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<p>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.</p>

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Urinary Complement proteome strongly linked to diabetic kidney disease progression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月7日

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  • 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,
  • Jonathan Levinsohn,
  • Kristina O’Neil,
  • Simon T. Dillon,
  • Michael Mauer,
  • Andrzej T. Galecki,
  • Barry I. Freedman,
  • Katalin Susztak,
  • Alessandro Doria,
  • Andrzej S. Krolewski,
  • Monika A. Niewczas

摘要

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.