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Remote effects of acute kidney injury in a porcine model


Mark A.J. Devonald

Saoirse E.

Simone De Brot

Louise J. Dunford

Llorenc Grau-Roma

Rebecca Fallman

Saoirse O'Sullivan

Weng Oh

Mark A. J. Devonald


© 2016 the American Physiological Society. Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g., AST:ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca2+] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.


Devonald, M. A., O’Sullivan, S. E., Gardner, D. S., De Brot, S., Dunford, L. J., Grau-Roma, L., …Devonald, M. A. J. (2016). Remote effects of acute kidney injury in a porcine model. AJP - Renal Physiology, 310(4), F259-F271.

Journal Article Type Article
Acceptance Date Nov 19, 2015
Online Publication Date Feb 15, 2016
Publication Date Feb 15, 2016
Deposit Date Feb 19, 2016
Publicly Available Date Feb 19, 2016
Journal American Journal of Physiology - Renal Physiology
Print ISSN 1931-857X
Electronic ISSN 1522-1466
Publisher American Physiological Society
Peer Reviewed Peer Reviewed
Volume 310
Issue 4
Pages F259-F271
Keywords ischemia-reperfusion; distant effects; cytokines; apoptosis; AKI
Public URL
Publisher URL


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