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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.

Objectives: There has been intense discussion on the effectiveness of continuous antibiotic prophylaxis for children with vesicoureteral reflux, and randomized, controlled trials are still needed to determine the effectiveness of long-term antibiotics for the prevention of acute pyelonephritis. In this multicenter, open-label, randomized, controlled trial, we tested the effectiveness of antibiotic prophylaxis in preventing recurrence of pyelonephritis and avoiding new scars in a sample of children who were younger than 30 months and vesicoureteral reflux., Methods: One hundred patients with vesicoureteral reflux (grade II, III, or IV) diagnosed with cystourethrography after a first episode of acute pyelonephritis were randomly assigned to receive antibiotic prophylaxis with sulfamethoxazole/trimethoprim or not for 2 years. The main outcome of the study was the recurrence of pyelonephritis during a follow-up period of 4 years. During follow-up, the patients were evaluated through repeated cystourethrographies, renal ultrasounds, and dimercaptosuccinic acid scans., Results: The baseline characteristics in the 2 study groups were similar. There were no differences in the risk for having at least 1 pyelonephritis episode between the intervention and control groups. At the end of follow-up, the presence of renal scars was the same in children with and without antibiotic prophylaxis., Conclusions: Continuous antibiotic prophylaxis was ineffective in reducing the rate of pyelonephritis recurrence and the incidence of renal damage in children who were younger than 30 months and had vesicoureteral reflux grades II through IV.

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.

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.

Many pathogenetic factors may enhance coagulation process and induce thrombosis. The Authors report a case of hemolytic-uremic syndrome, with marked evidence of macroscopic kidney thrombotic involvement, in which an important dyslipidemia (hypertriglyceridemia and hypercholesterolemia) was detected during the phase of clinical improvement. These findings, and the contemporary marked reduction of fibrinolytic activity, seem to be relevant pathogenetic factors in this case. The treatment with polyunsaturated fatty acids Omega 3 may have been helpful in modifying these serum abnormalities and maybe could have brought to the clinical improvement.

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.

Feto-neonatal hypoxia can cause a functional kidney impairment, which is often temporary and not clinically overt, but sometimes leading to acute renal failure. Hypoxic stress may result in a tubulo-interstitial damage, and kidney tubular enzymes determination has proved to be an easy, early, and non invasive method to define a tubular interstitial lesion. A major target of nephrotoxicity is the proximal tubular cell: alterations in brush-border membrane and cytoplasm result in increased turnover processes in the kidney cortex, following by a corresponding increased excretion of alanine-aminopeptidase (AAP) and N-acetyl-glucosaminidase (NAG) from the proximal tubular cells, long before glomerular or tubular functions are impaired. AAP and NAG excretion is directly correlated with the strength and the duration of toxic alteration of the proximal tubule. NAG and AAP have been already studied in the adults and the children; they have been chosen for this investigation with a double aim: 1) to define the amount of their urinary excretion in relation with gestational age at birth; 2) to evaluate if in the newborn, independently of the gestational age, their urinary concentration may be increased by ischaemic conditions caused by hypoxia. We studied 52 healthy newborns (7 preterm of 33-36 weeks and 45 full-term) and 16 newborns with feto-neonatal hypoxia (8 preterm of 26-36 weeks and full-term) at the forth day of life. Urinary NAG and AAP were assayed by colorimetric methods and the results expressed as mU/mg. creatininuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Fosfomycin trometamol (FT), an antibiotic active against the common urinary pathogens, may be demonstrated in adequate urine concentrations up to 36-48 h after a single oral dose of 1-2 g. This pharmacokinetic peculiarity seems to indicate that this antibiotic may be used in single doses in the therapy of lower urinary tract infections (UTIs) in infants and children. The efficacy and safety of FT in single oral doses was compared with those of netilmicin (NM), an aminoglycoside antibiotic with a demonstrated efficacy in bolus doses against UTIs, shown in a multicentric study. One hundred and thirty-five children with lower UTI, diagnosed on the basis of fever (less than 38 degrees C), erythrocyte sedimentation rate (less than 25 mm/l h) and C-reactive protein (less than 20 micrograms/ml), were included in the study: 71 received 2 g of FT, 64 5 mg/kg of NM. Cure, defined as persistence of sterile urine up to 30 days after therapy, was reached in 80.2% of children in the FT group and in 81.2% of children in the NM group. Persistence of infection was demonstrated in 7 and in 3 children, respectively. Recurrence of infection was noticed in 7 patients in the FT group and in 9 in the NM group. No differences between FT- and NM-treated children are demonstrable even if the patient population is analyzed according to the higher risk of UTI because of the presence of an anatomical and/or functional abnormality of the urinary tract or due to a previous tendency to recurrent UTIs. FT is as effective as NM in the treatment of lower UTIs in infants and children.

Neutropenia is the most common hematologic abnormality detected as consequence of Trimethoprim Sulfamethoxazole (TMP-SMX) therapy. Its incidence is evaluated in 27 children affected by urinary tract anomalies and treated with low doses of TMP SMX (2 + 10 mg/kg/die) for more than one month. A slight neutropenia was detected in 8 children (6 of these were in their first two years of life). In all the 27 cases a supplementation of folinic acid was started: a significant increase of PMN count was noted in all cases. Neutropenia can also appear after low (prophylactic) dosage of TMP-SMX, and can be prevented by concomitant administration of folinic acid.

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.)

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.

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 m 2 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 m 2 /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., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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., (© 2023 Pharmacotherapy Publications, Inc.)

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.)

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., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

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., (© 2021. IPNA.)

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., (© 2021 John Wiley & Sons Ltd.)

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.

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).

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., (© 2020 The Author Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

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 99m Tc 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., (© 2019 Japan Pediatric Society.)

Background: Selection of the appropriate radiologic investigation in a child after first febrile urinary tract infection (UTI) remains a contentious issue. This report investigated the effectiveness of renal bladder ultrasound (RBUS) and late 6 month dimercaptosuccinic acid (DMSA) renal scan in the detection of high-grade vesicoureteral reflux (VUR) after first febrile UTI in infants aged <1 year., Methods: A total of 387 infants aged <1 year with first febrile UTI who completed diagnostic follow up consisting of RBUS, voiding cystourethrogram (VCUG) and late 6 month DMSA scan were enrolled in the study. The effectiveness of RBUS and DMSA scan in the detection of high-grade VUR, including cost and benefit were assessed., Results: Abnormal RBUS was identified in 95 infants (24.5%). VUR was identified on VCUG in 79 (20.4%), of whom eight (2.1%) had high-grade VUR (grade IV-V). Abnormal renal parenchyma was identified on late 6 month DMSA scan in 22 infants (5.7%). The sensitivity of abnormal RBUS and of late 6 month DMSA scan in the prediction of high-grade VUR was 50% and 87.5%, and the proportion of infants who avoided unnecessary VCUG was 75.5% and 94.3%, respectively., Conclusions: Fifty percent of high-grade VUR was not identified on RBUS screening after first febrile UTI. Although late 6 month DMSA scan had higher sensitivity in the detection of high-grade VUR, with the added benefit of detection of renal scars, the practical application of this method was limited due to its high cost, radiation exposure and the associated delay in decision making., (© 2015 Japan Pediatric Society.)