Introduction: Nearly half of severely injured patients suffer acute kidney injury (AKI), but little is known about its pathogenesis or optimal management. We hypothesized that endothelial dysfunction, evidenced by elevated systemic soluble thrombomodulin (sTM) and syndecan-1, would be associated with higher incidence, worsened severity, and prolonged duration of AKI after severe trauma. Methods: A single-center cohort study of severely injured patients surviving 24 h from 2012 to 2016 was performed. Arrival plasma sTM and syndecan-1 were measured by ELISA. Outcomes included 7-day AKI incidence, stage, and prolonged AKI 2 days. The Kidney Disease Improving Global Outcomes guidelines were used for AKI diagnosis and staging. Univariate and multivariable analyses were performed. Results: Of 477 patients, 78% were male. Patients had a median age of 38 (interquartile ranges [IQR] 27-54) and injury severity score of 17 (IQR 10-26). AKI developed in 51% of patients. Those with AKI were older and displayed worse arrival physiology. Patients with AKI had higher plasma levels of syndecan-1 (median 34.9 ng/mL vs. 20.1 ng/mL) and sTM (6.5 ng/mL vs. 4.8 ng/mL). After adjustment, sTM and syndecan-1 were both associated with higher AKI incidence, worse AKI severity, and prolonged AKI duration. The strength and precision of the association of sTM and these outcomes were greater than those for syndecan-1. A sensitivity analysis excluding patients with AKI on arrival demonstrated the same relationship. Conclusions: Elevated sTM and syndecan-1, indicating endothelial dysfunction, were associated with higher incidence, worsened severity, and prolonged duration of AKI after severe trauma. Treatments that stabilize the endothelium hold promise for AKI treatment in severely injured patients.
Background: Recognition and clinical diagnosis of acute kidney injury (AKI) after trauma is difficult. The majority of trauma patients do not have a known true baseline creatinine, which makes application of the guidelines set forth by the international guidelines difficult to apply. Use of alternative biomarkers of renal dysfunction in trauma patients may be beneficial. We hypothesized that Urinary TIMP-2*IGFBP-7 would accurately predict AKI development in severely injured trauma patients.Methods: A prospective observational study of adult (≥16 years) trauma ICU patients was performed between 9/2018-3/2019. Urine was collected on ICU admission and was measured for TIMP-2*IGFBP-7. Univariate, multivariable, and receiver operating characteristic (ROC) curve analyses were performed utilizing the optimal threshold generated by a Youden index.Main Results: Of 88 included patients, 75% were male, with a median injury severity score was 27 (IQR 17-34), and age of 40 . Early AKI developed in 39 (44%) patients and of those, 7 (8%) required dialysis within 48 hours. Patients without early AKI had a TIMP-2*IGFBP-7 of 0.17 units (IQR 0.1-0.3) while patients with early AKI had a TIMP-2*IGFBP-7 of 0.46 units (IQR 0.17-1.29, p<0.001). On multivariable analyses,
Pseudomonas aeruginosa is an opportunistic pathogen that causes pneumonia in immunocompromised and intensive care unit (ICU) patients. During host infection, P. aeruginosa upregulates the type III secretion system (T3SS), which is used to intoxicate host cells with exoenzyme (Exo) virulence factors. Of the four known Exo virulence factors (U, S, T and Y), ExoU has been shown in prior studies to associate with high mortality rates. Preclinical studies have shown that ExoY is an important edema factor in lung infection caused by P. aeruginosa, although its importance in clinical isolates of P. aeruginosa is unknown. We hypothesized that expression of ExoY would be highly prevalent in clinical isolates and would significantly contribute to patient morbidity secondary to P. aeruginosa pneumonia. A single-center, prospective observational study was conducted at the University of Alabama at Birmingham Hospital. Mechanically ventilated ICU patients with a bronchoalveolar lavage fluid culture positive for P. aeruginosa were included. Enrolled patients were followed from ICU admission to discharge and clinical P. aeruginosa isolates were genotyped for the presence of exoenzyme genes. Ninety-nine patients were enrolled in the study. ExoY was present in 93% of P. aeruginosa clinical isolates. Moreover, ExoY alone (ExoY+/ExoU−) was present in 75% of P. aeruginosa isolates, compared to 2% ExoU alone (ExoY−/ExoU+). We found that bacteria isolated from human samples expressed active ExoY and ExoU, and the presence of ExoY in clinical isolates was associated with end-organ dysfunction. This is the first study we are aware of that demonstrates that ExoY is important in clinical outcomes secondary to nosocomial pneumonia.
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