Publications by authors named "Liane Correia-Costa"

19 Publications

  • Page 1 of 1

Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center.

J Bras Nefrol 2021 May 12. Epub 2021 May 12.

Centro Hospitalar Universitário do Porto, Centro Materno-Infantil do Norte, Unidade de Nefrologia Pediátrica, Porto, Portugal.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, which primarily affects preschool-aged children. This study's aim was to describe the clinical profile, management, and long-term outcome of the genetic aHUS patients admitted to a tertiary care pediatric nephrology center during 20 years.

Methods: We performed a retrospective analysis of the clinical records of all aHUS patients younger than 18 years with identified genetic mutations. Data on clinical features, genetic study, therapeutic interventions, and long-term outcomes were reviewed.

Results: Five cases of aHUS with an identified genetic mutation were included; all were inaugural cases with the youngest being 4 months old. Complement factor H gene mutation was identified in four patients. Therapeutic plasma exchange was performed for acute management in 4 patients, one of whom also needed acute renal replacement therapy (peritoneal dialysis). All patients went on complete remission, 2 had more than one relapse but only 1 of these progressed to chronic kidney disease during the follow-up period (median (25th-75th percentile), 136 (43.5-200.5) months).

Conclusion: In children, the prognosis of renal function seems to be strongly dependent on the genetic background, thus being crucial to perform genetic study in all aHUS cases. In our cohort, 2 patients presented genetic mutations not previously described. Recent innovations on the genetic field leading to the identification of new mutations has lead to a better understanding of aHUS pathogenesis, but further studies, focusing on the genotype-phenotype correlation, with longer follow-up periods, are needed.
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http://dx.doi.org/10.1590/2175-8239-JBN-2020-0199DOI Listing
May 2021

Impact of physical activity on redox status and nitric oxide bioavailability in nonoverweight and overweight/obese prepubertal children.

Free Radic Biol Med 2021 Feb 11;163:116-124. Epub 2020 Dec 11.

Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal; EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Portugal; Department of Pediatric Nephrology, Centro Materno-Infantil Do Norte, Centro Hospitalar Universitário Do Porto, Porto, Portugal. Electronic address:

Nutritional status might contribute to variations induced by physical activity (PA) in redox status biomarkers. We investigated the influence of PA on redox status and nitric oxide (NO) production/metabolism biomarkers in nonoverweight and overweight/obese prepubertal children. We performed a cross-sectional evaluation of 313 children aged 8-9 years (163 nonoverweight, 150 overweight/obese) followed since birth in a cohort study (Generation XXI, Porto, Portugal). Plasma total antioxidant status (P-TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-HO), myeloperoxidase (MPO) and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were assessed, as well as their association with variables of reported PA quantification (categories of PA frequency (>1x/week and ≤1x/week)and continuous PA index (obtained by the sum of points)) in a questionnaire with increasing ranks from sedentary to vigorous activity levels. U-NOx was significantly higher in children who presented higher PA index scores and higher PA frequency. Separately by BMI classes, U-NOx was significantly higher only in nonoverweight children who practiced PA more frequently (p = 0.037). In overweight/obese children, but not in nonoverweight, P-TAS was higher among children with higher PA frequency (p = 0.007). Homeostasis model assessment index (HOMA-IR) was significantly lower in more active overweight/obese children, but no differences were observed in nonoverweight children. In the fully adjusted multivariate linear regression models for P-TAS, in the overweight/obese group, children with higher PA frequency presented higher P-TAS. In the U-NOx models, U-NOx significantly increased with PA index, only in nonoverweight children. Our results provide additional evidence in support of a protective effect of physical activity, in nonoverweight by increasing NO bioavailability and in overweight/obese children by enhancing systemic antioxidant capacity and insulin sensitivity. These results highlight the importance of engaging in regular physical exercise, particularly among overweight/obese children, in which a positive association between oxidant status and cardiometabolic risk markers has been described.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.005DOI Listing
February 2021

Comparison of Kristjansson Respiratory Score and Wang Respiratory Score in infants with bronchiolitis in a hospital emergency department.

Hong Kong Physiother J 2020 Dec 21;40(2):145-153. Epub 2020 Aug 21.

Department of Obstetrics-Gynecology and Pediatrics, Faculty of Medicine, Universidade do Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.

Objective: Several respiratory scores have been created to evaluate bronchiolitis' severity level, but it is still not clear which is the best score. The aim of this study is to compare the Wang Respiratory Score (WRS) and the Kristjansson Respiratory Score (KRS) in the setting of an emergency room.

Methods: We performed a prospective observational study with 60 infants with bronchiolitis admitted to a paediatric emergency department. For both scores, we assessed inter-rater reliability between two different health professionals (physician and physiotherapist), internal consistency, and correlation with SpO testing the intraclass-correlation coefficient (ICC), weighted kappa, Cronbach coefficient and Spearman tests, respectively.

