Corticosteroids to prevent renal scarring in children with pyelonephritis: a systematic review and meta-analysis.

BACKGROUND: Acute pyelonephritis is a common infection in children that may cause renal scarring. The aim of this systematic review and meta-analysis was to analyse the use of corticosteroid treatment to prevent renal scarring. METHODS: We searched the PubMED, SCOPUS, Cochrane CENTRAL and Web of Science databases in June 2022 for (corticosteroid* or dexamethasone or prednisolone* or prednisone* or hydrocortisone*) AND pyelonephritis. Randomised controlled trials focusing on children were included. The intervention was corticosteroid treatment with antibiotics compared to antibiotics with or without a placebo. The main outcome was the presence of renal scars on dimercaptosuccinic acid scanning at follow-up. The evidence quality was assessed using the GRADE methodology and risk of bias 2.0 tool. We calculated the risk ratio (RR), absolute risk difference (RD) with 95% confidence intervals (CI) and the number needed to treat (NNT). We applied a fixed effects model due to low heterogeneity. RESULTS: We screened 872 abstracts and included five full texts. Renal scarring at follow-up was found in 31/220 (14.1%) patients in the corticosteroid groups and 76/278 (27.3%) in the control groups (RR 0.65, CI 0.44-0.96, RD - 13.2%, NNT 8). The evidence quality was moderate. Two studies reported adverse events with no differences between the groups. The risk of bias analysis showed some concerns in four studies. CONCLUSION: We found moderate quality evidence that adjuvant corticosteroid treatment could prevent renal scarring. Adverse events were insufficiently reported, and more research on their effectiveness and harm is therefore needed before using corticosteroids in clinical settings.

Protective role for C3aR in experimental chronic pyelonephritis.

Emerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar-/- ) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2-C3ar-/- ) mice exhibited a similar disease phenotype to global C3ar-/- mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar-/- mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection.

Cost-effectiveness of bacteriuria screening before urogynecologic surgery.

BACKGROUND: Currently, there is controversy over who requires preoperative screening for bacteriuria in the urogynecologic population and whether treating asymptomatic bacteriuria reduces postoperative urinary tract infection rates. OBJECTIVE: To evaluate the cost-effectiveness of selective, universal, and no preoperative bacteriuria screening protocols in women undergoing surgery for prolapse or stress urinary incontinence. STUDY DESIGN: A simple decision tree model was created from a societal perspective to evaluate cost and effectiveness of 3 strategies to prevent postoperative urinary tract infection: (1) a universal protocol where all women undergoing urogynecologic surgery are screened for bacteriuria and receive preemptive treatment if bacteriuria is identified; (2) a selective protocol, where only women with a history of recurrent urinary tract infection are screened and treated for bacteriuria; and (3) a no-screening protocol, where no women are screened for bacteriuria. Our primary outcome was the incremental cost-effectiveness ratio, calculated in cost per quality-adjusted life-years. Secondary outcomes were the number of urine cultures, postoperative urinary tract infections, and pyelonephritis associated with each strategy. Costs were derived from the Centers for Medicare & Medicaid Services, Healthcare Cost and Utilization Project, and Medical Expenditure Panel Survey. Clinical estimates were derived from published literature and data from a historic surgical cohort. Quality-of-life-associated utilities for urinary tract infection (0.73), pyelonephritis (0.66), and antibiotic use (0.964) were derived from the published literature using the HALex scale, reported directly by affected patients. One-way sensitivity analyses were performed over the range of reported values. RESULTS: In the base case scenario, selective screening is more costly (no screen: $101.69, selective: $101.98) and more effective (no screen: 0.096459 quality-adjusted-life-year, selective: 0.096464 quality-adjusted-life-year) than no screening, and is cost-effective, with an incremental cost-effectiveness ratio of $49,349 per quality-adjusted-life-year. Both selective screening and no screening dominate universal screening in being less costly (universal: $111.92) and more effective (universal: 0.096446 quality-adjusted-life-year), with a slightly higher rate of postoperative urinary tract infection (no screen: 17.1%, selective: 16.9%, universal: 16.6%). In 1-way sensitivity analyses, selective screening is no longer cost-effective compared with no screening when the cost of a urine culture exceeds $12, cost of a preoperative urinary tract infection exceeds $93, the cost of a postoperative urinary tract infection is below $339, the specificity of a urine culture is less than 96%, or preoperative bacteriuria rates in those without symptoms but a history of recurrent urinary tract infection is <23%. Universal screening only becomes cost-effective when the postoperative urinary tract infection rate increases to >50% in those without risk factors and untreated preoperative bacteriuria. When compared with no screening, selective screening costs an additional $104 per urinary tract infection avoided and $2607 per pyelonephritis avoided. Compared with selective screening, universal screening costs $4609 per urinary tract infection avoided and $115,223 per pyelonephritis avoided. CONCLUSION: Implementation of a selective preoperative bacteriuria protocol is cost-effective in most scenarios and associated with only a <1% increase in the 30-day postoperative urinary tract infection rate. No screening is cost-effective when cost of a preoperative urinary tract infection is high and the rate of preoperative bacteriuria in those without risk factors is low.

