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Objective: To analyse the timing of end stage renal disease in children with chronic kidney disease (CKD)., Design: A population-based cohort study., Setting: A nationwide registry (ItalKid Project) collecting information on all patients with CKD aged <20 years., Patients: 935 children with CKD secondary to renal hypodysplasia with or without urologic malformation. In a subgroup of patients (n=40) detailed pubertal staging was analysed in relation to CKD progression., Main Outcome Measures: Kidney survival (KS) was estimated using renal replacement therapy (RRT) as the end-point. Puberty was staged by identifying the pubertal growth spurt., Results: A non-linear decline in the probability of KS was observed, with a steep decrease during puberty: the probability of RRT was estimated to be 9.4% and 51.8% during the first and second decades of life, respectively. A break-point in the KS curve was identified at 11.6 and 10.9 years of age in male and female patients, respectively., Conclusions: The present analysis suggests that puberty is associated with increased deterioration of renal function in CKD. The mechanism(s) underlying this unique and specific (to children) pattern of progression have not yet been identified, but it may be that sex hormones play a role in this puberty-related progression of CKD.

Purpose: Recent studies suggest the efficacy of behavioral therapy for enuresis, even in cases of minor daytime voiding problems. We describe our experience with the clinical followup and behavioral therapy of children with primary enuresis., Materials and Methods: We followed 159 boys and 91 girls 5 to 17 years old with primary enuresis who were treated at 3 medical centers with a pediatric nephrology clinic during the last 3 years. A detailed voiding history was obtained. Each child was treated with a bladder training session, including an explanation of the enuretic process, daily diary recording and training to recognize bladder distention and increase voiding frequency., Results: A total of 226 children (90%) presented with 1 or more symptoms of bladder maturation delay and 13% reported behavioral constipation. Of the patients 185 (74%) completed the proposed treatment, including 111 (60%) who reported a positive and 21 (11%) who reported a partial response. In 53 children (29%) the treatment failed., Conclusions: Most children with enuresis have daytime symptoms when an accurate history is recorded. As shown by our data, the efficacy of behavioral therapy is comparable to that of desmopressin or alarm therapy but it requires good compliance of the child with the therapeutic plan. Age is not a determining factor in the success rate.

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.

Mutations in the COL4A5 gene, which encodes the a5 chain of type IV collagen, are found in a large fraction of patients with X-linked Alport syndrome. The recently discovered COL4A6, tightly linked and highly homologous to COL4A5, represents a second candidate gene for Alport syndrome. We analyzed 177 Italian Alport syndrome families by Southern blotting using cDNA probes from both COL4A5 and COL4A6. Nine unrelated families, accounting for 5% of the cases, were found to have a rearrangement in COL4A5. No rearrangements were found in COL4A6, with the exception of a deletion encompassing the 5' ends of both COL4A5 and COL4A6 genes in a patient with Alport syndrome and leiomyomatosis. COL4A5 rearrangements were all intragenic and included 1 duplication and 7 deletions. Polymerase chain reaction (PCR) analysis was carried out to characterize deletion and duplication boundaries and to predict the resulting protein abnormality. The two smallest deletions involved a single exon (exons 17 and 40, respectively), while the largest ones spanned exons 1 to 36. The clinical phenotype of patients in whom a rearrangement in COL4A5 was detected was severe, with progression to end-stage renal failure in juvenile age and hypoacusis occurring in most cases. These data have some important implications in the diagnosis of patients with Alport syndrome.

Clinical followup was performed in 73 neonates with a prenatal echographic suspicion of uropathy. Of 42 patients with a prenatal suspicion of unilateral hydronephrosis only 15 had pathological obstruction and 2 had multicystic dysplastic kidneys. Among 10 infants with a prenatal suspicion of bilateral hydronephrosis only 1 had true bilateral obstruction and 2 had unilateral obstruction. In 2 patients hydroureteronephrosis seen on prenatal echography was due to massive bilateral vesicoureteral reflux. In this group there was also a multicystic dysplastic kidney and 1 patient with bilateral cystic dysplasia. There was a prenatal suspicion of cystic disease in 8 infants. Postnatally, diagnosis was multicystic dysplastic kidney in 2 patients and a simple renal cyst in 4. The remaining 2 neonates had obstructive uropathy. Finally, of 13 neonates with a prenatal suspicion of anatomical-echo-structural abnormalities a definitive abnormality could be established in only 8. The predictive value of prenatal echography positive for obstructive uropathy was 34.6%.

Among 8,579 neonates born between February 1, 1981 and March 31, 1987, and cleared by prenatal sonography for significant urinary tract abnormality 158 subsequently were hospitalized because of signs or symptoms of urinary tract disease, predominantly urinary tract infection. Evaluation of these 158 patients revealed 24 with vesicoureteral reflux, 7 with duplicated systems (2 of which showed reflux), 1 with the syndrome of Fraley, 1 with pyelectasis and 5 with mild hydronephrosis (3 secondary to reflux and 2 with diethylenetriaminepentaacetic acid renal scans considered to be nonobstructed). There was no incidence of significant obstructive uropathy that had been missed by the previous prenatal sonography and that surfaced subsequently to cause morbidity in this series. The principal disorder of the urinary tract that may fail prenatal investigation is vesicoureteral reflux.

