Pilot Study of Association of Catechol-O-Methyl Transferase rs4680 Genotypes With Acute Kidney Injury and Tubular Stress After Open Heart Surgery

Albert, Christian; Kube, Johanna; Haase-Fielitz, Anja; Dittrich, Annemarie; Schanze, Denny; Zenker, Martin; Kuppe, Hermann; Hetzer, Roland; Bellomo, Rinaldo; Mertens, Peter R.; Haase, Michael

doi:10.2217/bmm.14.85

Cited by 11 publications

(17 citation statements)

References 27 publications

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“…The low-activity genotype (LL) was associated with AKI and more frequent administration of furosemide and RRT. However, results by Albert et al [ 39 ] and Kornek et al [ 37 ] suggest no association between this COMT polymorphism and AKI. Association between the C-allele of the endothelial NO synthase (eNOS) -786 T/C polymorphism (rs2070744), low creatinine clearance, and more frequent administration of RRT has also been reported [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Genetic predisposition to acute kidney injury – a systematic review

2015

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BackgroundThe risk of an individual to develop an acute kidney injury (AKI), or its severity, cannot be reliably predicted by common clinical risk factors. Whether genetic risk factors have an explanatory role poses an interesting question, however. Thus, we conducted a systematic literature review regarding genetic predisposition to AKI or outcome of AKI patients.MethodsWe searched Ovid SP (MEDLINE) and EMBASE databases and found 4027 references to AKI. Based on titles and abstracts, we approved 37 articles for further analysis. Nine were published only as abstracts, leaving 28 original articles in the final analysis. We extracted the first author, year of publication, study design, clinical setting, number of studied patients, patients with AKI, ethnicity of patients, studied polymorphisms, endpoints, AKI definition, phenotype, significant findings, and data for quality scoring from each article. We summarized the findings and scored the quality of articles.ResultsThe articles were quite heterogeneous and of moderate quality (mean 6.4 of 10).ConclusionsDespite different gene polymorphisms with suggested associations with development or severity or outcome of AKI, definitive conclusions would require replication of associations in independent cohort studies and, preferably a hypothesis-free study design.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0190-6) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Genetic predisposition to acute kidney injury – a systematic review

2015

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“…Evidence is robust that adverse peri-and postoperative events, including vasodilatory or cardiogenic shock and AKI are related to worse subsequent outcomes; such as the development of chronic kidney disease (CKD), and also of systolic and/or diastolic left ventricular dysfunction, congestive heart failure (CHF) and mortality [6,7,19]. Particularly AKI has been shown to be related to short-and long term mortality and morbidity in critical care patients [6,7,19] and also to the development and/or progression of CKD, cardiac dysfunction and overt heart failure [20][21][22][23][24][25]. Impairments in kidney function and in particular those patients in whom kidney parameters numerically recover to normal values were underestimated in the past and even slight changes in kidney function and have been identified as a major complication with significant prognostic implications [22,23,[25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…While all papers used the RIFLE classification for AKI definition, we used the latest definition by the Kidney Disease Improving Global Outcome (KDIGO) published in 2012 [4][5][6][7]. The authors stated that the RIFLE classification might be more robust for AKI diagnosis after cardiac surgery, but most recent evidence suggests that the KDIGO definition with its strict increase of SCr of 0.3 ml/dl within 48 h definition has an impact on shortand longterm outcome [20,21,[28][29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

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The COMT-Polymorphism is not Associated with the Incidence of Acute Kidney Injury after Cardiac Surgery: A Prospective Cohort Study

Oezkur

Magyar

Thomas

et al. 2017

Thorac cardiovasc Surg

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Background: The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. Recent studies suggest that the COMT rs4680 polymorphism is associated with the response to endogenous and exogenous catecholamines. There are, however, conflicting data regarding the COMT Met/Met phenotype being associated with an increased risk of acute kidney injury (AKI) after cardiac surgery. The aim of the current study is to prospectively investigate the impact of the COMT rs4680 polymorphism on the incidence of AKI in patients undergoing cardiac surgery. Methods: In this prospective single center cohort study consecutive patients hospitalized for elective cardiac surgery including cardiopulmonary-bypass (CPB) were screened for participation. Demographic clinical data, blood, urine and tissue samples were collected at predefined time points throughout the clinical stay. AKI was defined according to recent recommendations of the Kidney Disease Improving Global Outcome (KDIGO) group. Genetic analysis was performed after patient enrolment was completed. Results: Between April and December 2014, 150 patients were recruited. The COMT genotypes were distributed as follows: Val/Met 48.7%, Met/Met 29.3%, Val/Val 21.3%. No significant differences were found for demography, comorbidities, or operative strategy according to the underlying COMT genotype. AKI occurred in 35 patients (23.5%) of the total cohort, and no differences were evident between the COMT genotypes (20.5% Met/Met, 24.7% Val/Met, 25.0% Val/Val, p = 0.66). There were also no differences in the post-operative period, including ICU or in-hospital stay. Conclusions: We did not find statistically significant variations in the risk for postoperative AKI, length of ICU or in-hospital stay according to the underlying COMT genotype.

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“…In particular abnormally elevated cathecolamines can predispose to increased occurrence, severity and duration of AKI in cardiac surgical patients with COMT (cathecol-O-methyltransferase) gene polymorphism causing a decreased degradation of catecholamines [35]. Assessment of adrenergic genetic variants, with low versus high enzymatic activity, may provide additional insight into the individual risk assessment for AKI after cardiac surgery [36].…”

Section: Aki Perpetuation and The Role Of Persistent Neuroendocrine Amentioning

confidence: 99%

Neuroendocrine stress response: implications for cardiac surgery-associated acute kidney injury

Rio

Nicoara

Swaminathan

2017

Rom J Anaesth Int Care

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Surgical stress causes biochemical and physiologic perturbations of every homeostatic axis. These alterations include volume/baroreceptor regulation, sympathetic activation, parasympathetic suppression, neuroendocrine activation, acute phase response protein synthesis and secretion, immune response modulation and long-term behavioral adaptation. The kidney is central to the stress response because of its main role in the maintenance of water, electrolyte balance and hence, intracellular and extracellular compartments, including the intravascular volume. Acute kidney injury after cardiac surgery occurs as a result of numerous factors including ischemia-reperfusion, inflammation, oxidative stress, neurohormonal activation, metabolic factors, and nephrotoxicity or pigment nephropathy. The neuroendocrine stress response has a central role in initiating renal injury during cardiac surgery through an increased release of argininevasopressin and activation of the sympathetic nervous system and the intrarenal and systemic reninangiotensin-aldosterone system. The contribution of an exaggerated neuroendocrine stress response to cardiac surgery and cardiopulmonary bypass as key pathophysiologic mechanism for acute kidney injury after cardiac surgery represents an opportunity for scientific exploration.

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Pilot Study of Association of Catechol-O-Methyl Transferase rs4680 Genotypes With Acute Kidney Injury and Tubular Stress After Open Heart Surgery

Abstract: COMT genotype may associate with different patterns of renal functional changes and tubular stress biomarker release response after open heart surgery.

Cited by 11 publications

References 27 publications

Genetic predisposition to acute kidney injury – a systematic review

Genetic predisposition to acute kidney injury – a systematic review

The COMT-Polymorphism is not Associated with the Incidence of Acute Kidney Injury after Cardiac Surgery: A Prospective Cohort Study

Neuroendocrine stress response: implications for cardiac surgery-associated acute kidney injury

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