[Clinical and pathogenetic aspects of the treatment and prevention of pyelonephritis in children].

INTRODUCTION: Treatment of pyelonephritis in children should be combined, long-term and individual-based. The success of the therapy in children largely depends on the prompt appointment and the correct choice of antimicrobial therapy. AIM: To evaluate the efficiency of the dietary supplement "Cystenium II" in a group of children aged 7 to 14 years with a diagnosis of acute and chronic recurrent pyelonephritis in the acute phase. MATERIALS AND METHODS: A total of 60 children aged 7 to 14 years with a diagnosis of acute or chronic recurrent pyelonephritis in the acute stage were included in the study. The clinical group consisted of 30 patients (mean age 12.1+/-1.8 years), while the control group included 30 patients of mean age 11.2+/-1.7 years. In the control group patients received only standard antibiotic therapy, while in the clinical group it was combined with a dietary supplement "Cystenium II" 1 tablet 2 times a day with meals for 14 days. After the course of antibacterial treatment, the children in the clinical group continued to take the studied dietary supplement for another 14 days in order to prevent the recurrence of pyelonephritis. The results of treatment (patient's condition, presence of pain, dysuria, fever) were assessed on the 3rd, 7th, 14th day, 1 and 6 months after the start of treatment. A urinalysis was performed at the baseline, on the 7th and 14th days, as well as after 1 and 6 months. Urine culture was performed before and after antibiotic therapy at the baseline, on the 14th day, 1 and 6 months after the start of treatment. RESULTS: The main indicators of urinalysis (leukocytes, red blood cells, protein) returned to normal values in 26 (86.7%) patients of the clinical group and in 23 (76.7%) patients of the control group on the 7th day after the start of treatment. At the completion of the basic therapy (after 14 days) normal clinical parameters (absence of leukocyturia, microhematuria, proteinuria) were observed in all patients of the clinical group and in 28 (93.3%) patients of the control group. After a month of follow-up, the disturbances in urinalysis (leukocytes, red blood cells, protein) in the control group were again seen in 3 (10%) patients, as well as after 6 months. However, in the clinical group all patients had normal urinalysis (absence of leukocyturia, microhematuria, proteinuria) after 1 month and only in 1 (3.3%) case leukocyturia, as well as an increase in the number of red blood cells and protein was detected by 6 months. DISCUSSION: According to our results, the use of dietary supplements "Cystenium II" (manufactured by Akvion, Russia), due to the constituents of D-mannose (450 mg), cranberry fruit extract with a standardized activity of 500 mg (36 mg of proanthocyanidins) and vitamin C (60 mg), may cause anti-inflammatory and anti-adhesive effects (resolving of leukocyturia and bacteriuria). This allows to use the dietary supplement Cystenium II in children from 7 years of age in the combination therapy of acute pyelonephritis, as well as exacerbation of chronic pyelonephritis. The obtained results showed a high overall therapeutic efficacy of combination therapy using Cystenium II after 6 months from the start of treatment (relapse in 1 patient), in contrast to the control group (relapse in 6 patients). CONCLUSIONS: the use of dietary supplement "Cystenium II" allowed to reduce the number of repeated courses of antibiotic therapy in children during 6 months of follow-up and, most likely, reduced the frequency of development of chronic pyelonephritis after an acute inflammation. Therefore, the wide clinical use of dietary supplements "Cystenium II" for the combined treatment of acute and exacerbation of chronic pyelonephritis in children older than 7 years seems to be very reasonable.

