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Conditions, pathogenesis, and progression of diabetic kidney disease and early decliner in Japan
  1. Yui Yoshida1,2,
  2. Kosuke Kashiwabara1,3,
  3. Yosuke Hirakawa2,
  4. Tetsuhiro Tanaka2,
  5. Shinsuke Noso4,
  6. Hiroshi Ikegami4,
  7. Mitsuru Ohsugi5,
  8. Kohjiro Ueki6,
  9. Tomoya Mita7,
  10. Hirotaka Watada7,
  11. Daisuke Koya8,
  12. Koki Mise9,
  13. Jun Wada9,
  14. Miho Shimizu10,
  15. Takashi Wada11,
  16. Yumi Ito12,
  17. Ichiei Narita12,
  18. Naoki Kashihara13,
  19. Masaomi Nangaku2,
  20. Yutaka Matsuyama1
  1. 1Department of Biostatistics, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
  2. 2Division of Nephrology and Endocrinology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
  3. 3Biostatistics Division, Central Coordinating Unit, Clinical Research Support Center, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan
  4. 4Department of Endocrinology, Metabolism and Diabetes, Faculty of Medicine, Kindai University, Osakasayama, Osaka, Japan
  5. 5Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
  6. 6Diabetes Research Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
  7. 7Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
  8. 8Department of Diabetology & Endocrinology, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan
  9. 9Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan
  10. 10Division of Nephrology, Kanazawa University Hospital, Ishikawa, Japan
  11. 11Department of Nephrology and Laboratory Medicine, Kanazawa University, Ishikawa, Japan
  12. 12Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Science Institute of Nephrology, Niigata, Japan
  13. 13Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan
  1. Correspondence to Dr Masaomi Nangaku; mnangaku-tky{at}


Objective Glomerular filtration rate (GFR) decreases without or prior to the development of albuminuria in many patients with diabetes. Therefore, albuminuria and/or a low GFR in patients with diabetes is referred to as diabetic kidney disease (DKD). A certain proportion of patients with diabetes show a rapid progressive decline in renal function in a unidirectional manner and are termed early decliners. This study aimed to elucidate the prevalence of DKD and early decliners and clarify their risk factors.

Research design and methods This combination cross-sectional and cohort study included 2385 patients with diabetes from 15 hospitals. We defined DKD as a urinary albumin to creatinine ratio (ACR) ≥30 mg/gCr and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². We classified patients into four groups based on the presence or absence of albuminuria and a decrease in eGFR to reveal the risk factors for DKD. We also performed a trajectory analysis and specified the prevalence and risk factors of early decliners with sequential eGFR data of 1955 patients in five facilities.

Results Of our cohort, 52% had DKD. Above all, 12% with a low eGFR but no albuminuria had no traditional risk factors, such as elevated glycated hemoglobin, elevated blood pressure, or diabetic retinopathy in contrast to patients with albuminuria but normal eGFR. Additionally, 14% of our patients were early decliners. Older age, higher basal eGFR, higher ACR, and higher systolic blood pressure were significantly associated with early decliners.

Conclusions The prevalence of DKD in this cohort was larger than ever reported. By testing eGFR yearly and identifying risk factors in the early phase of diabetes, we can identify patients at high risk of developing end-stage renal disease.

  • chronic kidney disease
  • chronic diabetic complications
  • GFR

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  • Contributors YY contributed data interpretation, conducted statistical analysis, and wrote the first draft of the manuscript. KK and YM supervised programming for statistical analysis. YH, TT, MN, SN, HI, MO, KU, TW, TM, DK, KM, JW, MS, HW, YI, IN, and NK collected data, reviewed, and revised the manuscript.

  • Funding This work was supported by Japan Agency for Medical Research and Development under Grant Number JP19ek0210095h001.

  • Competing interests J-DREAMS is supported by Ministry of Health, Labour and Welfare, Japan Agency for Medical Research and Development, Japan Diabetes Society, Nippon Boehringer Ingelheim, Eli Lilly, Novo Nordisk Pharma, and Abbott Japan. KU reports lecture fees from Eli Lilly, Nippon Boehringer Ingelheim, Novo Nordisk, and Abbott Japan; grants and endowments from Eli Lilly, Nippon Boehringer Ingelheim, and Novo Nordisk.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement The inspection and usage of the raw data in this study is restricted according to the ethical approval. All data relevant to the study are included in the article or uploaded as supplementary information.

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