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]

IgA nephropathy and IgA vasculitis with nephritis, albeit rare, represent two relatively frequent glomerular conditions in childhood. Compared to adults, pediatric IgA nephropathy has a more acute presentation, most frequently with synpharyngitic macrohematuria and histologically with more intense inflammation and less intense chronic damage. Management of these conditions is controversial and supported by little high-quality evidence. The paucity of evidence is due to the disease heterogeneity, its inter-ethnic variability, and the difficulty of extrapolating data from adult studies due to the peculiarities of the condition in children. IgA vasculitis with nephritis is a kidney manifestation of a systemic disorder, typical of the pediatric age, in which both the diagnosis of kidney involvement and its management are poorly defined, and an interdisciplinary approach is crucial. Both conditions can have a profound and long-lasting impact on kidney function and the global health of affected children. The International Pediatric Nephrology Association has therefore convened a diverse international group of experts from different disciplines to provide guidance on the recommended management of these conditions in children and to establish common definitions and define priorities for future high-quality, evidence-based collaborative studies for the benefit of children., (© 2024. The Author(s).)

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]

The parenchymal growth of 80 kidneys with vesicoureteral reflux (VUR), 50 of them surgically corrected, has been evaluated by calculating the ratio between bipolar thickness (BT) and the kidney length (KL), as measured radiographically. We consider this ratio provides a more precise evaluation of the morphologic and functional state of the refluxing kidney as it corresponded closely with the planimetric measurement of the area of renal parenchyma (ARP) in the 12 kidneys where this has also been calculated. Eighteen out of 30 medically treated refluxing kidneys showed a BT/KL ratio inferior to the 2 SD value for age at the time of diagnosis. A worsening BT/KL ratio has been observed in 6 out of 30 kidneys in which reflux ceased spontaneously and in 11 out of 50 which have been corrected surgically. The unfavourable outcome, as far as this parameter is concerned, in the medically treated cases seems to be due to the recurrence of urinary tract infection (UTI); while there is non so clear explanation for it in cases which have been surgically corrected.

The purpose of this study was to assess the incidence of symptomatic urinary tract infection (U.T.I.) and malformations, such as vesico-ureteral reflux (V.U.R.), in the Trieste area. Data were collected in the framework of a survey based on the application of a protocol on urinary infections between 1979 and 1983. The U.T.I. incidence was found to be 1.38% of the 0-14-year-old residents, with a higher frequency in females (2.36%) than in males (0.46%). As regards V.U.R., the incidence in the population studied turned out to be 0.25%, with a females/males ratio of 4:1. Striking differences in incidence data were observed according to the age of U.T.I. and V.U.R. diagnosis and to the infection level (cystitis or pyelonephritis). The incidence of renal scarring resulted to be extremely low, which can be ascribed to the early diagnosis in our cases.