The clinical utility of intrapartum screening urinalysis for the prevention of postpartum pyelonephritis.

OBJECTIVES: Urinary tract infection (UTI) is the most common bacterial infection to complicate pregnancy. Medical authorities recommend screening for asymptomatic bacteriuria (ASB) in pregnancy; albeit there is no consensus on ideal timing and frequency for testing. Due to the persistent physiologic changes of pregnancy postpartum, a recent trend to perform urinalysis upon presentation for delivery has been adopted at our institution and various satellite hospitals to putatively minimize cases of postpartum pyelonephritis. The aim of this study is to examine whether routine testing with urinalysis and screening for ASB following suspicious urinalysis with treatment can decrease the incidence of postpartum pyelonephritis, and to determine whether certain urinalysis parameters are more predictive of a positive urine culture. STUDY DESIGN: A retrospective chart review study of all term deliveries was conducted over two years at the American University of Beirut Medical Center, a university teaching hospital. A total of 2359 deliveries of women with no increased susceptibility to UTIs were reviewed. None had urinary symptoms upon presentation. Urinary parameters including time of urinalysis and urine culture collection with respect to time of delivery, corresponding results and mode of urine collection were correlated to intrapartum course, incidence of ASB and of postpartum pyelonephritis. RESULTS: The incidence of ASB among women presenting for delivery was 4.83 %, with Escherichia coli as the most commonly detected pathogen. The presence of nitrite on urinalysis was significantly associated with a positive urine culture (p-value<0.001). Women with history of antenatal ASB or UTI were more likely to have ASB intrapartum with an odds ratio of 3.14 (95 % CI 1.71-5.75, p-value <0.001). Intrapartum urinalysis with subsequent diagnosis and treatment of ASB did not significantly affect the incidence of postpartum pyelonephritis (p-value 0.280). Similarly, intrapartum urinalysis in the setting of positive history of antenatal ASB or UTI did not increase the incidence of postpartum pyelonephritis compared to women with no such history (p-value 0.659). CONCLUSIONS: Urinalysis screening intrapartum does not decrease the incidence of postpartum pyelonephritis. Universal urinalysis screening intrapartum is not warranted and should be reserved for women reporting urinary symptoms and/or women at high risk of UTI.

Developmental loss, but not pharmacological suppression, of renal carbonic anhydrase 2 results in pyelonephritis susceptibility.

Carbonic anhydrase II knockout (Car2-/-) mice have depleted numbers of renal intercalated cells, which are increasingly recognized to be innate immune effectors. We compared pyelonephritis susceptibility following reciprocal renal transplantations between Car2-/- and wild-type mice. We examined the effect of pharmacological CA suppression using acetazolamide in an experimental murine model of urinary tract infection. Car2-/- versus wild-type mice were compared for differences in renal innate immunity. In our transplant scheme, mice lacking CA-II in the kidney had increased pyelonephritis risk. Mice treated with acetazolamide had lower kidney bacterial burdens at 6 h postinfection, which appeared to be due to tubular flow from diuresis because comparable results were obtained when furosemide was substituted for acetazolamide. Isolated Car2-/- kidney cells enriched for intercalated cells demonstrated altered intercalated cell innate immune gene expression, notably increased calgizzarin and insulin receptor expression. Intercalated cell number and function along with renal tubular flow are determinants of pyelonephritis risk.

[Is there still no alternative to long-term antibacterial prophylaxis?] / Ist die antibakterielle Langzeitprophylaxe immer noch alternativlos?

In infants and children, the strategy of antibacterial long-term infection prophylaxis is more widely used in the protection against urinary tract infections (UTIs) than for hardly any other indication. Development of resistance, side effects of chemotherapeutic agents and acceptance problems require an intensive search for alternatives in the prophylaxis of UTIs. In this context, substances such as D­mannose, probiotics and herbal preparations are gaining increasing attention, whereby the effectiveness of which, especially in children, still needs proof through therapy studies. This also applies to approaches to vaccine prevention. However, prophylaxis must not be limited to the prescription of medicines. Equally important are the treatment of bladder dysfunction and constipation as well as the elimination of other predisposing factors. There are alternatives to antibiotic prophylaxis for UTIs. However, in cases with a high risk of recurrence and pyelonephritis, it is still currently the better alternative.

