Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients

Abstract

Background/Aims: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that circulating mitochondrial DNA, which has a similar structure with bacterial DNA, correlates with systemic inflammatory state and predicts cardiovascular event in new PD patients. Methods: We measured plasma mitochondrial DNA level by quantitative polymerase chain reaction (PCR) in 197 new PD patients and 150 patients with chronic kidney disease. PD patients were followed for 24 months for the development of cardiovascular event, hospitalization, and patient survival. Results: There was a stepwise increase in plasma mitochondrial DNA level with worsening renal function. The average plasma mitochondrial DNA level was 18.0 ± 1.2 PCR cycles. Plasma mitochondrial DNA level correlated with serum CRP level (r = -0.538, p < 0.0001). At 24 months, the event-free survival was 67.4%, 66.4%, 63.4% and 44.2% for plasma mitochondrial DNA level quartiles I, II, III and IV, respectively (p = 0.049). After adjusting for confounders, plasma mitochondrial DNA level, malnutrition-inflammation score, and baseline arterial pulse wave velocity were independent predictors of composite cardiovascular end-point; each doubling in plasma mitochondrial DNA level confers 16.0% (95% confidence interval, 2.5 - 31.3%, p = 0.001) excess in risk. Plasma mitochondrial DNA also correlated with the number of hospital admission (r = -0.218, p = 0.002) and duration of hospitalization for cardiovascular reasons (r = -0.232, p = 0.001). Conclusion: Plasma mitochondrial DNA level significantly correlates with systemic inflammatory state, and is a strong predictor of cardiovascular event as well as the need of hospitalization in new PD patients.

Depression Does Not Predict Clinical Outcome of Chinese Peritoneal Dialysis Patients After Adjusting for the Degree of Frailty

“…It should be noted, however, that our local policy mandates hospital admission for many intervention procedures, such as cardiac catheterization and colonoscopy. Unfortunately, we do not have the detailed breakdown on the cause of hospitalization for our patients, but the gure in this study is similar to our previous reports [29,30].…”

Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease

“…The second study indicates that an increased circulating free-mtDNA content (which might be different from cell-derived mtDNA content) correlates with a systemic inflammatory state and is a strong predictor of cardiovascular events. 22 We observed a highly significant and linear inverse relationship between mtDNA copy number and prevalent CVD, which was attenuated but remained significant with additional adjustment for kidney function and CVD risk factors (Table 2). Interestingly, we did not observe a significant association with cardiovascular deaths during the 4 years of follow-up.…”

“…[40][41][42] Studies in various patients indeed revealed a higher cell-free mtDNA copy number in patients with clinical outcomes. 22,43,44 Strengths and limitations of the study To our knowledge, this is largest reported study of mtDNA copy numbers in CKD patients using prespecified and centrally adjudicated outcome measures. Moreover, it is the first study demonstrating a strong association between mtDNA copy numbers and risk of mortality and infections in patients with moderately severe CKD.…”

Gender-Specific Differences in Peritoneal Dialysis

“…From 1997 to 2008 the number of PD patients increased in developing countries more than in developed countries, and in 2008, 11% of the global dialysis population was performing PD [2-4]. Several studies showed an initial survival benefit of PD in the first 2 years compared to hemodialysis [2, 5, 6], and very recent data from the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) showed that patient survival has improved over the last 20 years for both PD and hemodialysis (HD) [7].…”