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Research Article
Akira Fujimori
Konan Medical Center
Corresponding Author
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Background: Decreased erythropoietin levels and impaired iron metabolism due to excessive hepcidin levels are responsible for renal anaemia in patients undergoing haemodialysis. Recently, erythroferrone (ERFE) has been identified as a factor that regulates hepcidin. In addition, fibroblast growth factor 23 (FGF23), which has been recognized as a phosphorus-regulating hormone, appears to be involved in haematopoietic regulation. Clarification of the detailed mechanism of haematopoiesis could lead to the improvement of renal anaemia treatment.
Methods: Epoetin beta pegol (CERA) was administered to patients undergoing haemodialysis at week 0, and the same amount of CERA with saccharated ferric oxide (SFO) was administered at week 4. The changes in haematopoiesis-related biomarkers, including ERFE, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), and inflammatory markers, were examined.
Results: Administration of CERA increased ERFE levels, decreased hepcidin levels, and stimulated iron usage for haematopoiesis, leading to an increase in reticulocytes (Ret) and haemoglobin (Hb). Simultaneous administration of SFO with CERA (CERA + SFO) significantly attenuated the responses of ERFE, Ret, and Hb compared with CERA alone. Although iFGF23 levels were not affected by either CERA or CERA + SFO, cFGF23 was significantly elevated from baseline after CERA. Since cFGF23 levels were not affected by CERA + SFO, cFGF23 levels after CERA + SFO were significantly lower than those after CERA alone. The ratio of iFGF23 to cFGF23 (i/cFGF23 ratio) was significantly higher after CERA + SFO than that after CERA alone. In addition, high-sensitivity C-reactive protein (hsCRP) levels were significantly higher after CERA + SFO than after CERA alone.
Conclusion: Administration of SFO suppressed haematopoietic responses induced by CERA. Elevation of i/cFGF23 ratio and hsCRP could account for the inhibitory effects of SFO on haematopoiesis.
This study was registered with the University Hospital Medical Information Network (ID UMIN000016552).
Keywords
Fibroblast growth factor 23, Erythroferrone, Hepcidin, Epoetin beta pegol, Saccharated ferric oxide
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Supplementary Figure S1. Correlation between ERFE and Rec During the observation period, the values fluctuated, and Ln(ERFE) and Ln(Ret) showed a significant positive correlation with r = 0.765 (p < 0.0001) Abbreviations: ERFE erythroferrone, Ret reticulocyte Supplementary Figure S2. Correlation between ERFE and HEPC During the observation period, the values fluctuated, and Ln(ERFE) and Ln(HEPC) showed a significant negative correlation with r = -0.866 (p < 0.0001) Abbreviations: ERFE erythroferrone, HEPC hepcidin-25
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CURRENT STATUS: Under Review
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Editorial decision: Major revision
On 05 Feb, 2021
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Reviewers agreed
On 24 Jan, 2021
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On 18 Jan, 2021
Editor invited
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Subject Areas
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This preprint is under consideration at BMC Nephrology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Akira Fujimori
Konan Medical Center
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 20 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 05 Feb, 2021
Reviews received
Received 01 Feb, 2021
Reviewers agreed
On 24 Jan, 2021
Reviewers invited
Invitations sent on 18 Jan, 2021
Editor assigned
On 18 Jan, 2021
Editor invited
On 18 Jan, 2021
Submission checks complete
On 18 Jan, 2021
First submitted
On 09 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Decreased erythropoietin levels and impaired iron metabolism due to excessive hepcidin levels are responsible for renal anaemia in patients undergoing haemodialysis. Recently, erythroferrone (ERFE) has been identified as a factor that regulates hepcidin. In addition, fibroblast growth factor 23 (FGF23), which has been recognized as a phosphorus-regulating hormone, appears to be involved in haematopoietic regulation. Clarification of the detailed mechanism of haematopoiesis could lead to the improvement of renal anaemia treatment.
Methods: Epoetin beta pegol (CERA) was administered to patients undergoing haemodialysis at week 0, and the same amount of CERA with saccharated ferric oxide (SFO) was administered at week 4. The changes in haematopoiesis-related biomarkers, including ERFE, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), and inflammatory markers, were examined.
Results: Administration of CERA increased ERFE levels, decreased hepcidin levels, and stimulated iron usage for haematopoiesis, leading to an increase in reticulocytes (Ret) and haemoglobin (Hb). Simultaneous administration of SFO with CERA (CERA + SFO) significantly attenuated the responses of ERFE, Ret, and Hb compared with CERA alone. Although iFGF23 levels were not affected by either CERA or CERA + SFO, cFGF23 was significantly elevated from baseline after CERA. Since cFGF23 levels were not affected by CERA + SFO, cFGF23 levels after CERA + SFO were significantly lower than those after CERA alone. The ratio of iFGF23 to cFGF23 (i/cFGF23 ratio) was significantly higher after CERA + SFO than that after CERA alone. In addition, high-sensitivity C-reactive protein (hsCRP) levels were significantly higher after CERA + SFO than after CERA alone.
Conclusion: Administration of SFO suppressed haematopoietic responses induced by CERA. Elevation of i/cFGF23 ratio and hsCRP could account for the inhibitory effects of SFO on haematopoiesis.
This study was registered with the University Hospital Medical Information Network (ID UMIN000016552).
Figure 1
Figure 2
Figure 3
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