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A nationwide survey of MYH9-related disease in Japan

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Abstract

Background

MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, Döhle body-like granulocyte inclusions, and nephropathy, which may progress to end-stage kidney disease (ESKD). However, information on the effects of renin-angiotensin system (RAS) inhibitors on kidney survival is currently lacking and the outcomes of kidney replacement therapy (KRT) in MYH9-RD are largely unknown.

Methods

We conducted a cross-sectional nationwide survey by sending questionnaires to 145 institutions in Japan and analyzed data for 49 patients.

Results

The median patient age was 27 years. Genetic analysis was performed in 37 (76%) patients. Twenty-four patients (65%) had MYH9 variants affecting the motor domain of non-muscle myosin heavy chain-IIA, and these patients had poorer kidney survival than those with variants affecting the tail domain (P = 0.02). There was no significant difference in kidney survival between patients treated with and without RAS inhibitors. Hemodialysis and peritoneal dialysis were performed in 16 and 7 patients, respectively. There were no major bleeding complications during the perioperative period or during follow-up, except for one patient. Most of the 11 patients who underwent kidney transplantation required perioperative red cell concentrate transfusions, but there was no graft loss during the median posttransplant observational period of 2.0 (interquartile range, 1.3–6.8) years.

Conclusion

Our study demonstrated no beneficial effect of RAS inhibitors on kidney function in patients with MYH9-RD, indicating the need for further studies with more patients. All modalities of KRT are feasible options for MYH9-RD patients who progress to ESKD, with adequate attention to bleeding complications.

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Abbreviations

MYH9-RD:

MYH9-Related disease

NMMHC-IIA:

Non-muscle myosin heavy chain-IIA

ESKD:

End-stage kidney disease

MD:

Motor domain

TD:

Tail domain

RAS:

Renin-angiotensin system

KRT:

Kidney replacement therapy

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Acknowledgements

We thank Drs. Norikazu Shimizu (Department of pediatrics, Toho University Medical Center Ohashi Hospital), Yuko Hamasaki and Junya Hashimoto (Department of Nephrology, Faculty of Medicine, Toho University), Yoji Sasahara (Department of Pediatrics, Tohoku University), Makoto Ogura (Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine), Mitsutaka Shiota (Department of Pediatrics, Kitano Hospital), Akira Yoshida (Department of Pediatrics, Japanese Red Cross Wakayama Medical Center), Shoichiro Kanda (Department of Pediatrics, Tokyo University), Sachiyo Kamimura (Division of Pediatrics, Department of Reproductive and Developmental Medicine, University of Miyazaki), Takashi Matsumoto (Division of Nephrology, Department of Medicine, Kurume University School of Medicine), Ohno Toshiyuki (Department of Pediatrics Komaki City Hospital), Hiroshi Kogawa (Ina Hospital), Hideki Matsushima (Division of Nephrology, Seirei Mikatahara General Hospital), Satoshi Sasaki (Department of Pediatrics, Hokkaido University), Yoko Ohwada (Department of Pediatrics, Dokkyo Medical University), Atsuyuki Morishima (Department of Nephrology and Hypertension, Sumitomo Hospital), Yasufumi Otsuka (Department of Pediatrics, Saga University), Kei Nishiyama (Department of Pediatrics, Kyushu University), Takao Suzuki (Division of Nephrology, Kobe City Medical Center General Hospital), Masashi Nishida (Department of Pediatrics, Kyoto Prefectural University of Medicine), Yoko Kato (Department of Pediatrics, Jikei University School of Medicine), Yukiko Kitahata (Kikyokai Orion Clinic), Yasuo Kimura (Shinkashiwa Clinic), Hiroshi Saito and Yuno Takahashi (Department of Pediatrics, Nihon University), Mikihiko Fujishima (Sanai Hospital Yahaba Clinic), Michihiro Ohya (Taihei-kai Omori Clinic), Hiroshi Sato (Division of Nephrology Endocrinology and Vascular Medicine Tohoku University Graduate School of Medicine), Hirokazu Kanegane (Department of Pediatrics, Toyama Medical and Pharmaceutical University), Tomoyoshi Kimura (Japan Community Health care Organization Sendai Hospital Kidney Center), Kazuo Dan (Department of Hematology, Nihon Medical School), Takeshi Matsuyama (Department of Pediatrics, Fussa Hospital), Akio Furuse (Department of Pediatrics Japanese Red Cross Kumamoto Hospital) and Yasuo Horikoshi (Shizuoka Children's Hospital) for their contributions to the study. We thank Susan Furness, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript

Funding

This work was supported by “Research on Rare and Intractable Diseases, Health and Labor Sciences Research Grants” from the Ministry of Health, Labour and Welfare (Grant No. 20FC1028), Japan.

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Authors and Affiliations

  1. Department of Pediatric Nephrology, Tokyo Women’s Medical University, 8-1, Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan

    Yoko Shirai, Kenichiro Miura & Motoshi Hattori

  2. Department of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Riku Hamada

  3. Department of Pediatrics, Kitasato University School of Medicine, Kanagawa, Japan

    Kenji Ishikura

  4. School of Health Science, Gifu University of Medical Science, Seki, Japan

    Shinji Kunishima

Authors
  1. Yoko Shirai
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  2. Kenichiro Miura
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  3. Riku Hamada
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  4. Kenji Ishikura
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  5. Shinji Kunishima
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  6. Motoshi Hattori
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Contributions

Designed the study; contributed to pathological diagnosis; carried out experiments; performed statistical analysis. made the figures; drafted the paper; revised the paper; all authors approved the final version of the manuscript.

Corresponding author

Correspondence to Motoshi Hattori.

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The authors confirm that they have nothing to declare.

Ethical approval

The study was approved by the Institutional Review Board at Tokyo Women’s Medical University (approval number 4793-R).

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We applied opt-out method and the requirement for written informed consent was waived due to the retrospective nature of the study.

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Shirai, Y., Miura, K., Hamada, R. et al. A nationwide survey of MYH9-related disease in Japan. Clin Exp Nephrol 28, 40–49 (2024). https://doi.org/10.1007/s10157-023-02404-3

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  • DOI: https://doi.org/10.1007/s10157-023-02404-3

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