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Background: Many studies have demonstrated that dimercaptosuccinic acid (DMSA) scintigraphy is the most sensitive diagnostic method in the identification of irreversible renal lesions (scars) in children with previous episodes of acute pyelonephritis (APN). This study assessed the reliability of ultrasound in identifying reflux nephropathy in children with acute pyelonephritis with or without vesicoureteric reflux (VUR). Methods: Eighty children (45 female and 35 male, age range 5 months to 10 years, average age 2 years 1 month) with a positive history for at least one episode of APN participated in this study. All children underwent voiding cystourethrography, DMSA scintigraphy 4 to 8 months after the most recent episode of APN, and an ultrasound test evaluation less than 2 months after DMSA scintigraphy. Results: Voiding cystourethrograms showed VUR in 52 children (68%); 13 of these were bilateral, for a total of 65 refluxing kidney units of the 154 (42%) evaluated; DMSA scintigram was normal for 108 of 154 kidneys (70%). Of the 65 kidneys with VUR, DMSA scintigram displayed normal findings in 29 cases (45%) and pathologic findings in 36 (55%). In the 79 nonrefluxing kidneys, DMSA scintigram was normal in 69 cases (87%). The relative risk of scarring in VUR kidneys is 2.6. The ultrasound study recorded a maximum longitudinal diameter between the 5th and 95th percentiles in 80 of 89 (81%) kidneys without VUR and in 21 of 65 (32%) with VUR. A significant correlation was found between maximum longitudinal diameters and DMSA scintigraphic findings in kidneys with VUR and those without VUR, respectively. Conclusion: This study establishes that ultrasound scans, by means of a simple and reproducible measurement technique, maximum longitudinal diameter, have a predictive value with regard to the presence of scars, with few exceptions. This finding, in our opinion, could lead to a decrease in the number of invasive procedures, in particular DMSA scan, in patients with APN. [ABSTRACT FROM AUTHOR]

Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1–11% when using voiding cystourethrography (VCUG), while 11.9–61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR. [ABSTRACT FROM AUTHOR]

Background: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. Methods: We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20 ml/min/1.73 m2 after 1 year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1 year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. Results: Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. Conclusion: PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies. [ABSTRACT FROM AUTHOR]

Contrasting data refer to therapies for vesicoureteral reflux (VUR), such as surgical treatments and continuous antibiotic prophylaxis (CAP). This study evaluated the effectiveness of these approaches in children with VUR, analyzing the recurrence of febrile urinary tract infections (UTIs) and the resolution of VUR after the treatment. A total of 350 pediatric patients underwent contrast-enhanced voiding urosonography (ceVUS) to diagnose a VUR, whereas renal scintigraphy evaluated potential scars. After 12 months from the treatment, the VUR, the relapse of febrile UTIs, and reflux-related nephropathy were analyzed. Twenty-seven children had recurrent febrile UTIs after surgical therapy, with a greater rate of relapses observed in III and V VUR grades. Thirteen patients who underwent surgery had scars, independently of VUR grades and gender, with evidence of chronic renal failure at the end of the follow-up period. A total of 140 subjects were treated with CAP, and 30% of them continued to suffer from febrile UTIs. Ninety-five patients with VUR underwent ceVUS after 12 months, with persistent reflux in fifty-two patients. All of them had severe VUR, correlating with the age at diagnosis and gender. CAP therapy prevented scarring better than surgery, especially in children with III and V grades of VUR. A late onset of VUR or VUR involving neonatal patients is rarely a reversible process. This study identified predictors of success or failure of surgical or CAP therapies, evaluating the relapse of UTIs or persistent reflux after the treatment and giving prognostic information in children with VUR. [ABSTRACT FROM AUTHOR]

Fosfomycin, originally named phosphonomycin when it was first isolated from fermentation broth of Streptomyces species and synthesized at Merck in 1969. The phosphonic acid containing a structurally strained and reactive epoxide ring confers broad spectrum, bactericidal activity against gram‐positive and gram‐negative bacteria. Fosfomycin's small size and hydrophilicity permits broad tissues penetration. Although only fosfomycin tromethamine oral is approved for urinary tract infections (UTI) in the United States since 1996, the intravenous form has been utilized worldwide for over four decades. The increasing rates of multidrug‐resistant (MDR) infections with few novel treatment options available has spurred the recent interest in fosfomycin. Fosfomycin's high urinary concentration, broad spectrum of activity against MDR pathogens, and favorable safety profile offers a valuable oral option for treating UTI, one of the most common bacterial infections in childhood. The ability of fosfomycin to penetrate biofilm and reported activity against intracellular pathogens may further its importance in childhood diseases such as Chronic Granulomatous Disease, Salmonellosis, and Listeriosis. More data are needed to further define optimal Pharmacodynamic target, as well as Pharmacokinetic, safety and outcomes for repeated oral and intravenous dosing of fosfomycin in infants and children in systemic infections. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) represents one of the most common infectious diseases and a major cause of antibiotic prescription in children. To prevent recurrent infections and long-term complications, low-dose continuous antibiotic prophylaxis (CAP) has been used. However, the efficacy of CAP is controversial. The aim of this document was to develop updated guidelines on the efficacy and safety of CAP to prevent pediatric UTIs. Methods: A panel of experts on pediatric infectious diseases, pediatric nephrology, pediatric urology, and primary care was asked clinical questions concerning the role of CAP in preventing UTIs in children. Overall, 15 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results: The use of CAP is not recommended in children with a previous UTI, with recurrent UTIs, with vesicoureteral reflux (VUR) of any grade, with isolated hydronephrosis, and with neurogenic bladder. CAP is suggested in children with significant obstructive uropathies until surgical correction. Close surveillance based on early diagnosis of UTI episodes and prompt antibiotic therapy is proposed for conditions in which CAP is not recommended. Conclusions: Our systematic review shows that CAP plays a limited role in preventing recurrences of UTI in children and has no effect on its complications. On the other hand, the emergence of new antimicrobial resistances is a proven risk. [ABSTRACT FROM AUTHOR]

