Kipyo Kim1, Su Woong Jung2, Won-Hee Cho3, Haena Moon2, Kyung Hwan Jeong2, Jin Sug Kim2, Sang-Ho Lee2, Shin Young Ahn4, Dong Ho Yang5, Hong Joo Lee6, Dong-Young Lee7, Ju-Young Moon2, Yang Gyun Kim8. 1. Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University, Incheon, Republic of Korea. 2. Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. 3. Department of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea. 4. Division of Nephrology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. 5. Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea. 6. Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Republic of Korea. 7. Division of Nephrology, Department of Internal Medicine, Veterans Healthcare System Medical Center, Seoul, Republic of Korea. 8. Division of Nephrology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea, apple8840@hanmail.net.
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.
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.
Authors: Javier Jaramillo-Morales; Berfu Korucu; Mindy M Pike; Loren Lipworth; Thomas Stewart; Samuel A E Headley; Michael Germain; Gwenaelle Begue; Baback Roshanravan; Katherine R Tuttle; Jonathan Himmelfarb; Cassianne Robinson-Cohen; T Alp Ikizler; Jorge L Gamboa Journal: Am J Physiol Renal Physiol Date: 2021-11-29
Authors: Caroline Trumpff; Jeremy Michelson; Claudia J Lagranha; Veronica Taleon; Kalpita R Karan; Gabriel Sturm; Daniel Lindqvist; Johan Fernström; Dirk Moser; Brett A Kaufman; Martin Picard Journal: Mitochondrion Date: 2021-04-09 Impact factor: 4.160