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Introduction. One of the most serious complications of acute febrilepyelonephritis in children is the development of renal scar. Thisstudy aimed to investigate the effect of dexamethasone on urinarycytokine levels and renal scar in children with acute pyelonephritis.Methods. In a double-blind randomized clinical trial, 60 childrenaged 3 months to 12 years with acute febrile pyelonephritis enrolled.The experimental group was treated with a combination of antibioticand dexamethasone, and the control group underwent treatmentwith antibiotic and placebo. The urinary levels of interleukin -6(UIL-6) and -8 (UIL-8) were measured before treatment as baselineand were repeated four days later.Results. 52 cases (23 patients with mean age of 34.19 ± 30.82 monthsin the dexamethasone group, and 29 patients with mean age of50.55 ± 44.41 months in the control group) completed the study. Inthe control group, the UIL-6 and UIL-8 level became significantlylower after four days treatment (P < .05). In the dexamethasonegroup, there was a statistically significant difference between bothUIL-6 and UIL-8 levels before and after treatment (P < .05). Inpatients who had scar on DMSA scan, the mean UIL-8 and UIL-6levels were significantly high before and after treatment.Conclusion. Results of this study showed that dexamethasone plusantibiotic have no clear superiority to antibiotic therapy alone indecreasing inflammatory cytokines and scar formation. We foundout that patients with scar had sustained high levels of biomarkersbefore and after treatment.

The mechanisms that maintain sterility in the urinary tract are incompletely understood; however, recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Ribonuclease 7 (RNase 7), a potent antimicrobial peptide contributing to urinary tract sterility, is expressed by intercalated cells in the renal collecting tubules and is present in the urine at levels sufficient to kill bacteria at baseline. Here, we characterize the expression and function of RNase 7 in the human urinary tract during infection. Both quantitative real-time PCR and enzyme-linked immunosorbant assays demonstrated increases in RNASE7 expression in the kidney along with kidney and urinary RNase 7 peptide concentrations with infection. While immunostaining localized RNase 7 production to the intercalated cells of the collecting tubule during sterility, its expression during pyelonephritis was found to increase throughout the nephron but not in glomeruli or the interstitium. Recombinant RNase 7 exhibited antimicrobial activity against uropathogens at low micromolar concentrations by disrupting the microbial membrane as determined by atomic force microscopy. Thus, RNase 7 expression is increased in the urinary tract with infection and has antibacterial activity against uropathogens at micromolar concentrations.

In this study, we aimed to evaluate the usefulness of urinary β2-microglobulin (U-β2MG) for diagnosing acute focal bacterial nephritis (AFBN) among upper urinary tract infections (UTIs). This retrospective study was performed at a single institution and included patients younger than 16 years of age diagnosed with upper UTIs. Patients were divided into the AFBN group and acute pyelonephritis (APN) group. Levels of U-β2MG corrected using urinary creatinine (U-β2MG/Ucre) were compared between groups. A multiple regression analysis was performed using Log(U-β2MG/Ucre) as a dependent factor and the diagnosis (AFBN or APN), age, sex, hydronephrosis grade, urinary pH, and fever interval before admission as independent factors. To discriminate AFBN and APN, thresholds of U-β2MG/Ucre and C-reactive protein (CRP) levels were measured using the receiver-operating characteristic curve. Nineteen patients and 37 patients with AFBN and APN, respectively, were analyzed. The U-β2MG/Ucre level differed significantly between the AFBN and APN groups (10762 μg/gCr vs. 1525 μg/gCr, respectively; P = 0.007). The multiple regression analysis indicated that the Log(U-β2MG/Ucre) value of the AFBN group was considerably higher than that of the APN group (P = 0.004). The threshold values of U-β2MG/Ucre and CRP levels were 2070 μg/gCr and 5.7 mg/dL, respectively. Sensitivity and specificity were 0.95 and 0.68, respectively, when both thresholds were used. Conclusions : The U-β2MG/Ucre level of patients with AFBN was significantly higher than that of patients with APN. Therefore, U-β2MG/Ucre could be used to discriminate between AFBN and APN. What is Known: • U-β2MG can aid in discriminating between upper and lower UTIs; however, using both U-β2MG and procalcitonin allows for more accurate differentiation What is New: • U-β2MG may be useful for discriminating between AFBN and APN in upper UTIs. Assessing both U-β2MG and CRP levels may improve the diagnosis of AFBN without invasive imaging tests

