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Urinary tract infections are one of the most common and serious bacterial infections in a pediatric population. So far, they have mainly been related to age, gender, ethnicity, socioeconomic level, and the presence of underlying anatomical or functional, congenital, or acquired abnormalities. Recently, both innate and adaptive immunities and their interaction in the pathogenesis and the development of UTIs have been studied. The aim of this study was to assess the role and the effect of the two most frequent polymorphisms of TLR4 Asp299Gly and Thr399Ile on the development of UTIs in infants and children of Greek origin. We studied 51 infants and children with at least one episode of acute urinary tract infection and 109 healthy infants and children. We found that 27.5% of patients and 8.26% of healthy children carried the heterozygote genotype for TLR4 Asp299Gly. TLR4 Thr399Ile polymorphism was found to be higher in healthy children and lower in the patient group. No homozygosity for both studied polymorphisms was detected in our patients. In the group of healthy children, a homozygote genotype for TLR4 Asp299Gly (G/G) as well as for TLR4 Thr399Ile (T/T) was showed (1.84% and 0.92 respectively). These results indicate the role of TLR4 polymorphism as a genetic risk for the development of UTIs in infants and children of Greek origin. [ABSTRACT FROM AUTHOR]

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and systemic vasculitis (AAGNV) is uncommon in childhood. Methods: This is a retrospective study of AAGNV cases diagnosed over a 13-year period in a tertiary pediatric nephrology department. Results: Thirteen cases of AAGNV were identified: seven Wegener granulomatosis (WG) and six microscopic polyangiitis (MPA). Acute renal failure/nephrotic range proteinuria (NRP) was found in 77 % of the patients (4 with WG, all with MPA). Eleven (85 %) patients showed necrotizing glomerulonephritis (NGN), with ≥50 % crescents identified in nine patients (69 %) (4 with WG, 5 with MPA). Treatment with methylprednisolone, cyclophosphamide and plasma exchange resulted in extra-renal remission and antibody reduction in all patients and renal function improvement/stabilization in 77 % of the patients. Three patients, all without oliguria at presentation and few sclerotic lesions, had normal renal function at follow-up. Chronic kidney disease (CKD) stages 2 and 3-4 were observed in four (WG) and three (MPA) patients, respectively. Three patients (23 %) developed end stage renal disease: two were MPA patients with severe presentation (markedly impaired glomerular filtration rate, oliguria, NRP, crescentic NGN, glomerular sclerosis) and one was a WG patient with extensive interstitial fibrosis/tubular atrophy. Conclusions: Severe renal involvement was more common in children with MPA than WG. Treatment with methylprednisolone, cyclophosphamide and plasma exchange induced extra-renal remission/serological response and renal function improvement/stabilization. Markedly decreased GFR, oliguria, NRP, and chronic glomerular lesions at presentation were predictors of poor outcome. [ABSTRACT FROM AUTHOR]

Background: Acute pyelonephritis (APN) is one of the most significant bacterial infections in infancy and early childhood, and can lead to permanent kidney damage and chronic renal failure. Objective: To evaluate interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in the urine of children with renal scarring (RS), searching for clinical information about the immuno-inflammatory process that contributes to RS. Methods: Urine concentrations of IL-6 and IL-8 were evaluated in 50 children, 33 with RS detected after an episode of acute pyelonephritis (group A) and 17 children with a history of acute pyelonephritis, but without RS (group B). These children were divided into four groups: groupA, 23 children with RS and vesicoureteral reflux (VUR); groupA, 10 children with RS without VUR; group B, 13 children without RS and without VUR; group B, 4 children without RS, but with VUR. None of them had had urinary tract infection for a minimum of 6 months. To avoid dilution effects, urinary levels of IL-6 and IL-8 were expressed as the ratio of cytokine to urinary creatinine (pg/mg). Results: Urinary IL-8 levels were below the lower detection limit in all samples. IL-6 was detectable in the majority of children with RS and below the detection limits in the urine samples of children without RS. There were no statistically significant differences between urinary interleukin-6 levels in children with and those without VUR. There was a significant relationship between the grade of renal scars, the time passed since the last episode of acute pyelonephritis and the urinary levels of IL-6 ( p < 0.0001 and p < 0.04 respectively). Conclusion: Further experimental studies are required to demonstrate the correlation between histopathology and urinary cytokine levels. [ABSTRACT FROM AUTHOR]

Background. X-linked nephrogenic diabetes insipidus (NDI) is a rare polyuric disorder caused by inactivating mutations in the arginine vasopressin receptor Type 2 (AVPR2) gene.Methods. NDI patients from six unrelated families were subjected to mutational analysis of the AVPR2 gene. In-depth in vitro characterization of novel AVPR2 mutants by a combination of functional and immunological techniques provided further insight into molecular mechanisms causing receptor dysfunction.Results. Mutational analysis revealed four novel (A89P, G107R, Q174R, W208X) and three recurrent (V277A, R337X, ΔR247-G250) mutations within the AVPR2 gene. One family carried the missense mutation R337X and a 12-bp deletion (ΔR247-G250), corresponding to a fragment in the third intracellular loop (ICL3), which was not genetically linked to R337X. The functionally tested missense mutations A89P, G107R and Q174R led to reduced receptor cell surface expression in transfected COS-7 cells, most probably due to misfolding and intracellular retention, and consequently to reduction or loss of agonist-mediated cyclic adenosine monophosphate formation. Deletion of R247-G250 had no effect on receptor function in vitro. Comparison with other mammalian AVPR2 orthologs showed that this part of the ICL3 is structurally not conserved and, therefore, less relevant for receptor function. In contrast, all missense mutations (A89P, G107R, Q174R, V277A) affect receptor positions that were fully preserved during mammalian evolution.Conclusion. Our results provide valuable information about residues critical for AVPR2 folding, trafficking and function and proof that these mutations are responsible for causing NDI in the affected subjects. [ABSTRACT FROM PUBLISHER]

