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Effects of LDL apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia

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Abstract

Background

Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria.

Methods

This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6–12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6 months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24 months after therapy initiation.

Results

LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6 months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls.

Conclusion

Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia.

Trial registration

Trial registration number: jRCTs042180076.

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Data sharing statement

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

We wish to thank the investigators of the LICENSE study.

Funding

The LICENSE study was funded by Kaneka Inc. The LICENSE study was sponsored by NPO Heart and Fukushima Medical University. The funders had no role in in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Author information

Author notes

  1. Takashi Wada and Akinori Hara contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology and Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, 13-1 Takara-machi, KanazawaKanazawa, 920-8641, Japan

    Takashi Wada & Norihiko Sakai

  2. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan

    Takashi Wada, Akinori Hara & Norihiko Sakai

  3. Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan

    Eri Muso, Hiroyuki Suzuki & Tatsuo Tsukamoto

  4. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    Shoichi Maruyama & Sawako Kato

  5. Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Japan

    Kengo Furuichi & Hitoshi Yokoyama

  6. Innovative Clinical Research Center (iCREK), Kanazawa University Hospital, Kanazawa, Japan

    Kenichi Yoshimura & Tadashi Toyama

  7. Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Mariko Miyazaki

  8. Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Matsudo, Japan

    Eiichi Sato

  9. Divisions of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

    Masanori Abe

  10. Division of Nephrology and Hypertension, Department of Internal Medicine, St Marianna University School of Medicine, Kanagawa, Japan

    Yugo Shibagaki

  11. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Ichiei Narita, Shin Goto & Yuichi Sakamaki

  12. Department of Nephrology, Shizuoka General Hospital, Shizuoka, Japan

    Noriko Mori & Satoshi Tanaka

  13. Department of Nephrology, Fujita Health University School of Medicine, Aichi, Japan

    Yukio Yuzawa & Midori Hasegawa

  14. Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Takeshi Matsubara

  15. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Jun Wada & Katsuyuki Tanabe

  16. Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

    Kosuke Masutani & Yasuhiro Abe

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

    Kazuhiko Tsuruya

  18. Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Shouichi Fujimoto & Shuji Iwatsubo

  19. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

    Akihiro Tsuda

  20. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

    Hitoshi Suzuki

  21. Division of Nephrology, Department of General Medicine, University of Fukui School of Medical Sciences, Fukui, Japan

    Kenji Kasuno

  22. Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kochi, Japan

    Yoshio Terada

  23. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan

    Takeshi Nakata

  24. Department of Nephrology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan

    Noriaki Iino

  25. Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Tadashi Sofue

  26. Department of Nephrology, Kyoto Katsura Hospital, Kyoto, Japan

    Hitomi Miyata

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

    Toshiaki Nakano

  28. Department of Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, Kamakura, Japan

    Takayasu Ohtake & Shuzo Kobayashi

Authors
  1. Takashi Wada
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  2. Akinori Hara
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  3. Eri Muso
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  4. Shoichi Maruyama
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  5. Sawako Kato
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  6. Kengo Furuichi
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  42. Shuzo Kobayashi
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Consortia

LICENSE study Group

Corresponding author

Correspondence to Takashi Wada.

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Conflict of interest

EM reports honoraria for scientific lectures from Kaneka Inc. SK reports consultancy of Kaneka Inc. for clinical trials. The remaining authors report no conflicts of interest.

Research involving human participants

These studies were conducted in accordance with the ethical principles of the Helsinki Declaration, the Pharmaceutical Affairs Law, and good clinical practice, and the study was approved by the Institutional Review Board of each participating study center. All study patients provided informed consent prior to the start of treatment. The study was registered at jRCT under the identifier number jRCTs042180076.

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Wada, T., Hara, A., Muso, E. et al. Effects of LDL apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia. Clin Exp Nephrol 25, 1–8 (2021). https://doi.org/10.1007/s10157-020-01959-9

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  • DOI: https://doi.org/10.1007/s10157-020-01959-9

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