Clinical and Experimental Nephrology

, Volume 22, Issue 5, pp 1174–1181 | Cite as

Butyrylcholinesterase level as an independent factor of erythropoiesis-stimulating agent resistance in patients on maintenance hemodialysis: a single-center cross-sectional study

  • Teppei OkamotoEmail author
  • Shingo Hatakeyama
  • Yoshimi Tanaka
  • Kengo Imanishi
  • Tooru Takashima
  • Fumitada Saitoh
  • Takuya Koie
  • Tadashi Suzuki
  • Chikara Ohyama
Original article



Erythropoiesis-stimulating agent (ESA) responsiveness is related to the nutritional status of patients on hemodialysis (HD). Serum butyrylcholinesterase (BChE), an alpha-glycoprotein, may decrease in case of malnutrition. We investigated whether BChE was independently related to ESA resistance in patients on HD.


The laboratory data and ESA resistance index (ERI), defined as ESA dosage per week divided by dry weight and hemoglobin, were investigated in 215 patients on HD between July and September 2017. Malnutrition was defined as Geriatric Nutritional Risk Index (GNRI) of < 91.2. The patients were stratified into two groups: ERI-high (ERI ≥ 9.44) and ERI-low (ERI < 9.44) groups. Variables such as patient’s background, medication, and laboratory data were compared between the two groups. The optimal cutoff value of BChE for higher ERI was determined using receiver operating characteristic analysis. Factors independently associated with higher ERI were determined using multivariate logistic regression analysis.


The median and optimal cutoff values of ERI and BChE were 6.51 and 200 IU/L, respectively. The study included 71 (33%) and 144 (67%) patients in the ERI-high and ERI-low groups, respectively. Significant between-group differences were observed concerning age, hemoglobin, ESA dose, lipid profiles, serum albumin, body mass index, GNRI, iron metabolism markers, ferric medicines, and BChE. Multivariate analysis showed that BChE < 200 IU/L (odds ratio 3.67; 95% confidence interval 1.73–7.77) continued to be an independent factor associated with higher ERI after adjusting for potential confounders, which was a similar odds ratio as GNRI < 91.2.


BChE may be an independent indicator of ESA resistance.


Erythropoietin Butyrylcholinesterase Erythropoiesis-stimulating agent resistance Hemodialysis Geriatric Nutritional Risk Index 



We thank Sakiko Fujita, Akiko Kimura, Mieko Kawamura, Chizu Kawase, Kumiko Sato, and Masahiko Tezuka for their invaluable help with data collection. We would like to appreciate Enago ( for English language support.

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interest exists.

Human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number 2017-089) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Registration of clinical trials

The trial is registered in the UMIN Clinical Trials Registry UMIN000028064.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Japanese Society of Nephrology 2018

Authors and Affiliations

  • Teppei Okamoto
    • 1
    Email author
  • Shingo Hatakeyama
    • 2
  • Yoshimi Tanaka
    • 1
  • Kengo Imanishi
    • 1
  • Tooru Takashima
    • 1
  • Fumitada Saitoh
    • 1
  • Takuya Koie
    • 2
  • Tadashi Suzuki
    • 3
  • Chikara Ohyama
    • 2
  1. 1.Department of UrologyOyokyo Kidney Research Institute Aomori HospitalAomoriJapan
  2. 2.Department of UrologyHirosaki University Graduate School of MedicineHirosakiJapan
  3. 3.Department of UrologyOyokyo Kidney Research InstituteOzawaJapan

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