Kidney Week

Abstract: FR-OR33

Altered Muscle Bioenergetic in CKD: Focus on Inorganic Phosphate and Acidosis

Session Information

• Exercise and Kidney Health: From Bench to Smartphone
  October 25, 2024 | Location: Room 4, Convention Center
  Abstract Time: 05:20 PM - 05:30 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1500 Health Maintenance, Nutrition, and Metabolism

Authors

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

Dungeng Peng, DrPH

• Wang, Zuofei, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Zuofei Wang

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

Anthony Charles Dematteo

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

Mert Demirci, MD

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

Gwenaelle Begue, PhD

• Jue, Thomas, University of California Davis, Davis, California, United States

Thomas Jue, 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 chronic kidney disease (CKD) commonly experience fatigue. Muscle acidosis and inorganic phosphate accumulation have been widely associated with fatigue in the non-CKD population. We hypothesized that altered muscle bioenergetics (inorganic phosphate and pH) are present in patients with CKD and associated with physical performance measurements.

Methods

In a cross-sectional study, we evaluated 63 participants: 20 with CKD stage 3-5 not on hemodialysis (HD), 20 on hemodialysis, and 23 matched controls with no history of CKD). Muscle bioenergetics was evaluated using ³¹ phosphorus magnetic resonance spectroscopy at resting and after sub-maximal exercise. The relative concentration inorganic phosphate was obtained using AMARES and jMRUI. Intracellular pH was calculated from the chemical shift of the inorganic phosphate signal relative to phosphocreatine. Inorganic phosphate levels after exercise were fitted to a mono-exponential function to determine the time constant tau (τ).

Results

Groups were matched by gender, body mass index, and history of diabetes and hypertension. Plasma phosphate levels were higher in patients on HD. We found that resting intracellular pH was slightly but significantly lower in patients on HD and with CKD 3-5 compared to controls (Figure 1A). The concentration of inorganic phosphate at the end of exercise was significantly higher in patients on HD (Figure 1B). The constant tau of inorganic phosphate decrease after exercise was prolonged in patients on HD compared to the other two groups (Figure 1C), and it was associated with the six-minute walk distance (rho= -0.45, p<0.001). These changes were not associated with phosphate or bicarbonate levels in plasma.

Conclusion

Our results suggest that intracellular energy metabolism is impaired in patients with CKD. The changes in inorganic phosphate mirror our previous findings of impaired mitochondrial function in CKD and may play a role in physical activity in this population. Further studies should evaluate the contribution of intracellular acidosis or increased inorganic phosphate on fatigue in patients with CKD.

Funding

• NIDDK Support