{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:24:43Z","timestamp":1778804683980,"version":"3.51.4"},"reference-count":50,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["kidney-international.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Kidney International"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1016\/j.kint.2023.03.034","type":"journal-article","created":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T09:29:23Z","timestamp":1682242163000},"page":"279-292","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"title":["Kidney medullary sodium chloride concentrations induce neutrophil and monocyte extracellular DNA traps that defend against pyelonephritis in\u00a0vivo"],"prefix":"10.1016","volume":"104","author":[{"given":"Adrian","family":"Goldspink","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olena","family":"Babyak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Brauns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Milleck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne M.","family":"Breloh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne V.","family":"Fleig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Jobin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann","family":"Haller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Wagenlehner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan Hinrich","family":"Br\u00e4sen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Kurts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibylle","family":"von Vietinghoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.kint.2023.03.034_bib1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41585-020-0362-4","article-title":"Epidemiology, definition and treatment of complicated urinary tract infections","volume":"17","author":"Wagenlehner","year":"2020","journal-title":"Nat Rev Urol"},{"key":"10.1016\/j.kint.2023.03.034_bib2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrurol.2010.190","article-title":"The epidemiology of urinary tract infection","volume":"7","author":"Foxman","year":"2010","journal-title":"Nat Rev Urol"},{"key":"10.1016\/j.kint.2023.03.034_bib3","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1146\/annurev-physiol-052521-121810","article-title":"Innate bacteriostatic mechanisms defend the urinary tract","volume":"84","author":"Munoz","year":"2022","journal-title":"Annu Rev Physiol"},{"key":"10.1016\/j.kint.2023.03.034_bib4","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/s41585-021-00477-x","article-title":"Molecular determinants of disease severity in urinary tract infection","volume":"18","author":"Ambite","year":"2021","journal-title":"Nat Rev Urol"},{"key":"10.1016\/j.kint.2023.03.034_bib5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1681\/ASN.2020030362","article-title":"Neutrophil-macrophage imbalance drives the development of renal scarring during experimental pyelonephritis","volume":"32","author":"Ruiz-Rosado","year":"2021","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.kint.2023.03.034_bib6","article-title":"Renal medullary osmolytes NaCl\u00a0and urea differentially modulate human tubular cell cytokine expression and monocyte recruitment","author":"Schmitz","year":"2022521258","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.kint.2023.03.034_bib7","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2014.01.006","article-title":"Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium","volume":"156","author":"Schiwon","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.kint.2023.03.034_bib8","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.cell.2017.07.022","article-title":"Renal sodium gradient orchestrates a dynamic antibacterial defense zone","volume":"170","author":"Berry","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.kint.2023.03.034_bib9","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abc5739","article-title":"Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder","volume":"6","author":"Lacerda Mariano","year":"2020","journal-title":"Sci Adv"},{"key":"10.1016\/j.kint.2023.03.034_bib10","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1126\/science.aat5031","article-title":"Spatiotemporal immune zonation of the human kidney","volume":"365","author":"Stewart","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.kint.2023.03.034_bib11","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.immuni.2015.03.011","article-title":"C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages","volume":"42","author":"Hoeffel","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.kint.2023.03.034_bib12","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.51756","article-title":"Yolk-sac-derived macrophages progressively expand in the mouse kidney with age","volume":"9","author":"Ide","year":"2020","journal-title":"Elife"},{"key":"10.1016\/j.kint.2023.03.034_bib13","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1038\/s41467-020-16158-z","article-title":"Distinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins","volume":"11","author":"Liu","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.kint.2023.03.034_bib14","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-physiol-021113-170350","article-title":"Advances in understanding the urine-concentrating mechanism","volume":"76","author":"Sands","year":"2014","journal-title":"Annu Rev