Circulating cell-free mitochondrial DNA (ccf-mtDNA) may induce systemic inflammation, a common condition chronic kidney disease (CKD), by acting as a damaged-associated molecular pattern. We hypothesized that in patients with moderate to severe CKD, aerobic exercise would reduce ccf-mtDNA levels. We performed a post hoc analysis of a multicenter randomized trial (NCT01150851), measuring plasma concentrations of ccf-mtDNA at baseline and two and four months after aerobic exercise and caloric restriction. A total of 99 participants had baseline ccf-mtDNA, and 92 completed the study. The median age was 57 years, 44% were female, 23% had diabetes, and 92% had hypertension. After adjusting for demographics, blood pressure, BMI, diabetes, and eGFR, median ccf-mtDNA concentrations at baseline, two, and four months were 3.62, 3.08, 2.78 picomolar for the usual activity group, and 2.01, 2.20, 2.67 picomolar for the aerobic exercise group, respectively. A 16.1% greater increase per month in ccf-mtDNA was seen in aerobic exercise versus usual activity (p = 0.024) that was more pronounced with the combination of aerobic exercise and caloric restriction (29.5% greater 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 usual activity and was more marked in the aerobic exercise and caloric restriction group (181.7% increase, 95% CI 41.1-462.2; p = 0.003). There was no statistically significant correlation between markers of oxidative stress and inflammation with ccf-mtDNA. Our data indicate that aerobic exercise increased ccf-mtDNA levels in patients with moderate-to-severe CKD.

Keywords: aerobic exercise; caloric restriction; chronic kidney disease; mitochondrial DNA.