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Research for correlation between ESA resistance and serum hepcidin concentration

Research for correlation between ESA resistance and serum hepcidin concentration

60

The mean age of the study population was 68.3 +- 10.1 years, and 41 patients were male and 19 were female. The mean dialysis vintage was 93.4 +- 94.9 months. The primary diseases of CKD were chronic glomerulonephritis in 18 patients (30.0%), diabetic nephropathy in 22 patients (36.7%), nephrosclerosis in 10 patients (16.7%), and others (including unknown) in 10 patients (16.7%). The major comorbidities included hypertension in 55 patients (91.7%), secondary hyperparathyroidism in 49 patients (81.7%), hyperphosphatemia in 45 patients (75.0%), diabetes in 32 patients (53.3%), hyperkalemia in 27 patients (45.0%), and dyslipidemia in 22 patients (36.7%). The median (IQR) hepcidin level was 8.15 (1.00-23.85) ng/mL and the median (IQR) ERI was 0.042 (0.023-0.086) microgram/kg/g/dL.

Sixty patients were enrolled in this study. The three categories of ESA dose (low, medium, and high) were 21, 20, and 19 patients, respectively. Analyses of IL-6 and EPO levels were conducted in 58 patients and analyses of other factors were conducted in 60 patients, because blood sampling for IL-6 and blood EPO levels could not be performed in one patient each in the medium-dose and high-dose ESAs, respectively.

No adverse events related to the conduct of this observational study.

Analyses were performed after natural log transformation for hepcidin, ERI, dose, hemodialysis history, WBC, blood glucose, total bilirubin, AST, ALT, gamma-GTP, ALP, serum ferritin, and hs-CRP, IL-6, EPO. [Primary endpoint] There was a significant negative correlation coefficient between hepcidin levels and ERIs (r= -0.438, p=0.0005). [Secondary endpoints] Positive correlations with hepcidin levels were identified in BMI, pulse, MCH, MCHC, WBC, cholinesterase, serum iron, TSAT, serum ferritin, and hs-CRP. Negative correlations with hepcidin levels were identified in ESA dose, Kt/V, Ht levels, RBC, UIBC, TIBC, and blood EPO levels. In addition, hepcidin levels were significantly higher in patients who received oral iron-containing preparations than in those not receiving these preparations. Hepcidin-25 levels were significantly higher in patients in ferritin >= 100 ng/mL and TSAT >= 20%, and ferritin < 100 ng/mL and TSAT >= 20% compared with ferritin < 100 ng/mL and TSAT < 20%. Multiple regression analysis was performed with hepcidin levels as the objective variable and ERI, Ht, TSAT, serum ferritin, hs-CRP, and oral iron administration as explanatory variables. The coefficient of determination was 0.7073. The partial regression coefficients for each explanatory variable were as follows; ERI; -0.546 (p=0.0025), Ht; -0.172 (p=0.0013), TSAT; 0.044 (p=0.0278), serum ferritin; 0.839 (p=0.0009), hs-CRP; 0.441 (p<.0001), oral iron-containing preparations; 1.122 (p=0.0035).

A negative correlation was shown between ERI and hepcidin levels in 60 Japanese patients receiving hemodialysis. Multiple regression analyses showed that ERI, Ht, TSAT, ferritin, hs-CRP, and oral iron-containing preparations displayed a dominant relationship with hepcidin-25 levels. The results suggest that hepcidin levels might be associated with ERI, Ht, TSAT, serum ferritin, hs-CRP, and the administration of oral iron-containing preparations.

Dec. 26, 2025

Oct. 31, 2025

https://link.springer.com/article/10.1007/s10157-025-02783-9

No

https://jrct.mhlw.go.jp/latest-detail/jRCT1031230345

Mitobe Yuko

Torii Pharmaceutical Co., Ltd.

Torii Nihonbashi Bldg., 4-1,Nihonbashi-Honcho 3-chome, Chuo-ku, Tokyo

yuko.mitobe@torii.co.jp

Mitobe Yuko

Torii Pharmaceutical Co., Ltd.

Torii Nihonbashi Bldg., 4-1,Nihonbashi-Honcho 3-chome, Chuo-ku, Tokyo

+81-3-3231-6811

yuko.mitobe@torii.co.jp

Complete

Sept. 04, 2023

Observational

(1) Patients aged 18 years or older at the time of informed consent
(2) Patients receiving hemodialysis (including hemodiafiltration) 3 times a week for at least 12 weeks prior to informed consent
(3) Patients receiving ESA treatment for at least 8 weeks prior to informed consent, and whose latest ESA treatment interval is within 4 weeks
(4) Patients who have been administered the same type of ESA for at least 8 weeks prior to informed consent, and the administration interval and dose of the last two times are same (Epogin, Espo, and Epoetin Alfa Biosimilar are considered the same type of ESA)
(5) Patients who are assessed to have no health problems for the participation in this study by principal investigator or co-investigators

(1) Patients with severe complications such as cerebral, hepatic, renal, cardiac, pulmonary, gastrointestinal, hematological, endocrine, metabolic or psychiatric disease
(2) Those who have participated in other clinical trials involving medical devices or clinical research involving interventions within 12 weeks prior to this study
(3) Patients judged to be unsuitable as research subjects by principal investigator or co-investigators

Both

Anemia with CKD

Correlation between ERI and serum hepcidin concentration

Research the correlation between subject background or various laboratory tests and serum hepcidin concentrations

+81-3-5213-0028

Aug. 10, 2023

none