Abstract: SA-PO0297
Proteomic Analysis Uncovers Key Molecular Signatures and Pathway Alterations in Diabetic Nephropathy
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
- Ali, Hamad, Kuwait University, Safat, Al Asimah Governorate, Kuwait
- Abu-Farha, Mohamed, Dasman Diabetes Institute, Kuwait City, Al Asimah Governate, Kuwait
- Abubaker, Jehad, Dasman Diabetes Institute, Kuwait City, Al Asimah Governate, Kuwait
- Malik, Mohammad Zubbair, Dasman Diabetes Institute, Kuwait City, Al Asimah Governate, Kuwait
- Bahbahani, Yousif, Dasman Diabetes Institute, Kuwait City, Al Asimah Governate, Kuwait
- Al-Mulla, Fahd, Dasman Diabetes Institute, Kuwait City, Al Asimah Governate, Kuwait
Background
Diabetic nephropathy (DN) is a serious complication of type 2 diabetes and a leading cause of end-stage renal disease. Early detection and intervention are critical for slowing disease progression, yet reliable non-invasive biomarkers and mechanistic insights remain limited.
Methods
This pilot cross-sectional study used label-free proteomics to analyze plasma from DN patients (n=18) and healthy controls (n=14) via DIA and DDA on high-resolution LC-MS/MS. Differential proteins were identified and analyzed using multivariate statistics, clustering, ROC curves, and pathway enrichment.
Results
Partial Least Squares Discriminant Analysis (PLS-DA) and PCA demonstrated clear separation between healthy and DN groups, reflecting distinct proteomic profiles. A total of 577 proteins were differentially expressed, with key proteins such as PCSK1 (p<0.001, fold change=8), KLK6 (p<0.0001, fold change=4.9), and VEGFA (p<0.01, fold change=6.7) showing progressive upregulation in DN, while LYVE1 (p<0.001, fold change=-2.7) and FUCO2 (p<0.01, fold change=-3.5) were consistently downregulated. Functional enrichment analysis revealed dysregulation in inflammatory signaling, metabolic regulation, and renal developmental pathways. Notably, IL-4/IL-13 signaling, transcriptional activity, and cytokine-mediated immune responses were upregulated in DN, while renal remodeling, insulin signaling, and protein metabolism were downregulated.
Conclusion
This study highlights distinct and progressive proteomic changes across healthy and DN states, identifying candidate biomarkers and revealing key disrupted pathways involved in disease progression. These findings provide valuable insights for early detection and therapeutic targeting in diabetic nephropathy.