Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (i.e. affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12, and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3, and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

Background COVID-19 is usually less severe and has lower case fatality in children than in adults. We aimed to characterise the clinical features of children and adolescents hospitalised with laboratory-confirmed SARS-CoV-2 infection and to evaluate the risk factors for COVID-19-related death in this population. MethodsWe did an analysis of all patients younger than 20 years who had quantitative RT-PCR-confirmed COVID-19 and were registered in the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe, a nationwide surveillance database of patients admitted to hospital with severe acute respiratory disease in Brazil), between Feb 16, 2020, and Jan 9, 2021. The primary outcome was time to recovery (discharge) or in-hospital death, evaluated by competing risks analysis using the cumulative incidence function. FindingsOf the 82 055 patients younger than 20 years reported to SIVEP-Gripe during the study period, 11 613 (14•2%) had available data showing laboratory-confirmed SARS-CoV-2 infection and were included in the sample. Among these patients, 886 (7•6%) died in hospital (at a median 6 days [IQR 3-15] after hospital admission), 10 041 (86•5%) patients were discharged from the hospital, 369 (3•2%) were in hospital at the time of analysis, and 317 (2•7%) were missing information on outcome. The estimated probability of death was 4•8% during the first 10 days after hospital admission, 6•7% during the first 20 days, and 8•1% at the end of follow-up. Probability of discharge was 54•1% during the first 10 days, 78•4% during the first 20 days, and 92•0% at the end of follow-up. Our competing risks multivariate survival analysis showed that risk of death was increased in infants younger than 2 years (hazard ratio 2•36 [95% CI 1•94-2•88]) or adolescents aged 12-19 years (2•23 [1•84-2•71]) relative to children aged 2-11 years; those of Indigenous ethnicity (3•36 [2•15-5•24]) relative to those of White ethnicity; those living in the Northeast region (2•06 [1•68-2•52]) or North region (1•55 [1•22-1•98]) relative to those in the Southeast region; and those with one (2•96 [2•52-3•47]), two (4•96 [3•80-6•48]), or three or more (7•28 [4•56-11•6]) pre-existing medical conditions relative to those with none.Interpretation Death from COVID-19 was associated with age, Indigenous ethnicity, poor geopolitical region, and pre-existing medical conditions. Disparities in health care, poverty, and comorbidities can contribute to magnifying the burden of COVID-19 in more vulnerable and socioeconomically disadvantaged children and adolescents in Brazil.

Epidemiological studies have demonstrated rates of incontinence and enuresis as high as 20% in school-age children. This cross-sectional study aimed to investigate the prevalence of lower urinary tract (LUT) symptoms in 739 children aged 6-12 years enrolled in three government schools with different socioeconomic levels in Minas Gerais, Brazil. Symptoms of LUT were evaluated using a modified version of the Dysfunction Voiding Scoring System in which the cutoff point considered as an indicator of LUT dysfunction is >6 for girls and >9 for boys. Children with a score indicative of symptoms received an educational booklet on the functioning of the LUT and were sent for clinical evaluation. LUT dysfunction symptoms were detected in 161 (21.8%) children. Symptoms were most frequent in girls (p < 0.001), children aged 6-8 (p < 0.028), and attended the school with the lowest social level (p < 0.001). Intestinal constipation was the most prevalent finding (30.7%), independent of LUT score. The most common urinary symptoms in children with an elevated score were diurnal urinary incontinence (30.7%), holding maneuvers (19.1%), and urinary urgency (13.7%). Stress factors were associated in 28.4% of children. Our findings suggest that LUT symptoms must be investigated carefully at routine pediatric visits.

The purpose of this study was to report the outcome of infants with antenatal hydronephrosis. Between May 1999 and June 2006, all patients diagnosed with isolated fetal renal pelvic dilatation (RPD) were prospectively followed. The events of interest were: presence of uropathy, need for surgical intervention, RPD resolution, urinary tract infection (UTI), and hypertension. RPD was classified as mild (5-9.9 mm), moderate (10-14.9 mm) or severe (>or=15 mm). A total of 192 patients was included in the analysis; 114 were assigned to the group of non-significant findings (59.4%) and 78 to the group of significant uropathy (40.6%). Of 89 patients with mild dilatation, 16 (18%) presented uropathy. Median follow-up time was 24 months. Twenty-seven patients (15%) required surgical intervention. During follow-up, UTI occurred in 27 (14%) children. Of 89 patients with mild dilatation, seven (7.8%) presented UTI during follow-up. Renal function, blood pressure, and somatic growth were within normal range at last visit. The majority of patients with mild fetal RPD have no significant findings during infancy. Nevertheless, our prospective study has shown that 18% of these patients presented uropathy and 7.8% had UTI during a medium-term follow-up time. Our findings suggested that, in contrast to patients with moderate/severe RPD, infants with mild RPD do not require invasive diagnostic procedures but need strict clinical surveillance for UTI and progression of RPD.