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Background: Enuresis is one of the most common childhood problems. Our study aimed to evaluate children with enuresis by renal bladder ultrasound (RBUS) to detect urological abnormalities and to compare the sonographic findings with control group. Methods: Our study included 30 children with primary monosymptomatic nocturnal enuresis (PMNE). Another 30 matched children with normal continence to urine were assigned as controls. The 2 groups were subjected to urine analysis, serum creatinine, and RBUS. Results: Ultrasound showed abnormality in 10% of case group, which was not significantly different from controls (p = 1.000). Conclusion: Abnormalities discovered by ultrasonography in PMNE are more than in control group but without statistical significance and do not require invasive diagnostic tests. Children with sonographic abnormalities appear to be more resistant to treatment. We concluded that ultrasound is not necessary in MPNE and should be done in patients resistant to treatment. [ABSTRACT FROM AUTHOR]

Primary monosymptomatic nocturnal enuresis is a common clinical condition in childhood and affects the psychosocial development of the child. The management of this clinical condition, which includes the preschool and adolescence period, is very important for child development. Diagnostic evaluation should be performed in terms of diabetes mellitus, diabetes inspidus, neurogenic bladder, spinal anomalies, and congenital urogenital system anomalies. Treatment modalities in primary monosymptomatic nocturnal enuresis include enuretic alarm therapy, behavioral therapy, and pharmacological treatments such as desmopressin, tricyclic antidepressants, and anticholinergics. There are also experimental treatments such as percutaneous nerve stimulation, acupuncture, and manual therapy. In this study, we examined randomized controlled studies in the literature that included alarm monotherapy and combined therapy. We aimed to present the efficacy, advantages, and disadvantages of combined treatment with the results of the studies. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is one of the most common infectious diseases in the pediatric population and represents a major cause of antibiotic consumption and hospitalization in children. Considering the ongoing controversies on the management of pediatric UTI and the challenges due to increasing antimicrobial resistance, the aim of the present study was to evaluate the level of agreement on UTI management in pediatric age in Emilia-Romagna Region, Italy, and to assess on the basis of recent studies whether there is the need to change current recommendations used by primary care pediatricians, hospital pediatricians, and pediatric surgeons in everyday clinical practice to possibly improve outcomes. This consensus provides clear and shared indications on UTI management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date collection of statements on procedures to follow for pediatric UTI, in order to guide physicians in the management of the patient, standardize approaches, and avoid abuse and misuse of antibiotics. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best therapeutic management in cases with antimicrobial resistance and real usefulness of long-term antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Purpose: Delta neutrophil index (DNI) indicates immature granulocytes in peripheral blood and has been confirmed to be effective as a prognostic factor for neonatal sepsis. Also, it has been reported to have diagnostic value in acute pyelonephritis and in predicting vesicoureteral reflux (VUR) in the infant. We conducted the study to verify whether DNI is also helpful in the entire pediatric age group with febrile urinary tract infection (UTI). Methods: Medical records of children hospitalized for febrile UTIs were analyzed retrospectively. All subjects underwent kidney ultrasound and voiding cystourethrography. In the group with and without VUR, we compared sex and age, and the following laboratory values: the white blood cell count, neutrophil, polymorphonuclear leucocyte, eosinophil, hemoglobin, platelet count, C-reactive protein, DNI value, and the finding of ultrasound. Results: A total of 315 patients (163 males and 152 females; range, 0-127 months) were eligible, and 41 patients (13%) had VUR. As a result of univariate analysis, the white blood cell count, neutrophil, DNI, and ultrasonic abnormalities were high in the reflux group, and the hemoglobin and lymphocyte fraction values were low. The value of DNI and the abnormal ultrasound were significantly higher in the reflux group on the multivariate analysis. The area under the curve value of the receiver operating curve was higher in DNI (0.640; 95% confidence interval, 0.536-0.744; P=0.004), and the DNI cutoff value for VUR prediction was 1.85%. Conclusions: We identified that ultrasound findings and DNI values were helpful predictors of VUR in pediatric febrile UTIs. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are a significant clinical problem that pregnant women and children commonly experience. Escherichia coli is the primary causative organism, along with several other gram-negative and gram-positive bacteria. Antimicrobial drugs are commonly prescribed to treat UTIs in these patients. Conventional treatment can range from using broad-spectrum antimicrobial drugs for empirical or prophylactic therapy or patient-tailored therapy based on urinary cultures and sensitivity to prospective antibiotics. The ongoing emergence of multi-drug resistant pathogens has raised concerns related to commonly prescribed antimicrobial drugs such as those used routinely to treat UTIs. Consequently, several natural medicines have been explored as potential complementary therapies to improve health outcomes in patients with UTIs. This review discusses the effectiveness of commonly used natural products such as cranberry juice/extracts, ascorbic acid, hyaluronic acid, probiotics, and multi-component formulations intended to treat and prevent UTIs. The combination of natural products with prescribed antimicrobial treatments and use of formulations that contained high amounts of cranberry extracts appear to be most effective in preventing recurrent UTIs (RUTIs). The incorporation of natural products like cranberry, hyaluronic acid, ascorbic acid, probiotics, Canephron® N, and Cystenium II to conventional treatments of acute UTIs or as a prophylactic regimen for treatment RUTIs can benefit both pregnant women and children. Limited information is available on the safety of natural products in these patients' populations. However, based on limited historical information, these remedies appear to be safe and well-tolerated by patients. [ABSTRACT FROM AUTHOR]

