title: Genetic predisposition to acute kidney injury induced by severe sepsis.
abstract: OBJECTIVE
  The aim of this study was to demonstrate that candidate gene polymorphisms are associated with an increased risk of acute kidney injury (AKI).
  
  
  METHODS
  Patients admitted to the intensive care unit with the diagnosis of severe sepsis and an expected intensive care unit length of stay more than 48 hours were included. Genetic polymorphisms studied included angiotensin-converting enzyme insertion/deletion (polymerase chain reaction); tumor necrosis factor α -376, - 308, and -238; interleukin-8 -251; vascular endothelial growth factor (VEGF) +405 and +936; and pre-B-cell colony-enhancing factor -1001 (TaqMan SNP genotyping assay, Life Technologies, Grand Island, NY). Acute kidney injury was defined as the risk, injury, and failure categories, as per the RIFLE (risk, injury, failure, loss, end-stage kidney disease) classification.
  
  
  RESULTS
  One hundred thirty-nine patients were included, 65 of whom developed AKI. In univariate analysis, the VEGF +936 CC and the pre-B-cell colony-enhancing factor -1001 GG genotypes were associated with AKI. In multivariate analysis, Simplified Acute Physiology Score II score (odds ratio [95% confidence interval], 1.06 [1.03-1.09]), chronic arterial hypertension (3.15 [1.39-7.15]), and the presence of the VEGF +936 CC genotype (3.41 [1.19-9.79]) were associated with AKI.
  
  
  CONCLUSIONS
  This is the first study demonstrating an association between the VEGF +936 CC genotype and the risk to develop AKI in patients with severe sepsis.
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, CIBERES, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cardinal-Fernández
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferruelo
authors.forename: Mariam
authors.initials: M
authors.lastname: El-Assar
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.forename: Félix
authors.initials: F
authors.lastname: Gómez-Gallego
authors.forename: Ana
authors.initials: A
authors.lastname: Martín-Pellicer
authors.forename: Fernando
authors.initials: F
authors.lastname: Frutos-Vivar
authors.forename: Oscar
authors.initials: O
authors.lastname: Peñuelas
authors.forename: Nicolás
authors.initials: N
authors.lastname: Nin
authors.forename: Andrés
authors.initials: A
authors.lastname: Esteban
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
mesh_terms: D018806:APACHE; D058186:Acute Kidney Injury / Q000235:genetics*; D000368:Aged; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D018805:Sepsis / Q000150:complications*; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Acute kidney injury; Genetic predisposition; Polymorphism; Severe sepsis; Vascular endothelial growth factor