Kidney Week

Abstract: FR-OR32

Skeletal Muscle Extracellular Matrix in Patients on Hemodialysis

Session Information

• Exercise and Kidney Health: From Bench to Smartphone
  October 25, 2024 | Location: Room 4, Convention Center
  Abstract Time: 05:10 PM - 05:20 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1500 Health Maintenance, Nutrition, and Metabolism

Authors

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

Jorge Gamboa, MD, PhD

• Dematteo, Anthony Charles, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Anthony Charles Dematteo

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

Dungeng Peng, DrPH

• Demirci, Mert, University of California Davis, Davis, California, United States

Mert Demirci, MD

• 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

• Kim, Tae Youn, University of California Davis, Davis, California, United States

Tae Youn Kim, PhD, RN

• Smith, Lucas R., University of California Davis, Davis, California, United States

Lucas R. Smith, 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

Background

Frailty and sarcopenia are common in patients with chronic kidney disease (CKD). The extracellular matrix (ECM) plays an important role in muscle proliferation as the scaffold for muscle growth. We have previously shown that ECM gene expression is altered in patients on hemodialysis (HD). We now test the hypothesis that the content of collage, the major structural protein in skeletal muscle, is decreased in patients on HD.

Methods

In a cross-sectional study, we obtained vastus lateralis 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). Using data from RNA sequencing, we evaluated the gene expression of specific ECM genes. We also evaluated the collagen content using the hydroxyproline assay.

Results

We found the downregulation of 16 ECM genes between controls and MHD groups, and 24 ECM genes between CKD 3-5 and MHD groups. There was no difference in ECM gene expression between controls and patients with CKD 3-5. COL4A1, which encodes for alpha 1 chain of type IV collagen, and DCN, which encodes for decorin, were among these genes (Figure 1 A and B). Total collagen content was also decreased in patients on MHD compared to the other two groups (Figure 1C).

Conclusion

Our results suggest a reduced content of ECM components in skeletal muscle in patients on MHD. Alterations in ECM remodeling may play a role in sarcopenia in CKD. ECM not only provides structural support but also inhibits atrophic factors, such as myostatin inhibition by decorin. Further studies should identify potential targets of the ECM pathways to prevent sarcopenia and frailty in CKD.

Funding

• NIDDK Support