Changes in renal medulla gene expression in a pre-clinical model of post cardiopulmonary bypass acute kidney injury

BMC Genomics

Gavin J Murphy³  Massimo Caputo¹  Gianni D Angelini²  Maimuna Sheikh²  Nishith N Patel²  Mohamed T Ghorbel² 

[1] RUSH University Medical Center, Chicago, IL, USA;Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Level 7, Bristol Royal Infirmary; Upper Maudlin Street, Bristol BS2 8HW, UK;Deparment of Cardiovascular Sciences, University of Leceister, Leceister, UK

关键词: Gene expression;    Cardiopulmonary bypass;    Acute kidney injury;   

Others  :  1128440
DOI  :  10.1186/1471-2164-15-916

 received in 2014-01-21, accepted in 2014-10-08,  发布年份 2014

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2014 Ghorbel et al.; licensee BioMed Central Ltd.

【 图 表 】

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