Genetic predisposition to acute kidney injury induced by severe sepsis

• Published in: Journal of critical care 2013-08, Vol.28 (4), p.365-370
• Main Authors: Cardinal-Fernández, Pablo, MD, Ferruelo, Antonio, BSc, El-Assar, Mariam, PhD, Santiago, Catalina, PhD, Gómez-Gallego, Félix, PhD, Martín-Pellicer, Ana, MD, Frutos-Vivar, Fernando, MD, Peñuelas, Oscar, MD, Nin, Nicolás, MD, PhD, Esteban, Andrés, MD, PhD, Lorente, José A., MD, PhD
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Acute Kidney Injury - genetics; Aged; APACHE; Cardiovascular disease; Chi-Square Distribution; Classification; Critical Care; Deoxyribonucleic acid; DNA; Female; Fluids; Genetic predisposition; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Humans; Hypertension; Intensive Care Units; Kidney diseases; Length of Stay - statistics & numerical data; Male; Middle Aged; Mortality; Multivariate analysis; Polymerase Chain Reaction; Polymorphism; Polymorphism, Genetic; Risk Factors; Sepsis; Sepsis - complications; Severe sepsis; Statistics, Nonparametric; Values; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Ventilation
• ISSN: 0883-9441; 1557-8615
• DOI: 10.1016/j.jcrc.2012.11.010

Abstract Purpose The aim of this study was to demonstrate that candidate gene polymorphisms are associated with an increased risk of acute kidney injury (AKI). Materials and 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. Conclusion 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.