Renal Scarring in Children with Primary Vesicoureteral Reflux Disease

Aims:To determine the incidence of renal scarring among patients with primary vesicoureteral reflux (VUR) and the possible risk factor(s), we studied 69 children (42 girls and 27boys) with VUR attending the Pediatric opd.Study Design:Prospective Observational study.Place and duration of Study:Department of pediatrics,Sher I Kashmir Institute of Medical Sciences,Srinagar, Kashmir between June 2017 to June 2018.Methodology:All the patients were assessed for VUR grade by voiding cystoureterography and for presence of renal scarring by (99 m) technetium dimercapto–succinic acid scintigraphy. Results:Grade of reflux and number of urinary tract infection (UTI) episodes (≥3) were found to be statistically significant risk factors for renal scarring (P <0.05). However,there was no significant association with gender,familial history and laterality of the disease (P >0.05). Similarly, there was no statistically significant difference of frequency of renal scarring among the different age groups (P >0.05).Conclusions:It was concluded that recurrences of UTI and VUR severity are significant risk factors for renal scarring in children with VUR. Therefore,identification of VUR at an early age may offer the opportunity to prevent episodes of UTI and possible formation of renal scars that may result in end-stage renal failure

Reconsideration of urine culture for the diagnosis of acute pyelonephritis in children: a new challenging method for diagnosing acute pyelonephritis / 소아과

Acute pyelonephritis (APN) should be detected and treated as soon as possible to reduce the risk of the development of acquired renal scarring. However, in the medical field, urine culture results are not available or considered when the prompt discrimination of APN is necessary and empirical treatment is started. Furthermore, urine culture cannot discriminate APN among children with febrile urinary tract infection (UTI) (pyelitis, lower UTI with other fever focus). Therefore, the usefulness of urine culture for diagnostic purposes is small and the sampling procedure is invasive. Congenital hypoplastic kidney is the most common cause of chronic kidney injury in children. Thus, it is desirable that a main target be detected as early as possible when imaging studies are performed in children with APN. However, if APN does not recur, no medical or surgical treatment or imaging studies would be needed because the acquired renal scar would not progress further. Therefore, the long-term prognosis of APN in young children, particularly infants, depends on the number of recurrent APN, not other febrile UTI. New methods that enable prompt, practical, and comfortable APN diagnosis in children are needed as alternatives to urinary catheterization for urine culture sampling.

The impact of surgical intervention on renal function in cystinuria / O impacto da intervenção cirúrgica sobre a função renal na cistinúria

ABSTRACT Introduction: Cystinuria is an autosomal recessive disorder due to intestinal and renal transport defects in cystine and dibasic amino acids, which result in recurrent urolithiasis and surgical interventions. This study aimed to assess the impact of surgical interventions on renal function by analyzing estimated glomerular filtration rates. Methods: Thirteen pediatric patients with cystinuria, who were followed-up in a single tertiary institution between 2004 and 2016, were included in the study. Medical records were reviewed to collect data on clinical presentation of patients, urine parameters, stone formation, medical treatment, surgical intervention, stone recurrence after surgical procedure, stone analysis, ultrasonography, 99m-technetium dimercaptosuccinic acid (99mTc-DMSA) radionuclide imaging results, and follow-up time. Creatinine clearances estimated by modified Schwartz (eGFR) formula before and after surgery were used to assess renal function and compared statistically. Results: Nine patients (69.2%) had renal scarring which were detected with 99mTc-DMSA radionuclide imaging. In ten patients (76.9%), open surgical intervention for stones were needed during follow-up. Significant difference was not detected between eGFR before and after surgical intervention (mean 92 versus 106, p = 0.36). Nine of the patients (69.2%) were stone free in the last ultrasonographic examination. Relapses of stone after surgery were seen in 66.6% of patients who underwent surgical intervention. Conclusions: Surgical interventions for urinary stones are commonly required in patients with cystinuria. Renal scarring is a prevalent finding in cystinuric patients. Surgical interventions have no negative impact on eGFR in patients with cystinuria according to the present study.

