Abstract: PO1754
Effects of Caloric Restriction and Aerobic Exercise on Circulating Cell-Free Mitochondrial DNA in Patients with Moderate-to-Severe CKD
Session Information
- Health Maintenance, Nutrition, and Metabolism
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1300 Health Maintenance, Nutrition, and Metabolism
Authors
- Jaramillo Morales, Javier, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Korucu, Berfu, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Pike, Mindy, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Headley, Sam A., Springfield College, Springfield, Massachusetts, United States
- Roshanravan, Baback, University of California Davis, Davis, California, United States
- Tuttle, Katherine R., University of Washington, Seattle, Washington, United States
- Himmelfarb, Jonathan, University of Washington, Seattle, Washington, United States
- Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Gamboa, Jorge, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Understanding mechanisms for increased oxidative stress and inflammation in patients with chronic kidney disease (CKD) is vital due to their role in the pathophysiology of this population. Circulating cell-free mitochondrial DNA (ccf-mtDNA) is released to the plasma and believed to promote inflammation by acting as a damaged-associated molecular pattern. Previous studies suggested that in patients with kidney disease, ccf-mtDNA increases and may induce inflammation. Past investigations in patients with CKD have found that aerobic exercise decreases inflammation. We hypothesized that in patients with moderate to severe CKD, aerobic exercise would reduce plasma levels of ccf-mtDNA.
Methods
We performed a post hoc analysis of a multi-center pilot randomized trial of aerobic exercise and caloric restriction (NCT01150851). We measured ccf-mtDNA in plasma at baseline and two and four months after four interventions (aerobic exercise (EX), caloric restriction (CR), EX + CR, usual activity and usual diet). A multivariable model adjusted for age, race, sex, systolic BP, BMI, diabetes, and eGFR was done
Results
Of a cohort of 111 participants who were randomized, 99 had baseline ccf-mtDNA levels, and 92 completed the study. The median age was 57 years old, 44% were female, and 92% had diabetes. Plasma ccf-mtDNA median concentrations at baseline, two, and four months were 3.62, 3.08, 2.78 pM for the usual activity group, and 2.01, 2.20, 2.67 pM for the aerobic exercise group. There was a 16.1% increase per month in ccf-mtDNA in the aerobic exercise group compared to the usual activity group (p = 0.024), especially with the combination of aerobic exercise and caloric restriction (29.5% increase per month). After four months of intervention, ccf-mtDNA increased in the aerobic exercise group by 81.6% (95% confidence intervals [CI] 8.2-204.8; p = 0.024) compared to the usual activity group, but it was only observed in the aerobic exercise and caloric restriction group (181.7% increase, 95% CI 41.1-462.2; p = 0.003)
Conclusion
Our data suggest that aerobic exercise increases plasma ccf-mtDNA levels in patients with CKD stages 3-4, more profoundly in ones with a combination of caloric restriction.
Funding
- NIDDK Support