TY - JOUR
T1 - Urinary Complement proteome strongly linked to diabetic kidney disease progression
AU - Md Dom, Zaipul I.
AU - Moon, Salina
AU - Satake, Eiichiro
AU - Hirohama, Daigoro
AU - Palmer, Nicholette D.
AU - Lampert, Heather
AU - Ficociello, Linda H.
AU - Abedini, Amin
AU - Fernandez, Karen
AU - Liang, Xiujie
AU - Pickett, Sara
AU - Levinsohn, Jonathan
AU - O’Neil, Kristina
AU - Dillon, Simon T.
AU - Mauer, Michael
AU - Galecki, Andrzej T.
AU - Freedman, Barry I.
AU - Susztak, Katalin
AU - Doria, Alessandro
AU - Krolewski, Andrzej S.
AU - Niewczas, Monika A.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105012758624
UR - https://www.scopus.com/pages/publications/105012758624#tab=citedBy
U2 - 10.1038/s41467-025-62101-5
DO - 10.1038/s41467-025-62101-5
M3 - Article
C2 - 40775226
AN - SCOPUS:105012758624
SN - 2041-1723
VL - 16
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 7291
ER -
