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Decline in estimated glomerular filtration rate is associated with risk of end-stage renal disease in type 2 diabetes with macroalbuminuria: an observational study from JDNCS

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Abstract

Background

There is increased interest in surrogate endpoints for clinical trials of chronic kidney disease.

Methods

In this nationwide observational study of 456 patients with type 2 diabetes and clinically suspected diabetic nephropathy followed for a median of 4.2 years, we evaluated the association between estimated glomerular filtration rate (eGFR) and albuminuria at baseline or during follow-up and risk of ESRD.

Results

Low eGFR (<60 mL/min/1.73 m2) and macroalbuminuria at enrollment were independently associated with risk of ESRD. In patients with macroalbuminuria, both ≤−50% change and −50 to −30% change in eGFR over 1 and 2 years were predictive of ESRD. The higher cut point (≥50% decline in eGFR) was more strongly predictive but less common. Remission of macroalbuminuria to normo-/microalbuminuria at 1 and 2 years was associated with a lower incidence of ESRD than no remission; however, it was not a determinant for ESRD independently of initial eGFR and initial protein-to-creatinine ratio.

Conclusion

These results suggest that a ≥30% decline in eGFR over 1 or 2 years adds prognostic information about risk for ESRD in patients with type 2 diabetes and macroalbuminuria, supporting the consideration of percentage decline in eGFR as a surrogate endpoint among macroalbuminuric cases in type 2 diabetes. On the other hand, our study suggests that additional analyses on the relationship between remission of macroalbuminuria and risk of ESRD are needed in type 2 diabetes.

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Acknowledgements

The authors greatly acknowledge the help and assistance of many colleagues in all participating institutions with collecting the data for the JDNCS. We also sincerely thank Yuka Kuroshima (Kanazawa Medical University) and Yasuhito Imai, Shizuko Takahara, Yu Minagawa, Haruka Tsuzuku (Kanazawa University) for supporting this study.

Author information

Authors and Affiliations

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

    Miho Shimizu, Kengo Furuichi, Tadashi Toyama, Tomoaki Funamoto, Shinji Kitajima, Akinori Hara, Yukie Kurokawa, Hiroyuki Yamauchi & Takashi Wada

  2. Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Daisuke Ogawa

  3. Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Japan

    Daisuke Koya

  4. Izumigaoka Medical Clinic, Takaoka, Japan

    Kenzo Ikeda

  5. Department of Internal Medicine, Mizuho Hospital, Tsubata, Japan

    Yoshitaka Koshino & Yukie Kurokawa

  6. Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Hideharu Abe

  7. Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Kiyoshi Mori

  8. Department of Nephrology and Hypertension, Fukushima Medical University School of Medicine, Fukushima, Japan

    Masaaki Nakayama

  9. Department of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan

    Yoshio Konishi

  10. First Department of Internal Medicine, Nara Medical University, Kashihara, Japan

    Ken-ichi Samejima & Masaru Matsui

  11. Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan

    Tomohito Gohda

  12. Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan

    Kei Fukami

  13. Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan

    Daisuke Nagata

  14. Second Department of Internal Medicine, University of Toyama, Toyama, Japan

    Hidenori Yamazaki

  15. Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan

    Yukio Yuzawa

  16. Health Administration Center, Niigata University, Niigata, Japan

    Yoshiki Suzuki

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

    Shouichi Fujimoto

  18. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Shoichi Maruyama & Sawako Kato

  19. Naito Medical Clinic, Toyama, Japan

    Takero Naito

  20. Innovative Clinical Research Center, Kanazawa University Hospital, Kanazawa, Japan

    Kenichi Yoshimura

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

    Hitoshi Yokoyama

  22. Department of Nephrology and Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan

    Takashi Wada

Authors
  1. Miho Shimizu
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  2. Kengo Furuichi
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  3. Tadashi Toyama
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  4. Tomoaki Funamoto
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  5. Shinji Kitajima
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  6. Akinori Hara
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  7. Daisuke Ogawa
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  8. Daisuke Koya
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  9. Kenzo Ikeda
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  10. Yoshitaka Koshino
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  11. Yukie Kurokawa
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  12. Hideharu Abe
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  13. Kiyoshi Mori
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  14. Masaaki Nakayama
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  15. Yoshio Konishi
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  16. Ken-ichi Samejima
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  17. Masaru Matsui
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  18. Hiroyuki Yamauchi
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  19. Tomohito Gohda
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  20. Kei Fukami
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  21. Daisuke Nagata
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  22. Hidenori Yamazaki
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  23. Yukio Yuzawa
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  24. Yoshiki Suzuki
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  25. Shouichi Fujimoto
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  26. Shoichi Maruyama
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  27. Sawako Kato
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  28. Takero Naito
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  29. Kenichi Yoshimura
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  30. Hitoshi Yokoyama
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  31. Takashi Wada
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Consortia

Research Group of Diabetic Nephropathy, the Ministry of Health, Labour, and Welfare of Japan and Japan Agency for Medical Research and Development

Corresponding author

Correspondence to Takashi Wada.

Ethics declarations

Conflict of interest

The authors have declared that no conflict of interest exists.

Human and animal rights

Informed consent was obtained from all participants included in this study. The study protocol was approved by the ethical review board of the JSN (No. 5) and all participating institutions [Kanazawa University (No. 767)].

Funding source

This study was supported in part by a Grant-in-Aid for Diabetic Nephropathy Research from the Ministry of Health, Labour and Welfare of Japan, a Grant-in-Aid for Diabetic Nephropathy and Nephrosclerosis Research from the Ministry of Health, Labour and Welfare of Japan, and a Grant-in-Aid for Practical Research Project for Renal Diseases from the Japan Agency for Medical Research and Development. This study was also supported in part by JSPS KAKENHI Grant no. 17K08979.

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Shimizu, M., Furuichi, K., Toyama, T. et al. Decline in estimated glomerular filtration rate is associated with risk of end-stage renal disease in type 2 diabetes with macroalbuminuria: an observational study from JDNCS. Clin Exp Nephrol 22, 377–387 (2018). https://doi.org/10.1007/s10157-017-1467-9

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  • DOI: https://doi.org/10.1007/s10157-017-1467-9

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