The levels of HDL subfractions and their oxidized subfraction particles differed among patients with CKD. The increasing levels of oxHDL subfractions might cause a high frequency of CVD events in such patients.
A recent study demonstrated the association between inflammation, iron metabolism and fibroblast growth factor (FGF) 23. The present clinical study aimed to assess associations between anemia, iron metabolism and FGF23 in hemodialysis (HD) patients. This prospective observational study examined a cohort of prevalent HD patients (n = 282). Blood samples were obtained before dialysis sessions to measure baseline levels of hemoglobin (Hb), transferrin saturation (TSAT), ferritin, albumin-adjusted calcium (Ca), phosphate (P), intact (i)-PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact (i)-FGF23, high sensitive (hs)-CRP, and interleukin-6. After the baseline measurement, study patients were followed-up for 6 months. Biochemical measurements were subsequently performed at 1 (Hb), 2 (TSAT and ferritin) or 3 (Ca, P and hs-CRP) month intervals. Doses of ESAs and intravenous iron supplementation during the study period were recorded. i-FGF23 was positively correlated with Ca, P, i-PTH and inversely correlated with TSAT and ferritin. However, levels of Hb and hs-CRP and doses of ESAs during the study period did not differ among the i-FGF23 tertiles, with levels of ferritin and TSAT in the higher i-FGF23 tertile being consistently lower than in the middle to lower i-FGF23 tertiles. Multivariate repeated measures analysis indicated that the higher i-FGF23 tertile was independently associated with repeated measurements of ferritin, but not of TSAT. Doses of intravenous iron supplementation were significantly increased in the higher i-FGF23 tertile in multivariate models. In conclusion, high i-FGF23 levels may be associated with prolongation of low levels of ferritin, resulting in increased usages of iron supplementation in HD patients.
Continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) might differently affect iron metabolism and erythropoiesis in patients on hemodialysis (HD). This prospective study examined a cohort of patients on HD who had received either intravenous CERA every 2 or 4 weeks (N = 25) or DA once each week (N = 47). Blood was sampled before HD sessions on days 0, 2, 4, 7 and 14, and on days 0, 3, 5, 7 and 14 from patients who were injected with ESA at the beginning and end of the dialysis week, respectively. Changes in factors indicating erythropoiesis and biomarkers of iron metabolism were examined. Hemoglobin levels were maintained in the target range between 10.0 and 11.0 g/dL and ferritin levels at baseline and during the study period were similar between the DA and CERA groups. Levels of hepcidin 25 decreased from days 2-3 to day 5 and returned to the baseline at day 7 in the DA group, whereas those and transferrin saturation were serially suppressed from days 2-3 to day 14 in the CERA group. Levels of soluble transferrin receptor and reticulocyte counts were significantly elevated from days 4-5 to day 14 by CERA. Both DA and CERA stabilized erythropoiesis, but CERA might mobilize iron from body stores more effectively than DA in patients on HD.
Background
This study aimed to determine associations among short- and long-acting erythropoiesis stimulating agents (ESAs), changes in serum fibroblast growth factor 23 (FGF23) and biomarkers of iron metabolism.
Methods
Among 108 patients on hemodialysis (HD), 44 received every 2 weeks or monthly doses of continuous erythropoiesis receptor activator (CERA), 31 received weekly doses of darbepoetin-α, 24 received three doses per week of epoetin-β and 9 were not treated with an ESA. Intact and C-terminal FGF23 and transferrin saturation (TSAT), ferritin, erythroferrone and hepcidin 25 were measured in blood samples collected before the HD session at the end of the dialysis week (baseline, Day 0) and on Days 3, 5, 7 and 14 thereafter.
Results
Levels of ferritin, hepcidin 25 and erythroferrone as well as TSAT were significantly decreased or elevated in patients treated with CERA compared with other types of ESAs. Levels of C-terminal FGF23 increased in all groups during the observation period. Levels of intact FGF23 and ratios of intact FGF23 to C-terminal FGF23 gradually decreased between Days 3 and 7 in the CERA but not in the other groups. Multivariate models associated changes in hepcidin 25 and phosphate with those of intact FGF23.
Conclusion
The long-acting ESA CERA might influence levels of intact FGF23 by increasing FGF23 cleavage in patients on HD in association with prolonged hepcidin 25 suppression.
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