RESUMO Introdução: A cistinúria é um distúrbio autossômico recessivo causado por defeitos de transporte intestinal e renal da cistina e aminoácidos dibásicos que resultam em urolitíase recorrente e necessidade de intervenção cirúrgica. O presente estudo teve por objetivo avaliar o impacto das intervenções cirúrgicas sobre a função renal por meio da análise da taxa de filtração glomerular estimada. Métodos: Treze pacientes pediátricos com cistinúria acompanhados em uma instituição terciária entre 2004 e 2016 foram incluídos no estudo. Os prontuários médicos foram analisados e utilizados como fonte de dados sobre a apresentação clínica dos pacientes, parâmetros urinários, formação de cálculos, tratamento clínico, intervenção cirúrgica, recidiva de cálculos após procedimento cirúrgico, análise de cálculos, ultrassonografia, resultados de imagens com ácido dimercaptossuccínico marcado com tecnécio metaestável (99mTc-DMSA) e tempo de seguimento. A depuração de creatinina estimada pela fórmula modificada de Schwartz (TFGe) antes e após a cirurgia foi utilizada para avaliar e comparar estatisticamente os níveis de função renal. Resultados: Nove pacientes (69,2%) apresentaram cicatrizes renais detectadas por exame de imagem com 99mTc-DMSA. Dez pacientes (76,9%) necessitaram intervenção cirúrgica aberta por cálculo renal durante o seguimento. Não foram detectadas diferenças significativas entre os valores de TFGe anteriores e posteriores à intervenção cirúrgica (média de 92 vs. 106, p = 0,36). Nove pacientes (69,2%) não apresentaram cálculos no último exame ultrassonográfico. Recidivas de cálculos renais após cirurgia foram observadas em 66,6% dos pacientes submetidos a cirurgia. Conclusões: Intervenções cirúrgicas relativas a cálculos renais são frequentemente necessárias em pacientes com cistinúria. Cicatrizes renais são um achado prevalente em pacientes com cistinúria. De acordo com o presente estudo, cirurgia não afeta negativamente a TFGe de pacientes com cistinúria.

Asociación entre el reflujo vesicoureteral y la nefroesclerosis en las infecciones urinarias / Association of vesicoureteral reflux and renal scarring in urinary tract infections

Introducción. El objetivo del estudio fue investigar la relación entre reflujo vesicoureteral (RVU) y daño renal en pacientes con infección urinaria (IU) sin fiebre, primera IU febril e IU recurrente. El objetivo secundario, determinar si la proteína C-reactiva (PCR) actuaría como predictor de nefroesclerosis en las IU febriles. Población y métodos. Estudio prospectivo; pacientes pediátricos con IU sin fiebre, primera IU febril e IU recurrente. Los análisis de laboratorio de rutina incluyeron hemograma completo, urea, creatinina, análisis de orina completamente automatizado, urocultivo y PCR. Se realizó ecografía urológica luego del diagnóstico de IU, cistouretrografía miccional tras seis semanas y gammagrafía renal estática con ácido dimercaptosuccínico marcado con 99mTc tras seis meses a todos los participantes. Resultados. Participaron 47 niños con IU sin fiebre, 48 con primera IU febril y 61 con IU recurrente. Hubo una diferencia estadísticamente significativa entre los grupos respecto de RVU y nefroesclerosis (p= 0,001 y p= 0,011, respectivamente). También hubo una diferencia estadísticamente significativa respecto de nefroesclerosis entre los pacientes con y sin RVU (p= 0,001). Además, se estableció una diferencia estadísticamente significativa respecto de nefroesclerosis (p < 0,05) en los pacientes con PCR cinco veces mayor o menor que el valor de corte aceptado (5 mg/dl). Conclusión. La proporción de nefroesclerosis fue paralela a la frecuencia de RVU. Cuanto mayor era el grado de RVU, mayor era el daño renal. Se determinó una correlación positiva entre PCR elevada y nefroesclerosis, lo que señala esclerosis durante el diagnóstico de pielonefritis.

