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Association of urinary C-megalin with albuminuria and renal function in diabetes: a cross-sectional study (Diabetes Distress and Care Registry at Tenri [DDCRT 21])

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Abstract

Background

A urinary biomarker sensitive to glomerular functional or structural changes in diabetic kidney disease is required. This study examined whether urinary C-megalin reflects renal function or albuminuria in diabetes.

Methods

This was a cross-sectional study involving 1576 patients with type 1 or 2 diabetes. The exposure variables were estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), and the outcomes were urinary C-megalin excretion and concentration. Two-part models were used to examine the associations between eGFR and UACR with urinary C-megalin excretion or concentration.

Results

The UACR was linearly associated with urinary C-megalin excretion (per 100 mg/gCr of UACR; 11.8 fM/gCr [95% CI 8.9–14.7]). There was no association between decreasing eGFR and increasing urinary C-megalin excretion. The UACR was also linearly associated with the urinary C-megalin concentration (per 100 mg/gCr of UACR, 7.7 fM/L [95% CI 5.8–9.6]). At eGFR values > 60 mL/min/1.73 m2, the eGFR and urinary C-megalin concentration were inversely linearly related (per 10 mL/min/1.73 m2 decline, 7.7 fM/L [95% CI 0.2–15.1]).

Conclusion

Urinary C-megalin excretion as well as concentration levels are potentially useful biomarkers to detect early changes in diabetic kidney disease.

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The statistical codes generated during the current study are not publicly available due to subsequent use for ongoing research project but are available from the corresponding author on reasonable request.

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Acknowledgements

We would especially like to thank Yukari Moritsuji, Yuki Fujita, Noriko Nakamura, and Yoko Sakamoto (Department of Endocrinology, Tenri Hospital) for clerical support. Members of the Diabetes Distress and Care Registry at Tenri Study Group: Hitoshi Ishii, and Hirohito Kuwata (Department of Diabetology, Nara Medical University); Satoru Tsujii, Shintaro Okamura, Yasuaki Hayashino, and Masako Kitatani (Department of Endocrinology, Tenri Hospital); Satoshi Matsunaga (Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine); Yaeko Kondo and Naotaka Fujita (Department of Diabetes and Clinical Nutrition, Kyoto University); Rei Ueda (Second Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus); Rie Kurokawa (Osaka Medical Center and Research Institute for Maternal and Child Health); Masami Tanaka (Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine); Tsuyoshi Mashitani (Mashitani Clinic); and Miyuki Furuya (Furuya Clinic). Denka Seiken Co. Ltd. measured urinary C-megalin. This study was partially supported by the Manpei Suzuki Diabetes Foundation and the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant no. 25460641).

Funding

Denka Seiken Co. Ltd. measured urinary C-megalin; however, the company had no role in the study design, analysis and interpretation of data, writing of the manuscript, or the decision to submit the manuscript for publication. This study was partially supported by the Manpei Suzuki Diabetes Foundation and the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant no. 25460641); however, they had no role in the study design, data collection, analysis and interpretation of data, writing of the manuscript, or the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan

    Noriaki Kurita

  2. Department of Innovative Research and Education for Clinicians and Trainees (DiRECT), Fukushima Medical University Hospital, Fukushima, Japan

    Noriaki Kurita

  3. Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), Fukushima Medical University, Fukushima, Japan

    Noriaki Kurita

  4. Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto, Japan

    Noriaki Kurita

  5. Department of Clinical Laboratory, Tenri Hospital, Nara, Tenri, Japan

    Maki Kinoshita

  6. Department of Endocrinology, Tenri Hospital, Nara, Tenri, Japan

    Maki Fujimura, Kentaro Kurosawa, Yui Sakuramachi, Kiyoko Takano, Shintaro Okamura, Mako Kitatani, Satoru Tsujii & Yasuaki Hayashino

  7. Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor, MI, USA

    Edward C. Norton

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Consortia

Diabetes Distress and Care Registry at Tenri Study Group

  • Hitoshi Ishii
  • , Hirohito Kuwata
  • , Satoru Tsujii
  • , Shintaro Okamura
  • , Yasuaki Hayashino
  • , Masako Kitatani
  • , Satoshi Matsunaga
  • , Yaeko Kondo
  • , Naotaka Fujita
  • , Rei Ueda
  • , Rie Kurokawa
  • , Masami Tanaka
  • , Tsuyoshi Mashitani
  •  & Miyuki Furuya

Contributions

Conceptualization: NK; methodology: NK; investigation: MK, MF, KK, YS, KT, SO, MK, ST, YH; formal analysis: NK; writing—original draft preparation: NK; writing—review and editing: ECN, YH; funding acquisition: YH; resources: NK, MK, MF, KK, YS, KT, SO, MK, ST, YH; supervision: ECN, YH.

Corresponding author

Correspondence to Noriaki Kurita.

Ethics declarations

Conflict of interest

Drs. M. Kinoshita, MF, KK, YS, KT, SO, M. Kitatani, ST, NEC, and YH declare that they have no conflict of interest. Dr. Kurita has served as a senior scientist at the Institute for Health Outcomes and Process Evaluation research (iHope International, a non-profit organization), but he was not compensated for his contribution to this study. Denka Seiken Co. Ltd. contracted this study to iHope International.

Ethics approval

This study was approved by the institutional review board of Fukushima Medical University (approval no. 2966). The study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

Informed consent was obtained from all individual participants prior to their enrolment in the study.

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Members of the Diabetes Distress and Care Registry at Tenri Study Group are listed in the Acknowledgements.

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Kurita, N., Kinoshita, M., Fujimura, M. et al. Association of urinary C-megalin with albuminuria and renal function in diabetes: a cross-sectional study (Diabetes Distress and Care Registry at Tenri [DDCRT 21]). J Nephrol 35, 201–210 (2022). https://doi.org/10.1007/s40620-021-00995-2

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  • DOI: https://doi.org/10.1007/s40620-021-00995-2

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