Saccharated ferric oxide attenuates haematopoietic response induced by epoetin beta pegol in patients undergoing haemodialysis.
Aged
Anemia
/ drug therapy
Biomarkers
/ blood
Erythropoiesis
/ drug effects
Erythropoietin
/ therapeutic use
Female
Ferric Oxide, Saccharated
/ adverse effects
Fibroblast Growth Factor-23
/ blood
Humans
Iron
/ metabolism
Male
Peptide Hormones
/ metabolism
Polyethylene Glycols
/ therapeutic use
Renal Dialysis
Renal Insufficiency, Chronic
/ blood
Epoetin beta pegol
Erythroferrone
Fibroblast growth factor 23
Hepcidin
Saccharated ferric oxide
Journal
BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793
Informations de publication
Date de publication:
08 04 2021
08 04 2021
Historique:
received:
09
01
2021
accepted:
17
03
2021
entrez:
9
4
2021
pubmed:
10
4
2021
medline:
8
2
2022
Statut:
epublish
Résumé
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. 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. 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. 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 ).
Sections du résumé
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.
TRIAL REGISTRATION
This study was registered with the University Hospital Medical Information Network (ID UMIN000016552 ).
Identifiants
pubmed: 33832448
doi: 10.1186/s12882-021-02320-2
pii: 10.1186/s12882-021-02320-2
pmc: PMC8034147
doi:
Substances chimiques
Biomarkers
0
Erfe protein, human
0
FGF23 protein, human
0
Peptide Hormones
0
continuous erythropoietin receptor activator
0
Erythropoietin
11096-26-7
Polyethylene Glycols
3WJQ0SDW1A
Fibroblast Growth Factor-23
7Q7P4S7RRE
Iron
E1UOL152H7
Ferric Oxide, Saccharated
FZ7NYF5N8L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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