Prognostic role of circulating neutrophil extracellular traps levels for long-term mortality in new end-stage renal disease patients

Kim, Jwa-Kyung; Lee, Hoi Woul; Joo, Narae; Lee, Hyung Seok; Song, Young Rim; Kim, Hyung Jik; Kim, Sung Gyun

doi:10.1016/j.clim.2019.108263

Cited by 24 publications

(25 citation statements)

References 30 publications

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“…The clinical significance of this study is hard to overestimate, as it alerts physicians to concealed intrinsic problems in need to be addressed. This study buttresses the previous pilot investigation by the same group and furthers 2 other investigations reporting similar results [2-4]. Collectively, these innovative investigations not only advance the field of biomarkers for long-term morbidity and mortality but also importantly beacon further exploration of causes behind elevated post-dialysis cfDNA.…”

supporting

confidence: 84%

“…A simple balance sheet of total genomic DNA per cell being in the order of 6–7 pg, the number of circulating neutrophils, against the half-life of cfDNA being in the range of 10–15 min, and DNase constitutively present in the circulation, it becomes obvious that elevated levels of cfDNA are not exclusively a function of increased release of cellular DNA rather are significantly impacted by its impaired degradation by the DNases. Intriguingly, Kim et al [4] observed, to the contrary, that patients with highest DNase levels show increased risk of cardiovascular events, both nonfatal and fatal. These investigators, however, emphasized that the abundance of this enzyme is not necessarily proportional to its activity, implying that reduced DNase activity could potentially contribute to elevated levels of cfDNA.…”

mentioning

confidence: 99%

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NET Formation in Dialysis: A Valuable, albeit Mysterious and Enticing Predictor of Mortality

Goligorsky

2020

Am J Nephrol

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supporting

confidence: 84%

mentioning

confidence: 99%

NET Formation in Dialysis: A Valuable, albeit Mysterious and Enticing Predictor of Mortality

Goligorsky

2020

Am J Nephrol

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“…Repeated neutrophil damage during every dialysis session may be involved in increased susceptibility to infection, and MPO release enhances oxidative stress, resulting in a state of chronic microinflammation for dialysis patients 22 . Plasma MPO has been reported as an independent risk factor for all-cause mortality in HD patients 23 , 24 . In a previous report by Kamyar et al, MPO was higher in dialysis patients compared to non-dialysis controls, and cases with a particularly high MPO level showed a high death ratio of 1.81 compared to the moderate group 25 .…”

Section: Discussionmentioning

confidence: 99%

Enhanced neutrophil apoptosis accompanying myeloperoxidase release during hemodialysis

Fukushi

Yamamoto

Yoshida

et al. 2020

Sci Rep

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Biocompatibility of hemodialysis (HD) systems have been considerably improved. However, mortality and morbidity rates of patients have remained high, raising questions regarding the biocompatibility of current systems. In the present study, 70 patients on regular HD (51 males; mean age, 63 years; median duration of HD, 18 months) with high-performance membrane (polysulfone, 77%; polymethylmethacrylate, 23%) at Tohoku University Hospital were examined. Blood samples before and after HD, were subjected to measure apoptosis cells of white blood cells, plasma levels of the following molecules: myeloperoxidase (MPO), pentraxin 3 (PTX3), angiogenin, complements, and 17 cytokines. The main findings were as follows: significant decreases in leukocyte counts by dialysis, significant increases in apoptosis-positive leukocytes by dialysis (neutrophils and monocytes), and significant decrease in plasma angiogenin accompanying increase in plasma MPO and PTX3 levels, with no or only marginal changes in plasma pro-inflammatory cytokine levels and complement products by dialysis. The findings underlined the unsolved issue of bio-incompatibility of HD systems, and suggest the possible pathology of neutrophil apoptosis accompanying MPO release for the development of microinflammation in patients on HD.

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“…Increased circulating nucleosome levels in HD patients are closely associated with concentrations of myeloperoxidase (MPO), a lysosomal protein stored in neutrophil granules, indicating elevated levels of NETs in vivo [42]. Patients with the highest NETs levels had a significantly increased all-cause and cardiovascular mortality, even after adjusting traditional risk factors [42]. Associations between elevated cell-free DNA levels in dialyzed patients and the process of NETosis have been recently reviewed [43].…”

Section: Neutrophil Extracellular Trapsmentioning

confidence: 99%

“…Inappropriate PMNL priming is a central mediator of low-grade inflammation and oxidative stress in CKD patients [50]. Furthermore, primed neutrophils can lead to increased NETs formation under uremic conditions and are associated with endothelial dysfunction [42].…”

Section: Pmnl Primingmentioning

confidence: 99%

Immune Dysfunction in Uremia 2020

Cohen

2020

Toxins

108

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Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failure results in disturbed renal metabolic activities with reduced renin, erythropoietin, and vitamin D production, which adversely affects the immune system. Decreased kidney function also leads to reduced glomerular filtration and the retention of uremic toxins. A large number of uremic toxins with detrimental effects on immune cells have been identified. Besides small water-soluble and protein-bound compounds originating from the intestinal microbiome, several molecules in the middle molecular range, e.g., immunoglobulin light chains, retinol-binding protein, the neuropeptides Met-enkephalin and neuropeptide Y, endothelin-1, and the adipokines leptin and resistin, adversely affect immune cells. Posttranslational modifications such as carbamoylation, advanced glycation products, and oxidative modifications contribute to uremic toxicity. Furthermore, high-density lipoprotein from uremic patients has an altered protein profile and thereby loses its anti-inflammatory properties.

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Prognostic role of circulating neutrophil extracellular traps levels for long-term mortality in new end-stage renal disease patients

Cited by 24 publications

References 30 publications

NET Formation in Dialysis: A Valuable, albeit Mysterious and Enticing Predictor of Mortality

NET Formation in Dialysis: A Valuable, albeit Mysterious and Enticing Predictor of Mortality

Enhanced neutrophil apoptosis accompanying myeloperoxidase release during hemodialysis

Immune Dysfunction in Uremia 2020

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