Physiol"},{"key":"10.1016\/j.kint.2023.03.034_bib15","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1172\/JCI88532","article-title":"High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation","volume":"127","author":"Kitada","year":"2017","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.kint.2023.03.034_bib16","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aay3850","article-title":"A\u00a0high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation","volume":"12","author":"Jobin","year":"2020","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.kint.2023.03.034_bib17","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41577-018-0113-4","article-title":"Sodium in the microenvironment regulates immune responses and tissue homeostasis","volume":"19","author":"M\u00fcller","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.kint.2023.03.034_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0073439","article-title":"Salt-dependent chemotaxis of macrophages","volume":"8","author":"M\u00fcller","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.kint.2023.03.034_bib19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000722","article-title":"NCX1 represents an ionic Na+ sensing mechanism in macrophages","volume":"18","author":"Neubert","year":"2020","journal-title":"PLoS Biol"},{"key":"10.1016\/j.kint.2023.03.034_bib20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.gdata.2015.11.016","article-title":"Transcriptional profiling of dendritic cells matured in different osmolarities","volume":"7","author":"Chessa","year":"2016","journal-title":"Genom Data"},{"key":"10.1016\/j.kint.2023.03.034_bib21","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.831844","article-title":"High salt induces a delayed activation of human neutrophils","volume":"13","author":"Mazzitelli","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.kint.2023.03.034_bib22","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.kint.2018.06.029","article-title":"Renal transplant recipients receiving loop diuretic therapy have increased urinary tract infection rate and altered medullary macrophage polarization marker expression","volume":"94","author":"Casper","year":"2018","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2023.03.034_bib23","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ"},{"key":"10.1016\/j.kint.2023.03.034_bib24","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nm.4294","article-title":"An emerging role for neutrophil extracellular traps in noninfectious disease","volume":"23","author":"Jorch","year":"2017","journal-title":"Nat Med"},{"key":"10.1016\/j.kint.2023.03.034_bib25","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.3390\/cells10081932","article-title":"A\u00a0fragile balance: does neutrophil extracellular trap formation drive pulmonary disease progression?","volume":"10","author":"Block","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.kint.2023.03.034_bib26","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nchembio.1735","article-title":"Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation","volume":"11","author":"Lewis","year":"2015","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.kint.2023.03.034_bib27","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1084\/jem.20100239","article-title":"PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps","volume":"207","author":"Li","year":"2010","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.kint.2023.03.034_bib28","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1182\/blood-2014-07-587709","article-title":"PAD4-deficiency does not affect bacteremia in polymicrobial sepsis and ameliorates endotoxemic shock","volume":"125","author":"Martinod","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.kint.2023.03.034_bib29","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1186\/cc11442","article-title":"Depletion of neutrophil extracellular traps in\u00a0vivo results in hypersusceptibility to polymicrobial sepsis in mice","volume":"16","author":"Meng","year":"2012","journal-title":"Crit Care"},{"key":"10.1016\/j.kint.2023.03.034_bib30","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/s41467-019-09040-0","article-title":"Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis","volume":"10","author":"Mohanty","year":"2019","journal-title":"Nat Commun"},{"key":"10.1016\/j.kint.2023.03.034_bib31","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ekir.2018.11.005","article-title":"Clinical implications of excessive neutrophil extracellular trap formation in renal autoimmune diseases","volume":"4","author":"van Dam","year":"2019","journal-title":"Kidney Int Rep"},{"key":"10.1016\/j.kint.2023.03.034_bib32","article-title":"Neutrophil extracellular traps: a potential therapeutic target in MPO-ANCA associated vasculitis?","volume":"12","author":"O\u2019Sullivan","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.kint.2023.03.034_bib33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006151","article-title":"Characterization of early-phase neutrophil extracellular traps in urinary tract infections","volume":"13","author":"Yu","year":"2017","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.kint.2023.03.034_bib34","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1038\/s41467-021-23881-8","article-title":"TcpC inhibits neutrophil extracellular trap formation by enhancing ubiquitination mediated degradation of peptidylarginine deiminase 4","volume":"12","author":"Ou","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.kint.2023.03.034_bib35","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1161\/CIRCRESAHA.113.301934","article-title":"Increased