title: Genetic and clinical risk factors for fluid overload following open-heart surgery.
abstract: BACKGROUND
  Post-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.
  
  
  METHODS
  Perioperative 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/kg ≥ the 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).
  
  
  RESULTS
  Homozygous 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.
  
  
  CONCLUSIONS
  A 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.
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: T B
authors.initials: TB
authors.lastname: Enger
authors.forename: H
authors.initials: H
authors.lastname: Pleym
authors.forename: R
authors.initials: R
authors.lastname: Stenseth
authors.forename: A
authors.initials: A
authors.lastname: Wahba
authors.forename: V
authors.initials: V
authors.lastname: Videm
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D001803:Blood Transfusion / Q000706:statistics & numerical data; D001835:Body Weight; D006348:Cardiac Surgical Procedures; D015897:Comorbidity; D000075202:Contraindications; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006440:Hemofiltration; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007431:Intraoperative Complications / Q000453:epidemiology; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000209:etiology* / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D058949:Uromodulin / Q000235:genetics*; D014883:Water-Electrolyte Imbalance / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology
chemical_list: D000960:Hypolipidemic Agents; C548612:UMOD protein, human; D058949:Uromodulin