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Hyporesponsiveness to erythropoiesis-stimulating agent as a prognostic factor in Japanese hemodialysis patients: the Q-Cohort study

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Abstract

Background

Previous epidemiological evidence has suggested that responsiveness to erythropoiesis-stimulating agents (ESAs) is related to prognosis in hemodialysis (HD) patients. We investigated the effects of hyporesponsiveness to ESA on mortality and cardiovascular events in Japanese HD patients, taking modifying factors into account.

Methods

A total of 2,905 Japanese HD patients aged ≥18 years who received ESA treatment were prospectively followed up for 4 years. Responsiveness to ESA was estimated using an erythropoietin resistance index (ERI), defined as erythropoietin dosage per week divided by post-HD weight and hemoglobin value (U/kg/week/g/dl). Patients were divided into three groups by tertiles of ERI levels: low ERI, ≤5.10; intermediate ERI, 5.11–9.43; high ERI, ≥9.44. Risk estimates were calculated by a Cox proportional hazards model, adjusting for potential confounders.

Results

During follow-up, 482 patients died from any causes. The 4-year survival rate decreased linearly with higher ERI levels, being 87.5, 82.9, and 72.0 % for low, intermediate, and high ERI group (p for trend <0.001). Compared with the low ERI group, the multivariate-adjusted hazard ratio (mHR) was significantly higher in the high ERI group [mHR, 1.64 (95 % confidence interval, 1.27–2.11)]. In the high ERI group, patients with Kt/V ≥ 1.57 had a significantly lower risk of death from any causes compared with those with Kt/V ≤ 1.56 [mHR, 0.73 (0.54–0.98)].

Conclusion

Our findings suggest that ESA responsiveness can be considered a significant prognostic factor in Japanese HD patients.

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Acknowledgments

We thank the participants in the Q-Cohort Study, members of the Society for the Study of Kidney Disease, and all personnel at participating institutions involved in the study. The following personnel (institutions) participated in the study: Takashi Ando (Hakozaki Park Internal Medicine Clinic); Takashi Ariyoshi (Ariyoshi Clinic); Koichiro Goto (Goto Clinic); Fumitada Hattori (Nagao Hospital); Harumichi Higashi (St Mary’s Hospital); Tadashi Hirano (Hakujyuji Hospital); Kei Hori (Munakata Medical Association Hospital); Takashi Inenaga (Ekisaikai Moji Hospital); Hidetoshi Kanai (Kokura Memorial Hospital); Shigemi Kiyama (Kiyama Naika); Tetsuo Komota (Komota Clinic); Hiromasa Kuma (Kuma Clinic); Toshiro Maeda (Kozenkai-Maeda Hospital); Junichi Makino (Makino Clinic); Dai Matsuo (Hirao Clinic); Chiaki Miishima (Miishima Clinic); Koji Mitsuiki (Japanese Red Cross Fukuoka Hospital); Kenichi Motomura (Motomura Naika Clinic); Sadatoshi Nakamura (Kokura Daiichi Hospital); Hidetoshi Nakamura (Kokura Daiichi Hospital); Koichi Nakashima (Ohashi Internal Circulatory Clinic); Nobumitsu Okita (Shiroishi Kyoritsu Hospital); Shinichiro Osato (Osato Jin Clinic); Sakura Sakamoto (Fujiyamato Spa Hospital); Keiko Shigematsu (Shigematsu Clinic); Kazumasa Shimamatsu (Shimamatsu Naika Iin); Yoshito Shogakiuchi (Shin-Ai Clinic); Hiroaki Takamura (Hara Hospital); Kazuhito Takeda (Iizuka Hospital); Asuka Terai (Chidoribashi Hospital); Hideyoshi Tanaka (Mojiko-Jin Clinic); Suguru Tomooka (Hakozaki Park Internal Medicine Clinic); Jiro Toyonaga (Fukuoka Renal Clinic); Hiroshi Tsuruta (Steel Memorial Yawata Hospital); Ryutaro Yamaguchi (Shiseikai Hospital); Taihei Yanagida (Saiseikai Yahata General Hospital); Tetsuro Yanase (Yanase Internal Medicine Clinic); Tetsuhiko Yoshida (Hamanomachi Hospital); Takahiro Yoshimitsu (Gofukumachi Kidney Clinic, Harasanshin Hospital); Koji Yoshitomi (Yoshitomi Medical Clinic). This study was supported by the Kidney Foundation (H19 JKFB 07-13, H20 JKFB 08-8, H23 JKFB 11-11) and the Japan Dialysis Outcome Research Foundation (H19-076-02, H20-003).

Conflict of interest

The authors declare that they have no relevant financial interests.

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Authors and Affiliations

  1. Fukuoka Renal Clinic, Fukuoka, Japan

    Rieko Eriguchi & Satoru Fujimi

  2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Rieko Eriguchi, Masatomo Taniguchi, Toshiharu Ninomiya, Kazuhiko Tsuruya & Takanari Kitazono

  3. Division of Nephrology and Dialysis Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan

    Hideki Hirakata

  4. Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kazuhiko Tsuruya

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  1. Rieko Eriguchi
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  2. Masatomo Taniguchi
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Correspondence to Kazuhiko Tsuruya.

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Eriguchi, R., Taniguchi, M., Ninomiya, T. et al. Hyporesponsiveness to erythropoiesis-stimulating agent as a prognostic factor in Japanese hemodialysis patients: the Q-Cohort study. J Nephrol 28, 217–225 (2015). https://doi.org/10.1007/s40620-014-0121-9

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  • DOI: https://doi.org/10.1007/s40620-014-0121-9

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