Introduction. The aim was to investigate the relationship between vesicoureteral reflux (VUR) and renal damage in non-febrile, febrile for the first time and recurrent urinary tract infection (UTI) patients. The secondary aim was to determine whether C-reactive protein (CRP) in febrile UTIs could be a predictor of renal scarring. Population and methods. This prospective study included non-febrile, febrile for the first time and recurrent pediatric UTI cases. The routine lab analyses comprised a complete blood count, urea, creatinine, fully automated urinalysis, urine culture and CRP analyses. All the participants were examined using urine ultrasonography subsequent to their UTI diagnosis, voiding cystourethrography (VCUG) after six weeks and Tc-99m dimercaptosuccinic acid (DMSA) static renal scintigraphy after six months. Results. There were included 47 children with non-febrile UTIs, 48 with first febrile UTIs and 61 with recurrent UTIs. A statistically significant difference was found among the groups in terms of VUR and renal scarring (p= 0.001 and p= 0.011, respectively). A statistically significant difference was also found in terms of renal scarring between patients with and without VUR (p= 0.001). Moreover, a statistically significant difference was also present in relation to renal scarring (p <0.05) in patients with five-fold lower or higher CRP values than the accepted cut-off value (5mg/dl). Conclusion. The ratio of renal scars detected was found to be parallel to the VUR frequency. The higher the VUR grade, the more renal damage was found. A positive correlation between elevated CRP and renal scarring was determined, indicating the presence of scarring during the diagnosis of pyelonephritis.

Comparación entre algoritmos de imágenes tras una primera infección urinaria febril en niños / Algorithms imaging tests comparison following the first febrile urinary tract infection in children

Objetivos. Comparar la sensibilidad diagnóstica, los costos y las dosis de radiación entre algoritmos de imágenes de la Sociedad Argentina de Pediatría de 2003 y 2015, y las guías británicas y americanas luego de una primera infección urinaria (IU) febril. Población y métodos. Los criterios de inclusión fueron niños ≤ 2 años con primera IU febril con ecografía normal, cistouretrografía miccional y centellografía con ácido dimercaptosuccínico según el algoritmo de la Sociedad Argentina de Pediatría de 2003, asistidos entre los años 2003 y 2010. Las comparaciones entre algoritmos se realizaron por simulación retrospectiva. Resultados. 80 pacientes cumplieron con los criterios de inclusión; 51 (63%) presentaron reflujo vesicoureteral (RVU); 6% de alto grado; escaras en 6 (7,5%); costo: 404 000 $; radiación: 160 milisievert. Aplicando el algoritmo de la Sociedad Argentina de Pediatría de 2015, se hubiera omitido el diagnóstico de 4 RVU y 2 escaras, con un costo de 301 800 $ y 124 milisievert de radiación. Las guías británicas y americanas hubieran omitido los diagnósticos de todos los RVU y escaras con costos de 23 000 $ y 40 000 $, respectivamente, y 0 de radiación. Conclusión. Los protocolos intensos tienen alta sensibilidad para detectar RVU y escaras, pero conllevan altos costos y dosis de radiación con beneficios cuestionables.

Objectives. To compare the diagnostic sensitivity, costs and radiation doses of imaging tests algorithms developed by the Argentine Society of Pediatrics in 2003 and 2015, against British and American guidelines after the first febrile urinary tract infection (UTI). Population and Methods. Inclusion criteria: children < 2 years old with their first febrile UTI and normal ultrasound, voiding cystourethrography and dimercaptosuccinic acid scintigraphy, according to the algorithm established by the Argentine Society of Pediatrics in 2003, treated between 2003 and 2010. The comparisons between algorithms were carried out through retrospective simulation. Results. Eighty (80) patients met the inclusion criteria; 51 (63%) had vesicoureteral reflux (VUR); 6% of the cases were severe. Renal scarring was observed in 6 patients (7.5%). Cost: ARS 404,000. Radiation: 160 millisieverts. With the Argentine Society of Pediatrics' algorithm developed in 2015, the diagnosis of 4 VURs and 2 cases of renal scarring would have been missed. The cost of this omission would have been ARS 301,800 and 124 millisieverts of radiation. British and American guidelines would have missed the diagnosis of all VURs and all cases of renal scarring, with a related cost of ARS 23,000 and ARS 40,000, respectively and 0 radiation. Conclusion. Intensive protocols are highly sensitive to VUR and renal scarring, but they imply high costs and doses of radiation, and result in questionable benefits.

