title: Circulatory mitochondrial DNA is a pro-inflammatory agent in maintenance hemodialysis patients.
abstract: Chronic inflammation is highly prevalent in maintenance hemodialysis (MHD) patients, and it has been shown to be a strong predictor of morbidity and mortality. Mitochondrial DNA (mtDNA) released into circulation after cell damage can promote inflammation in patients and animal models. However, the role and mechanisms of circulatory mtDNA in chronic inflammation in MHD patients remain unknown. Sixty MHD patients and 20 health controls were enrolled in this study. The circulatory mtDNA was detected by quantitative real-time PCR assay. Plasma interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were quantitated by ELISA assay. Dialysis systems in MHD patients and in vitro were used to evaluate the effect of different dialysis patterns on circulatory mtDNA. Circulatory mtDNA was elevated in MHD patients comparing to that of health control. Regression analysis demonstrated that plasma mtDNA was positively associated with TNF-α and the product of serum calcium and phosphorus, while negatively associated with hemoglobin and serum albumin in MHD patients. MtDNA induced the secretion of IL-6 and TNF-α in the THP-1 cells. Single high-flux hemodialysis (HF-HD) and on line hemodiafiltration (OL-HDF) but not low-flux hemodialysis (LF-HD) could partially reduce plasma mtDNA in MHD patients. In vitro, both HD and hemofiltration (HF) could fractional remove mtDNA. Collectively, circulatory mtDNA is elevated and its level is closely correlated with chronic inflammation in MHD patients. HF-HD and HDF can partially reduce circulatory mtDNA in MHD patients.
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Hongdi
authors.initials: H
authors.lastname: Cao
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Shen
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Song
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Weichun
authors.initials: W
authors.lastname: He
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Chunsun
authors.initials: C
authors.lastname: Dai
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D004272:DNA, Mitochondrial / Q000097:blood*; D005260:Female; D017583:Hemodiafiltration / Q000009:adverse effects; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects; D012307:Risk Factors
chemical_list: D016207:Cytokines; D004272:DNA, Mitochondrial; D018836:Inflammation Mediators