Abstract

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 “RBC trapping directly promotes tubular injury independent of extending ischemia time.” 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 min 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 min 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.

Details

Title
Extravasation of Blood and Blood Toxicity Drives Tubular Injury from RBC Trapping in Ischemic AKI
Author
McLarnon, Sarah R 1 ; Johnson, Chloe 1 ; Sun, Jingping 1 ; Wei, Qingqing 2 ; Csanyi, Gabor 3   VIAFID ORCID Logo  ; O'Herron, Phillip 1 ; Marshall, Brendan 2 ; Giddens, Priya 1 ; Sullivan, Jennifer C 1 ; Barrett, Amanda 4 ; O'Connor, Paul M 1   VIAFID ORCID Logo 

 Department of Physiology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA 
 Department of Anatomy and Cell Biology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA 
 Department of Pharmacology and Toxicology, Augusta University , 30912, Augusta, GA , USA 
 Department of Pathology, Medical College of Georgia, Augusta University , 30912, Augusta, GA , USA 
Publication year
2023
Publication date
2023
Publisher
Oxford University Press
e-ISSN
26338823
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3191818234
Copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of American Physiological Society. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.