Risk factors for renal scarring in children / 临床儿科杂志

Renal scarring can cause hypertension, proteinuria, chronic kidney disease, and even end stage renal disease. To understand the risk factors of renal scarring in children is helpful for its early detection, diagnosis, prevention, and treatment. High grade vesicoureteric reflux, recurrent urinary tract infection, and delayed treatment are risk factors for kidney scarring. However, there are still some controversies about the relationship between renal scarring and the some factors such as gender, age, and congenital factors. Recent studies have found that noninvasive urine indicators such as urine neutrophil gelatinase associated lipid delivery protein, urinary endothelin-1, and risk prediction models can predict the formation of renal scar. However, prophylactic use of antibiotics can reduce occurance of urinary tract infections, but do not reduce the risk of renal scarring. This article reviews the possible risk factors and predictors of renal scarring in children, providing a basis for early detection, timely intervention, and effective prevention of it in clinic, so as to reduce the formation and progression of renal scarring.

Advances in diagnosis and treatment of urinary tract infection in children / 国际儿科学杂志

Urinary tract infection is one of the common infectious diseases in pediatrics.Early recognition and treatment can effectively prevent the formation of renal scarring,which has important significance for the long-term prognosis of kidney.This paper summarizes the literature on children's urinary tract infections in recent years,and describes the status of domestic research on clinical manifestation,laboratory examination,diagnostic criteria and treatment,in order to provide reference and basis for clinical diagnosis and treatment of urinary tract infections in children.

Atualização da abordagem de infecção do trato urinário na infância / Update on the approach of urinary tract infection in childhood

Resumo Objetivo: A infecção do trato urinário (ITU) é a infecção bacteriana mais comum na infância. A ITU pode ser o evento sentinela para alteração renal subjacente. Ainda há muitas controvérsias com relação ao tratamento adequado da ITU. Neste artigo de revisão, discutimos as últimas recomendações para diagnóstico, tratamento, profilaxia e imagiologia da ITU na infância, com base em comprovação e, na sua ausência, no consenso de especialistas. Fonte de dados: Os dados foram coletados após uma revisão da literatura e pesquisa no Pubmed, Embase, Scopus e Scielo. Resumo dos dados: No primeiro ano de vida, as ITUs são mais comuns em meninos (3,7%) do que em meninas (2%). Os sinais e sintomas da ITU são muito inespecíficos, principalmente em neonatos e durante a infância. A febre é o único sintoma em muitos casos. Conclusões: O histórico clínico e exame físico podem sugerir ITU, porém a confirmação deve ser feita por urocultura. Antes da administração de qualquer agente antimicrobiano, deve ser feita coleta de urina. Durante a infância, a coleta de urina adequada é essencial para evitar resultados falso-positivos. O diagnóstico e o início do tratamento imediatos são importantes na prevenção de cicatriz renal de longo prazo. Neonatos febris com ITUs devem ser submetidos a ultrassonografia renal e da bexiga, Agentes antibacterianos intravenosos são recomendados para neonatos e neonatos jovens. Recomendamos também a exclusão de uropatias obstrutivas o mais rapidamente possível e posterior refluxo vesico-ureteral, caso indicado. A profilaxia deve ser considerada em casos de elevada susceptibilidade a ITU e risco elevado de danos renais.

Abstract Objective: Urinary tract infection (UTI) is the most common bacterial infection in childhood. UTI may be the sentinel event for underlying renal abnormality. There are still many controversies regarding proper management of UTI. In this review article, the authors discuss recent recommendations for the diagnosis, treatment, prophylaxis, and imaging of UTI in childhood based on evidence, and when this is lacking, based on expert consensus. Sources: Data were obtained after a review of the literature and a search of Pubmed, Embase, Scopus, and Scielo. Summary of the findings: In the first year of life, UTIs are more common in boys (3.7%) than in girls (2%). Signs and symptoms of UTI are very nonspecific, especially in neonates and during childhood; in many cases, fever is the only symptom. Conclusions: Clinical history and physical examination may suggest UTI, but confirmation should be made by urine culture, which must be performed before any antimicrobial agent is given. During childhood, the proper collection of urine is essential to avoid false-positive results. Prompt diagnosis and initiation of treatment is important to prevent long-term renal scarring. Febrile infants with UTIs should undergo renal and bladder ultrasonography. Intravenous antibacterial agents are recommended for neonates and young infants. The authors also advise exclusion of obstructive uropathies as soon as possible and later vesicoureteral reflux, if indicated. Prophylaxis should be considered for cases of high susceptibility to UTI and high risk of renal damage.

