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dc.contributor.authorHaase-Fielitz, Anjaen
dc.contributor.authorHaase, Michaelen
dc.contributor.authorBellomo, Rinaldoen
dc.contributor.authorLambert, Gavinen
dc.contributor.authorMatalanis, Georgeen
dc.contributor.authorStory, David Aen
dc.contributor.authorDoolan, Laurieen
dc.contributor.authorBuxton, Brian Fen
dc.contributor.authorGutteridge, Geoffrey Aen
dc.contributor.authorLuft, Friedrich Cen
dc.contributor.authorSchunck, Wolf-Hagenen
dc.contributor.authorDragun, Duskaen
dc.identifier.citationJournal of the American Society of Nephrology : Jasn 2009; 20(6): 1393-403en
dc.description.abstractEnzymatic pathways involving catechol-O-methyltransferase (COMT) catabolize circulating catecholamines. A G-to-A polymorphism in the fourth exon of the COMT gene results in a valine-to-methionine amino acid substitution at codon 158, which leads to thermolability and low ("L"), as opposed to high ("H"), enzymatic activity. We enrolled 260 patients postbypass surgery to test the hypothesis that COMT gene variants impair circulating catecholamine metabolism, predisposing to shock and acute kidney injury (AKI) after cardiac surgery. In accordance with the Hardy-Weinberg equilibrium, we identified 64 (24.6%) homozygous (LL), 123 (47.3%) heterozygous (HL), and 73 (28.1%) homozygous (HH) patients. Postoperative catecholamines were higher in homozygous LL patients compared with heterozygous HL and homozygous HH patients (P < 0.01). During their intensive care stay, LL patients had both a significantly greater frequency of vasodilatory shock (LL: 69%, HL: 57%, HH: 47%; P = 0.033) and a significantly longer median duration of shock (LL: 18.5 h, HL: 14.0 h, HH: 11.0 h; P = 0.013). LL patients also had a greater frequency of AKI (LL: 31%, HL: 19.5%, HH: 13.7%; P = 0.038) and their AKI was more severe as defined by a need for renal replacement therapy (LL: 7.8%, HL: 2.4%, HH: 0%; P = 0.026). The LL genotype associated with intensive care and hospital length of stay (P < 0.001 and P = 0.002, respectively), and we observed a trend for higher mortality. Cross-validation analysis revealed a similar graded relationship of adverse outcomes by genotype. In summary, this study identifies COMT LL homozygosity as an independent risk factor for shock, AKI, and hospital stay after cardiac surgery. ( number, NCT00334009).en
dc.subject.otherAcute Kidney Injury.etiologyen
dc.subject.otherCardiac Surgical Procedures.adverse effects.mortalityen
dc.subject.otherCatechol O-Methyltransferase.genetics.metabolismen
dc.subject.otherIntensive Careen
dc.subject.otherLength of Stayen
dc.subject.otherMiddle Ageden
dc.subject.otherPolymorphism, Single Nucleotideen
dc.subject.otherProspective Studiesen
dc.titleDecreased catecholamine degradation associates with shock and kidney injury after cardiac surgery.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of the American Society of Nephrology : JASNen
dc.identifier.affiliationDepartment of Intensive Care, Austin Health, Melbourne, Australiaen
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.openairecristype Care- Analytics Research and Evaluation (DARE) Centre- Surgery- Surgery-
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