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The authors reflect on the risk stratification for children with only one functioning kidney and the possible risks faced by a solitary functioning kidney (SFK). Also cited are the hyperfiltration hypothesis stating that reduced number of nephrons could cause glomerular hyperfiltration which may result in hypertension, albuminuria, and glomerulosclerosis, and the risk factors like genetic, perinatal, and urinary tract abnormalities.

Purpose: Vesicoureteral reflux (VUR) is a risk factor for various renal problems like recurrent urinary tract infections (UTIs), pyelonephritis, renal scarring, hypertension, and other renal parenchymal defects. The interventions followed by pediatricians include low-dose antibiotic treatment, surgical correction, and endoscopy. This meta-analysis aimed to assess the advantages and drawbacks of various primary VUR treatment options. Search Strategy: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of journals, and abstracts from conference proceedings were all used to find randomized controlled trials. The articles were retrieved from 1985 till 2020. Twenty articles were used for the data analysis. Criteria for Selection: Surgery, long-term antibiotic prophylaxis, noninvasive techniques, and any mix of therapies are also options for treating VUR. Collection and Interpretation of Data: Two authors searched the literature separately, determining research qualifications, assessing accuracy, and extracting and entering results. The odds ratio (OR) of these studies was used to construct the forest plot. The random-effects model was used to pool the data. Also, the random-effects model was used with statistical significance at a p value < 0.05 to assess the difference in side effects after treatment of VUR using different modalities. Results: We found no statistically significant differences between surgery plus antibiotics and antibiotic alone-treated patients in terms of recurrent UTIs (OR = 0.581; 95% confidence interval [CI] 0.259–1.30), renal parenchymal defects (OR = 1.149; 95% CI 0.75–1.754), and renal scarring (OR = 1.042; 95% CI 0.72–1.50). However, the risk of developing pyelonephritis after surgical treatment of VUR was lesser than that in the conservative approach, that is, antibiotics (OR = 0.345; 95% CI 0.126–0.946.), positive urine culture (OR = 0.617; 95% CI 0.428–0.890), and recurrent UTIs were more common in the placebo group than in the antibiotic group (p < 0.05; OR = 0.639; 95% CI 0.436–0.936) which is statistically significant. Conclusion: Based on current research, we recommend that a child with a UTI and significant VUR be treated conservatively at first, with surgical care reserved for children who have issues with antimicrobials or have clinically significant VUR that persists after several years of follow-up. [ABSTRACT FROM AUTHOR]

