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Prevalence, treatment status, and predictors of anemia and erythropoietin hyporesponsiveness in Japanese patients with non-dialysis-dependent chronic kidney disease: a cross-sectional study

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Abstract

Background

Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) has been highlighted as a potential risk factor for cardiovascular disease in patients with chronic kidney disease (CKD).

Methods

We assessed cross-sectionally the prevalence, associated factors, and treatment status of anemia and ESA hyporesponsiveness in 4460 non-dialysis-dependent CKD patients enrolled in a multicenter cohort in Japan. Anemia was defined as a hemoglobin (Hb) level of less than 11 g/dL or receiving ESA therapy. ESA hyporesponsiveness was defined by the erythropoietin-resistance index (ERI), which was the erythropoietin dose per week divided by body weight and Hb level (U/kg/week/g/dl).

Results

Of the 4460 patients, 1050 (23.5%) had anemia. ESAs were administered to 626 patients, reaching a percentage of 57.5% of patients with stage G5 CKD. However, the ESA treatment rate was only 49.0% in patients with a hemoglobin level of < 11 g/dL. The proportion of patients receiving iron supplementation was lower than that of patients receiving ESAs regardless of CKD stage or hemoglobin level, and a significant proportion of patients did not receive iron supplementation, even those with iron deficiency. The ERI increased with CKD stage progression, and the multiple regression analysis showed that age, female sex, body mass index, cholesterol, glomerular filtration rate, and intact parathyroid hormone level were independent contributors.

Conclusions

Our findings demonstrate that many Japanese patients with non-dialysis-dependent CKD receiving ESAs fail to maintain adequate hemoglobin levels. These results suggest the need for interventions for ESA hyporesponsiveness factors in addition to iron supplementation.

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Acknowledgements

The authors thank the participants in the FKR study, the members of the FKR Study Group, and all personnel at participating institutions involved in the study. The authors specifically thank Satoru Fujimi (Fukuoka Renal Clinic), Hideki Hirakata (Fukuoka Renal Clinic), Tadashi Hirano (Hakujyuji Hospital), Tetsuhiko Yoshida (Hamanomachi Hospital), Takashi Deguchi (Hamanomachi Hospital), Koji Mitsuiki (Harasanshin Hospital), Kiichiro Fujisaki (Iizuka Hospital), Keita Takae (Japanese Red Cross Fukuoka Hospital), Masanori Tokumoto (Japanese Red Cross Fukuoka Hospital), Akinori Nagashima (Japanese Red Cross Karatsu Hospital), Ritsuko Katafuchi (Kano Hospital), Hidetoshi Kanai (Kokura Memorial Hospital), Kenji Harada (Kokura Memorial Hospital), Tohru Mizumasa (Kyushu Central Hospital), Takanari Kitazono (Kyushu University), Toshiaki Nakano (Kyushu University), Toshiharu Ninomiya (Kyushu University), Kumiko Torisu (Kyushu University), Shigeru Tanaka (Kyushu University), Shunsuke Yamada (Kyushu University), Akihiro Tsuchimoto (Kyushu University), Yuta Matsukuma (Kyushu University), Sho Shimamoto (Kyushu University), Hiromasa Kitamura (Kyushu University), Hiroto Hiyamuta (Fukuoka University), Dai Matsuo (Munakata Medical Association Hospital), Yusuke Kuroki (National Fukuoka-Higashi Medical Center), Hiroshi Nagae (National Fukuoka-Higashi Medical Center), Masaru Nakayama (National Kyushu Medical Center), Kazuhiko Tsuruya (Nara Medical University), Masaharu Nagata (Shin-eikai Hospital), Taihei Yanagida (Steel Memorial Yawata Hospital), and Shotaro Ohnaka (Tagawa Municipal Hospital). Finally, the authors thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Shigeru Tanaka, Hiromasa Kitamura, Takanari Kitazono & Toshiaki Nakano

  2. Department of Nephrology, Nara Medical University, Nara, Japan

    Kazuhiko Tsuruya

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  1. Shigeru Tanaka
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  2. Hiromasa Kitamura
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Contributions

S.T. contributed to the study design, acquisition of data, statistical analysis, interpretation of data, and drafting of the manuscript. H.K. contributed to the interpretation of data and drafting of the manuscript. T.N. contributed to the study design, statistical analysis, interpretation of data, and drafting of the manuscript. K.T. and T.K. contributed to the critical revision of the manuscript and study supervision. All the authors provided critical reviews of the manuscript and approved the final version.

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Correspondence to Toshiaki Nakano.

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Supplementary file1 (EPS 1647 KB)

Supplementary Figure 1. Histogram of distribution of the erythropoietin resistance index

Supplementary file2 (EPS 1660 KB)

Box plots of erythropoietin resistance index according to CKDstage. Abbreviation: CKD, chronic kidney disease.The line inside each box represents the median, the upper and lower limits of the boxesrepresent the 25th and 75th percentiles, respectively. The whiskers depict the 10th and 90thpercentiles. Closed circles represent outliers

Supplementary file3 (DOCX 30 KB)

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Tanaka, S., Kitamura, H., Tsuruya, K. et al. Prevalence, treatment status, and predictors of anemia and erythropoietin hyporesponsiveness in Japanese patients with non-dialysis-dependent chronic kidney disease: a cross-sectional study. Clin Exp Nephrol 26, 867–879 (2022). https://doi.org/10.1007/s10157-022-02227-8

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  • DOI: https://doi.org/10.1007/s10157-022-02227-8

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