Association of Renal and Bladder Ultrasonography Findings with Urinary Tract Infection Recurrence, High-Grade Vesicoureteral Reflux, and Renal Scarring

INTRODUCTION: This study investigated whether renal and bladder ultrasonography (RBUS) findings performed in children with the first incidence of febrile urinary tract infection (UTI) can predict UTI recurrence, high-grade vesicoureteral reflux (high-grade VUR), or acquired renal scarring (aRS). METHODS: In all, 917 children who were admitted to our hospital from January 2001 to October 2010, owing to the first incidence of febrile UTI were enrolled in this study. All children underwent RBUS during admission. The mean followup was 7.9 months (standard deviation [SD]+/-13.3). UTI recurrence rates were calculated according to various clinical parameters. By using bivariate and multiple logistic regression analyses, we determined whether age, sex, abnormal RBUS findings, abnormal dimercaptosuccinic acid renal scan findings, or RBUS findings parameters were predictive of UTI recurrence, high-grade VUR, or aRS. RESULTS: On RBUS, hydronephrosis and congenital anomaly of the kidney and urinary tract significantly predicted UTI recurrence. A small kidney, hydroureter, hydronephrosis, cortical thinning, and increased parenchymal echogenicity significantly predicted high-grade VUR. However, their odds ratios (OR) are low compared to normal RBUS findings (recurrent UTI: OR 0.432 and 0.354 vs. 0.934, respectively, high-grade VUR: .019, 0.329, 0.126, 0.058, and 0.188 vs. 2.082, respectively). No RBUS findings significantly predicted aRS. Recurrent UTI, highgrade VUR, and abnormal RBUS findings significantly predicted aRS (OR of 4.80, 4.61, and 2.58, respectively). CONCLUSION: RBUS is necessary to exclude severe congenital renal scarring, obstructive uropathy, and renal abscess at the first incidence of febrile UTI and is helpful in determining the need for subsequent clinical imaging.

A Case with Abrupt Progression of Renal Scarring or Abrupt Deterioration of Renal Function Associated with Vesicoureteral Reflux

Abrupt progression of renal scarring associated with vesicoureteral reflux (VUR) is rare in males over 2 years old of age. We report a 5 year old boy with sustained unilateral high grade VUR who experienced abrupt progression of renal scarring; he had a relative renal radionuclide uptake of 38% at 2 years of age that dropped to 8% after three years. Per his parent's wishes, he took prophylactic antibiotics for 25 months after his first febrile urinary tract infection (UTI) at 4 months old without surgical management. One episode of recurrent breakthrough infection occurred at the age of 2 years. This observation reminds us that a recommending surgical management for sustained high grade VUR associated with renal scarring might be needed. Close follow up of DMSA for renal scanning, and long term follow up of patients after the first febrile UTI are important.

Antibiotic sensitivity patterns in childhood urinary tract infections.

Objectives To assess the current antibiotic sensitivity pattern of urinary pathogens and compare it with the pattern 5 years previously. Method A retrospective analysis was performed on 2650 urine samples in 1997 and 2062 samples in 2002 received by the medical laboratory at the Teaching Hospital, Peradeniya from the paediatric ward and paediatric clinics. Results In 1997 there were 155 urine culture reports with significant colony counts of >105 for which ABSTs were performed. 111 were from males and 44 from females. In 2002 there were 278 positive cultures of which 179 were from males and 99 from females. Predominant organism was the coliform, accounting for 90% of isolates in both 1997 and 2002. In 1997 nalidixic acid and nitrofurantoin had high sensitivities of 73.8% and 73.1% respectively, while ciprofloxacin and mecillinam had low sensitivities of 51.9% and 35.5%. In 2002 coamoxiclav had the highest antibiotic sensitivity of 86.7%, while nitrofurantoin, nalidixic acid and norfloxacin had high sensitivities of 80%, 76.6% and 75.7% respectively. Ciprofloxacin and mecillinam had low sensitivity levels both in 1997 and 2002. A change was seen in cotrimoxazole and cephalexin, which had low sensitivities of 40.2% and 54.8% in 1997 and relatively higher sensitivities of 63.8% and 69.2% in 2002 respectively.

