Abstract
BackgroundAcute 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.ResultsAdult 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.ConclusionPost 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-916) contains supplementary material, which is available to authorized users.
Highlights
Acute kidney injury (AKI) is a common and serious complication of cardiac surgery using cardiopulmonary bypass (CPB)
CPB was characterised by a reduction in mean arterial blood pressure (MABP) and circulating haematocrit, as is typically observed clinically
We noted a tendency to increase by CPB for Factor 5. This microarray-based gene expression profiling study confirms the existence of transcriptomic changes of the renal medulla in response to post-CPB AKI
Summary
Acute kidney injury (AKI) is a common and serious complication of cardiac surgery using cardiopulmonary bypass (CPB). Cardiopulmonary bypass (CPB) is a major contributor to AKI post-cardiac surgery [6] Attempts to ameliorate this injury in clinical studies have, to date been unsuccessful [7]. We have identified medullary hypoxia and an apparently paradoxical elevation in cellular ATP levels in the outer medulla in association with intra-renal vasoconstriction and endothelial dysfunction in kidneys exhibiting AKI as defined clinically at 24 hours post CPB in the swine model [14]. The aim of the current study was to investigate global transcriptomic alterations in the renal medulla in post CPB kidneys in this model in order to gain greater insight into the pathogenesis of this condition
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