Background: Acute pyelonephritis (APN) in pediatric patients may lead to kidney scarring and is one of the main causes of permanent kidney damage. The incidence of kidney scarring after one febrile urinary tract infection (UTI) is reported to range from 2.8 to 15%, with the percentage rising to 28.6% after ≥ 3 febrile UTIs. Corticosteroids may have a role in the reduction of kidney scar formation and urine cytokine levels. The possible benefit of adjuvant corticosteroid administration in the reduction of kidney scar formation in children with APN has been recently examined in randomized controlled trials (RCTs). Objectives: The aim of this meta-analysis was to provide a summary of the current literature about the efficacy and safety of adjuvant corticosteroid administration in the reduction of kidney scar formation in children with APN. Data sources: An extensive literature search through major databases (PubMed/MEDLINE and Scopus) was carried out for RCTs from inception until October 12, 2022, investigating the efficacy and safety of adjuvant corticosteroids in preventing kidney scarring in children with APN. A risk ratio with 95% CI was used for dichotomous outcomes. Results: In total, 5 RCTs with 918 pediatric patients with APN were included in the study. Adjuvant corticosteroid treatment revealed a statistically significant reduction in kidney scarring (95% CI 0.42–0.95, p = 0.03), without increasing the risk of adverse events like bacteremia, prolonged hospitalization, or recurrence of UTI. Limitations: There were limitations regarding sample size (n = 498 children), different classes of corticosteroids (methylprednisolone or dexamethasone), different routes of corticosteroid administration (intravenous or oral), and different day courses (3-day or 4-day course). Conclusions: Adjuvant corticosteroid administration seems to have a beneficial effect on kidney scar reduction in children with APN. Future studies should focus on the evaluation of the efficacy and safety of corticosteroids in kidney scarring reduction after APN to strengthen the results of our study. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is the second most common bacterial infection, after otitis media, in infants and children. The mechanisms of disease susceptibility and the role of immunity in the pathogenesis of UTI in children have been evaluated. In recent years, Toll-Like Receptors (TLRs) have been recognized as specific components of the innate immune system constituting important mediators in host immune recognition. The aim of the present study was to determine ΤLR2 and TLR4 expression during the acute phase of UTI in infants and children by measuring the CD14/TLR2 and CD14/TLR4 expression on monocytes. We also attempted to compare the TLRs expression with the immunological status of the patients to healthy children. The study group consisted of 60 children (36 females and 24 males) and the control group included 60 age-matched pediatric subjects (27 females and 33 males). In our study, no antibody deficiency was found either in the children with UTI or in healthy subjects. There might be a connection between low IgA, IgG, and IgG subclasses serum levels and UTI as there was a statistically significant difference between patients and healthy children. A higher expression of CD14/TLR2 was revealed in patients (90,07%) compared to controls (85,48%) as well as CD14/TLR4 in patients (90,53%) compared to controls (87,25%) (statistically significant difference, p<0,05). The results of this study could provide new understanding of UTIs’ pathogenesis in children. [ABSTRACT FROM AUTHOR]

Background: In recent years, pulse wave velocity (PWV) has emerged as a surrogate marker of cardiovascular disease in children with cardiovascular risk factors. The aims of the present study were to identify determinants of PWV in children according to their weight status and to investigate the role of peripheral blood pressure and central hemodynamic parameters in the association between PWV and obesity. Methods: We included in the study healthy children and adolescents randomly selected from a school-based blood pressure screening study. All participants underwent ambulatory blood pressure monitoring and 24-h pulse wave analysis. Results: Overweight and obese children had higher 24-h PWV, 24-h peripheral and central systolic blood pressure (SBP), and cardiac output than normal weight ones. Children with both overweight and hypertension presented the highest 24-h PWV values (p < 0.001). Peripheral and central SBP, body mass index (BMI), and hemodynamic parameters, including stroke volume, cardiac output, total peripheral resistance, and cardiac index, were all associated with 24-h PWV. However, in stepwise regression analysis, 24-h peripheral and central SBP and cardiac index, but not BMI, were independent predictors of 24-h PWV. There were statistically significant differences in 24-h blood pressure and hemodynamic parameters among those on the lower and highest 24-h PWV quartile, but there were no significant differences in BMI among 24-h PWV quartile groups. Conclusions: Arterial stiffness is higher in overweight and obese children in the co-presence of hypertension. Peripheral and central SBP are the main determinants of 24-h PWV independent of weight status. [ABSTRACT FROM AUTHOR]

Maternal diet before and during pregnancy plays an important role for the developing fetus. Any eating disorder in this period can cause transient or/and permanent negative effects on the mother and her offspring. [ABSTRACT FROM AUTHOR]