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Background: The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial., Methods: In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months., Results: A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non- Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups., Conclusions: In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non- E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Vanin-1, an epithelial glycosylphosphatidylolinositol (GPI)-anchored pantetheinase, is a valuable marker of renal injury., Purpose: The aim of this study was to assess the predictive value of vanin-1 in acute pyelonephritis (APN) in comparison to the conventional serum inflammatory markers in children aged 1-24 months with the first episode of urinary tract infection (UTI)., Material and Methods: Urinary vanin-1, vanin-1/Cr ratio, WBC, CRP, PCT were analysed in 58 children with febrile UTI and in 18 children with non-febrile UTI. Febrile UTI group was divided into APN subgroup ( n =  29) and non-APN subgroup ( n =  29), based on the results of Tc-99m-ethylenedicysteine scan., Results: The mean vanin-1 level was higher in the APN group compared to the non-febrile UTI group ( p =  0.02) and did not differ between APN and non-APN subgroup. In univariate analysis, vanin-1 ( p =  0.042), CRP ( p <  0.001), PCT ( p <  0.001), and WBC ( p =  0.022), were associated with APN, but only vanin-1 ( p =  0.048) and CRP ( p =  0.002) were independent markers of APN. In ROC analysis, vanin-1, with its best cut-off value of 16.53 ng/mL, had worse diagnostic profile (AUC 0.629, sensitivity 58,6%, specificity 63.8%) than CRP, PCT and WBC (AUC: 0.937; 0.880; 0.667, respectively)., Conclusions: Vanin-1 is not useful for predicting APN, since its diagnostic value is inferior to other conventional serum inflammatory markers.

Early diagnosis of urinary tract infection (UTI) is challenging in infants due to unspecific symptoms, difficulty in urine collection and possible contamination. The aim of this study was to assesses the usefulness of serum and urine neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL, respectively) in the diagnosis of febrile and non-febrile UTI in infants. This prospective observational study enrolled 66 infants with the first episode of UTI and 18 healthy controls. At the time of enrollment, sNGAL, uNGAL, urinalysis, urine culture, white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and serum creatinine (sCr) were assessed. We found that, on average, both sNGAL and uNGAL levels were significantly higher in febrile UTI, compared to non-febrile UTI and controls. In turn, the mean sNGAL level, but not uNGAL, was significantly higher in the non-febrile UTI group compared to controls. sNGAL positively correlated with WBC, CRP, ESR and PCT, and uNGAL with CRP and leukocyturia. The receiver operating curves (ROC) demonstrate that the optimum cut-off of 76.2 ng/ml for sNGAL (sensitivity 92.9%, specificity 94.4%, and the area under the curve (AUC) of 0.98) and of 42.2 ng/ml for uNGAL (sensitivity 73.8%, specificity 72.2%, and AUC of 0.76) for diagnosing febrile UTI and 39.0 ng/ml for sNGAL (sensitivity 83.3%, specificity 55.6%, and AUC of 0.70) for diagnosing non-febrile UTI. In conclusion, serum NGAL is an excellent marker for the early diagnosis of febrile UTI, with sensitivity and specificity higher than those of urine NGAL. Diagnostic sensitivity of serum NGAL is smaller in non-febrile infants suffering from UTI, and urine NGAL is not useful for this purpose at all.

Urolithiasis in children occurs with the incidence of 0.1-5%. Risk factors such as metabolic disorders, recurrent urinary tract infections and/or congenital abnormalities of urinary tract are detected in 75-85% of children with urolithiasis. Staghorn calculi is associated with delayed diagnosis and treatment of urinary tract infection caused by specific organisms, which produce the enzyme urease, promoting generation of ammonia and hydroxide from urea. We present two boys with staghorn calculi recognized in 8th and 31st month of age. The reason for performing ultrasonography was urinary tract infection in both boys. The younger child was previously healthy, with no symptoms of urolithiasis, the older one had recurrent urinary tract infections caused by Proteus mirabilis, episodes of anxiety and abdominal pain. Laboratory test and imaging studies excluded congenital abnormalities in the urinary tract and typical metabolic causes of urolithiasis in both boys. Treatment of infection-related stones in the younger child included two extracorporeal shock-wave lithotripsy (ESWL). In the older child, both ESWL and operation were performed. Staghorn calculi were composed of mixtures of magnesium ammonium phosphate (struvite) and calcium carbonate (apatite) and confirmed to be identified as infection-related stones. During follow-up in a nephrology outpatient clinic, values of blood pressure, renal ultrasonography, kidney function test were normal and no symptoms of urinary tract infections were clinically present. In patients with recurrent urinary tract infections, urolithiasis should be taken into consideration. The majority of staghorn calculi is often asymptomatic and can be diagnosed with an ultrasonography study performed routine or during urinary tract infection.

Unlabelled: Biliary sludge and/or biliary pseudolithiasis occur in patients treated with ceftriaxone with prevalence of 3-57%. Biliary obstruction can be the cause of the acute gallbladder enlargement. It is a minor complication, that usually does not give clinical symptoms and resolves once the drug is discontinued. The authors present a case of a 5-month old boy treated for the acute pyelonephritis. Routine ultrasound, performed on the 5th day of treatment with ceftriaxone, showed gallbladder enlargement. In the consecutive studies small gallblader sludge was visible. Patient had no symptoms related to the gallbladder enlargement. Ultrasound performed 6 weeks from the drug discontinuation was completely normal., Conclusions: Patients treated with ceftroiaxone should be monitored for biliary sludge and pseudolithiasis.

Background: The aim of this study was to assess relations between the clinical course of UTI, IL-6 and IL-8 levels, and the presence of inflammatory changes detected by renal scintigraphy using 99mTc-DMSA (DMSA)., Material/methods: We studied 33 children aged 1-24 months (mean 7.1+/-5.8 months) with first-time UTI. The subjects were divided in two groups: with fever (group I, n=10) and without fever (group II, n=23). Inflammatory markers (ESR, CRP, leukocyte count), urinary IL-6 and IL-8 level, and DMSA scan were evaluated in all children., Results: Urinary IL-6 and IL-8 levels [IL-6, IL-8/creatinine (pg/mg)] were significantly higher in group I than in group II (Il-6 level: 39.4+/-41.1 vs. 6.3+/-13.7, p<0.01; IL-8 level: 791.1+/-1143.6 vs. 36+/-87.9, p<0.001). We found positive correlation between urinary IL-6 and IL-8 levels and ESR, CRP, and leukocyte count (IL-6: r=0.43, p<0.05; r=0.46, p<0.05; and r=0.59, p<0.001, respectively; IL-8: r=0.55, p<0.05; r=0.72, p<0.0001; and r=0.44, p<0.05, respectively). We found no relation between urinary cytokine levels and the presence of inflammatory changes detected by DMSA scanning, despite slightly higher mean urinary cytokine levels in children with inflammatory changes in DMSA scan., Conclusions: We found significantly higher IL-6 and IL-8 levels in children with febrile UTI and elevated inflammatory markers. IL-6 and IL-8 levels do not differentiate between acute pyelonephritis and UTI in children to age 24 months.