Antibiotics for asymptomatic bacteriuria in pregnancy.

BACKGROUND: Asymptomatic bacteriuria is a bacterial infection of the urine without any of the typical symptoms that are associated with a urinary infection, and occurs in 2% to 15% of pregnancies. If left untreated, up to 30% of mothers will develop acute pyelonephritis. Asymptomatic bacteriuria has been associated with low birthweight and preterm birth. This is an update of a review last published in 2015. OBJECTIVES: To assess the effect of antibiotic treatment for asymptomatic bacteriuria on the development of pyelonephritis and the risk of low birthweight and preterm birth. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) on 4 November 2018, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening. Trials using a cluster-RCT design and quasi-RCTs were eligible for inclusion, as were trials published in abstract or letter form, but cross-over studies were not. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 15 studies, involving over 2000 women. Antibiotic treatment compared with placebo or no treatment may reduce the incidence of pyelonephritis (average risk ratio (RR) 0.24, 95% confidence interval (CI) 0.13 to 0.41; 12 studies, 2017 women; low-certainty evidence). Antibiotic treatment may be associated with a reduction in the incidence of preterm birth (RR 0.34, 95% CI 0.13 to 0.88; 3 studies, 327 women; low-certainty evidence), and low birthweight babies (average RR 0.64, 95% CI 0.45 to 0.93; 6 studies, 1437 babies; low-certainty evidence). There may be a reduction in persistent bacteriuria at the time of delivery (average RR 0.30, 95% CI 0.18 to 0.53; 4 studies; 596 women), but the results were inconclusive for serious adverse neonatal outcomes (average RR 0.64, 95% CI 0.23 to 1.79, 3 studies; 549 babies). There were very limited data on which to estimate the effect of antibiotics on other infant outcomes, and maternal adverse effects were rarely described. Overall, we judged only one trial at low risk of bias across all domains; the other 14 studies were assessed as high or unclear risk of bias. Many studies lacked an adequate description of methods, and we could only judge the risk of bias as unclear, but in most studies, we assessed at least one domain at high risk of bias. We assessed the quality of the evidence for the three primary outcomes with GRADE software, and found low-certainty evidence for pyelonephritis, preterm birth, and birthweight less than 2500 g. AUTHORS' CONCLUSIONS: Antibiotic treatment may be effective in reducing the risk of pyelonephritis in pregnancy, but our confidence in the effect estimate is limited given the low certainty of the evidence. There may be a reduction in preterm birth and low birthweight with antibiotic treatment, consistent with theories about the role of infection in adverse pregnancy outcomes, but again, the confidence in the effect is limited given the low certainty of the evidence. Research implications identified in this review include the need for an up-to-date cost-effectiveness evaluation of diagnostic algorithms, and more evidence to learn whether there is a low-risk group of women who are unlikely to benefit from treatment of asymptomatic bacteriuria.

