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Alport syndrome (AS) is the second most common cause of inherited chronic kidney disease. This disorder is caused by genetic variants on COL4A3, COL4A4 and COL4A5 genes. These genes encode the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). The heterodimer COL4A3A4A5 constitutes the majority of the GBM, and it is essential for the normal function of the glomerular filtration barrier (GFB). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing leakage of red blood cells and albumin into the urine, and compromise the architecture of the GFB, inducing inflammation and fibrosis, thus resulting in kidney damage and loss of renal function. The advances in DNA sequencing technologies, such as next-generation sequencing, allow an accurate diagnose of AS. Due to the important risk of the development of progressive kidney disease in AS patients, which can be delayed or possibly prevented by timely initiation of therapy, an early diagnosis of this condition is mandatory. Conventional biomarkers such as albuminuria and serum creatinine increase relatively late in AS. A panel of biomarkers that might detect early renal damage, monitor therapy, and reflect the prognosis would have special interest in clinical practice. The aim of this systematic review is to summarize the biomarkers of renal damage in AS as described in the literature. We found that urinary Podocin and Vascular Endothelial Growth Factor A are important markers of podocyte injury. Urinary Epidermal Growth Factor has been related to tubular damage, interstitial fibrosis and rapid progression of the disease. Inflammatory markers such as Transforming Growth Factor Beta 1, High Motility Group Box 1 and Urinary Monocyte Chemoattractant Protein- 1 are also increased in AS and indicate a higher risk of kidney disease progression. Studies suggest that miRNA-21 is elevated when renal damage occurs. Novel techniques, such as proteomics and microRNAs, are promising.

To evaluate the association between obesity indices and blood pressure (BP) at 4 years of age, in each sex, and to quantify to which extent this association is mediated by inflammation and insulin resistance (IR). We studied 1250 4-year-old children selected from the population-based birth cohort Generation XXI. Associations between body mass index (BMI) z-score and waist-to-height ratio (WHtR), office BP, inflammation (high sensitivity C-reactive protein) and IR (HOMA-IR index) were assessed. Path Analysis, a modified multivariate regression approach, was applied to test causal models and quantify direct and indirect effects of predictors of systolic (SBP) and diastolic BP (DBP). SBP and DBP increased significantly with BMI and WHtR in both sexes. There was a strong direct association (explaining 74.1-93.2% of the total association) of both measures of adiposity with SBP, in both sexes. This association was additionally indirectly mediated by IR, particularly regarding WHtR (20.5% in girls and 9.4% in boys). Mediation by inflammation did not reach statistical significance in either sex. Regarding DBP, the direct effect of adiposity was strong (>95% for BMI and WHtR in boys) and the mediation by IR was much smaller in boys than in girls. The direct association between adiposity and BP in healthy 4-year-old children is strong and IR plays an important mediating role. The strength of effects of IR and inflammation suggests sex differences in the complex interplay between BP, adiposity and inflammation.

In a trial involving infants with grade III, IV, or V vesicoureteral reflux and no previous UTI, continuous antibiotic prophylaxis for 2 years provided a small but significant benefit in preventing a first UTI.

Purpose Embedding physical activity in the undergraduate curricula of frontline health professionals is one of the policies recommended by the World Health Organization and the European Commission to promote health-enhancing physical activity (HEPA). The VANGUARD project is supported by the European Union Erasmus+ Programme, and aims to embed physical activity in the undergraduate curricula of healthcare professionals in European countries. Within this project, this work aimed to describe the bespoke development of a physical activity and health course integrated into the undergraduate medical curriculum of a Portuguese Medical School. Project or policy description The School of Medicine and Biomedical Sciences of the University of Porto (ICBAS) was the invited Medical School to implement the VANGUARD project in Portugal - led by the Institute of Public Health of the University of Porto (ISPUP). An auscultation process with the undergraduate medical students was held to evaluate the importance of HEPA in their curriculum and assess the preferred operational characteristics of including a physical activity and health course in the Integrated Master’s degree in Medicine. A course proposal structure was then developed by the VANGUARD project Portuguese team from ISPUP, the Director of the Integrated Master’s degree in Medicine, and the Coordinator of the Medical Education Office of ICBAS, based on the students’ acceptability, the Medical School constraints, and VANGUARD project goals and resources. The course integrates 26 lessons, from physical activity technical terminology, epidemiology and guidelines, going through its relation with noncommunicable diseases (using #MovementForMovement resources), to Portuguese National Health Service brief intervention tools and community-based exercise programs - in a total of 20 hours of contact, including continuous evaluation and final case studies analysis. The course will be offered on an optional basis to 2nd-year medical students, on an online training platform, using a self-paced learning method. After embedding this course in ICBAS, it will be presented to the Council of Portuguese Medical Schools to be scaled up nationally. Conclusions Medical doctors and Medical Schools are key stakeholders in HEPA promotion, especially in the health sector. Successful implementation of HEPA policies requires tailored solutions to organizations and direct involvement of target groups in policy development.

