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Urinary C-megalin as a novel biomarker of progression to microalbuminuria: A cohort study based on the diabetes Distress and Care Registry at Tenri (DDCRT 22)

  • Author Footnotes
    1 Hiroki Nishiwaki and Kakuya Niihata contributed equally to this work.
    Hiroki Nishiwaki
    Correspondence
    Corresponding author at: Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Kanagawa 227-8501, Japan.
    Footnotes
    1 Hiroki Nishiwaki and Kakuya Niihata contributed equally to this work.
    Affiliations
    Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan

    Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Kanagawa 227-8501, Japan

    Showa University Research Administration Center (SURAC), Showa University, Shinagawa, Tokyo 142-8555, Japan
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  • Author Footnotes
    1 Hiroki Nishiwaki and Kakuya Niihata contributed equally to this work.
    Kakuya Niihata
    Footnotes
    1 Hiroki Nishiwaki and Kakuya Niihata contributed equally to this work.
    Affiliations
    Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan
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  • Maki Kinoshita
    Affiliations
    Department of Clinical Laboratory, Tenri Hospital, Nara, Tenri 632-8552, Japan
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  • Maki Fujimura
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Kentaro Kurosawa
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Yui Sakuramachi
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Kiyoko Takano
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Satoshi Matsunaga
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Shintaro Okamura
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Mako Kitatani
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Satoru Tsujii
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Yasuaki Hayashino
    Affiliations
    Department of Endocrinology, Tenri Hospital, Tenri, Nara 632-8552, Japan
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  • Noriaki Kurita
    Affiliations
    Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan

    Department of Innovative Research and Education for Clinicians and Trainees (DiRECT), Fukushima Medical University Hospital, Fukushima, Fukushima 960-1295, Japan

    Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), Fukushima Medical University, Fukushima 960-1295, Japan

    Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto 604-8006, Japan
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  • Diabetes Distress Care Registry at Tenri Study Group
    Author Footnotes
    2 Members of the Diabetes Distress and Care Registry at Tenri Study Group are listed in the Appendix.
  • Author Footnotes
    1 Hiroki Nishiwaki and Kakuya Niihata contributed equally to this work.
    2 Members of the Diabetes Distress and Care Registry at Tenri Study Group are listed in the Appendix.

      Abstract

      Aims

      Megalin is a multiligand receptor expressed in proximal tubular cells that reabsorbs filtered albumin and correlates cross-sectionally with albuminuria. We investigated the association between urinary C-megalin levels and the incidence of microalbuminuria in patients with diabetes mellitus.

      Methods

      This cohort study included 752 patients with type 1 or 2 diabetes mellitus and a urinary albumin-to-creatinine (Cr) ratio (UACR) within the normoalbuminuric range (<30 mg/g Cr). The association between urinary C-megalin and persistent microalbuminuria, accounting for the possible interaction between baseline UACR and urinary C-megalin, was estimated using a Cox proportional hazards model.

      Results

      During a median follow-up period of 1.99 years, 179 cases of persistent microalbuminuria were observed. The association between urinary C-megalin and persistent microalbuminuria was UACR-dependent (P for interaction < 0.001), with the highest association observed in the absence of UACR (per 100 fM/gCr of urinary C-megalin: adjusted hazard ratio, 1.13; 95% CI 1.07–1.19), gradually decreasing as UACR increased to 30 mg/g Cr. UACR dependence was confirmed by sensitivity analyses according to low-normal (<10 mg/gCr) or high-normal (10–<30 mg/gCr) UACR.

      Conclusions

      Urinary C-megalin is associated with progression to microalbuminuria, especially in those with low-normal UACR levels, and its usefulness to identify high risk patients requires further investigation.

      Keywords

      Abbreviations:

      UACR (urinary albumin-to-creatinine ratio), HR (hazard ratio), CI (confidence interval)
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