atherosclerotic lesion formation and vascular leukocyte accumulation in renal impairment are mediated by interleukin-17A","volume":"113","author":"Ge","year":"2013","journal-title":"Circ Res"},{"key":"10.1016\/j.kint.2023.03.034_bib36","doi-asserted-by":"crossref","DOI":"10.1172\/JCI154225","article-title":"Neutrophil extracellular traps regulate ischemic stroke brain injury","volume":"132","author":"Denorme","year":"2022","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.kint.2023.03.034_bib37","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1189\/jlb.4RI1014-521R","article-title":"Extracellular traps and macrophages: new roles for the versatile phagocyte","volume":"97","author":"Boe","year":"2015","journal-title":"J\u00a0Leukoc Biol"},{"key":"10.1016\/j.kint.2023.03.034_bib38","first-page":"3","article-title":"Macrophage extracellular traps: a scoping review","volume":"10","author":"Doster","year":"2018","journal-title":"J\u00a0Innate Immun"},{"key":"10.1016\/j.kint.2023.03.034_bib39","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.24437","article-title":"Diverse stimuli engage different neutrophil extracellular trap pathways","volume":"6","author":"Kenny","year":"2017","journal-title":"eLife"},{"key":"10.1016\/j.kint.2023.03.034_bib40","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1021\/bi061180d","article-title":"Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization","volume":"45","author":"Luo","year":"2006","journal-title":"Biochemistry"},{"key":"10.1016\/j.kint.2023.03.034_bib41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3389\/fimmu.2018.00359","article-title":"Hypertonic saline suppresses NADPH oxidase-dependent neutrophil extracellular trap formation and promotes apoptosis","volume":"9","author":"Nadesalingam","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.kint.2023.03.034_bib42","doi-asserted-by":"crossref","first-page":"7961","DOI":"10.1167\/iovs.14-15332","article-title":"Hyperosmolar stress induces neutrophil extracellular trap formation: implications for dry eye disease","volume":"55","author":"Tibrewal","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.kint.2023.03.034_bib43","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nature11868","article-title":"Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells","volume":"496","author":"Kleinewietfeld","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.kint.2023.03.034_bib44","doi-asserted-by":"crossref","first-page":"6931","DOI":"10.1038\/ncomms7931","article-title":"Macrophages monitor tissue osmolarity and induce inflammatory response through NLRP3 and NLRC4 inflammasome activation","volume":"6","author":"Ip","year":"2015","journal-title":"Nat Commun"},{"key":"10.1016\/j.kint.2023.03.034_bib45","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.824907","article-title":"Neuroinflammation and neutrophils: modulation by ouabain","volume":"13","author":"Leite","year":"2022","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.kint.2023.03.034_bib46","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1002\/mrm.21402","article-title":"Sodium renal imaging in mice at high magnetic fields","volume":"58","author":"Neuberger","year":"2007","journal-title":"Magn Reson Med"},{"key":"10.1016\/j.kint.2023.03.034_bib47","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1002\/jmri.24732","article-title":"Characteristic time courses of cortical and medullary sodium signals measured by noninvasive 23 Na-MRI in rat kidney induced by furosemide: kidney sodium after furosemide infusion","volume":"41","author":"Liu","year":"2015","journal-title":"J\u00a0Magn Reson Imaging"},{"key":"10.1016\/j.kint.2023.03.034_bib48","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.kint.2020.04.056","article-title":"Visualization of sodium dynamics in the kidney by magnetic resonance imaging in a multi-site study","volume":"98","author":"Grist","year":"2020","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2023.03.034_bib49","doi-asserted-by":"crossref","DOI":"10.1016\/j.imbio.2019.11.002","article-title":"Neutrophil extracellular traps impair fungal clearance in a mouse model of invasive pulmonary aspergillosis","volume":"225","author":"Alflen","year":"2020","journal-title":"Immunobiology"},{"key":"10.1016\/j.kint.2023.03.034_bib50","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/ajh\/hpaa049","article-title":"Sodium handling and interaction in numerous organs","volume":"33","author":"Minegishi","year":"2020","journal-title":"Am J Hypertens"}],"container-title":["Kidney International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S008525382300265X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S008525382300265X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T01:05:36Z","timestamp":1758762336000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S008525382300265X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["S008525382300265X"],"URL":"https:\/\/doi.org\/10.1016\/j.kint.2023.03.034","relation":{},"ISSN":["0085-2538"],"issn-type":[{"value":"0085-2538","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Kidney medullary sodium chloride concentrations induce neutrophil and monocyte extracellular DNA traps that defend against pyelonephritis in\u00a0vivo","name":"articletitle","label":"Article Title"},{"value":"Kidney International","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.kint.2023.03.034","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}