Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up. RESULTS: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Non-surgical management in children with non-refluxing primary megaureter: a systematic review and meta-analysis.

BACKGROUND: Children with non-refluxing primary megaureter are mostly managed by a watchful approach with close follow-up and serial imaging. OBJECTIVES: This systematic review and meta-analysis aimed to determine whether there is sufficient evidence to support the current non-surgical management strategy in these patients. DATA SOURCES: A comprehensive search including electronic literature databases, clinical trial registries, and conference proceedings was performed. DATA SYNTHESIS METHODS: Outcomes were estimated as pooled prevalence. If meta-analytical calculations were not appropriate, outcomes were provided in a descriptive manner. RESULTS: Data from 8 studies (290 patients/354 renal units) were included. For the primary outcome, differential renal function estimated by functional imaging, meta-analysis was impossible due to reported data not being precise. Pooled prevalence for secondary surgery was 13% (95% confidence interval: 8-19%) and for resolution 61% (95% confidence interval: 42-78%). The risk of bias was moderate or high in most studies. LIMITATIONS: This analysis was limited by the low number of eligible studies with few participants and high clinical heterogeneity, and the poor quality of the available data. CONCLUSIONS: The low pooled prevalence of secondary surgical intervention and high pooled prevalence of resolution may support the current non-surgical management in children with non-refluxing primary megaureter. However, these results should be interpreted cautiously due to the limited available body of evidence. Future studies should overcome existing limitations of imaging methods by using standardized, comparable criteria and report outcome parameters in a quantitative manner. This would allow more sufficient data synthesis to provide evidence-based recommendations for clinical decision-making and counseling. SYSTEMATIC REVIEW REGISTRATION: The protocol was registered on PROSPERO under CRD42019134502.

Febrile Urinary Tract Infections in Children with Primary Non-Refluxing Megaureter: A Systematic Review and Meta-Analysis.

BACKGROUND: Knowledge of the baseline risk of febrile urinary tract infections in patients with primary non-refluxing megaureter can help clinicians to make informed decisions for offering continuous antibiotic prophylaxis. OBJECTIVE: The primary objective of this systematic review was to determine the pooled prevalence of febrile urinary tract infections in patients with primary non-refluxing megaureter selected for primary non-surgical management independent of associated attributed risk factors at initial presentation in order to assess the value of continuous antibiotic prophylaxis. METHODS: MEDLINE, EMBASE, and Cochrane Controlled Trials Register electronic databases were searched for eligible studies without language and time restriction. The systematic review was carried out following the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. (PROSPERO registration number CRD42018104752). RESULTS: Of 25 871 records, 16 studies (n=749 patients) were eligible for inclusion. The overall pooled prevalence of febrile urinary tract infections in patients with primary non-refluxing megaureter was 14.35% (95% confidence interval: 8.8-22.6). The calculated number needed to treat for patients on continuous antibiotic prophylaxis to prevent one single febrile urinary tract infection over the course of 1-2 years would be 4.3. CONCLUSION: Based on the current available evidence the use of continuous antibiotic prophylaxis for children with PM selected for primary non-surgical treatment should be taken into consideration, at least in patients with urinary outflow impairment, higher grade of ureteral dilatation, and for children in the first months of life.

Timing of voiding cystourethrography after febrile urinary tract infection in children: a systematic review.

BACKGROUND: Despite a trend towards early voiding cystourethrography (VCUG) after febrile urinary tract infection (fUTI) in children, clinical guidelines do not comment on the optimal timing and current practice varies considerably. OBJECTIVE: To assess whether the detection rate of vesicoureteric reflux (VUR) in children depends on the time period of VCUG procedure after onset of antibiotic therapy. METHODS: MEDLINE, EMBASE and Cochrane Controlled Trials Register electronic databases were searched for eligible studies without language or time restriction (19 November 2018). Inclusion criteria were (1) patients <18 years of age; (2) VCUG performed in patients with fUTI after onset of antibiotic therapy either in the same patient population or in two or more different patient populations within one study at different time periods; and (3) with reported detection rate of VUR. The systematic review was carried out following the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Of 4175 records, nine studies were included (number of patients, n=1745) for the main outcome prevalence of VUR by VCUG <8 days compared with VCUG ≥8 days after onset of antibiotic therapy. Pooled overall prevalence of VUR was not significantly different between the early and the late VCUG groups (risk ratio 0.98, 95% CI 0.81 to 1.19). Prevalence of VUR stratified by grade was not significantly different between the two groups. CONCLUSION: Early VCUG within 8 days after onset of antibiotic therapy does not affect the prevalence of VUR. TRIAL REGISTRATION NUMBER: CRD42018117545.