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Urinary Complement proteome strongly linked to diabetic kidney disease progression
Zaipul I Md Dom1,2, Salina Moon1, Eiichiro Satake1,2
1Research Division, Joslin Diabetes Center, Boston, MA, USA.
Nature Communications
|August 7, 2025
Summary
Urinary Complement system proteins are linked to diabetic kidney disease (DKD) progression and kidney failure risk. This finding could lead to new biomarkers for DKD treatments.
Area of Science:
- Nephrology
- Immunology
- Proteomics
Background:
- Diabetic kidney disease (DKD) progression remains poorly understood.
- Identifying reliable biomarkers for DKD progression is crucial for effective management.
Purpose of the Study:
- To investigate the role of the urinary Complement system proteome in DKD progression.
- To identify potential urinary biomarkers for predicting kidney failure risk in diabetic patients.
Main Methods:
- Utilized high-throughput proteomics, biostatistics, pathway analysis, and machine learning.
- Analyzed urinary proteomes from two prospective cohorts of type 1 and type 2 diabetes with advanced DKD.
- Validated findings in three additional early-to-moderate DKD cohorts.
Main Results:
- Top urinary Complement proteins (C2, C5a, CL-K1, C6, CFH, C7) strongly associated with 10-year kidney failure risk, independent of clinical factors.
- Associations were more pronounced in advanced DKD stages and stronger for urinary versus circulating proteins.
- Increased Complement protein and RNA expression observed in diabetic kidney tissue.
Conclusions:
- The Complement system is actively engaged in DKD progression.
- Urinary Complement proteins show potential as robust biomarkers for DKD progression and kidney failure.
- Findings pave the way for developing novel biomarker-guided therapeutic strategies for DKD.
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