Screening for Asymptomatic Bacteriuria in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Screening for asymptomatic bacteriuria can identify patients for whom treatment might be beneficial for preventing symptomatic infection and other health outcomes. Objective: To systematically review benefits and harms of asymptomatic bacteriuria screening and treatment in adults, including during pregnancy, to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed (publisher-supplied records), and Cochrane Collaboration Central Registry of Controlled Trials; surveillance through May 24, 2019. Study Selection: Randomized clinical trials (RCTs) and observational studies on benefits and harms of screening for asymptomatic bacteriuria; RCTs on benefits and harms of asymptomatic bacteriuria treatment. Eligible populations included unselected, asymptomatic individuals without known urinary tract conditions. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Random-effects meta-analysis was conducted to estimate benefits of the interventions. Main Outcomes and Measures: Symptomatic infection; function, morbidity, mortality; pregnancy complications and birth outcomes. Results: Nineteen studies (N = 8443) meeting inclusion criteria were identified. Two cohort studies (n = 5289) found fewer cases of pyelonephritis in the cohorts of screened pregnant women (0.5%) than within retrospective comparisons of unscreened cohorts (2.2% and 1.8%); the larger study estimated a statistically significant relative risk of 0.30 (95% CI, 0.15-0.60). No studies examined screening in nonpregnant populations. Among 12 trials of asymptomatic bacteriuria screening and treatment during pregnancy (n = 2377; 1 conducted within past 30 years), there were reduced rates of pyelonephritis (range, 0%-16.5% for the intervention group and 2.2%-36.4% for the control group; pooled risk ratio [RR], 0.24 [95% CI, 0.14-0.40]; 12 trials) and low birth weight (range, 2.5%-14.8% for the intervention group and 6.7%-21.4% for the control group; pooled RR, 0.64 [95% CI, 0.46-0.90]; 7 trials). There was no significant difference in infant mortality (pooled RR, 0.98 [95% CI, 0.29-3.26]; 6 trials). Five RCTs of asymptomatic bacteriuria treatment in nonpregnant adults (n = 777) did not report any significant differences in risk of infection, mobility, or mortality. Limited evidence on harms of screening or treatment was available, and no statistically significant differences were identified. Conclusions and Relevance: Screening and treatment for asymptomatic bacteriuria during pregnancy was associated with reduced rates of pyelonephritis and low birth weights, but the available evidence was not current, with only 1 study conducted in the past 30 years. Benefits of asymptomatic bacteriuria treatment in nonpregnant adult populations were not found. Trial evidence on harms of asymptomatic bacteriuria antibiotic treatment was limited.

Screening for Asymptomatic Bacteriuria in Adults: US Preventive Services Task Force Recommendation Statement.

Importance: Among the general adult population, women (across all ages) have the highest prevalence of asymptomatic bacteriuria, although rates increase with age among both men and women. Asymptomatic bacteriuria is present in an estimated 1% to 6% of premenopausal women and an estimated 2% to 10% of pregnant women and is associated with pyelonephritis, one of the most common nonobstetric reasons for hospitalization in pregnant women. Among pregnant persons, pyelonephritis is associated with perinatal complications including septicemia, respiratory distress, low birth weight, and spontaneous preterm birth. Objective: To update its 2008 recommendation, the USPSTF commissioned a review of the evidence on potential benefits and harms of screening for and treatment of asymptomatic bacteriuria in adults, including pregnant persons. Population: This recommendation applies to community-dwelling adults 18 years and older and pregnant persons of any age without signs and symptoms of a urinary tract infection. Evidence Assessment: Based on a review of the evidence, the USPSTF concludes with moderate certainty that screening for and treatment of asymptomatic bacteriuria in pregnant persons has moderate net benefit in reducing perinatal complications. There is adequate evidence that pyelonephritis in pregnancy is associated with negative maternal outcomes and that treatment of screen-detected asymptomatic bacteriuria can reduce the incidence of pyelonephritis in pregnant persons. The USPSTF found adequate evidence of harms associated with treatment of asymptomatic bacteriuria (including adverse effects of antibiotic treatment and changes in the microbiome) to be at least small in magnitude. The USPSTF concludes with moderate certainty that screening for and treatment of asymptomatic bacteriuria in nonpregnant adults has no net benefit. The known harms associated with treatment include adverse effects of antibiotic use and changes to the microbiome. Based on these known harms, the USPSTF determined the overall harms to be at least small in this group. Recommendations: The USPSTF recommends screening pregnant persons for asymptomatic bacteriuria using urine culture. (B recommendation) The USPSTF recommends against screening for asymptomatic bacteriuria in nonpregnant adults. (D recommendation).

La profilaxis antibiótica es innecesaria para prevenir las cicatrices renales tras infección urinaria en niños sanos / Antibiotic prophylaxis is unnecessary to prevent renal scarring after urinary tract infection in healthy children

Conclusiones de los autores del estudio: la profilaxis antibiótica no está indicada para la prevención de cicatrices renales tras la primera o segunda infección urinaria febril en niños sanos. Comentario de los revisores: la incidencia de cicatrices renales tras una infección urinaria febril en niños sanos es baja, en torno al 6%. No hay diferencias entre el grupo tratado profilácticamente con antibióticos y el grupo control, por lo que la administración de profilaxis antibiótica no está justificada

Authors' conclusions: antibiotic prophylaxis is not indicated for the prevention of renal scarring after a first or second symptomatic or febrile urinary tract infection in otherwise healthy children. Reviewers' commentary: incidence of renal scarring after febrile urinary tract infection in healthy children is low, around 6%. There are not differences between prophylaxis and control groups, so prophylactic antibiotic therapy is not justified

Beneficial effect of sugar-sweetened beverages on the risk of urinary tract infections.

