{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:14:02Z","timestamp":1789874042096,"version":"4.0.1"},"reference-count":83,"publisher":"American Physiological Society","issue":"6","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":247,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["IA2021RC3"],"award-info":[{"award-number":["IA2021RC3"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Heart Association Transformational","award":["970585"],"award-info":[{"award-number":["970585"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Red blood cell (RBC) trapping is common in ischemic acute kidney injury (AKI) and presents as densely packed RBCs that accumulate within and engorge the kidney medullary circulation. In this study, we tested the hypothesis that \u201cRBC trapping directly promotes tubular injury independent of extending ischemia time.\u201d Studies were performed on rats. Red blood cell congestion and tubular injury were compared between renal arterial clamping, venous clamping, and venous clamping of blood-free kidneys. Vessels were occluded for either 15 or 45\u2009min with and without reperfusion. We found that RBC trapping in the medullary capillaries occurred rapidly following reperfusion from renal arterial clamping and that this was associated with extravasation of blood from congested vessels, uptake of blood proteins by the tubules, and marked tubular injury. To determine if this injury was due to blood toxicity or an extension of ischemia time, we compared renal venous and arterial clamping without reperfusion. Venous clamping resulted in RBC trapping and marked tubular injury within 45\u2009min of ischemia. Conversely, despite the same ischemia time, RBC trapping and tubular injury were minimal following arterial clamping without reperfusion. Confirming the role of blood toward tubular injury, injury was markedly reduced in blood-free kidneys with venous clamping. Our data demonstrate that RBC trapping results in the rapid extravasation and uptake of blood components by tubular cells, causing toxic tubular injury. Tubular toxicity from extravasation of blood following RBC trapping appears to be a major component of tubular injury in ischemic AKI, which has not previously been recognized.<\/jats:p>","DOI":"10.1093\/function\/zqad050","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T16:13:49Z","timestamp":1693412029000},"source":"Crossref","is-referenced-by-count":5,"title":["Extravasation of Blood and Blood Toxicity Drives Tubular Injury from RBC Trapping in Ischemic AKI"],"prefix":"10.1152","volume":"4","author":[{"given":"Sarah R","family":"McLarnon","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"},{"name":"Department of Cell Biology and Physiology, School of Medicine, University of North Carolina , 27599, Chapel Hill, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingping","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4429-3031","authenticated-orcid":false,"given":"Gabor","family":"Csanyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"O'Herron","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Giddens","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Barrett","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7387-0184","authenticated-orcid":false,"given":"Paul M","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"issue":"3","key":"2024050208162195500_bib1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/ki.1984.171","article-title":"Role of the medullary perfusion defect in the pathogenesis of ischemic renal failure","volume":"26","author":"Mason","year":"1984","journal-title":"Kidney Int"},{"issue":"6","key":"2024050208162195500_bib2","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.semnephrol.2019.10.002","article-title":"Ischemic renal injury: can renal anatomy and associated vascular congestion explain why the medulla and not the cortex is where the trouble starts?","volume":"39","author":"Ray","year":"2019","journal-title":"Semin Nephrol"},{"issue":"3","key":"2024050208162195500_bib3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/archinte.1949.00220320003001","article-title":"Management of lower nephron nephrosis; 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