Aim: There are scanty data on the rate of abnormal Tc-99 m dimercaptosuccinic acid (DMSA) renal scintigraphy and associated factors in children older than 5 years with diagnosis of VUR. We do not have knowledge about which older children should undergo DMSA after VUR diagnosis. This study aims to assess the rate of abnormal DMSA findings and associated factors in children older than 5 years of age diagnosed with VUR. Materials and methods: We retrospectively reviewed the medical records of 258 children with VUR diagnosed at or older than 5 year age. 179 children [42 (23.5%) males and 137 (76.5%) females] with complete data were included. 268 reflux units were compared according to gender, bilaterality, grade, reflux phase at voiding cystourethrography, febrile urinary tract infection (fUTI), lower urinary tract dysfunction (LUTD), and DMSA findings with uni- and multivariate analysis. Results: The median age was 110 (60–216) months. VUR grades were I, II, and III in 197 (73.6%) units and IV–V in 71 (26.4%). 138 (51.5%) renal units had abnormal DMSA. VUR grade (p < 0.01), unilaterality (p = 0.048), and fUTI (p = 0.031) in univariate but only grade and unilaterality in multivariate analysis are significantly associated with abnormal DMSA. Although reflux at filling phase was predominant in high-grade VUR group, reflux at voiding phase (p = 0.006) in low–medium-grade (1–3) VUR was associated with abnormal DMSA. Conclusion: Children older than 5 years of age diagnosed with VUR should be regarded as a high-risk group for abnormal DMSA regardless of gender, unilaterality, grade, reflux phase, fUTI, and LUTD. [ABSTRACT FROM AUTHOR]

Aim: The treatment of vesicoureteral reflux (VUR) in infants is controversial. Subureteric injection is considered by some to be a popular alternative to long-term antibiotic prophylaxis. In this study, we reviewed our experience in endoscopic subureteric injection to correct highgrade reflux in infants with documented indications for antireflux surgery. Materials and Methods: The hospital records of patients with grade 4-5 VUR and breakthrough urinary tract infections who had undergone endoscopic subureteric injection in the first year of life between 2009 and 2016 were reviewed retrospectively. Radiologic success was defined as complete resolution of reflux determined via voiding cystourethrogram obtained at least three months after the injection, and clinical success was defined as the downgrading of reflux grade to below three and the absence of urinary infection. Results: A total of 23 patients (5 girls, 18 boys) with 34 high-grade refluxing units were included in this study. The mean age at first injection was 6.3±1.8 months (1-11 months). The radiologic success rate with initial injection was 61.7%, and it was 85.2% after repeated injections. The overall clinical success rate after first injection was 70.6% and 97.1% after repeated injections. The mean injected material volume was 0.34±0.27 (0.1-1) mL per ureter. Conclusion: The management of high-grade infantile reflux is still controversial with insufficient data. Published studies comparing endoscopic treatment and antibiotic prophylaxis have inconclusive results due to their wide range of success rates. Although it needs to be supported by prospective studies, endoscopic treatment is a successful alternative in high-grade VUR infants with breakthrough infection. [ABSTRACT FROM AUTHOR]

Background: Acute pyelonephritis (AP) is a common bacterial infection in childhood. Follow-up guidelines on these children are controversial. This study aimed to identify risk factors for kidney scarring and vesicoureteral reflux (VUR). Furthermore, international follow-up guidelines were used for simulation to evaluate sensitivity and specificity. Methods: Urinary culture-confirmed first-time AP patients (aged 0–14 years) were enrolled (n = 421) from review of patient charts. All underwent kidney ultrasound (US) and a technetium-99m-dimercaptosuccinic acid (DMSA) scan or technetium-99m-mercaptoacetyltriglycine scinti-renography (MAG3) at 4–6 months of follow-up. The international guidelines used for simulation were from the National Institute of Health UK (NICE), the American Association of Paediatrics (AAP) and the Swedish Paediatric Society (SPS). Results: 17.8% presented with an abnormal DMSA/MAG3 at follow-up, 7.1% were diagnosed with VUR grades III–V and 4.7% were admitted for surgery. Non-Escherichia coli infections, abnormal kidney US, elevated creatinine and delayed response to treatment (>48 h) were risk factors for abnormal DMSA findings and VUR grades III–V. NICE and SPS guidelines showed best sensitivity in diagnosing VUR grades III–V (75%) compared with AAP (56%). Conclusions: Risk factors are helpful in identifying the children in need of further investigations and minimizing invasive work-up for the rest. International guidelines on follow-up detect a varying number of children with kidney damage and/or significant VUR. Future work must focus on identifying more specific risk factors, better imaging, or specific biomarkers, to enhance sensitivity and specificity in detecting the children at high risk for developing recurrent infections and/or nephropathy. [ABSTRACT FROM AUTHOR]