Predictive Factors of Renal Scarring in Children with Acute Urinary Tract Infection / 대한핵의학회잡지

PURPOSE: The purpose of this study was to evaluate the usefulness of 99mTc DMSA scintigraphy on the dignosis of a renal scar in children with urinary tract infections. MATERIALS AND METHODS: Eighty three patients were included in this study, who were diagnosed as the urinary tract infection on the basis of symptom, urinalysis and urine culture. 99mTc DMSA scintigraphy and voiding cystoureterography were performed within 7days before the treatment in all patients. We classified the scintigraphic findings as follows: 1; a large hypoactive upper or lower pole. 2; a small hypoactive area. 3; single defect resulting in localized deformity of the outlines. 4; deformed outlines in a small or normal sized kidney. 5; multiple defects. 6; diffuse hypoactive kidney without regional impairment. Follow-up scintigraphy was done at least 6 months after the initial study. When the abnormality on the initial scintigraphy was not completely resolved on the follow-up scan, the lesion was defined as containing a scar. RESULTS: One hundred and fifteen renal units of 166 units (69.3%) showed abnormal findings on the DMSA scintigraphy. 65 units (56.5%) was diagnosed as containing renal scars on follow-up scintigraphies. Incidences of renal scar among renal units showing pattern 3, 4 and 5 on the initial scan was 75%, 78% and 78%, respectively. Whereas many of renal units showing 1, 2 and 6 pattern were recovered (65%, 76%, 50%). Sensitivity, specificity and accuracy of pattern-based DMSA scintigraphic findings on the diagnosis of renal scar was 76.9%, 85.1% and 81.9%, respectively. VUR was significantly associated with the renal scar when the initial DMSA shows unrecoverable findings (pattern 3, 4, 5). Odds ratio of the renal scar in a kidney showing unrecoverable initial scintigraphic findings was 19.1. Odds ratio in a kidney with mild or moderate-to-severe VUR was 3.5 and 14.4 respectively. CONCLUSION: In the urinary tract infection, renal scar was significantly developed in a kidney showing unrecoverable findings on the initial DMSA scan and VUR on voiding cystoureterography.

Urinary Excretion of Various Urinary Proteins in Children with Vesicoureteral Reflux

PURPOSE: This study aimed to examine the excretion of various urinary proteins in children with a history of urinary tract infection(UTI), with or without vesicoureteral reflux(VUR) or reflux nephropathy, and to identify means of predicting the severity of VUR or the presence of reflux nephropathy as indicated by these markers, and to know how these markers are changed after resolution of VUR. METHODS: We studied 30 children with previous UTI, without VUR and renal scarring(group I), 12 children with VUR, without evidence of renal scarring(group II), and 34 children with VUR and renal scarring(group III). 24-hour or 12-hour urine beta2 microglobulin(beta2 MG), microalbumin and N- acetyl-beta-D-glucosaminidase(NAG) were measured in each child. Urinary protein excretions were analyzed according to the degree of VUR(mild VUR : a grade reflux I-III, severe VUR : a grade reflux IV-V). Cases of bilateral VUR were graded by the higher grade of reflux detected. A total of 46 children with primary VUR were followed. Among these patients, VUR was completely resolved in 16 children. Voiding cystourethrography(VCUG) and DMSA scan were performed every year. Values for urinary markers were estimated every year. RESULTS: 24 or 12 hour urine microalbumin and NAG excretions were significantly increased in group III compared to group I(microalbumin : 27.7+/-26.0 mg/gCr vs 15.0+/-10.7 mg/gCr, P<0.05, NAG : 15.2+/-18.7 U/gCr vs 3.4+/-2.2 U/gCr, P<0.05). Urinary beta2 MG excretions were not significantly different between groups. Urinary NAG excretions were elevated in the group of children with severe VUR compared to mild VUR(26.8+/-27.1 U/gCr vs 7.6+/-3.8 U/gCr, P<0.05). After resolution of VUR, urinary microalbumin and NAG excretions were decreased(P<0.05). CONCLUSION: Urinary microalbumin and NAG may be useful clinical indicators to predict the presence of reflux nephropathy and the resolution of VUR. Especially, urinary NAG excretions may be used as a possible method to predict the severity of VUR.