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Comparison of steroid-pulse therapy and combined with mizoribine in IgA nephropathy: a randomized controlled trial

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Abstract

Background

The significance of immunosuppressants as an adjunct treatment with corticosteroids for IgA nephropathy (IgAN) has not been well demonstrated. This study was performed to compare two treatment regimens, steroid-pulse therapy or combined with mizoribine (MZR) in progressive IgAN.

Methods

Study design was a prospective randomized controlled trial of 40 patients with moderate to severe glomerular injuries who were randomly administered either pulse methylprednisolone followed by a 25-month course of oral prednisolone (P group, n = 20) or in combination with MZR (150 mg/day for 24 months, M + P group, n = 20). The primary endpoint was a reduction of proteinuria by ≥50 % of the baseline value. Secondary endpoints were increased serum creatinine (Cr) by ≥50 %, or a decrease in estimated glomerular filtration rate by ≤50 %.

Results

Twenty-five months after the initiation of treatment, urinary protein excretion significantly declined from the median of 0.98 to 0.17 g/gCr in the P group (P < 0.05) and from 1.01 to 0.38 g/gCr in the M + P group (P < 0.05). There was no statistical difference in the serial changes of proteinuria between two groups (P = 0.81). All patients reached the primary endpoint, and the cumulative incidence of the reduction of proteinuria was not significantly different (P = 0.76). No patient reached the secondary endpoint during the 25 months of treatment.

Conclusions

Both therapeutic regimens significantly reduced the levels of proteinuria. We could not find the additional effect of MZR in combination with steroid-pulses in this small-scale controlled trial. Steroid-pulse therapy with a 25-month course of oral steroids seems to be effective for progressive IgAN.

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Acknowledgments

We thank Drs. Kei Hori, Kazuhito Takeda, and Tetsuhiko Yoshida for their help designing the early version of this study. We also thank Drs. Takashi Inenaga, Akinori Nagashima, Masaru Nakayama, Hidetoshi Kanai, Hiroshi Tsuruta, Harumichi Higashi, Tadashi Hirano, Hiroshi Tanaka, and Atsumi Harada for treatment of the patients, and data collection. This study was funded by The Kidney Foundation, Japan. We are deeply grateful to Asahi Kasei Pharma for providing MZR, because the use of MZR for IgAN is not covered by health insurance in Japan.

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Author notes

    Authors and Affiliations

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

      Kosuke Masutani, Akihiro Tsuchimoto, Takanari Kitazono & Kazuhiko Tsuruya

    2. Department of Clinical Epidemiology and Biostatistics, Graduate School of Medicine, Osaka University, Suita, Japan

      Tomomi Yamada

    3. Division of Nephrology, Harasanshin Hospital, Fukuoka, Japan

      Makoto Hirakawa

    4. Nephrology and Dialysis Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan

      Koji Mitsuiki & Hideki Hirakata

    5. Kidney Unit, National Fukuoka-Higashi Medical Center, Koga, Japan

      Ritsuko Katafuchi

    6. 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. Kosuke Masutani
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    Consortia

    West Japan Study Group for Therapy of IgA Nephropathy Investigators

    Corresponding author

    Correspondence to Kazuhiko Tsuruya.

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    Conflict of interest

    Honoraria: Takanari Kitazono (Bayer Pharmaceutical Co., Bristol-Myers Squibb Co., Daiichi-Sankyo Co.), Kazuhiko Tsuruya (Chugai Pharmaceutical Co., Kyowa Hakko Kirin Co.)

    Funding

    This study was funded by The Kidney Foundation, Japan.

    Research funding

    Takanari Kitazono (Astellas Pharma Inc., Daiichi-Sankyo Co., Eisai Co., Kyowa Hakko Kirin Co., Mitsubishi Tanabe Pharma Co., MSD K.K., Ono Pharmaceutical Co., Otsuka Pharmaceutical Co., Sanofi-Aventis Pharmaceutical Co., Takeda Pharmaceutical Co.), Kazuhiko Tsuruya (Chugai Pharmaceutical Co., Kyowa Hakko Kirin Co., Otsuka Pharmaceutical Co., Takeda Pharmaceutical Co.)

    Endowed department: Kazuhiko Tsuruya (Baxter).

    Additional information

    K. Masutani and A. Tsuchimoto equally contributed to this study.

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    Masutani, K., Tsuchimoto, A., Yamada, T. et al. Comparison of steroid-pulse therapy and combined with mizoribine in IgA nephropathy: a randomized controlled trial. Clin Exp Nephrol 20, 896–903 (2016). https://doi.org/10.1007/s10157-016-1226-3

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    • DOI: https://doi.org/10.1007/s10157-016-1226-3

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