Abstract Background The diagnosis of pyelonephritis in cats is challenging and development of a noninvasive and accurate biomarker is needed. Hypotheses Serum amyloid A (SAA) is increased in cats with pyelonephritis, but not in cats with other urinary tract diseases. Animals A cohort of 125 cats (149 observations). Methods This was a prospective study. Group 1 included cats with a diagnosis of pyelonephritis either confirmed by bacterial culture of pelvic urine (Group 1a) or presumed (1b). Group 2 included cats for which pyelonephritis was ruled out (with certainty: Group 2a or judged unlikely: Group 2b). SAA concentration was compared between groups, and accuracy of SAA for the diagnosis of pyelonephritis was calculated using a Receiver Operating Characteristic (ROC) curve analysis. Results Median SAA concentration was significantly higher in Group 1a (86.8 mg/L [73.3; 161.5]; n = 8) than in Group 2a (4 mg/L [1.8; 5.6], n = 19; P < .001) and in Group 2b (5.4 mg/L [3.1; 9.7], n = 113; P < .001). It was also significantly higher in Group 1b (98.8 mg/L [83.1; 147.3]; n = 9) than in Group 2b (P < .001) and Group 2a (P < .001). Optimal diagnostic cut-off for SAA concentration was 51.3 mg/L. yielding a sensitivity of 88% (95% confidence interval: [64%; 99%]) and a specificity of 94% (95% confidence interval: [88%; 97%]). Conclusions and Clinical Importance Measurement of SAA could be used to rule out pyelonephritis in the case of low suspicion of the disease. Increased SAA concentration is suggestive of pyelonephritis despite a lack of specificity.

Activated polymorphonuclear neutrophils (PMN) release neutrophil extracellular traps (NETs) composed of a web-like DNA core, concomitant with nuclear histones, granular peptides and enzymes. NETs in human urine and their potential role in human urinary tract infections (UTI) pathogenesis is still understudied. This pilot study aimed to analyze presence of NETs in urine samples of patients with different types of UTI. Urine and blood samples were collected from three cohorts: group (A) included females ( = 24) with cystitis ( = 10), pyelonephritis ( = 6), and asymptomatic bacteriuria ( = 8); group (B) composed of males with catheter-associated UTI ( = 20) and a control group (C) consisting of healthy patients of mixed gender ( = 20). NETs in urine samples were confirmed by immunofluorescence-based detection of neutrophil elastase and citrullinated histone. The presence of granular enzymes (myeloperoxidase, cathelicidin), calprotectin (subunits S100A8, S100A9) and CD15 PMN were detected by ELISA, western blot and flow cytometry, respectively. To study potential associations of NETs with the respective UTI microbiome, bacterial spectrum of each urine sample was estimated by 16S rRNA gene analysis. On average, 23.29% ± 16.89% of PMN forming NETs were detected in group A [subgroups cystitis (27.72% ± 17.88%), pyelonephritis (22.75% ± 12.91%), asymptomatic bacteriuria (18.17% ± 17.14%)] and 30.63% ± 17.88% in group B, with no differences observed between UTI groups, including patients with asymptomatic bacteriuria. For the control group (group C), a low incidence of NET-releasing cells was observed (0.32% ± 1.42%), resulting in a significant difference ( < 0.05) when compared to all UTI groups studied. Furthermore, different NET-phenotypes [i. e. spread NETs ( NETs), diffuse NETs ( NETs) and aggregated NETs ( NETs)] were detected in both UTI groups. The presence of NET-associated proteins was confirmed in all UTI groups, but absent in the control samples. Microbiome analyses revealed a reduced microbial variability within UTI samples with the predominance of the bacterial family . Overall, PMN-derived NETs were consistently found in all UTI samples, suggesting a role of NETs in diverse UTI pathologies. Future studies should investigate its utility as an inflammatory biomarker in clinical human UTI.