Purpose: We designed a multicenter, retrospective study to investigate the current trends in initial management of reflux with respect to European Association of Urology (EAU) Guidelines in Urology clinics of our country.Materials and Methods: The study group consisted of 1988 renal units (RU) of 1345 patients treated surgically due to vesicoureteral reflux (VUR) (between years 2003 and 2017) in nine different institutions. Patients were divided into two groups according to time of initial treatment and also grouped according to risk factors by "EAU guidelines on VUR."Results: In this series, 1426 RUs were treated initially conservatively and 562 RUs were initially treated with surgery. In initially surgically treated group, success rates of surgery decreased significantly in low and moderate risk groups after 2013 (P = .046, P = .0001, respectively), while success rates were not significantly different in high risk group (P = .46). While 26.6% of patients in low risk group were initially surgically treated before 2013, this rate has increased to 34.6% after 2013, but the difference was not statistically significant (P = .096). However, performing surgery as the initial treatment approach increased significantly in both moderate and high risk groups (P = .000 and P = .0001, respectively) after 2013. Overall success rates of endoscopic treatments and ureteroneocystostomy (UNC) operations were 65% and 92.9% before 2013 and 60% and 78.5% after 2013, respectively. Thus, the overall success rate for surgery was 72.6%. There was significant difference between success rates of UNC operations before and after 2013 (P = .000), while the difference was not significant in the injection group (P = .076).Conclusion: Current trends in management of reflux in our country do not yet follow the EAU guidelines on VUR in low and moderate risk groups despite these reliable and accepted guidelines were expected to influence our daily approach. [ABSTRACT FROM AUTHOR]

Background: This study investigated whether performing kidney ultrasound (KUS) only in children presenting either a pathogen other than E. coli at their first febrile urinary tract infection (fUTI) or experiencing fUTI recurrence would increase missed diagnoses of kidney anomalies. Methods: Patients aged 2–36 months with fUTI who underwent KUS evaluation from 2 January 2013 to 31 June 2018 were enrolled. Cystourethrography was performed after pathological KUS or recurring fUTIs. Thereafter, we retrospectively assessed the detection rate of kidney anomalies through performing KUS only in patients with atypical pathogen at first fUTI or with recurring fUTIs. Results: In 263 patients included, the isolated pathogen was E. coli in 223 cases (84.8%) and atypical in 40 cases (15.2%). KUS detected kidney anomalies in 14/223 (6.3%) of fUTIs caused by E. coli and in 11/40 (27.5%) of fUTIs caused by an atypical pathogen (OR 5.5, 95%CI 2.5–14.5). Cystourethrography was performed in 40 patients and vesicoureteral reflux (VUR) found in 20 cases. None of the high grade VUR diagnoses or other kidney anomalies would have been lost through a different diagnostic protocol that required the presence of an atypical pathogen at the first fUTI or a fUTI recurrence to perform the KUS. Conclusions: A diagnostic protocol that requires presence of an atypical pathogen at the first fUTI or a second episode of fUTI to perform the KUS would allow a reduction in the number of negative ultrasounds with a negligible risk of missed diagnoses of kidney anomalies. [ABSTRACT FROM AUTHOR]

Vesico-ureteral reflux (VUR) has long been recognized as associated with urinary tract infections (UTIs), renal scarring, and chronic kidney disease (CKD). The concept of "reflux nephropathy" was born, whereby the VUR was considered the culprit, predisposing to recurrent UTIs and providing a conduit whereby the infection could ascend to the kidneys resulting in scarring and destruction. The more severe grades of reflux were thought to place the young child at particular risk of CKD. The question being asked in this pro/con debate is whether VUR is indeed the culprit responsible for a significant proportion of children with CKD, a number of whom progress to end-stage kidney failure (ESKF), and is thus important to find and treat, or is it an innocent bystander associated with CKD and ESKF but not the cause. We believe the latter and will present convincing evidence supported by large scale prospective randomized controlled trials that VUR is not the ogre it was thought to be and is not important to find following a UTI (with some exceptions). [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract infection (UTI) in childhood is a common reason for a visit to the GP. The clinical picture is often non-specific, which leads to a challenge in their recognition, diagnosis and treatment. Objective: to review the scientific literature for a period of 40 years on the epidemiology and clinical features of urinary tract infections in childhood with a view to providing up-to-date data and optimizing their diagnosis and treatment, as well as assessing the role of the GP in this whole process. Material and methods: Analysis of literature sources according to the PubMed and Google Scholar databases for a period of 40 years. Results: Analysis of studies and reports shows that there is an increase in the number of UTIs in children in early childhood with a predominance among girls. Prolonged wearing of diapers and lack of accustoming of the child to urinate in a potty can be pointed out as a probable reason. On the other hand, knowledge of the most common symptoms of UTI by the GP, regular preventive examinations and screening lead to timely diagnosis, treatment and follow-up of children, which plays a significant role in preventing disability at a later stage. A very important step towards the prevention of UTI in infants is to perform early ultrasound examinations up to 6 months of age. Conclusions: Prevention is always better than the best treatment. Knowing the patient from the first day of birth, monitoring the physical and neuropsychological development on a monthly basis and regular preventive examinations enable the general practitioner to be a leader in the fight against UTI in childhood. [ABSTRACT FROM AUTHOR]

