title: Changes in renal medulla gene expression in a pre-clinical model of post cardiopulmonary bypass acute kidney injury.
abstract: BACKGROUND
  Acute kidney injury (AKI) is a common and serious complication of cardiac surgery using cardiopulmonary bypass (CPB). The pathogenesis is poorly understood and the study of AKI in rodent models has not led to improvements in clinical outcomes. We sought to determine the changes in renal medullary gene expression in a novel and clinically relevant porcine model of CPB-induced AKI.
  
  
  RESULTS
  Adult pigs (n = 12 per group) were randomised to undergo sham procedure, or 2.5 hours CPB. AKI was determined using biochemical (Cr51 EDTA clearance, CrCl, urinary IL-18 release) and histological measures. Transcriptomic analyses were performed on renal medulla biopsies obtained 24 hours post intervention or from sham group. Microarray results were validated with real-time polymerase chain reaction and Western Blotting.Of the transcripts examined, 66 were identified as differentially expressed in CPB versus Sham pig's kidney samples, with 19 (29%) upregulated and 47 (71%) down-regulated. Out of the upregulated and downregulated transcripts 4 and 16 respectively were expression sequence tags (EST). The regulated genes clustered into three classes; Immune response, Cell adhesion/extracellular matrix and metabolic process. Upregulated genes included Factor V, SLC16A3 and CKMT2 whereas downregulated genes included GST, CPE, MMP7 and SELL.
  
  
  CONCLUSIONS
  Post CPB AKI, as defined by clinical criteria, is characterised by molecular changes in renal medulla that are associated with both injury and survival programmes. Our observations highlight the value of large animal models in AKI research and provide insights into the failure of findings in rodent models to translate into clinical progress.
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Level 7, Bristol Royal Infirmary; Upper Maudlin Street, Bristol BS2 8HW, UK. m.ghorbel@bris.ac.uk.
authors.forename: Mohamed T
authors.initials: MT
authors.lastname: Ghorbel
authors.forename: Nishith N
authors.initials: NN
authors.lastname: Patel
authors.forename: Maimuna
authors.initials: M
authors.lastname: Sheikh
authors.forename: Gianni D
authors.initials: GD
authors.lastname: Angelini
authors.forename: Massimo
authors.initials: M
authors.lastname: Caputo
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Murphy
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007679:Kidney Medulla / Q000378:metabolism*; D008969:Molecular Sequence Data; D017423:Sequence Analysis, RNA; D013552:Swine
chemical_list: D015415:Biomarkers