{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:47:18Z","timestamp":1747187238613,"version":"3.40.5"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1099222","GNT1161319"],"award-info":[{"award-number":["GNT1099222","GNT1161319"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bile cast nephropathy (BCN) is an underdiagnosed cause of acute kidney injury (AKI). The precise pathogenesis of bilirubin tubular toxicity remains unknown. The aim of this study is to explore the cellular and molecular pathophysiology of human BCN. Paraffin\u2010embedded sections of renal biopsy tissue from a BCN patient were stained by immunohistochemistry (IHC) for oxidative stress (4\u2010hydroxynonenal), immune cell subpopulations, including dendritic cells (CD1c), macrophages (CD68) and T cells (CD3), and inflammasome activation by staining for active\u2010caspase\u20101 and the inflammasome adaptor protein, ASC (apoptosis\u2010associated speck\u2010like protein containing a caspase activation and recruitment domain). Quantitative analyses of IHC staining were compared to healthy renal cortical tissue. We identified yellow to brown granular casts within the BCN case, consistent with the presence of bile pigment. The presence of bile pigment was associated with strong tubular 4\u2010hydroxynonenal staining intensity, a marker of oxidative stress. Diffuse tubulointerstitial inflammatory cell infiltrate was detected, with elevated CD1c, CD68 and CD3 staining. Foci of inflammasome activity were co\u2010localized with this intense immune cell infiltration, with increased active\u2010caspase\u20101 and ASC staining. Our findings are the first to suggest that bile casts may lead to oxidative stress and trigger the inflammasome signalling cascade, leading to interstitial inflammation and driving AKI pathobiology.<\/jats:p><jats:p><jats:boxed-text content-type=\"box\" position=\"float\"><jats:caption><jats:title>SUMMARY AT A GLANCE<\/jats:title><\/jats:caption><jats:p>The report suggests that bile casts may lead to oxidative stress and trigger the inflammasome signalling cascade, leading to interstitial inflammation and driving bile cast nephropathy pathobiology.<\/jats:p><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/nep.13696","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T11:55:02Z","timestamp":1580385302000},"page":"502-506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of inflammation and inflammasome activation in human bile cast nephropathy"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-8483","authenticated-orcid":false,"given":"Kurt T. K.","family":"Giuliani","sequence":"first","affiliation":[{"name":"Kidney Health Service Royal Brisbane and Women's Hospital  Herston Queensland Australia"},{"name":"Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"},{"name":"Faculty of Medicine University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Kassianos","sequence":"additional","affiliation":[{"name":"Kidney Health Service Royal Brisbane and Women's Hospital  Herston Queensland Australia"},{"name":"Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"},{"name":"Faculty of Medicine University of Queensland  Brisbane Queensland Australia"},{"name":"Institute of Health and Biomedical Innovation\/School of Biomedical Sciences Queensland University of Technology  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Kildey","sequence":"additional","affiliation":[{"name":"Kidney Health Service Royal Brisbane and Women's Hospital  Herston Queensland Australia"},{"name":"Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anca","family":"Grivei","sequence":"additional","affiliation":[{"name":"Kidney Health Service Royal Brisbane and Women's Hospital  Herston Queensland Australia"},{"name":"Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangju","family":"Wang","sequence":"additional","affiliation":[{"name":"Kidney Health Service Royal Brisbane and Women's Hospital  Herston Queensland Australia"},{"name":"Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacobus","family":"Ungerer","sequence":"additional","affiliation":[{"name":"Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"},{"name":"Faculty of Medicine University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Francis","sequence":"additional","affiliation":[{"name":"Anatomical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Healy","sequence":"additional","affiliation":[{"name":"Kidney Health Service Royal Brisbane and Women's Hospital  Herston Queensland Australia"},{"name":"Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"},{"name":"Faculty of Medicine University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro F. H.","family":"Gois","sequence":"additional","affiliation":[{"name":"Kidney Health Service Royal Brisbane and Women's Hospital  Herston Queensland Australia"},{"name":"Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland Health Support Queensland  Herston Queensland Australia"},{"name":"Faculty of Medicine University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00039.2014"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-42876-7.00026-0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.78"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i27.6328"},{"key":"e_1_2_6_6_1","first-page":"1458","article-title":"Human kidney histopathology in acute obstructive jaundice: a prospective study","volume":"22","author":"Uslu A","year":"2010","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2016.08.023"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqx030"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.08.028"},{"key":"e_1_2_6_10_1","first-page":"170","article-title":"A case of mononucleosis infectiosa presenting with cholemic nephrosis","volume":"4","author":"Bredewold OW","year":"2011","journal-title":"NDT Plus"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.05.010"},{"key":"e_1_2_6_12_1","first-page":"229","article-title":"The pathology of jaundice\u2010related renal insufficiency: cholemic nephrosis revisited","volume":"19","author":"Betjes MG","year":"2006","journal-title":"J Nephrol"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2012.11.046"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R900012-JLR200"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000371689"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(00)82013-1"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252626999"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.040"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.03.035"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.207"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2018.05.005"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018101064"}],"container-title":["Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnep.13696","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.13696","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nep.13696","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.13696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:28:42Z","timestamp":1694046522000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nep.13696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,7]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1111\/nep.13696"],"URL":"https:\/\/doi.org\/10.1111\/nep.13696","archive":["Portico"],"relation":{},"ISSN":["1320-5358","1440-1797"],"issn-type":[{"type":"print","value":"1320-5358"},{"type":"electronic","value":"1440-1797"}],"subject":[],"published":{"date-parts":[[2020,2,7]]},"assertion":[{"value":"2020-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}