ABSTRACT
Background: Urinary tract infections (UTI) are common types of bacterial infection in children. UTI treatment is aimed to prevent complications including hypertension, proteinuria, and progression to chronic kidney disease. Activated neutrophils release chromatin-based structures associated with antimicrobial proteins called neutrophil extracellular traps (NETs). We aimed to describe the role of NET-associated markers in children with UTI as well as the role of NETs formation in a mouse model of UTI. Materials and methods: Markers of NETs including extracellular DNA (ecDNA), myeloperoxidase (MPO) and cathelicidin were analyzed in children with febrile UTI caused by E. coli (n = 98, aged 0.3-1.3 years) and in healthy controls (n = 50, 0.5-5.2 years). Moreover, an acute experimental model of UTI was performed on PAD4 knock-out mice with diminished NETs formation (n = 18), and on wild-type mice (n = 15). Results: Children with UTI had significantly higher urinary NETs markers including total ecDNA, nuclear DNA and mitochondrial DNA, altogether with MPO and cathelicidin. The concentrations of MPO and cathelicidin positively correlated with ecDNA (r = 0.53, p ≤ 0.001; r = 0.56, p ≤ 0.001, respectively) and the number of leukocytes in the urine (r = 0.29, p ≤ 0.05; r = 0.27, p ≤ 0.05, respectively). Moreover, urinary MPO was positively associated with cathelicidin (r = 0.61, p ≤ 0.001). In the experimental model, bacterial load in the bladder (20-fold) and kidneys (300-fold) was significantly higher in PAD4 knock-out mice than in wild-type mice. Conclusion: Higher urinary NETs makers-ecDNA, MPO and cathelicidin and their correlation with leukocyturia in children with UTI confirmed our hypothesis about the association between NETs and UTI in children. Higher bacterial load in mice with diminished NETs formation suggests that NETs are not only a simple consequence of UTI, but might play a direct role in the prevention of pyelonephritis and other UTI complications.
ABSTRACT
BACKGROUND: Obesity and hypertension represent serious health issues affecting the pediatric population with increasing prevalence. Hypovitaminosis D has been suggested to be associated with arterial hypertension. Serotonin by modulating nitric oxide synthase affect blood pressure regulation. The biological mechanism by which vitamin D specifically regulates serotonin synthesis was recently described. The aim of this paper is to determine the associations between vitamin D, serotonin, and blood pressure in obese children. METHODS: One hundred and seventy-one children were enrolled in the prospective cross-sectional study. Two groups of children divided according to body mass index status to obese (BMI ≥95th percentile; n = 120) and non-obese (n = 51) were set. All children underwent office and ambulatory blood pressure monitoring and biochemical analysis of vitamin D and serotonin. Data on fasting glucose, insulin, HOMA, uric acid, and complete lipid profile were obtained in obese children. RESULTS: Hypertension was found only in the group of obese children. Compared to the control group, obese children had lower vitamin D and serotonin, especially in winter. The vitamin D seasonality and BMI-SDS were shown as the most significant predictors of systolic blood pressure changes, while diastolic blood pressure was predicted mostly by insulin and serotonin. The presence of hypertension and high-normal blood pressure in obese children was most significantly affected by vitamin D deficiency and increased BMI-SDS. CONCLUSIONS: Dysregulation of vitamin D and serotonin can pose a risk of the onset and development of hypertension in obese children; therefore, their optimization together with reducing body weight may improve the long-term cardiovascular health of these children.