We present updated, evidence-based clinical practice guidelines from the Indian Society of Pediatric Nephrology (ISPN) for the management of urinary tract infection (UTI) and primary vesicoureteric reflux (VUR) in children. These guidelines conform to international standards; Institute of Medicine and AGREE checklists were used to ensure transparency, rigor, and thoroughness in the guideline development. In view of the robust methodology, these guidelines are applicable globally for the management of UTI and VUR. Seventeen recommendations and 18 clinical practice points have been formulated. Some of the key recommendations and practice points are as follows. Urine culture with > 10 4 colony forming units/mL is considered significant for the diagnosis of UTI in an infant if the clinical suspicion is strong. Urine leukocyte esterase and nitrite can be used as an alternative screening test to urine microscopy in a child with suspected UTI. Acute pyelonephritis can be treated with oral antibiotics in a non-toxic infant for 7-10 days. An acute-phase DMSA scan is not recommended in the evaluation of UTI. Micturating cystourethrography (MCU) is indicated in children with recurrent UTI, abnormal kidney ultrasound, and in patients below 2 years of age with non-E. coli UTI. Dimercaptosuccinic acid scan (DMSA scan) is indicated only in children with recurrent UTI and high-grade (3-5) VUR. Antibiotic prophylaxis is not indicated in children with a normal urinary tract after UTI. Prophylaxis is recommended to prevent UTI in children with bladder bowel dysfunction (BBD) and those with high-grade VUR. In children with VUR, prophylaxis should be stopped if the child is toilet trained, free of BBD, and has not had a UTI in the last 1 year. Surgical intervention in high-grade VUR can be considered for parental preference over antibiotic prophylaxis or in children developing recurrent breakthrough febrile UTIs on antibiotic prophylaxis., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Most studies regarding kidney outcomes in patients with Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome (STEC-HUS) focus on kidney status at last assessment. We aimed to describe patterns of changes in kidney function during follow-up and investigate associations between kidney function at 1st, 5th, and 10th year after onset and long-term kidney outcomes., Methods: Data of patients with STEC-HUS followed for at least 15 years were analyzed. Kidney function patterns were constructed considering kidney status at 1st, 5th, 10th, and ≥ 15 years and defined as (1) progressive, if patients changed from complete recovery to any chronic kidney disease (CKD) stage or if CKD worsened; (2) improvement, if they shifted from any CKD stage to complete recovery or to a milder stage; and (3) stable, if remained unchanged., Results: Of 152 patients included, after 1 year of follow-up, 47% had complete recovery, 22% CKD1, and 32% CKD2-5. At last assessment, 46% had complete recovery, 34% CKD1, and 19% CKD2-5. Despite percentages seeming similar, patients differed: 48% were stable, 27% improved, and 25% worsened. Further, 62% of patients with CKD2-4 in the 1st year normalized their glomerular filtration rate (GFR) thereafter. Comparison of kidney function between 1st, 5th, and 10th year to last assessment shows a stable pattern in 48, 59, and 69% respectively., Conclusions: Changes in kidney function showed a dynamic and complex behavior, with patients moving from one group to another. Consistently, kidney function neither at the 1st, 5th, or 10th year was representative of final outcome. Unexpectedly, two-thirds of patients with CKD2-4 after 1 year achieved normal eGFR later during follow-up., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: A substantial proportion of patients with Escherichia coli-hemolytic uremic syndrome (STEC-HUS) evolve to chronic kidney disease (CKD). The objectives of this study were to evaluate long-term kidney outcomes and to identify CKD predictors., Methods: In this single-center retrospective study, long-term outcomes of patients were analyzed according to the presence of complete recovery (CR) or CKD at last visit. Then, they were grouped into favorable (CR + CKD1) or poor (CKD2-5) outcome to compare predictors at diagnosis (sex, age, leukocytes, creatinine, hemoglobin, HUS severity score), dialysis duration, and follow-up time between them., Results: Of 281 patients followed up for a median of 12 years, 139 (49%) had CR, 104 (37%) CKD1, 27 (10%) CKD2-4, and 11 (4%) CKD5. Thirty-eight patients progressed to CKD2-5 after a median of 4.8 years, 7% in the first 5 years, increasing to 8%, 10%, and 14% after 5-10 years, 10-15 years, and > 15 years, respectively. They were younger, had higher baseline hemoglobin and leukocytes, and required longer dialysis and follow-up than those with favorable outcome. By multivariate analysis, days of dialysis and follow-up time remained as independent predictors of poor outcome. The best cutoff for days of dialysis was 10 days. After 5 years, 20% of those dialyzed ≥ 10 days evolved to CKD2-5 versus 1% of those non-dialyzed or dialyzed < 10 days., Conclusions: Fifty-one percent of patients evolved to CKD after 12 years of follow-up and 14% to CKD2-5. Ten days of dialysis was the best cutoff to recognize outcomes. In some cases, kidney damage was evident after 15 years of surveillance, highlighting the need for follow-up until adulthood in all STEC-HUS patients., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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]

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]

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]

Hemostasis preserves blood fluidity and prevents its loss after vessel injury. The maintenance of blood fluidity requires a delicate balance between pro-coagulant and fibrinolytic status. Endothelial cells (ECs) in the inner face of blood vessels maintain hemostasis through balancing anti-thrombotic and pro-fibrinolytic activities. Dyslipidemias are linked to hemostatic alterations. Thus, it is necessary a better understanding of the underlying mechanisms linking hemostasis with dyslipidemia. Statins are drugs that decrease cholesterol levels in the blood and are the gold standard for treating hyperlipidemias. Statins can be classified into natural and synthetic molecules, approved for the treatment of hypercholesterolemia. The classical mechanism of action of statins is by competitive inhibition of a key enzyme in the synthesis pathway of cholesterol, the HMG-CoA reductase. Statins are frequently administrated by oral ingestion and its interaction with other drugs and food supplements is associated with altered bioavailability. In this review we deeply discuss the actions of statins beyond the control of dyslipidemias, focusing on the actions in thrombotic modulation, vascular and cardiovascular-related diseases, metabolic diseases including metabolic syndrome, diabetes, hyperlipidemia, and hypertension, and chronic diseases such as cancer, chronic obstructive pulmonary disease, and chronic kidney disease. Furthermore, we were prompted to delved deeper in the molecular mechanisms by means statins regulate coagulation acting on liver, platelets, and endothelium. Clinical evidence show that statins are effective regulators of dyslipidemia with a high impact in hemostasis regulation and its deleterious consequences. However, studies are required to elucidate its underlying molecular mechanism and improving their therapeutical actions., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

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]