Background Despite their higher risk of developing severe disease, little is known about the burden of influenza in Portugal in children aged < 5 years old. This study aims to cover this gap by estimating the clinical and economic burden of severe influenza in children, in Portugal, during ten consecutive influenza seasons (2008/09-2017/18). Methods We reviewed hospitalizations in children aged < 5 years old using anonymized administrative data covering all public hospitals discharges in mainland Portugal. The burden of hospitalization and in-hospital mortality directly coded as due to influenza was supplemented by the indirect burden calculated from excess hospitalization and mortality (influenza-associated), estimated for four groups of diagnoses (pneumonia or influenza, respiratory, respiratory or cardiovascular, and all-cause), through cyclic regression models integrating the incidence of influenza. Means were reported excluding the H1N1pdm09 pandemic (2009/10). Results The mean annual number of hospitalizations coded as due to influenza was 189 (41.3 cases per 100,000 children aged < 5 years old). Hospitalization rates decreased with increasing age. Nine-in-ten children were previously healthy, but the presence of comorbidities increased with age. Children stayed, on average, 6.1 days at the hospital. Invasive mechanical ventilation was used in 2.4% of hospitalizations and non-invasive in 3.1%. Influenza-associated excess hospitalizations between 2008 and 2018 were estimated at 1,850 in pneumonia or influenza, 1,760 in respiratory, 1,787 in respiratory or cardiovascular, and 1,879 in all-cause models. A total of 95 influenza-associated excess deaths were estimated in all-cause, 14 in respiratory or cardiovascular, and 9 in respiratory models. Over ten years, influenza hospitalizations were estimated to have cost the National Health Service at least €2.9 million, of which 66.5% from healthy children. Conclusions Influenza viruses led to a high number of hospitalizations in children. Most were previously healthy. Results should lead to a reflection on the adequate preventive measures to protect this age group.

Dedicated pediatricians in emergency departments (EDs) may be beneficial, though no previous studies have assessed the related costs and benefits/harms. We aimed to evaluate the net benefits and costs of dedicated emergency pediatricians in a pediatric ED. Cost-consequences analysis of visits to a pediatric ED of a tertiary hospital. Two pediatric ED Medical Teams (MT) were compared: MT-A (May-September 2012), with general pediatrics physicians only; and MT-B (May-September 2013), with emergency dedicated pediatricians. The main outcomes analyzed were relevant clinical outcomes, patient throughput time and costs. We included 8,694 children in MT-A and 9,417 in MT-B. Medication use in the ED increased from 42.3% of the children in MT-A to 49.6% in MT-B; diagnostic tests decreased from 24.2% in MT-A to 14.3% in MT-B. Hospitalization increased from 1.3% in MT-A to 3.0% in MT-B; however, there was no significant difference in diagnosis-related group relative weight of hospitalized children in MT-A and MT-B (MT-A, 0.979; MT-B, 1.075). No differences were observed in ED readmissions or in patients leaving without being seen by a physician. The patient throughput time was significantly shorter in MT-B, with faster times to first medical observation. Within the cost domains analyzed, the total expenditures per children observed in the ED were 16% lower in MT-B: 37.87 euros in MT-A; 31.97 euros in MT-B. The presence of dedicated emergency pediatricians in a pediatric ED was associated with significantly lower waiting times in the ED, reduced costs, and similar clinical outcomes.

BackgroundPrenatal ethanol exposure has been shown to reduce nephron endowment in animal models, but the effect of alcohol during human pregnancy on postnatal kidney function has not been explored. We aim to investigate the potential association of maternal alcohol consumption during pregnancy with the offspring renal function, considering potential confounding by intrauterine growth and children’s current nutritional status.MethodsProspective longitudinal study in a random sample of 1093 children from a population-based birth cohort. Anthropometrics and estimated glomerular filtration rate (eGFR) were assessed at 7 years of age. Multiple linear regression models were fitted, adjusting for child’s gender, age, birthweight, and maternal age, education, prepregnancy nutritional status, and smoking.ResultsThirteen percent of mothers consumed alcohol during pregnancy. At 7 years of age, eGFR was significantly lower in children with prenatal alcohol exposure (134 ± 17 vs.138 ± 16 mL/min/1.73m2, p = 0.014). The effect was dose dependent and only present in overweight and obese children, among whom adjusted eGFR was −6.6(−12.0 to −1.1)mL/min/1.73m2 and −11.1(−21.3 to −1.2)mL/min/1.73m2 in those exposed to ≤ 40 g and to > 40 g of alcohol per week, respectively, compared to no consumption (ptrend = 0.002).ConclusionsPrenatal alcohol exposure has a dose-dependent adverse effect on renal function at school age in overweight and obese children.

