Abstract
BackgroundDecreased 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.MethodsEpoetin 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.ResultsAdministration 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.ConclusionAdministration 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 registrationThis study was registered with the University Hospital Medical Information Network (ID UMIN000016552).
Highlights
Decreased erythropoietin levels and impaired iron metabolism due to excessive hepcidin levels are responsible for renal anaemia in patients undergoing haemodialysis
We recently proposed that excessive iron storage could even hamper erythropoiesis or the differentiation of erythroid in the therapy for renal anaemia [1]
We examined the effects of Epoetin beta pegol (CERA) and saccharated ferric oxide (SFO) on inflammatory markers, such as high-sensitivity C-reactive protein (hsCRP) and Interleukin 6 (IL-6)
Summary
Decreased erythropoietin levels and impaired iron metabolism due to excessive hepcidin levels are responsible for renal anaemia in patients undergoing haemodialysis. As we recently reviewed, excessive iron storage may even impede erythropoiesis or the differentiation of erythroid precursors in the therapy for renal anaemia in patients undergoing haemodialysis [1]. We hypothesized that a major cause of the unresponsiveness to ESA in patients with massive iron storage could be an increase in hepcidin levels. An increase in hepcidin level has been presumed to be one of the major factors of renal anaemia, because animal models of chronic kidney disease (CKD), as well as sepsis, did not present anaemia or iron deficiency when hepcidin was knocked out [4, 5]. It is necessary to investigate the reaction of hepcidin to ESA and iron administration, and the relationship between hepcidin and haematopoiesis in the clinical setting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
