Genetic and clinical risk factors for fluid overload following open-heart surgery

BackgroundPost-operative fluid overload following cardiac surgery is associated with increased morbidity and mortality. We hypothesised that genetic variations and pre-operative clinical factors predispose some patients to post-operative fluid overload. MethodsPerioperative variables were collected prospectively for 1026 consecutive adults undergoing open-heart surgery at St. Olavs University Hospital, Norway from 2008-2010. Post-operative fluid overload was defined as a post-operative fluid balance/kgthe 90th percentile of the study population. Genotyping was performed for 31 single-nucleotide polymorphisms related to inflammatory/vascular responses or previously associated with complications following open-heart surgery. Data were analysed using logistic regression modelling, and the findings were internally validated by bootstrapping (n=100). ResultsHomozygous carriers of the common G allele of rs12917707 in the UMOD gene had a 2.2 times greater risk of post-operative fluid overload (P=0.005) after adjustment for significant clinical variables (age, duration of cardiopulmonary bypass, and intraoperative red cell transfusion). A genetic risk score including 14 single-nucleotide polymorphisms was independently associated with post-operative fluid overload (P=0.001). The number of risk alleles was linearly associated with the frequency of fluid overload (odds ratio per risk allele 1.153, 95 % confidence interval 1.056-1.258). Nagelkerke's R-2 increased with 7.5% to a total of 25% for the combined clinical and genetic model. Hemofiltration did not reduce the risk. ConclusionA common variation in the UMOD gene previously shown to be related to renal function was associated with increased risk of post-operative fluid overload following cardiac surgery. Our findings support a genetic susceptibility to disturbed fluid handling following cardiac surgery.