Kidney Week

Abstract: FR-OR29

RNA Sequencing Analysis of Skeletal Muscle in Moderate to Advanced CKD

Session Information

• Exercise and Kidney Health: From Bench to Smartphone
  October 25, 2024 | Location: Room 4, Convention Center
  Abstract Time: 04:40 PM - 04:50 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1500 Health Maintenance, Nutrition, and Metabolism

Authors

• Demirci, Mert, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Mert Demirci, MD

• Peng, Dungeng, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Dungeng Peng, DrPH

• Norman, Jennifer E., University of California Davis, Davis, California, United States

Jennifer E. Norman, MA, PhD

• Begue, Gwenaelle, California State University Sacramento, Sacramento, California, United States

Gwenaelle Begue, PhD

• Roshanravan, Baback, University of California Davis, Davis, California, United States

Baback Roshanravan, MD, MS, MPH, FASN

• Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Talat Alp Ikizler, MD, FASN

• Gamboa, Jorge, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Jorge Gamboa, MD, PhD

Background

Patients with moderate to advanced kidney disease suffer a higher prevalence of sarcopenia and frailty. MicroRNAs (miRNAs) play an important role in muscle cell proliferation and differentiation, as well as muscle hypertrophy and atrophy. We hypothesized that the miRNA expression profiling in skeletal muscle from patients with CKD is altered, and it would provide mechanistic insight into sarcopenia and frailty.

Methods

In a cross-sectional study, we performed small RNA sequencing 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 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.

Results

We identified 57 DEGs between controls and MHD groups, 43 DEGs between CKD 3-5 and MHD groups, and 16 DEGs between controls and patients with CKD 3-5 (Figure 1). The DEGs were found to be involved in cachexia (mir-450), muscle atrophy (miR-23), and muscle wasting/protein synthesis (miR-424). In patients with CKD, we observed an upregulation of miR-542, which has been associated with promoting mitochondrial dysfunction and enhancing SMAD 2/3 phosphorylation, a downstream effect of myostatin.

Conclusion

Our results suggest that miRNA expression profiling is altered in moderate to advanced CKD. The differential expressed miRNAs may explain the loss of muscle mass in CKD. Thus, miRNAs may enhance atrophy and inhibit muscle growth pathways. Further studies should identify the specific miRNA targets to prevent sarcopenia and frailty in CKD.

Funding

• NIDDK Support