Microarray analysis of gene expression profiles in the rat kidney demonstrates a local inflammatory response induced by cardiopulmonary bypass

<p>CONTEXTCardiopulmonary bypass (CPB) is a commonly used technique in cardiac surgery but is associated with acute, transient, renal dysfunction that has a negative impact on long-term survival.OBJECTIVETo unravel the molecular pathogenesis of renal injury following CPB.DESIGNTo obtain insight into the pathogenesis of renal dysfunction following CPB, we performed a microarray analysis of renal gene expression in the rat.SETTINGUniversity Medical Centre Groningen.INTERVENTIONRats underwent CPB or a sham procedure for 60min and were sacrificed at 60min, 1 and 5 days after the procedure.MAIN OUTCOME MEASURESRenal gene expression profile as determined by microarray analysis.RESULTSExpression of 420 genes was significantly altered in CPB compared to the sham procedure, and in 407 genes, this was evident in the acute phase (60min) following CPB. Gene ontology analysis revealed 28 of these genes were involved in inflammatory responses, with high expression of genes downstream of mitogen-activated protein-kinase (MAP-kinase) signalling pathways. Potent inducers identified are from the interleukin-6 cytokine family that consists of interleukin-6 and oncostatin M (OSM), which signal through the gp130-cytokine receptor complex. The plasma concentration of interleukin-6 was hugely increased by CPB as measured by ELISA. Expression of genes downstream of these signalling pathways that lead to production of chemokines, adhesion molecules and molecules involved in coagulative pathways, was upregulated.CONCLUSIONCPB induces an acute and local inflammatory response in the kidney, which might contribute to renal injury. The signalling pathways involved identified by gene expression analysis may represent pharmacological targets to limit renal injury following CPB.</p>