Abstract
BackgroundMitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. However, the effects of peritoneal dialysate cell-free mtDNA on intraperitoneal inflammation and peritoneal solute transport rate (PSTR) in peritoneal dialysis (PD) patients remain unclear.MethodsWe select the incident patients who began PD therapy between January 1, 2009, and December 30, 2010. Peritoneal dialysate was collected at the time of peritoneal equilibration test. The cell-free mtDNA, IL-6, IL-17A, TNF-α and IFN-γ were measured. All patients were followed till December 2017. The results were compared with PSTR and patient survival.ResultsOne hundred and eighty-nine patients were included in the study. The average age was 47.1 ± 13.5 years, 55.6% of the patients were males. The average PSTR was 0.66 ± 0.12, the median dialysate mtDNA levels were 4325 copies/ul. The median concentrations of IL-6, IL-17A, TNF-α and IFN-γ were 25.9, 10.8, 25.8 and 17.9 pg/ml, respectively. We found that dialysate mtDNA was significantly correlated with PSTR (r = 0.461, P < 0.001), IL-6 (r = 0.568, P < 0.001), TNF-α (r = 0.454, P < 0.001) and IFN-γ (r = 0.203, P = 0.005). After adjustment for multiple covariates, dialysate mtDNA levels were independently correlated with IL-6 and PSTR. Dialysate mtDNA levels were not associated with patient survival.ConclusionsWe found that dialysate mtDNA levels correlated with the degree of intraperitoneal inflammatory status in PD patients. Peritoneal effluent mtDNA was an independent determinant of PSTR but did not affect patient survival.
Highlights
Mitochondrial DNA released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models
Mitochondria was evolved from saprophytic bacteria to endosymbionts to organelles, and Mitochondrial DNA shows similarities to bacterial DNA [10]. mtDNA released into the extracellular space subsequent to cell injury and death acts as damage-associated molecular patterns (DAMPs) could induce inflammatory response through Toll-like receptor 9 (TLR9) pathway [11, 12]
In the present study, we found that dialysate mtDNA level was significantly associated with the degree of local intraperitoneal IL-6 level, and was a predictor of peritoneal solute transport rate (PSTR)
Summary
Mitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. The effects of peritoneal dialysate cell-free mtDNA on intraperitoneal inflammation and peritoneal solute transport rate (PSTR) in peritoneal dialysis (PD) patients remain unclear. MtDNA released into the extracellular space subsequent to cell injury and death acts as DAMPs could induce inflammatory response through Toll-like receptor 9 (TLR9) pathway [11, 12]. In PD patients, the PD catheters, long-term exposures to PD solutions and repeated peritonitis episodes could induce cell injury and death, which would lead to an abundant release of mtDNA into local intraperitoneal cavity. The purpose of the present study was to explore the relationships between mtDNA in peritoneal dialysate and intraperitoneal inflammation, PSTR and survival in PD patients
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