The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

How the 99mTc-DMSA scintigraphy findings are reflected in the adopted treatment of primary vesicoureteral reflux: One centre experience.

BACKGROUND: Renal changes may have long-term sequalae and prevention is a main goal of management of primary vesicoureteral reflux (VUR). AIM: This study aims to reveal how much 99mTc-DMSA scintigraphy findings are reflected in the adopted surgical or non-surgical treatment in children with diagnosed primary VUR and to give the clinicians information regarding their final therapeutic decision. PATIENTS AND METHODS: A total 207 children with primary VUR who underwent non-acute 99mTc-DMSA scan were retrospectively evaluated. The presence of renal changes, their grading, differential function asymmetry (<45%) and grade of VUR were compared with subsequent choice of therapy. RESULTS: Altogether 92 (44%) children had asymmetric differential function, 122 (59%) showed presence of renal changes, 79 (38%) had high-grade VUR (IV-V). Patients with renal changes had lower differential function (41%vs.48%) and higher grade of VUR. The incidence of high-grade changes (G3+G4B) afflicting more than one third of the kidney was significantly different between grade I-II, III and IV-V VUR (9%, 27%, 48%, respectively). Renal changes were detected in 76% of surgically and 48% of non-surgically treated patients, high-grade 99mTc-DMSA changes in 69% and 31%, respectively. In children with no scars/dysplasia (G0+G4A), non-surgical treatment prevailed in 77%. The independent predictors for surgical intervention were presence of renal changes and higher grade of VUR, but not functional asymmetry. DISCUSSION: Over the last 20 years, there has been a shift toward more non-surgical management of VUR. The long-term outcome of this approach should be thoroughly studied. This is the first study analysing renal status in VUR patients using 99mTc-DMSA scan and its grading regarding the adopted treatment. Renal changes in almost half of non-surgically treated children with VUR should be an indicator for earlier diagnosis and effective treatment of acute pyelonephritis and VUR. We recommend distinguishing grade III VUR, as a moderate-grade VUR, because it is linked to higher incidence of high-grade 99mTc-DMSA changes (G3+G4B); our findings of 65% of grade III VURs treated non-surgically should be cautionary. Grade III VUR does not mean a low-risk condition and should alert the clinician to evaluate the extent of renal changes and unmask high-risk cases. CONCLUSIONS: Our data strengthens the need to investigate the extent of renal changes in VUR patients regarding treatment decision. Performing 99mTc-DMSA scan individualizes the treatment of VUR patients; its grading can distinguish grade III-VUR as a separate risk entity because it differs significantly in terms of incidence of high-grade renal changes and chosen therapy.

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

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

Therapeutic Management of Children with Vesicoureteral Reflux.

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.

Recomendaciones sobre diagnóstico, manejo y estudio de la infección del tracto urinario en pediatría: rama de Nefrología de la Sociedad Chilena de Pediatría. Parte 1 / Recommendations on diagnosis, management and study of the urinary tract infection in pediatrics: nephrology Branch of the Chilean Society of Pediatrics. Part 1

Resumen: La infección del tracto urinario (ITU) es una de las infecciones bacterianas mas frecuentes en la edad pediátrica, pero su diagnóstico y manejo se pueden ver complicados por lo inespecífico de sus sín tomas y signos de presentación, la dificultad en la interpretación de los exámenes, especialmente en niños mas pequeños, y por un pronóstico respecto a daño renal muchas veces incierto. En los últimos años, se ha evidenciado una modificación significativa en el enfoque diagnostico y terapéutico de esta patología, surgiendo la necesidad de actualizar las recomendaciones previas. El propósito de esta re vision es contribuir a reducir la variabilidad de la práctica clínica en el manejo de ITU en la población pediátrica, mejorando la detección y manejo de la patología estructural y otros factores de riesgo de daño renal, evitando acciones innecesarias en aquellos niños con bajo riesgo. En esta primera parte, se presentan las recomendaciones en cuanto a diagnóstico y manejo de la ITU en pediatría. En la segunda parte se detalla su estudio, prevención y seguimiento.

Abstract: Urinary tract infection (UTI) is one of the most frequent bacterial infection in pediatrics. However, its diagnosis and management can be complicated due to the nonspecific clinical presentation, the difficulty of exams interpretation, especially in younger children, and an uncertain prognosis regar ding renal damage. In recent years, significant worldwide change has come in treatment, diagnosis, and images studies, we have decided to update the current recommendations on UTI management published by the Pediatric Nephrology branch of Chilean Pediatrics Society in previous years. The purpose of these recommendations is to reduce the variability of clinical practice in management of UTI in our pediatric population, favoring diagnostic and therapeutic interventions in the most ap propriate way, improving detection and management of structural pathology and other risk factors of renal damage, avoiding unnecessary actions in children with low risk. This first part includes diag nosis and treatment recommendations of urinary tract infection in pediatric age. In the second part the study, prevention and monitoring of urinary tract in pediatric age is detailed.

An update on renal scarring after urinary tract infection in children: what are the risk factors?