The purpose of this retrospective cohort study was to report the clinical course of children with primary vesicoureteral reflux (VUR). Between 1970 and 2004, 735 patients were diagnosed with VUR and were systematically followed in a single tertiary renal unit. Patients were followed up for a mean time of 76 months (6 months to 411 months). The events of interest were reflux resolution, renal damage, urinary tract infection (UTI), chronic kidney disease (CKD), and hypertension. Survival analysis was performed in order to evaluate reflux resolution and CKD. Renal damage was detected at admission in 319 patients (43.4%). Continuous low-dose antibiotic prophylaxis was administered to 624 patients (91.2%); 499 (73%) patients subsequently had no UTI or fewer than three episodes. The median time of persistence of reflux according to Kaplan-Meier analysis was 38 months for grade I/II [95% confidence interval (95% CI), 33-43], 98 months for grade III (95% CI, 78.5-105), and 156 months for grade IV/V (95% CI, 122-189). Twenty patients (3%) developed hypertension. It was estimated that the probability of CKD was 5% at 10 years after diagnosis of VUR; for children diagnosed after 1990 the probability of CKD was only 2%. Renal function impairment occurred in patients with severe bilateral reflux or in patients with contralateral renal hypoplasia. There has been an improvement of prognosis for patients diagnosed in the past 15 years.

Recent years has seen an increasing interest in the quality of life (QOL) of children with chronic kidney disease (CKD). The objective of this cross-sectional study was to investigate the prevalence of behavioral disorders and to assess the health-related QOL (HRQOL) in 136 patients with CKD. To estimate the prevalence of behavior disorders and analyze HRQOL, we used the Strengths and Difficulties Questionnaire (SDQ) and Pediatric Inventory of Quality of Life (PedsQL) Core Scales as assessment tools for both the patients and caregivers. When compared to healthy controls, the CKD group had significantly lower scores in almost all PedsQL domains. After adjustment, only absence of religion/other religions remained significantly associated with a lower global HRQOL score [odds ratio (OR) 6.2, P=0.009]. Among the parents, two factors remained significantly associated with a lower global HRQOL score: patients' age >10 years (OR 5.4, P=0.033) and absence of religion/other religions (OR 3.2, P=0.038). The CKD group demonstrated a higher proportion of behavioral and emotional disorders in all SDQ domains. There was a negative correlation between the presence of behavior and emotional disorders and HRQOL score (r= -0.552, P<0.001). Our findings suggest the importance of evaluating behavioral and social repercussions of CKD in order to improve the life quality of this pediatric population.

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SummaryBackground and objectives With the advent of fetal screening ultrasonography, the detection of congenital anomalies of the kidney and urinary tract (CAKUT) in utero has permitted early management of these conditions. This study aims to describe the clinical course of a large cohort of patients with prenatally detected nephrouropathies.Design, setting, participants, & measurements In this retrospective cohort study, 822 patients were prenatally diagnosed with CAKUT and systematically followed up at a tertiary Renal Unit for a median time of 43 months. Variables included in the analysis were sex, laterality, fetal ultrasonography (isolated versus associated hydronephrosis), and presence/absence of nephrouropathies. The events of interest were urinary tract infection, surgical interventions, hypertension, CKD, and death. Survival analyses were performed to evaluate time until occurrence of the events of interest.Results Urinary tract infection occurred in 245 (29.8%) children, with higher risk in females (hazard ratio=1.30, 95% confidence interval=1.02-1.70, P=0.05); 22 patients (2.7%) had hypertension, and 49 (6%) patients developed CKD. The risk of CKD was greater in patients with associated hydronephrosis (hazard ratio=5.20, 95% confidence interval=2.90-9.30, P,0.001). Twelve patients (1.5%) died during follow-up. Death was significantly associated with being born during the first period of the study (hazard ratio=6.00, 95% confidence interval=1.60-22.50, P,0.001), associated hydronephrosis (hazard ratio=9.30, 95% confidence interval=2.90-29.30, P,0.001), and CKD (hazard ratio=170.00, 95% confidence interval=41.00-228.00, P,0.001).Conclusions In our series, the clinical course of prenatally detected CAKUT was heterogeneous, and those infants with associated hydronephrosis at baseline were identified as a high-risk subgroup.