Urinary tract infections (UTI) are among the most common bacterial infections. Drinking more liquids increases the frequency of urination and it is recommended as part of the prevention and/or management of UTI. The intake of sugar-sweetened beverages (SSB) is associated with obesity, diabetes and metabolic syndrome. However, cola and other SSB increase liquid intake and diuresis and could, thus, affect the risk of UTI and its complications. We hypothesize that intake of cola has a protective effect on UTI and pyelonephritis. Using an animal model of UTI, we have confirmed that dehydration with minimal urine output leads to higher bacterial counts in the kidneys in comparison to control mice (p = 0.01). The intake of SSB increased liquid intake and thus also diuresis and decreased renal bacterial counts as a marker of induced pyelonephritis (p = 0.036). The preliminary results show that dehydration is a risk factor for UTI and that higher diuresis induced by drinking SSB might be protective against pyelonephritis. The underlying mechanisms could include increased voiding frequency but potentially also active compounds in cola such as caffeine. These findings might have implications for the management of individuals at high risk of UTI. Further studies should verify the hypothesis and evaluate the practical relevance of this concept.

The learning curve of contrast-enhanced 'microbubble' voiding urosonography-validation study.

INTRODUCTION: Vesicoureteral reflux (VUR) is a common pediatric urologic condition associated with urinary tract infection and pyelonephritis. It can be diagnosed via fluoroscopic voiding cystourethrogram (VCUG) and, more recently, contrast-enhanced voiding ultrasonography (ceVUS), which does not expose the patient to ionizing radiation. Voiding urosonography contrast agents used for the diagnosis of VUR have been widely available in Europe but were approved by the Food and Drug Administration for use in the United States only in 2016. OBJECTIVE: The objective was to optimize a protocol and compare the diagnostic performance of ceVUS to fluoroscopic VCUG in an academic medical center naïve to previous use of contrast-enhanced voiding urosonography. STUDY DESIGN: Thirty-nine patients referred for clinically indicated evaluation of VUR were enrolled between September 2016 and March 2017. Patients underwent contrast-enhanced ultrasonography with prediluted Lumason and under the same catheterization underwent fluoroscopic VCUG. Comparative grading was performed by pediatric radiologists on-site at the time of examination. RESULTS: Reflux was observed in 16 of 39 patients (20 of 64 renal units) ranging from grades 1 through 5. VCUG and ceVUS were concordant for detecting reflux in 10 of 39 patients (14 of 84 renal units) and excluding reflux in 23 of 39 patients (64 of 84 renal units) (Fig. 1). Using contrast enhanced voiding urosonography, 1 of 20 renal units had high-grade and 2 of 20 renal units had low-grade reflux that was not found on fluoroscopy. Using fluoroscopy, 1 of 20 renal units had high-grade and 2 of 20 renal units had low-grade reflux that had not been found on ceVUS. Two of 20 renal units were upgraded from low-grade on ceVUS to high-grade on fluoroscopy. This corresponds to a Cohen's kappa of 0.72 (confidence interval [CI] 0.54-0.91) or 'moderate.' DISCUSSION: During our investigation, we noted that there was a technical learning curve related to poor contrast mixing and the need to titrate the concentration of Lumason. However, over the course of the study, we were able to correct the technical aspects. Ultimately, our results showed good correlation between VCUG and Lumason ceVUS and only slightly less correlation than published studies by experienced centers. Future studies with voiding should allow for improved urethral visualization. CONCLUSION: While there is a considerable learning curve to the implementation of ceVUS for the diagnosis of pediatric VUR, these technical aspects can be corrected. Even a center previously naïve to contrast-enhanced ultrasound technology can, over a short period of time, demonstrate good correlation between VCUG and ceVUS in the diagnosis of VUR. Translation of ceVUS into clinical practice is an alternative to VCUG for diagnosis of reflux, is feasible, and can eliminate the radiation exposure associated with a VCUG.

