Acute kidney injury in hospitalized children with proteinuria: A multicenter retrospective analysis.

BACKGROUND AND OBJECTIVE: Acute kidney injury (AKI) is a common complication in hospitalized pediatric patients. Previous studies focused on adults found that proteinuria detected during an admission urinalysis is fit to serve as an indicator for AKI and associated clinical outcomes. The objective of this study is to evaluate if proteinuria on the first day of hospital services in hospitalized children is associated with AKI, need for renal replacement therapy, shock and/or antibiotic use, critical care services, and all-cause mortality at 30 days, hypothesizing that it is associated with these outcomes. METHODS: This is a retrospective cohort study using TriNetX electronic health record data of patients 2 to 18 years of age who underwent urinalysis laboratory testing on hospital admission, had three subsequent days of hospital or critical care services billing codes and creatinine laboratory values, and no pre-existing renal-related complex chronic condition. This study evaluated for the frequency, odds, and severity of AKI as defined by Kidney Disease: Improving Global Outcomes modified criteria and assessed for associated clinical outcomes. RESULTS: This study included 971 pediatric subjects [435 (44.7%) with proteinuria]. Proteinuria on the first day of hospital services was associated with an increased odds for higher severity AKI on any day of hospitalization (odds ratio [OR] 2.41, CI 1.8-3.23, p<0.001), need for renal replacement therapy (OR 4.58, CI 1.69-12.4, p = 0.001), shock and/or antibiotic use (OR 1.34, CI 1.03-1.75, p = 0.033), and all-cause mortality at 30 days post-admission (OR 10.0, CI 1.25-80.5, p = 0.013). CONCLUSION: Children with proteinuria on the first day of hospital care services may have an increased odds of higher severity AKI, need for renal replacement therapy, shock and/or antibiotic use, and all-cause mortality at 30 days post-admission, with no significant association found for critical care services, mechanical intubation, or inotrope or vasopressor use.

Clinical decision rule for obtaining peripheral blood cultures in febrile oncology patients.

BACKGROUND: The utility of peripheral blood cultures in pediatric oncology patients presenting with fever is controversial. A recent systematic review showed that about one in 40 bloodstream infections (BSIs) would be missed if only central venous line (CVL) cultures are obtained. OBJECTIVE: To derive a clinical decision rule for obtaining peripheral blood cultures in pediatric oncology patients presenting to a pediatric emergency department (PED) with fever and a CVL. DESIGN/METHOD: A retrospective chart review was performed on pediatric oncology patients referred to the PED for fever while on therapy. Logistic regression with a random intercept was used to determine independent predictors of BSI and generate a prediction model for obtaining peripheral blood cultures. The decision rule was generated from the best performance as measured by a receiver operator curve. Bootstrapping analysis was performed for internal validation. RESULTS: Predictors that were significant and independently associated with positive peripheral blood cultures included vasopressor support (odds ratio [OR] 16.5, 95% confidence interval [CI]: 2.80-97.71), acute myeloid leukemia (AML) diagnosis (OR 6.9, 95% CI: 1.81-25.98), hypotension (OR 4.0, 95% CI: 1.05-15.17), mucositis (OR 8.2, 95% CI: 2.48-27.01), and maximum temperature in PED ≥39°C (OR 6.6, 95% CI: 2.36-18.20). The area under the curve (AUC) for this model was 0.90 (95% CI: 0.82-0.97) in the derivation cohort and 0.90 (95% CI: 0.81-0.98) after the internal validation. CONCLUSIONS: We derived a clinical prediction model for deciding when to obtain peripheral blood cultures in febrile oncology patients with CVLs on active therapy. Future studies should focus on prospective and external validation of this diagnostic prediction tool.

Heart rate variability as a marker of recovery from critical illness in children.