BackgroundAccurately diagnosing urinary tract infections (UTI) in children with neuropathic bladders can be difficult given the lack of specificity of both clinical symptoms and routine screening tests. We aimed to identify a priori unknown classes/groups of children with neuropathic bladder with respect to symptoms and UA results and examine their relationships with odds of UTI.MethodsWe used latent class analysis (LCA) to identify unobserved classes/groups of children with neuropathic bladder based on symptoms and urinalysis (UA) results, respectively. Demographic and clinical data were gathered by retrospective chart review of a cohort with neuropathic bladder. Symptoms and UA results were obtained by chart review of visits where urine culture was ordered.ResultsAround 193 patients were included in UA results analysis and 179 in symptom-based analysis. Two latent classes of patients were identified with respect to symptoms, labeled “pyelonephritis class” and “cystitis class,” and two, with respect to UA results, were labeled “positive UA class” and “negative UA class.” The pyelonephritis class had significantly higher odds of UTI compared to the asymptomatic class. While odds of UTI in cystitis class were higher than the asymptomatic class, this difference was not statistically significant. Positive UA class had significantly higher odds of UTI compared to negative UA class.ConclusionTwo unobserved classes/groups exist in children with neuropathic bladder with respect to symptoms, corresponding to cystitis and pyelonephritis, and two classes of UA results that correspond with either a positive or negative UA. Our results suggest a differential approach to treatments may be considered.

This study presents a comprehensive review of the literature regarding the use of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a diagnostic tool for urinary tract infection (UTI) in children. Meta-analysis was conducted to evaluate the effectiveness of uNGAL in diagnosing UTI and differentiating acute pyelonephritis (APN) from other sites infection in pediatric patients. We searched PubMed, Web of Science, the Cochrane Library and EMBASE for reports published up to January 2023. We only included published literature that addressed the diagnosis of UTI and APN with the use of uNGAL in children aged 0-18 years. Two authors independently reviewed the included studies and extracted the corresponding data according to the inclusion and exclusion criteria. The sensitivity, specificity and area under the curve for each study were pooled by using a bivariate mixed-effects model. A total of 13 studies met the inclusion criteria for this review: 8 reported on uNGAL diagnosis of UTI, 2 on uNGAL diagnosis of APN, and 3 on both UTI and APN. Among all included studies, uNGAL had good sensitivity (0.88, 95% CI 0.79-0.94) and good specificity (0.86, 95% CI 0.78-0.92) for the diagnosis of UTI. The sensitivity and specificity of uNGAL for the diagnosis of APN were 0.79 (95% CI 0.72-0.85) and 0.78 (95% CI 0.50-0.93), respectively. uNGAL has good sensitivity and specificity in the diagnosis of UTI in children and is a promising marker. However, the use of uNGAL still does not provide significant advantages in the diagnosis of APN in children. Consequently, there is a need to optimize and further explore the assay for improved diagnostic accuracy.This study presents a comprehensive review of the literature regarding the use of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a diagnostic tool for urinary tract infection (UTI) in children. Meta-analysis was conducted to evaluate the effectiveness of uNGAL in diagnosing UTI and differentiating acute pyelonephritis (APN) from other sites infection in pediatric patients. We searched PubMed, Web of Science, the Cochrane Library and EMBASE for reports published up to January 2023. We only included published literature that addressed the diagnosis of UTI and APN with the use of uNGAL in children aged 0-18 years. Two authors independently reviewed the included studies and extracted the corresponding data according to the inclusion and exclusion criteria. The sensitivity, specificity and area under the curve for each study were pooled by using a bivariate mixed-effects model. A total of 13 studies met the inclusion criteria for this review: 8 reported on uNGAL diagnosis of UTI, 2 on uNGAL diagnosis of APN, and 3 on both UTI and APN. Among all included studies, uNGAL had good sensitivity (0.88, 95% CI 0.79-0.94) and good specificity (0.86, 95% CI 0.78-0.92) for the diagnosis of UTI. The sensitivity and specificity of uNGAL for the diagnosis of APN were 0.79 (95% CI 0.72-0.85) and 0.78 (95% CI 0.50-0.93), respectively. uNGAL has good sensitivity and specificity in the diagnosis of UTI in children and is a promising marker. However, the use of uNGAL still does not provide significant advantages in the diagnosis of APN in children. Consequently, there is a need to optimize and further explore the assay for improved diagnostic accuracy.

