stimulatory effect of EPO on ERFE production [13,14]; however, serum ERFE did not significantly correlate with hepcidin. In previous cross-sectional studies of CKD cohorts, strong associations between EPO and ERFE were observed [47], but associations between ERFE and hepcidin were variable [47][48][49], possibly contributed to by the multiple interrelated factors that affect hepcidin levels in CKD.…”

Section: Discussionmentioning

confidence: 91%

Associations among erythropoietic, iron-related, and FGF23 parameters in pediatric kidney transplant recipients

et al. 2021

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Background-In pediatric kidney transplant recipients, anemia is common and oftentimes multifactorial. Hemoglobin concentrations may be affected by traditional factors, such as kidney function and iron status, as well as novel parameters, such as fibroblast growth factor 23 (FGF23).Methods-Here, we evaluated associations among erythropoietic, iron-related, and FGF23 parameters in a cohort of pediatric kidney transplant recipients, hypothesizing that multiple factors are associated with hemoglobin concentrations.Results-In a cross-sectional analysis of 59 pediatric kidney transplant recipients (median (interquartile range) age 16.3 (13.5, 18.6) years, median estimated glomerular filtration rate (eGFR) 67 (54, 87) ml/min/1.73 m 2 ), the median age-related hemoglobin standard deviation score (SDS) was −2.1 (−3.3, −1.1). Hemoglobin SDS was positively associated with eGFR and calcium, and was inversely associated with erythropoietin (EPO), mycophenolate dose, and total, but not intact, FGF23. In multivariable analysis, total FGF23 remained inversely associated with hemoglobin SDS, independent of eGFR, iron parameters, EPO, and inflammatory markers, suggesting a novel FGF23-hemoglobin association in pediatric kidney transplant patients. In a subset of patients with repeat measurements, only delta hepcidin was inversely associated with delta hemoglobin SDS. Also, delta EPO positively correlated with delta erythroferrone (ERFE), and delta ERFE inversely correlated with delta hepcidin, suggesting a possible physiologic role for the EPO-ERFE-hepcidin axis in the setting of chronic kidney disease (CKD). Conclusion-Our study provides further insight into factors potentially associated with erythropoiesis in pediatric kidney transplant recipients.

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“…By suppressing hepcidin, ERFE promotes iron mobilization from storage cells and dietary iron absorption to improve iron availability for erythropoiesis. As a master regulator connecting erythropoiesis and iron metabolism, ERFE evokes much research interests in many research fields such as thalassemia, myelodysplastic syndromes, chronic kidney disease, anti-doping, hematopoietic stem cell transplant ( Kautz et al, 2015 ; Bondu et al, 2019 ; Hara et al, 2019 ; Ramirez Cuevas et al, 2020 ; Pirotte et al, 2021 ). Reported results demonstrated that ERFE concentrations significantly increased in animals and humans with normal or impaired kidney function after receiving exogenous erythropoiesis-stimulating agents (ESAs) ( Hanudel et al, 2018 ; Ramirez Cuevas et al, 2020 ; Robach et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamics of Erythroferrone Response to Erythropoietin in Rats

Wong

Krzyzanski

et al. 2022

Front. Pharmacol.

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Background: Erythroferrone (ERFE) is a hormone identified recently as a master regulator connecting iron homeostasis and erythropoiesis. Serum ERFE concentrations significantly increase in animals and humans with normal or impaired kidney function after receiving exogenous erythropoiesis-stimulating agents (ESAs), which suggests it might be a predictive factor for erythropoiesis. To evaluate whether ERFE is an early, sensitive biomarker for long-term erythropoietic effects of ESAs, we investigated the relationship between ERFE dynamics and time courses of major erythropoietic responses to ESA treatment.Methods: Healthy rats received single dose and multiple doses (thrice a week for 2 weeks) of recombinant human erythropoietin (rHuEPO) at three dose levels (100, 450, and 1350 IU/kg) intravenously. The rHuEPO and ERFE concentrations in plasma were determined at a series of time points after dosing. Erythropoietic effects including red blood cell count and hemoglobin concentrations were continuously monitored for 24 days (single dose) or 60 days (multiple doses). The expansion of erythroblasts in bone marrow was quantified by flow cytometry analysis.Results: ERFE significantly increased within a few hours and return to baseline at 24 h after rHuEPO treatment. The ERFE response was enhanced after repeated treatment, which was consistent with the observed expansion of erythroblasts in the bone marrow. In addition, the dynamics of ERFE showed double peaks at approximately 2 and 10 h after rHuEPO stimulation, and the ERFE baseline displayed a significant circadian rhythm. There was a strong positive correlation between peak values of short-term ERFE responses and the long-term hemoglobin responses.Conclusion: The stimulated release of ERFE is a rapid process within 24 h. The second peak in the ERFE response to rHuEPO suggests the presence of a feedback mechanism counterregulating the ESA stimulation. The early increase of ERFE at 2 h appears to be a predictor of the hemoglobin response at 14 days after single dose of rHuEPO. Under multiple-dose regimen, the enhanced ERFE responses still correlate with the peak hemoglobin responses. The ERFE baseline also exhibits a circadian rhythm.

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Hepcidin‐25/erythroferrone ratio predicts improvement of anaemia in haemodialysis patients treated with ferric citrate hydrate

Cited by 9 publications

References 18 publications

Disordered serum erythroferrone and hepcidin levels as indicators of the spontaneous abortion occurrence during early pregnancy in humans

Disordered serum erythroferrone and hepcidin levels as indicators of the spontaneous abortion occurrence during early pregnancy in humans

Associations among erythropoietic, iron-related, and FGF23 parameters in pediatric kidney transplant recipients

Dynamics of Erythroferrone Response to Erythropoietin in Rats

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