RESUMO
BACKGROUND: There is an increasing number of young adults living with congenital heart disease (CHD). The goal of this study was to ascertain the frequency of acute kidney injury (AKI) as well as the risk factors and outcomes associated with AKI in young adults with CHD after a surgical procedure. METHODS: This was a single-center retrospective cohort study including all patients 18 to 40 years of age with a diagnosis of CHD admitted to a quaternary care children's hospital cardiac intensive care unit postoperatively from 2004 to 2015. We defined AKI using the Kidney Disease Improving Global Outcomes criteria for serum creatinine. We explored potential susceptibilities and exposures for AKI using multivariable logistic regression and determined the association of AKI with duration of mechanical ventilation and length of stay using Poisson regression. RESULTS: In 699 consecutively admitted patients AKI occurred in 13.2%. Suspected sepsis (odds ratio [OR], 2.87; 95% confidence interval [CI], 1.17 to 7.05), exposure to calcineurin inhibitors (OR, 5.80; 95% CI, 1.06 to 31.59), vancomycin (OR, 3.35; 95% CI, 1.11 to 10.14), and piperacillin-tazobactam (OR, 4.12; 95% CI, 1.23 to 13.78) increased the odds of AKI even after controlling for age, ejection fraction, recent cardiac catheterization, repeat cardiopulmonary bypass, bypass time, cross-clamp time, and other potential nephrotoxic medications. AKI was associated with a longer duration of mechanical ventilation (OR, 1.47; 95% CI, 1.15 to 1.89) and intensive care unit length of stay (OR, 1.50; 95% CI, 1.30 to 1.72). CONCLUSIONS: AKI is common in young adults with CHD postoperatively and is associated with negative outcomes. The results highlight the importance future research and clinical efforts aimed at prevention and improved management of AKI in this patient group.
Assuntos
Injúria Renal Aguda/epidemiologia , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Tempo de Internação , Modelos Logísticos , Masculino , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto JovemRESUMO
Oedema factor (OF) and protective antigen (PA) are secreted by Bacillus anthracis, and their binary combination yields oedema toxin (OT). Following PA-mediated delivery to the cytosol, OF functions as an adenylate cyclase generating high levels of cAMP. To assess OT as a possible cause of tissue damage and cell death, a novel approach was developed, which utilized a developing zebrafish embryo model to study toxin activity. Zebrafish embryos incubated with OT exhibited marked necrosis of the liver, cranium and gastrointestinal tract, as well as reduced swim bladder inflation. The OT-treated embryos survived after all stages of development but succumbed to the toxin within 7 days. Additional analysis of specific cell lines, including macrophage and non-macrophage, showed OT-induced cell death is cell type-specific. There was no discernible correlation between levels of OF-generated cAMP and cell death. Depending on the type of cell analysed, cell death could be detected in low levels of cAMP, and, conversely, cell survival was observed in one cell line in which high levels of cAMP were found following treatment with OT. Collectively, these data suggest OT is cytotoxic in a cell-dependent manner and may contribute to disease through direct cell killing leading to tissue necrosis.