Acute pyelonephritis is a bacterial infection of the kidney and renal pelvis and should be suspected in patients with flank pain and laboratory evidence of urinary tract infection. Urine culture with antimicrobial susceptibility testing should be performed in all patients and used to direct therapy. Imaging, blood cultures, and measurement of serum inflammatory markers should not be performed in uncomplicated cases. Outpatient management is appropriate in patients who have uncomplicated disease and can tolerate oral therapy. Extended emergency department or observation unit stays are an appropriate option for patients who initially warrant intravenous therapy. Fluoroquinolones and trimethoprim/sulfamethoxazole are effective oral antibiotics in most cases, but increasing resistance makes empiric use problematic. When local resistance to a chosen oral antibiotic likely exceeds 10%, one dose of a long-acting broad-spectrum parenteral antibiotic should also be given while awaiting susceptibility data. Patients admitted to the hospital should receive parenteral antibiotic therapy, and those with sepsis or risk of infection with a multidrug-resistant organism should receive antibiotics with activity against extended-spectrum beta-lactamase–producing organisms. Most patients respond to appropriate management within 48 to 72 hours, and those who do not should be evaluated with imaging and repeat cultures while alternative diagnoses are considered. In cases of concurrent urinary tract obstruction, referral for urgent decompression should be pursued. Pregnant patients with pyelonephritis are at significantly elevated risk of severe complications and should be admitted and treated initially with parenteral therapy.

Abstract Background Specific biomarkers of pyelonephritis (PN) in cats are lacking. MicroRNAs (miRNAs) have diagnostic potential in human nephropathies. Objectives To investigate the presence/stability of miRNAs in whole urine of cats and the discriminatory potential of selected urinary miRNAs for PN in cats. Animals Twelve healthy cats, 5 cats with PN, and 13 cats with chronic kidney disease (n = 5), subclinical bacteriuria (n = 3), and ureteral obstructions (n = 5) recruited from 2 companion animal hospitals. Methods Prospective case-control study. Expression profiles of 24 miRNAs were performed by quantitative PCR (qPCR). Effect of storage temperature (4°C [24 hours], −20°C, and −80°C) was determined for a subset of miRNAs in healthy cats. Results Urinary miR-4286, miR-30c, miR-204, miR4454, miR-21, miR-16, miR-191, and miR-30a were detected. For the majority of miRNAs tested, storage at 4°C and −20°C resulted in significantly lower miRNA yield compared to storage at −80°C (mean log2fold changes across miRNAs from −0.5  ± 0.4 SD to −1.20 ± 0.4 SD (4°C versus −80°C) and from −0.7 ± 0.2 SD to −1.20 ± 0.3 SD (−20°C versus −80°C)). Cats with PN had significantly upregulated miR-16 with a mean log2fold change of 1.0 ± 0.4 SD, compared with controls (−0.1 ± 0.2, P = .01) and other urological conditions (0.6 ± 0.3, P = .04). Conclusions Upregulation of miR16 might be PN-specific, pathogen-specific (Escherichia coli), or both.

Background Early predictive biomarkers for the diagnosis and management of febrile urinary tract infections (UTIs) can be valuable diagnostic tools in children. Methods The study cohort comprised 73 pediatric patients with febrile UTIs [46 with acute pyelonephritis (APN) and 27 with lower UTIs] and 56 healthy children. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) levels and serum cystatin C (sCysC) levels were measured. Results The uNGAL/creatinine (Cr) and uKIM-1/Cr levels were higher in the UTI group than in the controls ( P  < 0.05). uNGAL/Cr and sCysC levels were higher in patients with APN than in those with lower UTIs ( P  < 0.05). uNGAL/Cr levels in both the APN and UTI groups decreased following the administration of antibiotics compared to those before treatment ( P  < 0.05). The uNGAL/Cr level was correlated with serum levels of white blood cells, C-reactive protein, CysC and with uKIM-1/Cr ( P  < 0.05). uKIM-1/Cr was also correlated with sCysC ( P  < 0.05). Receiver operating curve analyses showed good diagnostic profiles of uNGAL/Cr and uKIM-1/Cr for identifying UTIs [area under the curve (AUC) 0.9 and 0.66, respectively) and of uNGAL/Cr and sCysC for predicting APN (AUC 0.78 and 0.72, respectively). Conclusions Our results suggest that uNGAL, uKIM-1 and sCysC levels may be useful for predicting and managing febrile UTIs in children.