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

Acta Anaesthesiol Scand. 2014 May;58(5):539-48. doi: 10.1111/aas.12310. Epub 2014 Mar 14.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alleles
  • Blood Transfusion / statistics & numerical data
  • Body Weight
  • Cardiac Surgical Procedures*
  • Comorbidity
  • Contraindications
  • Female
  • Fluid Therapy / adverse effects
  • Genetic Predisposition to Disease
  • Genotype
  • Hemofiltration
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Intraoperative Complications / epidemiology
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Postoperative Complications / etiology*
  • Postoperative Complications / genetics
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • Uromodulin / genetics*
  • Water-Electrolyte Imbalance / etiology*
  • Water-Electrolyte Imbalance / genetics
  • Water-Electrolyte Imbalance / physiopathology

Substances

  • Hypolipidemic Agents
  • UMOD protein, human
  • Uromodulin