Abstract: TH-PO829
RNA Sequencing Analysis of Skeletal Muscle in Moderate to Advanced CKD
Session Information
- Health Maintenance, Nutrition, Metabolism
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance‚ Nutrition‚ and Metabolism
- 1400 Health Maintenance‚ Nutrition‚ and Metabolism
Authors
- Gamboa, Jorge, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Jaramillo Morales, Javier, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Ahmadi, Armin, University of California Davis, Davis, California, United States
- Begue, Gwenaelle, California State University Sacramento, Sacramento, California, United States
- Kim, Tae Youn, University of California Davis, Davis, California, United States
- Smith, Lucas R., University of California Davis, Davis, California, United States
- Roshanravan, Baback, University of California Davis, Davis, California, United States
- Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Patients with moderate to advanced kidney disease suffer a higher prevalence of sarcopenia and frailty. We hypothesized that the RNA expression profiling in skeletal muscle from patients with CKD will provide mechanistic insight into these abnormalities.
Methods
In a cross-sectional study, we performed RNA sequencing analysis and pathway analysis in skeletal muscle biopsies from three groups (matched for gender, body mass index, and history of diabetes); controls (n=13), patients with CKD 3-5 not yet on hemodialysis (n=13), and patients on maintenance hemodialysis (MHD, n=10). Total RNA was extracted and used to construct libraries for small and total RNA sequencing using Illumina NovaSeq 6000 system. Differentially expressed genes (DEGs) were identified with a false discovery rate (FDR) <0.05 and fold change > 2. Gene Set Enrichment Analysis (GSEA) was performed using WebGestaltR v0.4.4 to analyze RNA sequencing results and to identify the overrepresentation of cellular components and biological pathways.
Results
We identified 256 DEGs between controls and MHD groups, and 261 DEGs between CKD 3-5 and MHD groups (Figure 1). Notably, there were only 3 DEGs between controls and patients with CKD 3-5. GSEA showed that there is an enrichment of cellular components related to the extracellular matrix [18 DEGs (with enrichment ratio (ER) of 8.1, FDR< 1x10-7) in control vs MHD; and 24 DEGs (ER 10.1, FDR< 1x10-7) in CKD 3-5 vs. MHD] and collagen-containing extracellular matrix [14 DEGs (ER 8.5, FDR= 4x10-7) in control vs MHD; and 22 DEGs (ER 12.6, FDR< 1x10-7) in CKD 3-5 vs. MHD].
Conclusion
Our results suggest that there is altered remodeling of the extracellular matrix in moderate to advanced CKD. This may be associated with the progressive loss of muscle mass in CKD, which is replaced by adipose and/or fibrotic tissue through the differentiation of fibroadipogenic progenitors. Further studies should identify specific molecular and cellular pathways to prevent sarcopenia and frailty in CKD.
Funding
- NIDDK Support