AIM: The aim of this study was to present updated information on clinical, laboratory, and imaging risk factors and predictors of renal scarring after first or recurrent febrile UTIs, which may be associated with renal scarring. METHODS: PubMed was searched for current data on possible risk factors and predictors of renal scarring after febrile urinary tract infections in children. RESULTS: Recurrence of acute pyelonephritis is an independent risk factor for renal scarring, while the duration of fever before treatment initiation is mainly associated with acute pyelonephritis and its severity. Severe vesicoureteral reflux is an important independent risk factor for the development of renal scarring after a febrile urinary tract infection. CONCLUSIONS: Certain clinical parameters could be used to identify children at high risk for renal scarring after febrile urinary tract infection, helping clinicians to reserve dimercaptosuccinic acid scan for selected cases.

[Vesicoureteric reflux].

Vesicoureteric reflux (VUR) is defined as the retrograde passage of urine from the bladder into the upper parts of urinary system. The first symptoms may be seen in infancy, but may as well develop during entire life of the patient, in some patients being atypical. A quick diagnosis is of utmost importance since any delay in the treatment can cause many serious complications such as recurrent urinary tract infections (UTI), renal scarring development, hypertension and renal insufficiency.

Pregnancies in women with childhood vesicoureteral reflux.

OBJECTIVE: The frequency of pregnancy complications together with renal scarring and voiding dysfunction-related risk factors were investigated in a cohort of women with a history of childhood vesicoureteral reflux (VUR). DESIGN: A retrospective cross-sectional cohort study. POPULATION: Eighty-seven primi- or multiparous middle-aged women diagnosed with primary non-obstructive VUR in childhood. METHODS: Pregnancy outcome was assessed from case records and from patient interviews. Urine flow tests for voiding patterns, renal ultrasound for detecting scars, and blood samples for renal function were investigated. The median follow-up time was 38 years. MAIN OUTCOME MEASURES: Prevalence of pregnancy complications in women with childhood VUR in relation to renal scars and voiding abnormalities. RESULTS: Maternal complications were seen in 64% of the women and fetal complications in 13%. The women with renal scars (48/87) more often had hypertension (33%), proteinuria (40%) and urinary tract infections (42%) during pregnancy than women without scarring. The frequency of fetal complications was not increased by renal scarring or proteinuria during pregnancy. Urinary tract infections during pregnancy (33% of the women) and voiding abnormalities (18%) did not increase the frequency of fetal or maternal complications. The women with fetal complications were more predisposed to frequent urinary tract infections during adult life (55%) than were those without fetal complications (24%) (p = 0.04). CONCLUSIONS: The maternal complication rates in women with childhood VUR were increased only by renal scarring. Frequent urinary tract infections during adulthood seemed to predict an elevated risk of fetal complications.

Predictive risk factors in childhood urinary tract infection, vesicoureteral reflux, and renal scarring management.

Approaches to the management of children with urinary tract infection (UTI), vesicoureteral reflux (VUR), and renal scars have been challenged and have become controversial over the past decade. It is difficult to determine when, how, and which patients will benefit from the diagnosis and management of this condition. Therefore, the issues of diagnostic imaging, observation, follow-up, and intervention tend to be decided more on a case-by-case basis, rather than by using an algorithm. Over the past few years, there have been advances in the identification of risk factors that predispose patients with UTI to present with VUR, to develop recurrent UTIs and renal scars, to have deteriorating renal function, to show VUR improvement and/or spontaneous resolution, and to be candidates for and benefit from early surgical intervention.

Posterior urethral valves: Persistent renin angiotensin system activation after valve ablation and role of pre-emptive therapy with angiotensin converting enzyme-inhibitors on renal recovery.

AIM: To study renin angiotensin system (RAS) activity after posterior urethral valve ablation and the role of early induction of angiotensin converting enzyme-inhibitors (ACE-I) on the outcome of renal function. MATERIALS AND METHODS: Thirty four children underwent valve ablation in which therapy with ACE-I was started 40.5 ± 4.1 (range 32-47 months) formed the study group. Post-ACE-I data were collected after mean duration of 18.2 ± 4.0 (12-28 months). Plasma renin activity (PRA), urinary micro albumin, glomerular filtration rate (GFR), and serum creatinine, before and after therapy were monitored. RESULTS: Therapy with ACE-I resulted in a fall in micro albuminuria by 45.7% and 42.0% in patients without and with vesico ureteral reflux, respectively, and improvement in split renal function by 6.6% and 5.9% GFR respectively. A similar response was noted in patients without and with renal scars. CONCLUSION: The decline in renal function after valve ablation is accompanied by activation of RAS reflected in a gradual rise in PRA. Therapy with ACE-I stabilizes and then improves renal function, thereby, retarding the pace of renal damage.

Primary vesico-ureteric reflux: The need for individualised risk stratification.

The management of paediatric primary vesico-ureteric reflux (VUR) has undergone serial changes over the last decade. As this disorder is extremely heterogeneous, and high-quality prospective data are limited, the treatment strategies vary among centres. Current treatment options include observation only, continuous antibiotic prophylaxis, and surgery. Surgical intervention is indicated if a child has a breakthrough urinary tract infection (UTI) while on continuous antibiotic prophylaxis or if there are renal scars present. After excluding a secondary cause of VUR the physician should consider the risk factors affecting the severity of VUR and manage the child accordingly. Those factors include demographic factors (age at presentation, gender, ethnicity) and clinical factors (VUR grade, unilateral vs. bilateral, presence of renal scars, initial presentation, the number of UTIs, and presence of any voiding or bowel dysfunction). In this review we summarise the major controversial issues in current reports on VUR and highlight the importance of individualised patient management according to their risk stratification.