Associations between Cell-Free Mitochondrial DNA and Inflammation, and Their Clinical Implications for Patients on Hemodialysis: A Prospective Multicenter Cohort Study

Kipyo Kim, Su Woong Jung, Won Hee Cho, Haena Moon, Kyung Hwan Jeong, Jin Sug Kim, Sang Ho Lee, Shin Young Ahn, Dong Ho Yang, Hong Joo Lee, Dong Young Lee, Ju Young Moon, Yang Gyun Kim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)214-221
Number of pages8
JournalBlood Purification
Volume50
Issue number2
DOIs
Publication statusPublished - Feb 2021

Keywords

  • Cell-free mitochondrial DNA
  • Hemodialysis
  • Inflammation
  • Quality of life

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