The COMT-polymorphism is not associated with the incidence of acute kidney injury after cardiac surgery \u2013 a prospective cohort study

Mehmet Oezkur,Martin Wagner,Rainer G Leyh,Peter U Heuschmann,Andreas Reif,Attila Magyar,Phillip Thomas,Stefan Störk

doi:10.1186/s12882-018-0820-x

Abstract

BackgroundThe 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.MethodsIn 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.ResultsBetween 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.ConclusionsWe 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.

Highlights

The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation
In our prospective cohort study, we found that the patients undergoing cardiac surgery reflected the described distribution of the three COMT genotypes according to the Hardy-Weinberg Equilibrium
It seems plausible that variations in catecholamine degradation based on COMT genotype may be a result of linked polymorphisms, e.g. those with the Val/Val-genotype could present with more severe Cardio vascular disease (CVD) and accelerated CVD-progression only if they have altered mRNA secondary structure [13], which has been demonstrated in a Japanese population [14]

Summary

Introduction

The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. There are, conflicting data regarding the COMT Met/Met phenotype being associated with an increased risk of acute kidney injury (AKI) after cardiac surgery. Recent studies suggest that this COMT polymorphism is associated with substantial variance in the response to endogenous and exogenous catecholamines, frequently being referred to as “catecholamine resistance” [2, 4]. This phenomenon contributes to hemodynamic responses, e.g. hypotension and might being related to clinical outcomes. It has been reported that in particular patients undergoing cardiac surgery carrying the COMT Met/Met phenotype are at high risk for vasodilatory shock, AKI and prolonged ICU- and inhospital stay [4]. Data are conflicting as the association of COMT genotype with the described outcomes could not be confirmed by recent studies [6, 7]

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