{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:30:41Z","timestamp":1790739041006,"version":"4.1.0"},"reference-count":31,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/501100001505","name":"Health research council new zealand","doi-asserted-by":"crossref","award":["17\/425"],"award-info":[{"award-number":["17\/425"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK069403"],"award-info":[{"award-number":["R01 DK069403"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-17-1-0610"],"award-info":[{"award-number":["W81XWH-17-1-0610"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p>Acute kidney injury (AKI) remains a major global healthcare problem, and there is a need to develop human-based models to study AKI in vitro. Toward this goal, we have characterized induced pluripotent stem cell-derived human kidney organoids and their response to cisplatin, a chemotherapeutic drug that induces AKI and preferentially damages the proximal tubule. We found that a single treatment with 50 \u00b5M cisplatin induces hepatitis A virus cellular receptor 1 ( HAVCR1) and C-X-C motif chemokine ligand 8 ( CXCL8) expression, DNA damage (\u03b3H2AX), and cell death in the organoids but greatly impairs organoid viability. DNA damage was not specific to the proximal tubule but also affected the distal tubule and interstitial cell populations. This lack of specificity correlated with low expression of proximal tubule-specific SLC22A2\/organic cation transporter 2 ( OCT2) for cisplatin. To improve viability, we developed a repeated low-dose regimen of 4 \u00d7 5 \u00b5M cisplatin over 7 days and found this caused less toxicity while still inducing a robust injury response that included secretion of known AKI biomarkers and inflammatory cytokines. This work validates the use of human kidney organoids to model aspects of cisplatin-induced injury, with the potential to identify new AKI biomarkers and develop better therapies.<\/jats:p>","DOI":"10.1152\/ajprenal.00597.2019","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T12:10:21Z","timestamp":1583755821000},"page":"F971-F978","source":"Crossref","is-referenced-by-count":114,"title":["Evaluation of cisplatin-induced injury in human kidney organoids"],"prefix":"10.1152","volume":"318","author":[{"given":"Jenny L. M.","family":"Digby","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thitinee","family":"Vanichapol","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Przepiorski","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-833X","authenticated-orcid":false,"given":"Veronika","family":"Sander","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00179.2018"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61234-5"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2017.01.003"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9715"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00385.2019"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00085"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1101\/gad.329573.119"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94716"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019090876"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006030205"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3392"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506483102"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/967826"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90545.2008"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.06.018"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200215606"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00195.2018"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00285.2017"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0003-9"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.08.037"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nature15695"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e31812dfe1e"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08290-2"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-050214-013407"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00597.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T10:02:15Z","timestamp":1585044135000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajprenal.00597.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4,1]]}},"alternative-id":["10.1152\/ajprenal.00597.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00597.2019","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,1]]}}}