Saccharated Ferric Oxide Attenuates Haematopoietic Response Induced by Epoetin Beta Pegol in Patients Undergoing Haemodialysis
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
This is a list of supplementary files associated with this preprint. Click to download.
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
Posted 20 Jan, 2021
On 05 Feb, 2021
Received 01 Feb, 2021
Received 01 Feb, 2021
Received 01 Feb, 2021
Received 01 Feb, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
Invitations sent on 18 Jan, 2021
On 18 Jan, 2021
On 18 Jan, 2021
On 18 Jan, 2021
On 09 Jan, 2021
Saccharated Ferric Oxide Attenuates Haematopoietic Response Induced by Epoetin Beta Pegol in Patients Undergoing Haemodialysis
Posted 20 Jan, 2021
On 05 Feb, 2021
Received 01 Feb, 2021
Received 01 Feb, 2021
Received 01 Feb, 2021
Received 01 Feb, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
On 24 Jan, 2021
Invitations sent on 18 Jan, 2021
On 18 Jan, 2021
On 18 Jan, 2021
On 18 Jan, 2021
On 09 Jan, 2021
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