Cystitis and Pyelonephritis: Diagnosis, Treatment, and Prevention.

Urinary tract infections, including cystitis and pyelonephritis, are the most common bacterial infection primary care clinicians encounter in office practice. Dysuria and frequency in the absence of vaginal discharge and vaginal irritation are highly predictive of cystitis. Urine culture is recommended for the diagnosis and management of pyelonephritis, recurrent urinary tract infection, and complicated urinary tract infections. Antibiotics targeted toward Escherichia coli, Proteus, Klebsiella, and Staphylococcus saprophyticus are the recommended treatment. The duration of treatment varies by specific drug and type of infection, ranging from 3 to 5 days for uncomplicated cystitis to 7 to 14 days for pyelonephritis.

Lack of P2X7 Receptors Protects against Renal Fibrosis after Pyelonephritis with α-Hemolysin-Producing Escherichia coli.

Severe urinary tract infections are commonly caused by sub-strains of Escherichia coli secreting the pore-forming virulence factor α-hemolysin (HlyA). Repeated or severe cases of pyelonephritis can cause renal scarring that subsequently can lead to progressive failure. We have previously demonstrated that HlyA releases cellular ATP directly through its membrane pore and that acute HlyA-induced cell damage is completely prevented by blocking ATP signaling. Local ATP signaling and P2X7 receptor activation play a key role in the development of tissue fibrosis. This study investigated the effect of P2X7 receptors on infection-induced renal scarring in a murine model of pyelonephritis. Pyelonephritis was induced by injecting 100 million HlyA-producing, uropathogenic E. coli into the urinary bladder of BALB/cJ mice. A similar degree of pyelonephritis and mortality was confirmed at day 5 after infection in P2X7+/+ and P2X7-/- mice. Fibrosis was first observed 2 weeks after infection, and the data clearly demonstrated that P2X7-/- mice and mice exposed to the P2X7 antagonist, brillian blue G, show markedly less renal fibrosis 14 days after infection compared with controls (P < 0.001). Immunohistochemistry revealed comparable early neutrophil infiltration in the renal cortex from P2X7+/+ and P2X7-/- mice. Interestingly, lack of P2X7 receptors resulted in diminished macrophage infiltration and reduced neutrophil clearance in the cortex of P2X7-/- mice. Hence, this study suggests the P2X7 receptor to be an appealing antifibrotic target after renal infections.

Association between interleukin 8-receptor gene (CXCR1 and CXCR2) polymorphisms and urinary tract infection: Evidence from 4097 subjects.

AIM: The aim of this study was to determine whether a correlation exists between interleukin-8 receptor polymorphisms and urinary tract infection (UTI) susceptibility. METHODS: We systematically searched electronic databases including PubMed, Embase, China National Knowledge Infrastructure, and Web of Science up to 5 November 2017 to select appropriate studies that focused on C-X-C chemokine receptor type 1 and/or 2 (CXCR1, CXCR2) polymorphisms with susceptibility to UTI. Eight case-control studies including 2085 patients with UTI and 2012 controls were enrolled in this study. Seven studies of CXCR1 rs2234671 and two studies of rs3138086 were included in the meta-analyses. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were synthesized using fixed-effects or random-effects model according to heterogeneity. RESULTS: No significant correlations were found between CXCR1 rs2234671 and rs3138086 polymorphisms and UTI susceptibility. However, subgroup analysis showed that rs2234671 was associated with an increased risk of UTI under allelic comparisons (C vs. G, OR = 1.95, 95% CI = 1.07-3.55), heterozygous model (GC vs. GG, OR = 1.93, 95% CI = 1.06-3.50), and dominant model (GC + CC vs. GG, OR = 1.98, 95% CI = 1.07-3.69) in children, especially in paediatric patients with acute pyelonephritis (allelic, OR = 2.43, 95% CI = 1.28-4.60; heterozygous, OR = 2.40, 95% CI = 1.24-4.62; dominant, OR = 2.48, 95% CI = 1.26-4.88). Furthermore, these results remained the same after eliminating paediatric patients with vesicoureteral reflux. CONCLUSION: CXCR1 rs2234671 polymorphism might be associated with an increased risk of UTI in children.