This study assessed the long-term renoprotective effect of intensified blood-pressure control among children receiving a fixed high dose of an angiotensin-converting–enzyme inhibitor. Intensified blood-pressure control, achieved with additional medication, to reach a targeted 24-hour blood pressure in the low range of normal appeared to confer a substantial benefit with respect to a delay in the progression of renal disease among children with chronic kidney disease. However, reappearance of proteinuria after initial successful pharmacologic control was common. Intensified blood-pressure control to reach a targeted 24-hour blood pressure in the low range of normal appeared to confer a substantial benefit with respect to a delay in the progression of renal disease among children with chronic kidney disease. However, reappearance of proteinuria was common. Among both adults and children, chronic kidney disease tends to progress to end-stage renal failure, which is a major clinical problem. Systemic hypertension and glomerular hyperfiltration lead to progressive nephron damage. 1 – 3 Effective blood-pressure control delays the progression of renal disease in adults with chronic kidney disease, and antihypertensive agents that inhibit the renin–angiotensin system provide superior renoprotection, owing to their additional antiproteinuric, antiinflammatory, and antifibrotic properties. 4 – 7 Children comprise less than 1% of the total population with chronic kidney disease and often have congenital kidney malformations, urinary tract disorders, or genetic disorders that affect nephron formation or function. Hypertension . . .

Background Glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA), but this may lead to biased results when applied to subjects of abnormal body size. The aim of our study was to examine the impact of normalization to the BSA and alternative body size descriptors on measured and estimated GFR in overweight and obese children. Methods This was a cross-sectional study of 313 children aged 8–9 years old. GFR was measured by 24-h creatinine clearance (CrCl) and additionally estimated from serum creatinine and cystatin C (CysC) using the combined Zappitelli formula, both as absolute values and adjusted to various body size descriptors. The results were compared between 163 normal-weight, 89 overweight and 61 obese children. Results Compared to the normal-weight children, mean absolute GFR (both measured and estimated) was higher in the overweight and obese children, whereas BSA-adjusted GFR was lower. Linear regression models fitted in normal-weight children revealed equally close associations between absolute GFR and squared height, ideal body weight (IBW) and BSA derived from IBW. Normalization of GFR to the IBW-derived BSA completely eliminated the discrepancy between absolute and BSA-indexed GFR in overweight and obese children. Conclusions Indexing of GFR to BSA calculated from the ideal—rather than actual—body weight is a promising approach to avoid overcorrection when studying obese children. Further studies should assess the accuracy of this approach across the full range of age and BMI distribution.

Background Most modifiable risk factors for high blood pressure (BP), such as obesity and salt intake, are imprinted in childhood and persist into adulthood. The aim of our study was to evaluate the intake of salt in children and to assess its impact on BP taking into account gender and nutritional status. Methods A total of 298 children aged 8–9 years were evaluated in a cross-sectional study. Anthropometric measurements and 24-h ambulatory monitoring were performed, and salt intake was determined by 24-h urinary sodium excretion. Results The average estimated salt intake among the entire cohort of children enrolled in the study was 6.5 ± 2.2 g/day, and it was significantly higher in boys than in girls (6.8 ± 2.4 vs. 6.1 ± 1.9 g/day, respectively; p  = 0.018) and in overweight/obese children than in normal weight children (6.8 ± 2.4 vs. 6.1 ± 2.0 g/day, respectively; p  = 0.006). Salt intake exceeded the upper limit of the US Dietary Reference Intake in 72 % of children. Daytime systolic BP increased by 1.00 mmHg (95 % confidence interval 0.40–1.59) per gram of daily salt intake in overweight/obese boys, but not in normal weight boys or in girls. Conclusions Our results demonstrate an extremely high salt intake among 8- to 9-year-old Portuguese children. Higher salt intake was associated with higher systolic BP in boys, specifically in those who were overweight/obese. Longitudinal studies are needed to further evaluate the causal relationship between obesity and high BP and the mechanism by which salt intake modulates this relationship. Nonetheless, based on our results, we urge that dietary salt reduction interventions, along with measures to fight the global epidemic of obesity, be implemented as early in life as possible.