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Title: Decreased catecholamine degradation associates with shock and kidney injury after cardiac surgery.
Austin Authors: Haase-Fielitz, Anja;Haase, Michael;Bellomo, Rinaldo ;Lambert, Gavin;Matalanis, George ;Story, David A ;Doolan, Laurie;Buxton, Brian F ;Gutteridge, Geoffrey A;Luft, Friedrich C;Schunck, Wolf-Hagen;Dragun, Duska
Affiliation: Department of Intensive Care, Austin Health, Melbourne, Australia
Issue Date: 30-Apr-2009
Publication information: Journal of the American Society of Nephrology : Jasn 2009; 20(6): 1393-403
Abstract: Enzymatic 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).
Gov't Doc #: 19406978
DOI: 10.1681/ASN.2008080915
Journal: Journal of the American Society of Nephrology : JASN
Type: Journal Article
Subjects: Acute Kidney Injury.etiology
Cardiac Surgical Procedures.adverse effects.mortality
Catechol O-Methyltransferase.genetics.metabolism
Intensive Care
Length of Stay
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
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