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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. [ABSTRACT FROM AUTHOR]

Background and Aims: Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD.Methods and Results: We enrolled patients with moderate to severe CKD through a multi-center pilot randomized trial of diet and exercise in a 4-arm design (dietary restriction of 10%-15% reduction in caloric intake, exercise three times/week, combined diet and exercise, and control) (NCT01150851). Adipocytokines (adiponectin and leptin) were measured at the beginning and end of the study period as secondary outcomes. Treatment effect was analyzed in a multivariable model adjusted for baseline outcome values, age, gender, site and diabetes. A total of 122 participants were consented, 111 were randomized (42% female, 25% diabetic, and 91% hypertensive), 104 started intervention and 92 completed the study (Figure 1). Plasma adiponectin levels increased significantly in response to diet by 23% (95% CI: 0.2%, 49.8%, p = 0.048) among participants randomized to the caloric restriction and usual activity arm but not to exercise, whereas circulating leptin did not change by either treatment.Conclusion: Our data suggest that dietary caloric restriction increases plasma adiponectin levels in stage 3-4 CKD patients, with limited effect on leptin levels. These findings suggest the potential for improving the metabolic milieu of CKD with moderate calorie restriction. [ABSTRACT FROM AUTHOR]

Introduction Peripheral artery disease (PAD) affects 8.5 million Americans and thus improving our understanding of PAD is critical to developing strategies to reduce disease burden. The objective of the study was to determine the association of ABO blood type with ankle brachial index (ABI) as well as prevalent and incident PAD in a multi-ethnic cohort. Methods The Multi-Ethnic Study of Atherosclerosis includes non-Hispanic White, African, Hispanic, and Chinese Americans aged 45–84. ABO blood type was estimated using ABO genotypes in 6027 participants who had ABI assessed at the baseline exam. Associations with ABO blood type were evaluated categorically and under an additive genetic model by number of major ABO alleles. After excluding those with ABI > 1.4, prevalent PAD was defined as ABI ≤ 0.9 at baseline and incident PAD as ABI ≤ 0.9 for 5137 participants eligible for analysis. Results There were 222 prevalent cases and 239 incident cases of PAD. In African Americans, each additional copy of the A allele was associated with a 0.02 lower baseline ABI ( p = 0.006). Each copy of the A allele also corresponded to 1.57-fold greater odds of prevalent PAD (95% CI, 1.17–2.35; p = 0.004), but was not associated with incident PAD. No associations were found in other racial/ethnic groups for ABI, prevalent PAD, or incident PAD across all races/ethnicities. Conclusions Blood type A and the A allele count were significantly associated with baseline ABI and prevalent PAD in African Americans. Further research is needed to confirm and study the mechanisms of this association in African Americans. [ABSTRACT FROM AUTHOR]