PMID- 32862176 OWN - NLM STAT- MEDLINE DCOM- 20210806 LR - 20240226 IS - 1421-9735 (Electronic) IS - 0253-5068 (Linking) VI - 50 IP - 2 DP - 2021 TI - Associations between Cell-Free Mitochondrial DNA and Inflammation, and Their Clinical Implications for Patients on Hemodialysis: A Prospective Multicenter Cohort Study. PG - 214-221 LID - 10.1159/000510088 [doi] AB - BACKGROUND: Cell-free mitochondrial DNA (cf-mtDNA) has recently been in the spotlight as an endogenously produced danger molecule that can potentially elicit inflammation. However, its clinical and prognostic implications are uncertain in patients undergoing hemodialysis. METHODS: We examined the association of baseline cf-mtDNA categorized as tertiles with health-related quality of life (HRQOL), inflammatory cytokines, and mortality in a multicenter prospective cohort of 334 patients on hemodialysis. To better understand cf-mtDNA-mediated inflammation, we measured cytokine production after in vitro stimulation of bone marrow-derived macrophages (BMDMs) with mtDNA. RESULTS: The higher cf-mtDNA tertile had a longer dialysis vintage, a greater comorbidity burden, and increased levels of inflammatory markers, including high-sensitivity-C-reactive protein, tumor necrosis factor-alpha, CXCL16, and osteoprotegerin. In particular, mtDNA augmented inflammatory cytokine release from BMDMs by lipopolysaccharide, the levels of which are reported to be increased in hemodialysis patients. Although the patients with higher levels of cf-mtDNA generally had lower (poorer) scores for HRQOL, cf-mtDNA was not associated with all-cause mortality in hemodialysis patients. CONCLUSION: cf-mtDNA was correlated with poor clinical status and modestly associated with impaired quality of life in patients on hemodialysis. In proinflammatory milieu in end-stage renal disease, these associations may be attributed to the boosting effects of cf-mtDNA on inflammation. CI - (c) 2020 S. Karger AG, Basel. FAU - Kim, Kipyo AU - Kim K AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University, Incheon, Republic of Korea. FAU - Jung, Su Woong AU - Jung SW AD - Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. FAU - Cho, Won-Hee AU - Cho WH AD - Department of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea. FAU - Moon, Haena AU - Moon H AD - Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. FAU - Jeong, Kyung Hwan AU - Jeong KH AD - Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. FAU - Kim, Jin Sug AU - Kim JS AD - Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. FAU - Lee, Sang-Ho AU - Lee SH AD - Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. FAU - Ahn, Shin Young AU - Ahn SY AD - Division of Nephrology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. FAU - Yang, Dong Ho AU - Yang DH AD - Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea. FAU - Lee, Hong Joo AU - Lee HJ AD - Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Republic of Korea. FAU - Lee, Dong-Young AU - Lee DY AD - Division of Nephrology, Department of Internal Medicine, Veterans Healthcare System Medical Center, Seoul, Republic of Korea. FAU - Moon, Ju-Young AU - Moon JY AD - Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. FAU - Kim, Yang Gyun AU - Kim YG AD - Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea, apple8840@hanmail.net. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20200828 PL - Switzerland TA - Blood Purif JT - Blood purification JID - 8402040 RN - 0 (Cell-Free Nucleic Acids) RN - 0 (Cytokines) RN - 0 (DNA, Mitochondrial) SB - IM MH - Aged MH - Animals MH - Cell-Free Nucleic Acids/*blood/metabolism MH - Cells, Cultured MH - Cytokines/blood/metabolism MH - DNA, Mitochondrial/*blood/metabolism MH - Female MH - Humans MH - Inflammation/*blood/metabolism MH - Kidney Failure, Chronic/blood/metabolism/therapy MH - Macrophages/metabolism MH - Male MH - Mice, Inbred C57BL MH - Middle Aged MH - Prospective Studies MH - *Renal Dialysis MH - Mice OTO - NOTNLM OT - Cell-free mitochondrial DNA OT - Hemodialysis OT - Inflammation OT - Quality of life EDAT- 2020/08/31 06:00 MHDA- 2021/08/07 06:00 CRDT- 2020/08/31 06:00 PHST- 2020/04/26 00:00 [received] PHST- 2020/07/09 00:00 [accepted] PHST- 2020/08/31 06:00 [pubmed] PHST- 2021/08/07 06:00 [medline] PHST- 2020/08/31 06:00 [entrez] AID - 000510088 [pii] AID - 10.1159/000510088 [doi] PST - ppublish SO - Blood Purif. 2021;50(2):214-221. doi: 10.1159/000510088. Epub 2020 Aug 28.