Albumin-Keratin Casts Obstruct Renal Tubular and Vascular Lumens Following Kidney Ischemia
Introduction: We have recently reported that in ischemic acute kidney injury (AKI), red blood cell (RBC) trapping causes fluid extravasation from the congested capillary circulation and subsequent toxic injury to the surrounding tubules. The goal of this study was to identify the cause of the obstru...
| 發表在: | Kidney International Reports |
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| Main Authors: | , , , , , , , , , , , , , , , , |
| 格式: | Article |
| 語言: | 英语 |
| 出版: |
Elsevier
2026-04-01
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| 主題: | |
| 在線閱讀: | http://www.sciencedirect.com/science/article/pii/S2468024926025878 |
| _version_ | 1875911866039926784 |
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| author | Martina Bryant Olivia Boykin Olivia Mosley Angela Ajith Oliver Oglesby Konstantin Kurzin Carlee Harris Sadaf Husan Daniela Dokam Sarah R. McLarnon Jingping Sun Brendan Marshall Amanda Barrett Aaron Polichnowski Wendy B. Bollag David Mattson Paul M. O’Connor |
| author_facet | Martina Bryant Olivia Boykin Olivia Mosley Angela Ajith Oliver Oglesby Konstantin Kurzin Carlee Harris Sadaf Husan Daniela Dokam Sarah R. McLarnon Jingping Sun Brendan Marshall Amanda Barrett Aaron Polichnowski Wendy B. Bollag David Mattson Paul M. O’Connor |
| author_sort | Martina Bryant |
| collection | DOAJ |
| container_title | Kidney International Reports |
| description | Introduction: We have recently reported that in ischemic acute kidney injury (AKI), red blood cell (RBC) trapping causes fluid extravasation from the congested capillary circulation and subsequent toxic injury to the surrounding tubules. The goal of this study was to identify the cause of the obstruction leading to RBC trapping. Methods: Studies were performed in Sprague Dawley rats and human kidneys. Rats underwent warm arterial clamp ischemia for 45 minutes with 0 to 24 hours of reperfusion. New blood entering the kidney upon reperfusion of the kidney was tracked using Evans blue dye. At harvest, kidneys were fixed and histological analysis performed. Vascular and tubular casts from 4 human and 3 rat kidneys were isolated using laser dissection microscopy and their contents determined by mass spectrometry shotgun proteomics. Results: New blood entering the kidney appeared to be impeded in large renal veins by a homogeneous substance which stained blue in trichrome sections. Scanning electron microscopy revealed the substance to be a solid that conformed the shape of the encased RBCs. A similar substance was observed in the lumens of many tubules and small capillaries. Proteomic analysis identified albumin and keratins as major proteins present in the casts, and this was confirmed using immunohistochemistry. Conclusion: Our data indicate that albumin-keratin casts obstruct both vascular and tubular structures in the kidney following a period of ischemia. These casts may be the primary cause of vascular obstruction post-ischemia and likely lead to RBC trapping and associated acute tubular injury. |
| format | Article |
| id | doaj-art-e8c5ee9b8dfd4cbfa54ed8cc00c2a04d |
| institution | Directory of Open Access Journals |
| issn | 2468-0249 |
| language | English |
| publishDate | 2026-04-01 |
| publisher | Elsevier |
| record_format | Article |
| spelling | doaj-art-e8c5ee9b8dfd4cbfa54ed8cc00c2a04d2026-04-05T04:33:13ZengElsevierKidney International Reports2468-02492026-04-0111410635610.1016/j.ekir.2026.106356Albumin-Keratin Casts Obstruct Renal Tubular and Vascular Lumens Following Kidney IschemiaMartina Bryant0Olivia Boykin1Olivia Mosley2Angela Ajith3Oliver Oglesby4Konstantin Kurzin5Carlee Harris6Sadaf Husan7Daniela Dokam8Sarah R. McLarnon9Jingping Sun10Brendan Marshall11Amanda Barrett12Aaron Polichnowski13Wendy B. Bollag14David Mattson15Paul M. O’Connor16Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Cell Biology and Physiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Anatomy and Cell Biology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Pathology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USADepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA; Correspondence: Paul M. O’Connor, Department of Physiology, Medical College of Georgia, CB2206, Augusta University, Augusta, Georgia, USA.Introduction: We have recently reported that in ischemic acute kidney injury (AKI), red blood cell (RBC) trapping causes fluid extravasation from the congested capillary circulation and subsequent toxic injury to the surrounding tubules. The goal of this study was to identify the cause of the obstruction leading to RBC trapping. Methods: Studies were performed in Sprague Dawley rats and human kidneys. Rats underwent warm arterial clamp ischemia for 45 minutes with 0 to 24 hours of reperfusion. New blood entering the kidney upon reperfusion of the kidney was tracked using Evans blue dye. At harvest, kidneys were fixed and histological analysis performed. Vascular and tubular casts from 4 human and 3 rat kidneys were isolated using laser dissection microscopy and their contents determined by mass spectrometry shotgun proteomics. Results: New blood entering the kidney appeared to be impeded in large renal veins by a homogeneous substance which stained blue in trichrome sections. Scanning electron microscopy revealed the substance to be a solid that conformed the shape of the encased RBCs. A similar substance was observed in the lumens of many tubules and small capillaries. Proteomic analysis identified albumin and keratins as major proteins present in the casts, and this was confirmed using immunohistochemistry. Conclusion: Our data indicate that albumin-keratin casts obstruct both vascular and tubular structures in the kidney following a period of ischemia. These casts may be the primary cause of vascular obstruction post-ischemia and likely lead to RBC trapping and associated acute tubular injury.http://www.sciencedirect.com/science/article/pii/S2468024926025878acute kidney injurycastscytokeratinischemia-reperfusionred blood cell trapping |
| spellingShingle | Martina Bryant Olivia Boykin Olivia Mosley Angela Ajith Oliver Oglesby Konstantin Kurzin Carlee Harris Sadaf Husan Daniela Dokam Sarah R. McLarnon Jingping Sun Brendan Marshall Amanda Barrett Aaron Polichnowski Wendy B. Bollag David Mattson Paul M. O’Connor Albumin-Keratin Casts Obstruct Renal Tubular and Vascular Lumens Following Kidney Ischemia acute kidney injury casts cytokeratin ischemia-reperfusion red blood cell trapping |
| title | Albumin-Keratin Casts Obstruct Renal Tubular and Vascular Lumens Following Kidney Ischemia |
| title_full | Albumin-Keratin Casts Obstruct Renal Tubular and Vascular Lumens Following Kidney Ischemia |
| title_fullStr | Albumin-Keratin Casts Obstruct Renal Tubular and Vascular Lumens Following Kidney Ischemia |
| title_full_unstemmed | Albumin-Keratin Casts Obstruct Renal Tubular and Vascular Lumens Following Kidney Ischemia |
| title_short | Albumin-Keratin Casts Obstruct Renal Tubular and Vascular Lumens Following Kidney Ischemia |
| title_sort | albumin keratin casts obstruct renal tubular and vascular lumens following kidney ischemia |
| topic | acute kidney injury casts cytokeratin ischemia-reperfusion red blood cell trapping |
| url | http://www.sciencedirect.com/science/article/pii/S2468024926025878 |
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