Effects of caloric restriction and aerobic exercise on circulating cell-free mitochondrial DNA in patients with moderate to severe chronic kidney disease

Javier Jaramillo-Morales, Berfu Korucu, Mindy M. Pike, Loren Lipworth, Thomas Stewart, Samuel A.E. Headley, Michael Germain, Gwenaelle Begue, Baback Roshanravan, Katherine R. Tuttle, Jonathan Himmelfarb, Cassianne Robinson-Cohen, T. Alp Ikizler, Jorge L. Gamboa

Research output: Contribution to journalArticlepeer-review

Abstract

Circulating cell-free mitochondrial DNA (ccf-mtDNA) may induce systemic inflammation, a common condition in chronic kidney disease (CKD), by acting as a damage-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 2 and 4 mo after aerobic exercise and caloric restriction. A total of 99 participants had baseline ccf-mtDNA, and 92 participants completed the study. The median age of the participants was 57 yr, 44% were female and 55% were male, 23% had diabetes, and 92% had hypertension. After adjusting for demographics, blood pressure, body mass index, diabetes, and estimated glomerular filtration rate, median ccf-mtDNA concentrations at baseline, 2 mo, and 4 mo were 3.62, 3.08, and 2.78 pM for the usual activity group and 2.01, 2.20, and 2.67 pM 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), which was more pronounced with the combination of aerobic exercise and caloric restriction (29.5% greater increase per month). After 4 mo of intervention, ccf-mtDNA increased in the aerobic exercise group by 81.6% (95% confidence interval: 8.2–204.8, P = 0.024) compared with the usual activity group and was more marked in the aerobic exercise and caloric restriction group (181.7% increase, 95% confidence interval: 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.

Original languageEnglish (US)
Pages (from-to)F68-F75
JournalAmerican Journal of Physiology - Renal Physiology
Volume322
Issue number1
DOIs
StatePublished - Jan 2022
Externally publishedYes

Keywords

  • Aerobic exercise
  • Caloric restriction
  • Chronic kidney disease
  • Mitochondrial DNA

ASJC Scopus subject areas

  • Physiology
  • Urology

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