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Remote effects of acute kidney injury in a porcine model
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...
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| Published in: | American journal of physiology. Renal physiology 2016-02, Vol.310 (4), p.F259-F271 |
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| Main Authors: | , , , , , , , , |
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| container_end_page | F271 |
| container_issue | 4 |
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| container_title | American journal of physiology. Renal physiology |
| container_volume | 310 |
| creator | Gardner, David S De Brot, Simone Dunford, Louise J Grau-Roma, Llorenc Welham, Simon J M Fallman, Rebecca O'Sullivan, Saoirse E Oh, Weng Devonald, Mark A J |
| description | 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 [Ca(2+)] 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. |
| doi_str_mv | 10.1152/ajprenal.00389.2015 |
| format | article |
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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 [Ca(2+)] 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.</description><identifier>ISSN: 1931-857X</identifier><identifier>EISSN: 1522-1466</identifier><identifier>DOI: 10.1152/ajprenal.00389.2015</identifier><identifier>PMID: 26608790</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Acute Kidney Injury - complications ; Acute Kidney Injury - physiopathology ; Animals ; Apoptosis ; Biochemistry ; Blood Cell Count ; Cytokines ; Cytokines - biosynthesis ; Disease Models, Animal ; Edema - etiology ; Edema - pathology ; Electrolytes - blood ; Female ; Hippocampus - pathology ; Histopathology ; Hogs ; Immunity, Cellular - immunology ; Kidney diseases ; Liver - pathology ; Lung - pathology ; Reperfusion Injury - complications ; Reperfusion Injury - physiopathology ; Swine</subject><ispartof>American journal of physiology. Renal physiology, 2016-02, Vol.310 (4), p.F259-F271</ispartof><rights>Copyright © 2016 the American Physiological Society.</rights><rights>Copyright American Physiological Society Feb 15, 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-80ba0655969dec057c10992dd43b3ca8c7c95fad999a7d7bc0fc0ebaababfef33</citedby><cites>FETCH-LOGICAL-c378t-80ba0655969dec057c10992dd43b3ca8c7c95fad999a7d7bc0fc0ebaababfef33</cites><orcidid>0000-0002-6490-2412</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26608790$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gardner, David S</creatorcontrib><creatorcontrib>De Brot, Simone</creatorcontrib><creatorcontrib>Dunford, Louise J</creatorcontrib><creatorcontrib>Grau-Roma, Llorenc</creatorcontrib><creatorcontrib>Welham, Simon J M</creatorcontrib><creatorcontrib>Fallman, Rebecca</creatorcontrib><creatorcontrib>O'Sullivan, Saoirse E</creatorcontrib><creatorcontrib>Oh, Weng</creatorcontrib><creatorcontrib>Devonald, Mark A J</creatorcontrib><title>Remote effects of acute kidney injury in a porcine model</title><title>American journal of physiology. Renal physiology</title><addtitle>Am J Physiol Renal Physiol</addtitle><description>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 [Ca(2+)] 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.</description><subject>Acute Kidney Injury - complications</subject><subject>Acute Kidney Injury - physiopathology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Blood Cell Count</subject><subject>Cytokines</subject><subject>Cytokines - biosynthesis</subject><subject>Disease Models, Animal</subject><subject>Edema - etiology</subject><subject>Edema - pathology</subject><subject>Electrolytes - blood</subject><subject>Female</subject><subject>Hippocampus - pathology</subject><subject>Histopathology</subject><subject>Hogs</subject><subject>Immunity, Cellular - immunology</subject><subject>Kidney diseases</subject><subject>Liver - pathology</subject><subject>Lung - pathology</subject><subject>Reperfusion Injury - complications</subject><subject>Reperfusion Injury - physiopathology</subject><subject>Swine</subject><issn>1931-857X</issn><issn>1522-1466</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNpdkE1LxDAQhoMo7rr6CwQpePHSdZJsmuYoi1-wIIiCt5KmE2htm5q0h_33tvvhwdM7zDzvHB5CriksKRXsXledx1bXSwCeqiUDKk7IfLywmK6S5HScFadxKuTXjFyEUAEApYyekxlLEkilgjlJ37FxPUZoLZo-RM5G2gzj4rssWtxGZVsNfopIR53zpmwxalyB9SU5s7oOeHXIBfl8evxYv8Sbt-fX9cMmNlymfZxCriERQiWqQANCGgpKsaJY8ZwbnRpplLC6UEppWcjcgDWAuda5zi1azhfkbv-38-5nwNBnTRkM1rVu0Q0hozIRiq2YkCN6-w-t3OBHQzsqTThwNlF8TxnvQvBos86XjfbbjEI2ic2OYrOd2GwSO7ZuDr-HvMHir3M0yX8BOIF1wQ</recordid><startdate>20160215</startdate><enddate>20160215</enddate><creator>Gardner, David S</creator><creator>De Brot, Simone</creator><creator>Dunford, Louise J</creator><creator>Grau-Roma, Llorenc</creator><creator>Welham, Simon J M</creator><creator>Fallman, Rebecca</creator><creator>O'Sullivan, Saoirse E</creator><creator>Oh, Weng</creator><creator>Devonald, Mark A J</creator><general>American Physiological Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6490-2412</orcidid></search><sort><creationdate>20160215</creationdate><title>Remote effects of acute kidney injury in a porcine model</title><author>Gardner, David S ; De Brot, Simone ; Dunford, Louise J ; Grau-Roma, Llorenc ; Welham, Simon J M ; Fallman, Rebecca ; O'Sullivan, Saoirse E ; Oh, Weng ; Devonald, Mark A J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-80ba0655969dec057c10992dd43b3ca8c7c95fad999a7d7bc0fc0ebaababfef33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acute Kidney Injury - complications</topic><topic>Acute Kidney Injury - physiopathology</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Blood Cell Count</topic><topic>Cytokines</topic><topic>Cytokines - biosynthesis</topic><topic>Disease Models, Animal</topic><topic>Edema - etiology</topic><topic>Edema - pathology</topic><topic>Electrolytes - blood</topic><topic>Female</topic><topic>Hippocampus - pathology</topic><topic>Histopathology</topic><topic>Hogs</topic><topic>Immunity, Cellular - immunology</topic><topic>Kidney diseases</topic><topic>Liver - pathology</topic><topic>Lung - pathology</topic><topic>Reperfusion Injury - complications</topic><topic>Reperfusion Injury - physiopathology</topic><topic>Swine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gardner, David S</creatorcontrib><creatorcontrib>De Brot, Simone</creatorcontrib><creatorcontrib>Dunford, Louise J</creatorcontrib><creatorcontrib>Grau-Roma, Llorenc</creatorcontrib><creatorcontrib>Welham, Simon J M</creatorcontrib><creatorcontrib>Fallman, Rebecca</creatorcontrib><creatorcontrib>O'Sullivan, Saoirse E</creatorcontrib><creatorcontrib>Oh, Weng</creatorcontrib><creatorcontrib>Devonald, Mark A J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology. Renal physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gardner, David S</au><au>De Brot, Simone</au><au>Dunford, Louise J</au><au>Grau-Roma, Llorenc</au><au>Welham, Simon J M</au><au>Fallman, Rebecca</au><au>O'Sullivan, Saoirse E</au><au>Oh, Weng</au><au>Devonald, Mark A J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Remote effects of acute kidney injury in a porcine model</atitle><jtitle>American journal of physiology. Renal physiology</jtitle><addtitle>Am J Physiol Renal Physiol</addtitle><date>2016-02-15</date><risdate>2016</risdate><volume>310</volume><issue>4</issue><spage>F259</spage><epage>F271</epage><pages>F259-F271</pages><issn>1931-857X</issn><eissn>1522-1466</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>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 [Ca(2+)] 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.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>26608790</pmid><doi>10.1152/ajprenal.00389.2015</doi><orcidid>https://orcid.org/0000-0002-6490-2412</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of physiology. Renal physiology, 2016-02, Vol.310 (4), p.F259-F271 |
| issn | 1931-857X 1522-1466 |
| language | eng |
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| source | American Physiological Society Free |
| subjects | Acute Kidney Injury - complications Acute Kidney Injury - physiopathology Animals Apoptosis Biochemistry Blood Cell Count Cytokines Cytokines - biosynthesis Disease Models, Animal Edema - etiology Edema - pathology Electrolytes - blood Female Hippocampus - pathology Histopathology Hogs Immunity, Cellular - immunology Kidney diseases Liver - pathology Lung - pathology Reperfusion Injury - complications Reperfusion Injury - physiopathology Swine |
| title | Remote effects of acute kidney injury in a porcine model |
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