Remote effects of acute kidney injury in a porcine model
Background: Acute Kidney Injury (AKI) is a common and serious disease with no specific treatment. An episode of AKI may affect organs distant to 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 p...
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| Format: | Article |
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American Physiological Society
2016
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| Online Access: | https://eprints.nottingham.ac.uk/31848/ |
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| author | Gardner, David S. de Brot, Simone Dunford, Louise J. Grau-Roma, Llorenc Welham, Simon J.M. Fallman, Rebecca O'Sullivan, Saoirse Oh, Weng Devonald, Mark A.J. |
| author_facet | Gardner, David S. de Brot, Simone Dunford, Louise J. Grau-Roma, Llorenc Welham, Simon J.M. Fallman, Rebecca O'Sullivan, Saoirse Oh, Weng Devonald, Mark A.J. |
| author_sort | Gardner, David S. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background: Acute Kidney Injury (AKI) is a common and serious disease with no specific treatment. An episode of AKI may affect organs distant to 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 test the hypothesis that early effects of AKI on distant organs is by immune cell infiltration leading to inflammatory cytokine production, extravasation and edema.
Study Design: 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 48h reperfusion) and longer-term (5 weeks later) using immunofluorescence (for leucocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (electrolytes), blood hematology and chemistry (e.g. liver enzymes) and PCR (for inflammatory markers).
Results: AKI elicited significant, short-term (~24h) 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 [Ca++] increased; P=0.04). These effects largely resolved after 48h and no further histopathology, edema, apoptosis or immune cell infiltration was noted in liver, lung or hippocampus in the short- and longer-term.
Conclusions: 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 48h and no further remote organ histopathology, apoptosis, edema or immune cell infiltration was noted. |
| first_indexed | 2025-11-14T19:13:45Z |
| format | Article |
| id | nottingham-31848 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:13:45Z |
| publishDate | 2016 |
| publisher | American Physiological Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-318482020-05-04T17:37:05Z https://eprints.nottingham.ac.uk/31848/ Remote effects of acute kidney injury in a porcine model Gardner, David S. de Brot, Simone Dunford, Louise J. Grau-Roma, Llorenc Welham, Simon J.M. Fallman, Rebecca O'Sullivan, Saoirse Oh, Weng Devonald, Mark A.J. Background: Acute Kidney Injury (AKI) is a common and serious disease with no specific treatment. An episode of AKI may affect organs distant to 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 test the hypothesis that early effects of AKI on distant organs is by immune cell infiltration leading to inflammatory cytokine production, extravasation and edema. Study Design: 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 48h reperfusion) and longer-term (5 weeks later) using immunofluorescence (for leucocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (electrolytes), blood hematology and chemistry (e.g. liver enzymes) and PCR (for inflammatory markers). Results: AKI elicited significant, short-term (~24h) 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 [Ca++] increased; P=0.04). These effects largely resolved after 48h and no further histopathology, edema, apoptosis or immune cell infiltration was noted in liver, lung or hippocampus in the short- and longer-term. Conclusions: 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 48h and no further remote organ histopathology, apoptosis, edema or immune cell infiltration was noted. American Physiological Society 2016-02-15 Article PeerReviewed Gardner, David S., de Brot, Simone, Dunford, Louise J., Grau-Roma, Llorenc, Welham, Simon J.M., Fallman, Rebecca, O'Sullivan, Saoirse, Oh, Weng and Devonald, Mark A.J. (2016) Remote effects of acute kidney injury in a porcine model. American Journal of Physiology - Renal Physiology, 310 . F259-F271. ISSN 1522-1466 ischemia-reperfusion; distant effects; cytokines; apoptosis; AKI http://ajprenal.physiology.org/content/310/4/F259 doi:10.1152/ajprenal.00389.2015 doi:10.1152/ajprenal.00389.2015 |
| spellingShingle | ischemia-reperfusion; distant effects; cytokines; apoptosis; AKI Gardner, David S. de Brot, Simone Dunford, Louise J. Grau-Roma, Llorenc Welham, Simon J.M. Fallman, Rebecca O'Sullivan, Saoirse Oh, Weng Devonald, Mark A.J. Remote effects of acute kidney injury in a porcine model |
| title | Remote effects of acute kidney injury in a porcine model |
| title_full | Remote effects of acute kidney injury in a porcine model |
| title_fullStr | Remote effects of acute kidney injury in a porcine model |
| title_full_unstemmed | Remote effects of acute kidney injury in a porcine model |
| title_short | Remote effects of acute kidney injury in a porcine model |
| title_sort | remote effects of acute kidney injury in a porcine model |
| topic | ischemia-reperfusion; distant effects; cytokines; apoptosis; AKI |
| url | https://eprints.nottingham.ac.uk/31848/ https://eprints.nottingham.ac.uk/31848/ https://eprints.nottingham.ac.uk/31848/ |