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Identification of Differentially Expressed Genes and Pathways in Non-Diabetic CKD and Diabetic CKD by Integrated
Clara Barrios1,2,3, Marta Riera2,3, Eva Rodríguez1,2,3
1Department of Nephrology, Hospital del Mar, 08003 Barcelona, Spain.
International Journal of Molecular Sciences
|August 14, 2025
Summary
Diabetic chronic kidney disease (CKD_T2D) shows distinct molecular changes compared to non-diabetic CKD. Understanding these differences in gene expression is key for developing targeted treatments for kidney disease subtypes.
Area of Science:
- Nephrology
- Genomics
- Molecular Biology
Background:
- Chronic kidney disease (CKD) is a complex condition with diverse causes, including type 2 diabetes (T2D), hypertension, and autoimmune diseases.
- While diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share clinical signs, their underlying molecular mechanisms and distinctions remain unclear.
- Identifying specific molecular signatures is crucial for differentiating between diabetic and non-diabetic forms of CKD.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) and enriched biological pathways in CKD_T2D versus CKD_nonT2D cohorts.
- To compare molecular profiles of CKD_T2D with autoimmune (CKD_nonT2D_AI) and hypertensive (CKD_nonT2D_HT) subtypes.
- To elucidate the transcriptomic landscape differentiating diabetic and non-diabetic kidney disease.
Main Methods:
- Integrative transcriptomic analysis of publicly available gene expression datasets from human kidney tissues (glomerular and tubulointerstitial).
- Utilized data from Gene Expression Omnibus (GEO) and ArrayExpress.
- Performed differential gene expression analysis and Gene Set Enrichment Analysis (GSEA).
Main Results:
- Significant overlap in DEGs between CKD_T2D and CKD_nonT2D, with CKD_T2D showing more pronounced gene expression alterations.
- Hypertensive CKD exhibited greater transcriptomic similarity to CKD_T2D than autoimmune CKD.
- Key DEGs related to fibrosis, inflammation, and complement activation (e.g., Tgfb1, Timp1, Cxcl6, C1qa/B) were altered in diabetic samples.
- GSEA indicated immune pathway enrichment in glomeruli and metabolic pathway enrichment in tubulointerstitium for CKD_T2D.
Conclusions:
- The transcriptomic profile of CKD_T2D demonstrates more significant immune and metabolic dysregulation compared to non-diabetic CKD.
- Distinct molecular mechanisms underlie diabetic versus non-diabetic forms of CKD.
- Findings support the development of tailored therapeutic strategies for specific CKD subtypes.
