Abstract: SA-PO0292
Shared and Unique Urinary Biomarkers in Diabetic Nephropathy vs. Lupus Nephritis Based on 7000-Plex Urinary Proteomics
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 2
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Maruvada, Vinaika, University of Houston, Houston, Texas, United States
- Ma, Yewei, University of Houston, Houston, Texas, United States
- Vanarsa, Kamala, University of Houston, Houston, Texas, United States
- Saxena, Ramesh, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Mohan, Chandra, University of Houston, Houston, Texas, United States
Background
Diabetic nephropathy (DKD) and lupus nephritis (LN) are distinct glomerular diseases with different underlying mechanisms but overlapping clinical and laboratory features. We applied a high-dimensional urinary proteomic screen to identify urinary molecular signatures that are shared or unique, comparing DKD to LN.
Methods
Urine samples from individuals with DKD (n=13), LN (n=34) and healthy subjects (N=12) were analyzed using a 7000-plex aptamer-based proteomic platform. Protein concentrations were creatinine-normalized. Volcano plots were generated to visualize upregulated and downregulated proteins based on fold change and statistical significance. Receiver operating characteristic (ROC) analysis was used to assess discriminatory performance. Functional enrichment analysis was conducted to characterize biological pathways associated with differentially expressed proteins.
Results
1039 proteins were shared between DKD and LN (810 increased, 229 decreased) compared to healthy urine, A total 4217 proteins elevated only in LN were enriched for DNA-binding transcription factor binding and the Wnt signaling pathway, while 29 proteins elevated only in DKD were enriched for complement binding and negative regulation of complement activation. Of 4,889 urinary proteins were differentially expressed between LN and DKD (p<0.1), with 4,815 upregulated in LN urine and 74 upregulated in DKD. Of these proteins, the 10 proteins most diagnostic of LN exhibited ROC AUC>0.87 while the 10 proteins most diagnostic of DKD exhibited ROC AUC>0.75, as shown in the Volcano plot.
Conclusion
Urinary proteomic profiling using a 7000-plex platform successfully identified distinct biomarker signatures that differentiate LN and DKD from healthy controls, and from each other. Functional enrichment analysis revealed that proteins elevated in LN ONLY were associated with immune activation pathways, including GTPase activity, Wnt signaling, and transcription factor binding. In contrast, proteins enriched in DKD ONLY were linked to complement activation, complement binding and opsonin binding, indicating involvement of innate immune mechanisms and fibrotic processes.