Summary
Acute kidney injury (AKI) represents a sudden reduction in renal function and is a
major clinical problem with a high mortality rate. Despite decades of research, there
are currently no direct therapies for AKI. The failure of therapeutic approaches identified
in rodents to translate to human beings has led to questions regarding the appropriateness
of these models. Our recent data indicate that there are two distinct processes driving
tubular injury in the commonly used rat model of warm bilateral renal ischemia reperfusion
injury, which often is used to mimic ischemic AKI. One results from the period of
warm ischemia, manifesting as sublethal injury and coagulative necrosis of the proximal
tubules in the renal cortex. This is the predominate type of injury observed 24 hours
after reperfusion and the most well studied. The other results from red blood cell
congestion of the outer medullary vasculature. This type of injury manifests as cell
sloughing, along with the later formation of heme casts that fill distal nephron segments.
Cell sloughing from congestion is most prominent in the early hours after reperfusion
and often is masked by regeneration of the tubular epithelium by 24 hours postischemia.
In this review, we argue that injury from outer medullary red blood cell congestion
reflects the pathology observed in human kidneys and likely is representative of injury
in most cases of ischemic AKI after shock. Greater focus on this congestive injury
is likely to lead to improved translation in AKI.
Keywords
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Article info
Publication history
Published online: January 04, 2023
Footnotes
Financial support: Supported by National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases grant ISAC 21AU4231, National Institutes of Health National Heart, Lung, and Blood Institute grant P01 HL134604, and an American Heart Association Transformational Project Award 970585 (P.M.O.), and by National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases grant F31 DK127683 (S.C.M.).
Conflict of interest statement: none.
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