Urinary tract infection is a bacterial infection that commonly occurs in children. Vesicoureteral reflux is a major underlying precursor condition of urinary tract infection, and an important disorder in the field of pediatric urology. Vesicoureteral reflux is sometimes diagnosed postnatally in infants with fetal hydronephrosis diagnosed antenatally. Opinions vary regarding the diagnosis and treatment of vesicoureteral reflux, and diagnostic procedures remain debatable. In terms of medical interventions, options include either follow‐up observation in the hope of possible spontaneous resolution of vesicoureteral reflux with growth/development or provision of continuous antibiotic prophylaxis based on patient characteristics (age, presence/absence of febrile urinary tract infection, lower urinary tract dysfunction and constipation). Furthermore, there are various surgical procedures with different indications and rationales. These guidelines, formulated and issued by the Japanese Society of Pediatric Urology to assist medical management of pediatric vesicoureteral reflux, cover the following: epidemiology, clinical practice algorithm for vesicoureteral reflux, syndromes (dysuria with vesicoureteral reflux, and bladder and rectal dysfunction with vesicoureteral reflux), diagnosis, treatment (medical and surgical), secondary vesicoureteral reflux, long‐term prognosis and reflux nephropathy. They also provide the definition of bladder and bowel dysfunction, previously unavailable despite their close association with vesicoureteral reflux, and show the usefulness of diagnostic tests, continuous antibiotic prophylaxis and surgical intervention using site markings. [ABSTRACT FROM AUTHOR]

In an era of increasing antimicrobial resistance, there are limited treatment options available to treat multidrug-resistant organisms in paediatric patients. Fosfomycin is an antibiotic defined as 'critically important' by The World Health Organization due to its potential efficacy against multidrug-resistant bacteria and is increasingly cited in the international literature as a promising antimicrobial for combating sepsis in an era of increasing antimicrobial resistance. With broad-spectrum cover that includes both Gram-positive and Gram-negative organisms and both parenteral and oral formulations available, fosfomycin provides a promising treatment option for paediatric patients. This review summarises fosfomycin's spectrum of activity, published efficacy in paediatric patients, safety considerations and pharmacokinetic data, as well as identifying current clinical trials delineating pharmacokinetic parameters and safety parameters in neonatal sepsis which will provide further information regarding the use of fosfomycin in neonatal and paediatric infections. Limitations regarding the current standards for fosfomycin susceptibility definitions, variations in dosing regimens and the potential mechanisms for resistance are also discussed. [ABSTRACT FROM AUTHOR]

Background: Neonates with congenital urinary tract dilatation (UTD) may have an increased risk of urinary tract infections (UTI). At present, the management of these patients is controversial and the utility of continuous antibiotic prophylaxis (CAP) remains uncertain as the literature presents contradicting evidence. The aim of this observational study was to assess UTI occurrence in children with prenatal diagnosis of urinary collecting system dilatation without antibiotic prophylaxis.Methods: Between June 2012 and August 2016, we evaluated the incidence of UTI and the clinical and ultrasonography evolution in 407 children with a prenatally diagnosed UTD. All subjects underwent two prenatal ultrasounds scans (USs) at 20 weeks and 30 weeks of gestation and within 1 month of birth. Patients with a confirmed diagnosis of UTD underwent US follow-up at 6, 12 and 24 months of life. According to the UTD classification system stratify risk, after birth UTD were classified into three groups: UTD-P1 (low risk group), UTD-P2 (intermediate risk group), and UTD-P3 (high risk group). Voiding cystourethrogram was performed in all patients who presented a UTI and in those with UTD-P3. No patient underwent CAP.Results: Postnatal US confirmed UTD in 278 out of 428 patients with the following rates: UTD-P1 (126), UTD-P2 (95) and UTD-P3 (57). During postnatal follow-up, 6.83% patients presented a UTI (19 out of 278). Eleven out of 19 had vesicoureteral reflux (VUR), and other four were diagnosed with obstructive uropathy and underwent surgical correction. Five patients presented a UTI reinfection.Conclusion: The occurrence of UTI in patients with urinary collecting system dilatation was low. The recent literature reports an increased selection of multirestistant germs in patients with VUR exposed to CAP. This study constitutes a strong hint that routine continuous antibiotic prophylaxis could be avoided in patients with UTD. [ABSTRACT FROM AUTHOR]

Aim: Our aim was to update the recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children, which were endorsed in 2012 by the Italian Society of Pediatric Nephrology.Methods: The Italian recommendations were revised on the basis of a review of the literature published from 2012 to October 2018. We also carried out an ad hoc evaluation of the risk factors to identify children with high-grade vesicoureteral reflux or renal scarring, which were published in the previous recommendations. When evidence was not available, the working group held extensive discussions, during various meetings and through email exchanges.Results: Four major modifications have been introduced. The method for collecting urine for culture and its interpretation has been re-evaluated. We have reformulated the algorithm that guides clinical decisions to proceed with voiding cystourethrography. The suggested antibiotics have been revised, and we have recommended further restrictions of the use of antibiotic prophylaxis.Conclusion: These updated recommendations have now been endorsed by the Italian Society of Pediatric Nephrology and the Italian Society for Pediatric Infectivology. They can also be used to compare other recommendations that are available, as a worldwide consensus in this area is still lacking. [ABSTRACT FROM AUTHOR]

