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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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

      editorial
      *
      American Journal of Nephrology
      S. Karger AG
      Dialysis, Mortality, Predictors

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          Extracellular DNA NET-Works With Dire Consequences for Health

          Neutrophils play a central role in innate immune defense. Advances in neutrophil biology have brought to light the capacity of neutrophils to release their decondensed chromatin and form large extracellular DNA networks called neutrophil extracellular traps (NETs). NETs are produced in response to many infectious and non-infectious stimuli and, together with fibrin, block the invasion of pathogens. However, their formation in inflamed blood vessels produces a scaffold that supports thrombosis, generates neo-antigens favoring autoimmunity, and aggravates damage in ischemia/reperfusion injury. NET formation can also be induced by cancer, and promotes tumor progression. Formation of NETs within organs can be immediately detrimental, such as in lung alveoli, where they affect respiration, or be harmful over longer periods of time. For example, NETs initiate excessive deposition of collagen, resulting in fibrosis, thus likely contributing to heart failure. Here, we summarize the latest knowledge on NET generation and discuss how excessive NET formation mediates propagation of thrombosis and inflammation and, thereby contributes to various diseases. There are many ways in which NET formation could be averted or NETs neutralized to prevent their detrimental consequences, and we will provide an overview of these possibilities.
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            Neutrophil Extracellular Traps in Host Defense

            Neutrophils are produced in the bone marrow and then patrol blood vessels from which they can be rapidly recruited to a site of infection. Neutrophils bind, engulf, and efficiently kill invading microbes via a suite of defense mechanisms. Diverse extracellular and intracellular microbes induce neutrophils to extrude neutrophil extracellular traps (NETs) through the process of NETosis. Here, we review the signaling mechanisms and cell biology underpinning the key NETosis pathways during infection and the antimicrobial functions of NETs in host defense.
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              Circulating cell-free DNA in hemodialysis patients predicts mortality.

              Circulating cell-free DNA (CFD) appears following cell damage and DNA release, and increases in hemodialysis (HD) patients particularly following HD. We hypothesized that CFD is an integrative marker of tissue damage and can be an independent predictor for all-cause mortality in HD patients. In a prospective study, CFD levels before and after HD were evaluated in 31 chronic HD patients with no acute disease, using the reported rapid non-cumbersome inexpensive fluorometric assay developed in our laboratory. Follow-up levels were assessed at 18 months in 22 patients. All-cause mortality was a primary endpoint. During 42 months of follow-up, 13 of the 31 (41.9%) patients died. The decedents were older than the survivors (mean age 69.9 versus 61.5 years, P = 0.06), but did not differ in end-stage renal disease (ESRD) duration, gender, albumin and hemoglobin, diabetes mellitus and weight. Post-dialysis CFD levels were significantly lower in survivors (median 688 versus 880 ng/mL, P = 0.01). The sensitivity and specificity of CFD levels of 850 ng/mL to predict 42 months (3.5 years) mortality were 73 and 75%, respectively, and the area under the receiver-operating characteristic curve was 0.77 [95% confidence interval (CI) 0.60-0.94]. The Cox proportional hazard regression model showed that CFD higher than 850 ng/mL adjusted for age, ESRD duration, weight and creatinine (stepwise model) was highly predictive of all-cause death with a hazard ratio of 8.0 (95% CI 2.3-28.5, P = 0.001). Post-dialysis CFD level is an independent predictor of all-cause mortality in patients undergoing HD. We propose that CFD detection is an inexpensive applicable tool for identifying patients at risk and their follow-up.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2020
                December 2020
                26 October 2020
                : 51
                : 11
                : 849-851
                Affiliations
                New York Medical College at Touro University, Valhalla, New York, USA
                Author notes
                *Michael S. Goligorsky, Alvin I Goodman Chair of Nephrology, Professor of Medicine, Pharmacology and, Physiology, Director, Renal Research Institute, New York Medical College, Basic Science Building C23, Valhalla, NY 10595 (USA), michael_goligorsky@nymc.edu
                Article
                510772 Am J Nephrol 2020;51:849–851
                10.1159/000510772
                33105137
                d02ce502-d81d-4848-9672-0dec4d39ec2d
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 06 August 2020
                : 06 August 2020
                Page count
                Figures: 1, Pages: 3
                Categories
                Commentary

                Cardiovascular Medicine,Nephrology
                Predictors,Mortality,Dialysis
                Cardiovascular Medicine, Nephrology
                Predictors, Mortality, Dialysis

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