Abstract: FR-PO994
Skeletal Muscle Mitochondrial Dysfunction in Patients with CKD and Heart Failure (HF)
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Demirci, Mert, Vanderbilt University Division of Nephrology and Hypertension, Nashville, Tennessee, United States
- Jaramillo Morales, Javier, Vanderbilt University Division of Nephrology and Hypertension, Nashville, Tennessee, United States
- Roshanravan, Baback, University of California Davis, Division of Nephrology, Sacramento, California, United States
- Zalawadiya, Sandip K., Vanderbilt University Division of Cardiovascular Medicine, Nashville, Tennessee, United States
- Ikizler, Talat Alp, Vanderbilt University Division of Nephrology and Hypertension, Nashville, Tennessee, United States
- Gamboa, Jorge, Vanderbilt University Medical Center, Division of Clinical Pharmacology, Nashville, Tennessee, United States
Background
Skeletal muscle dysfunction is a well-known cause of decreased physical performance and quality of life in patients with CKD and HF. While muscle mitochondrial dysfunction has been proposed as a possible mechanism in patients with either CKD or HF. The incremental effect of co-existing HF and CKD is not studied in detail. We hypothesized that the presence of HF and CKD is associated with worse mitochondrial function and physical performance compared to CKD alone.
Methods
In this cross-sectional study, we examined 24 patients, 6 with CKD Stage 3-5 with a clinical diagnosis of HF, and 18 with CKD Stage 3-5 without HF. Patients on dialysis were excluded. 31Phosphorus magnetic resonance spectroscopy (31P-MRS) was used to measure PCr recovery time after exercise. A longer PCr recovery results in a greater time constant tau (τ), which indicates worsening mitochondrial function. Physical performance was measured with the six-minute walk test (6MWT) and repeated chair stand test.
Results
Groups were similar in terms of age, gender, race, and eGFR. Patients with co-existing CKD and HF presented a prolonged time constant compared to patients with CKD alone [CKD/HF: 77.825 (71.2, 82.515) vs. CKD alone: 48.41 (41.13 , 49.175), p<0.001, Figure 1A] Patients with co-existing CKD and HF walked a shorter distance than patients with CKD alone [CKD/HF: 372 (294, 395) vs. CKD alone: 491 (417, 519.5) meters, median (IQR), p=0.003, Figure 1B].
Conclusion
Our results suggest that presence of HF worsens mitochondrial dysfunction in patients with moderate to advanced CKD. Similar adverse impact of HF is observed in physical performance measures. Future studies should evaluate the mechanisms leading to muscle dysfunction in these two chronic diseases to provide new insights into novel therapeutic targets.
Figure 1
Demographic Table
Funding
- NIDDK Support