Background: We previously reported that the top‐down approach (TDA) for infants with febrile urinary tract infections (fUTI) could prevent recurrent fUTI (r‐fUTI) but produced a high number of false‐positives on acute‐phase 99mTc dimercaptosuccinic acid (DMSA) renal scintigraphy. Therefore we compared the ultrasonography‐oriented approach (USOA) with TDA from the viewpoint of prevention of r‐fUTI. Methods: The TDA was applied between July 2010 and February 2014 and the USOA was applied between March 2014 and April 2017 in infants with first fUTI. In the USOA group, voiding cystourethrography (VCUG) was performed in the case of abnormality on acute‐phase renal bladder ultrasonography (RBUS) or on chronic‐ phase DMSA, which were performed in all cases. The frequency of r‐fUTI was compared between the TDA group and USOA group retrospectively. Results: Seventy‐four infants (52 male) and 79 infants (60 male) received TDA or USOA, respectively. No significant differences were found between the TDA and USOA groups in male : female ratio, age in months at initial onset of fUTI, observation period, or number of cases of r‐fUTI (TDA group, n = 4; USOA group, n = 5). Seventy‐four DMSA scintigraphy and 25 VCUG were carried out in the USOA group, and 111 DMSA scintigraphy and 34 VCUG in the TDA group. Conclusions: Both USOA and TDA were valid for prevention of r‐fUTI, but USOA was superior to TDA with regard to the reduced number of patients undergoing VCUG and DMSA. [ABSTRACT FROM AUTHOR]

In recent years, progress has been made on understanding the relationship between vesicoureteral reflux (VUR) and urinary tract infection (UTI). The findings on recent prospective, randomized, controlled studies have questioned the conventional VUR clinical significance and, therefore, have challenged the traditional diagnostic and therapeutic recommendations. These new studies have redefined the pathogenic role of vesicoureteral reflux in UTI as well as have disputed the routine use of urinary antibiotic prophylaxis to prevent UTI and renal damage in VUR patients. The time to overinvestigate and treat the vast majority of otherwise healthy children who have an uncomplicated UTI with long-term antibiotic prophylaxis seems to be over. Is there a role of severe VUR in the development of chronic renal disease and renal failure? New ideas are needed to answer these questions with the goal to avoid repeating past mistakes when therapeutic choices were based on expert opinions rather than facts. [ABSTRACT FROM AUTHOR]

Recurrent urinary tract infection (rUTI) continues to challenge pediatric care providers. The diagnosis of an rUTI can be difficult, especially in young febrile children. Antibiotic resistance rates continue to rise, which limits oral treatment options. Prophylactic antibiotics are used commonly to manage rUTI, but their use increases the risk of rUTI with antibiotic-resistant strains without significantly reducing renal scarring. Alternative therapies for rUTI include probiotics and anthocyanidins (eg, cranberry extract) to reduce gut colonization by uropathogens and prevent bacterial adhesion to uroepithelia, but efficacy data for these treatments are sparse. The future of rUTI care rests in addressing the following contemporary issues: best diagnostic practices, risk factors associated with rUTI, and the prevention of recurrent infection. In this review, we summarize the state of the art for each of these issues and highlight future studies that will aim to take an alternative approach to managing rUTI. [ABSTRACT FROM AUTHOR]

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Purpose: We evaluated the cost-effectiveness of antimicrobial prophylaxis to prevent recurrent UTIs in children with vesicoureteral reflux based on the RIVUR trial.Materials and methods: A decision tree model compared strategies of antimicrobial prophylaxis vs. placebo in children with reflux using results from the RIVUR trial. Risk reduction was 50% based on intention to treat analysis. Costs were based on Medicare reimbursement and data in literature. The model incorporated costs of medications, imaging and complications such as pyelonephritis, likelihood of surgery and loss of work. One- and two-way sensitivity analyses were performed evaluating the effect of changing variables on the cost-effectiveness of antibiotic prophylaxis in preventing recurrent UTIs.Results: Mean costs were higher for treatment vs. placebo at $3092 and $2932, respectively, with 12.7 fewer infections per 100 children. One-way sensitivity analyses showed that antibiotics would be cost equivalent if the yearly medical cost was $386, rate of recurrent UTI increased to 32%, antibiotic risk reduction was 63%, or rate of pyelonephritis in the placebo group was 48%. Two-way analyses modifying antibiotic cost, risk reduction of antibiotics and probability of infection showed areas where antibiotics could be more cost-effective than placebo.Conclusions: Antibiotic prophylaxis is associated with marginally higher costs compared with placebo, but significantly fewer infections. A slight decrease in antibiotic cost or increase in recurrent UTIs on placebo may result in prophylaxis being more cost-effective. We recognize that the marginal overall cost in antibiotics may have a substantial impact on the quality of life for the individual patient and family. [ABSTRACT FROM AUTHOR]