OBJECTIVES: The purpose of this study was to Identify whether changes in heart rate variability (HRV) could be detected as critical illness resolves by comparing HRV from the time of pediatric intensive care unit (PICU) admission with HRV immediately prior to discharge. We also sought to demonstrate that HRV derived from electrocardiogram (ECG) data from bedside monitors can be calculated in critically-ill children using a real-time, streaming analytics platform. METHODS: This was a retrospective, observational pilot study of 17 children aged 0 to 18 years admitted to the PICU of a free-standing, academic children's hospital. Three time-domain measures of HRV were calculated in real-time from bedside monitor ECG data and stored for analysis. Measures included: root mean square of successive differences between NN intervals (RMSSD), percent of successive NN interval differences above 50 ms (pNN50), and the standard deviation of NN intervals (SDNN). RESULTS: HRV values calculated from the first and last 24 hours of PICU stay were analyzed. Mixed effects models demonstrated that all three measures of HRV were significantly lower during the first 24 hours compared to the last 24 hours of PICU admission (p<0.001 for all three measures). In models exploring the relationship between time from admission and log HRV values, the predicted average HRV remained consistently higher in the last 24 hours of PICU stay compared to the first 24 hours. CONCLUSION: HRV was significantly lower in the first 24 hours compared to the 24 hours preceding PICU discharge, after resolution of critical illness. This demonstrates that it is feasible to detect changes in HRV using an automated, streaming analytics platform. Continuous tracking of HRV may serve as a marker of recovery in critically ill children.

Alcohol worsens acute lung injury by inhibiting alveolar sodium transport through the adenosine A1 receptor.

OBJECTIVE: Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na(+) transport in the lung. METHODS: We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderate to severe intoxication and measured the rate of alveolar fluid clearance and Na,K-ATPase expression in peripheral lung tissue and assessed the effect of alcohol on survival during exposure to hyperoxia. We used primary rat alveolar type II cells to investigate the mechanisms by which alcohol regulates alveolar Na(+) transport. RESULTS: Exposure to alcohol reduced alveolar fluid clearance, downregulated Na,K-ATPase in the lung tissue and worsened hyperoxia-induced lung injury. Alcohol caused an increase in BAL fluid adenosine levels. A similar increase in lung adenosine levels was observed after exposure to hyperoxia. In primary rat alveolar type II cells alcohol and adenosine decreased the abundance of the Na,K-ATPase at the basolateral membrane via a mechanism that required activation of the AMPK. CONCLUSIONS: Alcohol decreases alveolar fluid clearance and impairs survival from acute lung injury. Alcohol induced increases in lung adenosine levels may be responsible for reduction in alveolar fluid clearance and associated worsening of lung injury.

Lung-specific loss of the laminin α3 subunit confers resistance to mechanical injury.

Laminins are heterotrimeric glycoproteins of the extracellular matrix that are secreted by epithelial cells and which are crucial for the normal structure and function of the basement membrane. We have generated a mouse harboring a conditional knockout of α3 laminin (Lama3(fl/fl)), one of the main laminin subunits in the lung basement membrane. At 60 days after intratracheal treatment of adult Lama3(fl/fl) mice with an adenovirus encoding Cre recombinase (Ad-Cre), the protein abundance of α3 laminin in whole lung homogenates was more than 50% lower than that in control-treated mice, suggesting a relatively long half-life for the protein in the lung. Upon exposure to an injurious ventilation strategy (tidal volume of 35 ml per kg of body weight for 2 hours), the mice with a knockdown of the α3 laminin subunit had less severe injury, as shown by lung mechanics, histology, alveolar capillary permeability and survival when compared with Ad-Null-treated mice. Knockdown of the α3 laminin subunit resulted in evidence of lung inflammation. However, this did not account for their resistance to mechanical ventilation. Rather, the loss of α3 laminin was associated with a significant increase in the collagen content of the lungs. We conclude that the loss of α3 laminin in the alveolar epithelium results in an increase in lung collagen, which confers resistance to mechanical injury.