Associations between Cell-Free Mitochondrial DNA and Inflammation, and Their Clinical Implications for Patients on Hemodialysis: A Prospective Multicenter Cohort Study
Autor: | Hong Joo Lee, Yang Gyun Kim, Dong Ho Yang, Kyung Hwan Jeong, Ju-Young Moon, Su Woong Jung, Sang-Ho Lee, Shin Young Ahn, Kipyo Kim, Won-Hee Cho, Haena Moon, Jin Sug Kim, Dong-Young Lee |
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Rok vydání: | 2020 |
Předmět: |
Male
Oncology medicine.medical_specialty medicine.medical_treatment Inflammation DNA Mitochondrial Proinflammatory cytokine Osteoprotegerin Renal Dialysis Internal medicine Animals Humans Medicine Prospective Studies Prospective cohort study Cells Cultured Dialysis Aged business.industry Macrophages Hematology General Medicine Middle Aged Mice Inbred C57BL Cytokine Nephrology Cytokines Kidney Failure Chronic Female Hemodialysis medicine.symptom business Cell-Free Nucleic Acids Cohort study |
Zdroj: | Blood Purification. 50:214-221 |
ISSN: | 1421-9735 0253-5068 |
Popis: | 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. |
Databáze: | OpenAIRE |
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