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Urinary Complement proteome strongly linked to diabetic kidney disease progression

Author

Listed:
  • Zaipul I. Md Dom

    (Joslin Diabetes Center
    Harvard Medical School)

  • Salina Moon

    (Joslin Diabetes Center)

  • Eiichiro Satake

    (Joslin Diabetes Center
    Harvard Medical School)

  • Daigoro Hirohama

    (Perelman School of Medicine
    Perelman School of Medicine
    Perelman School of Medicine)

  • Nicholette D. Palmer

    (Wake Forest University School of Medicine)

  • Heather Lampert

    (Joslin Diabetes Center
    Harvard Medical School
    One Medical)

  • Linda H. Ficociello

    (Joslin Diabetes Center
    Harvard Medical School
    Global Medical Office)

  • Amin Abedini

    (Perelman School of Medicine
    Perelman School of Medicine
    Perelman School of Medicine
    University of Maryland Medical System)

  • Karen Fernandez

    (Joslin Diabetes Center
    Harvard College
    Stanford University)

  • Xiujie Liang

    (Perelman School of Medicine
    Perelman School of Medicine
    Perelman School of Medicine)

  • Sara Pickett

    (Joslin Diabetes Center
    The University of Texas Health Science Center)

  • Jonathan Levinsohn

    (Perelman School of Medicine
    Perelman School of Medicine
    Perelman School of Medicine)

  • Kristina O’Neil

    (Joslin Diabetes Center)

  • Simon T. Dillon

    (Harvard Medical School
    Beth Israel Deaconess Medical Center)

  • Michael Mauer

    (University of Minnesota)

  • Andrzej T. Galecki

    (University of Michigan
    University of Michigan)

  • Barry I. Freedman

    (Wake Forest University School of Medicine)

  • Katalin Susztak

    (Perelman School of Medicine
    Perelman School of Medicine
    Perelman School of Medicine)

  • Alessandro Doria

    (Joslin Diabetes Center
    Harvard Medical School)

  • Andrzej S. Krolewski

    (Joslin Diabetes Center
    Harvard Medical School)

  • Monika A. Niewczas

    (Joslin Diabetes Center
    Harvard Medical School)

Abstract

Diabetic kidney disease (DKD) progression is not well understood. Using high-throughput proteomics, biostatistical, pathway and machine learning tools, we examine the urinary Complement proteome in two prospective cohorts with type 1 or 2 diabetes and advanced DKD followed for 1,804 person-years. The top 5% urinary proteins representing multiple components of the Complement system (C2, C5a, CL-K1, C6, CFH and C7) are robustly associated with 10-year kidney failure risk, independent of clinical covariates. We confirm the top proteins in three early-to-moderate DKD cohorts (2,982 person-years). Associations are especially pronounced in advanced kidney disease stages, similar between the two diabetes types and far stronger for urinary than circulating proteins. We also observe increased Complement protein and single cell/spatial RNA expressions in diabetic kidney tissue. Here, our study shows Complement engagement in DKD progression and lays the groundwork for developing biomarker-guided treatments.

Suggested Citation

  • Zaipul I. Md Dom & Salina Moon & Eiichiro Satake & Daigoro Hirohama & Nicholette D. Palmer & Heather Lampert & Linda H. Ficociello & Amin Abedini & Karen Fernandez & Xiujie Liang & Sara Pickett & Jona, 2025. "Urinary Complement proteome strongly linked to diabetic kidney disease progression," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62101-5
    DOI: 10.1038/s41467-025-62101-5
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