Introduction We determined factors associated with abnormal imaging and recurrent infections after a first febrile urinary tract infection (UTI) in children younger than 3 years. Materials and Methods We retrospectively reviewed the records of all patients treated at our institute during the years 2000-2009, for a first febrile UTI in children younger than 3 years, who underwent ultrasonography and voiding cystourethrography. We evaluated data regarding factors potentially associated with abnormal ultrasonography and voiding cystourethrography results and recurrence of infections, and formulated a risk score system to assess risk of reflux and high-grade reflux. Results There were 282 patients. The only factor predicting abnormal ultrasonogram was non-Escherichia coli infection. Risk factors for vesicoureteral reflux included abnormal ultrasonogram, atypical infection, non-E. coli infection and infection recurrence. Patients with no identified risk factors for vesicoureteral reflux were unlikely to have high-grade reflux. Higher risk scores were associated with a higher risk for reflux. Non-E. coli infection was the only statistically significant predictor of infection recurrence. Conclusion All children younger than 3 years with first febrile UTI should undergo ultrasonography. Thereafter, patients with no predictive factors for vesicoureteral reflux may be followed up without further imaging. A non-E. coli infection is associated with reflux and infection recurrence. [ABSTRACT FROM AUTHOR]

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Randomised controlled trials (RCTs) provide the most reliable way to evaluate the benefits and harms of interventions. Participants are divided into groups using methods that balance the characteristics (both known and unknown) of the participants between treatment groups; thus, differences in outcomes are due to the interventions administered. From Cochrane Kidney and Transplant's Specialised Register, a comprehensive registry of trials in kidney disease, we identified 482 trials involving children. The vast majority concerned urinary tract infection (UTI; 134) and nephrotic syndrome (136). Most were small, with a median enrolment of 46 children, with only 26 trials enrolling 200 or more participants, and of these, 18 involved children with UTI. We discuss a number of important advances in the care of children with UTI with or without vesico-ureteric reflux, nephrotic syndrome, chronic kidney disease (CKD) and kidney transplantation that have been driven largely by trials in these conditions. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial prophylaxis is recommended for the prevention of urinary tract infections (UTI) in high-risk children. However, there is growing concern about the use of β-lactams as prophylaxis and subsequent development of antibiotic resistance. Methods: In this prospective, randomized, crossover controlled trial we compared cotrimoxazole (SXT) and second-generation cephalosporins (2GC) as UTI prophylaxis in children ranging in age from 1 to 60 months. Eligible patients were 1:1 randomized to receive either SXT or 2GC for the initial 6-month period (1 course), then switched to the other antimicrobial agent class for the subsequent course, with switching continuing after each course until the end of the study. Urethral orifice cultures (UOCs) were obtained at the time of switching antimicrobial prophylaxis. Results: Among 97 children (mean age 13.6 months) on prophylaxis, breakthrough UTIs occurred during 13.3 % (10/75) of SXT courses and 10.3 % (8/78) of 2GC courses ( p = 0.62). 2GC failed earlier than SXT (mean ± standard error: 0.81 ± 0.1 vs. 2.37 ± 0.36 months, respectively; p = 0.028). Pseudomonas aeruginosa and Enterococcus spp. were more frequently isolated after 2GC courses than after SXT courses [22.6 vs. 4.8 % ( p = 0.02) and 20.7 vs. 4.8 % ( p = 0.035), respectively]. Prophylaxis with 2GC significantly increased resistance to both 2GC and SXT, while SXT prophylaxis did not affect susceptibility to 2GC. Conclusions: While SXT and 2GC appear to be equally efficacious as UTI prophylaxis in children, the latter exert a broader effect on patients' flora and development of bacterial resistance, suggesting that SXT may be more appropriate for UTI prophylaxis than 2GC. [ABSTRACT FROM AUTHOR]

Acute pyelonephritis is one of the most serious bacterial illnesses during childhood. Escherichia coli is responsible in most cases, however other organisms including Klebsiella, Enterococcus, Enterobacter, Proteus, and Pseudomonas species are being more frequently isolated. In infants, who are at major risk of complications such as sepsis and meningitis, symptoms are ambiguous and fever is not always useful in identifying those at high risk. A diagnosis of acute pyelonephritis is initially made on the basis of urinalysis; dipstick tests for nitrites and/or leukocyte esterase are the most accurate indicators of infection. Collecting a viable urine sample for urine culture using clean voided methods is feasible, even in young children. No gold standard antibiotic treatment exists. In children appearing well, oral therapy and outpatient care is possible. New guidelines suggest less aggressive imaging strategies after a first infection, reducing radiation exposure and costs. The efficacy of antibiotic prophylaxis in preventing recurrence is still a matter of debate and the risk of antibiotic resistance is a warning against its widespread use. Well-performed randomized controlled trials are required in order to better define both the imaging strategies and medical options aimed at preserving long-term renal function. [ABSTRACT FROM AUTHOR]