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Decreased catecholamine degradation associates with shock and kidney injury after cardiac surgery

Item Type:Article
Title:Decreased catecholamine degradation associates with shock and kidney injury after cardiac surgery
Creators Name:Haase-Fielitz, A. and Haase, M. and Bellomo, R. and Lambert, G. and Matalanis, G. and Story, D. and Doolan, L. and Buxton, B. and Gutteridge, G. and Luft, F.C. and Schunck, W.H. and Dragun, D.
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. (ClinicalTrials.gov number, NCT00334009).
Keywords:Cardiac Surgical Procedures, Catechol O-Methyltransferase, Catecholamines, Intensive Care, Acute Kidney Failure, Length of Stay, Single Nucleotide Polymorphism, Prospective Studies, Shock, Vasodilation
Source:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
Page Range:1393-1403
Date:June 2009
Official Publication:https://doi.org/10.1681/ASN.2008080915
PubMed:View item in PubMed

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