Results: The inter-rater reliability was higher in KRS (ICC 0.79) and the Cronbach and weighted kappa had similar values in KRS versus WRS. The correlation between the KRS/WRS and SpO was poor/moderate upon admission and discharge for the first observer and the second observer.

Conclusions: While the internal consistency was similar in both scores, inter-rater reliability of KRS was higher than WRS, which allows us to conclude that it would have more consistent results when used to assess bronchiolitis' level of severity by health personnel in a busy hospital emergency room.
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http://dx.doi.org/10.1142/S1013702520500146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526056PMC
December 2020

Socioeconomic disadvantage and health in early childhood: a population-based birth cohort study from Portugal.

Pediatr Res 2020 09 31;88(3):503-511. Epub 2020 Jan 31.

EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.

Background: Measuring early socioeconomic inequalities in health provides evidence to understand the patterns of disease. Thus, our aim was to determine which children's health outcomes are patterned by socioeconomics and to what extent the magnitude/direction of the differences vary by socioeconomic measure and outcome.

Methods: Data on early childhood (4 years) health was obtained from Generation XXI birth cohort (n = 8647). A total of 27 health outcomes and 13 socioeconomic indicators at the individual level and neighbourhood level were used to calculate the relative index of inequality (RII).

Results: Socioeconomic inequalities were evident across 21 of the 27 health outcomes. Education, occupation and income more often captured inequalities, compared with neighbourhood deprivation or employment status. Using highest maternal education as reference category, we observed that seizures (RII = 8.64), obesity (2.94), abdominal obesity (2.66), urinary tract infection (2.26), language/speech problems (2.24), hypertension (2.08) and insulin resistance (1.33) were heavily socially patterned, much more common in disadvantaged children. Contrastingly, eczema (0.26) and rhinitis (0.26) were more common among more advantaged children.

Conclusions: Socioeconomic inequalities were evident for almost every health outcome assessed, although with varying magnitude/direction according to the socioeconomic indicator and outcome. Our results reinforce that the social gradient in health manifests early in childhood.
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http://dx.doi.org/10.1038/s41390-020-0786-9DOI Listing
September 2020

Prenatal alcohol exposure affects renal function in overweight schoolchildren: birth cohort analysis.

Pediatr Nephrol 2020 04 9;35(4):695-702. Epub 2019 Dec 9.

EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.

Background: Prenatal 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.

Methods: Prospective 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.

Results: Thirteen 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/1.73m, 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/1.73m and -11.1(-21.3 to -1.2)mL/min/1.73m in those exposed to ≤ 40 g and to > 40 g of alcohol per week, respectively, compared to no consumption (p = 0.002).

Conclusions: Prenatal alcohol exposure has a dose-dependent adverse effect on renal function at school age in overweight and obese children.
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http://dx.doi.org/10.1007/s00467-019-04429-xDOI Listing
April 2020

Childhood Obesity and Impact on the Kidney.

Nephron 2019 25;143(1):8-11. Epub 2018 Oct 25.

EPIUnit, Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.

Obesity is known to be associated with a myriad of cardiovascular and metabolic comorbidities. In children, several longitudinal studies have shown that obesity consequences start early in life and accompany the obese child into adulthood, implying a higher risk of adverse cardiovascular events. More recently, data related to the possible role of obesity in the risk of kidney disease in adults, independently of diabetes, has started to become more available. In children, the evidence is scarcer, but it has also been acknowledged that obesity acts as a risk factor for disease progression when kidney impairment already exists, thereby increasing the risk of death among children with end-stage renal disease (ESRD). Besides this, there is also evidence that otherwise healthy overweight and obese children have a significant increase in the risk of all-cause ESRD later in life. The potential mechanisms underlying this association need to be further discussed in order to allow the setting in motion of preventive strategies to halt chronic kidney disease development and progression.
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http://dx.doi.org/10.1159/000492826DOI Listing
July 2020

Maternal Smoking: A Life Course Blood Pressure Determinant?

Nicotine Tob Res 2018 05;20(6):674-680

EPIUnit, Institute of Public Health, University of Porto, Portugal.

Introduction: Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children.

Methods: We evaluated 4295 of Generation XXI children, recruited at birth in 2005-2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and children's BP measured. Linear regression models were fitted to estimate the association between maternal smoking and children's BP.

Results: Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and child's body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (β = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (β = 0.08, 95% CI 0.03 to 0.13 before conception; β = 0.07, 95%CI 0.02 to 0.12; β = 0.04, 95%CI -0.02 to 0.10; and β = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and β = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels.

Conclusion: Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged.

Implications: Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking-before pregnancy, during pregnancy, and 4 years after delivery-was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.
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http://dx.doi.org/10.1093/ntr/ntx117DOI Listing
May 2018

Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children.

Pediatr Nephrol 2017 Aug 23;32(8):1411-1422. Epub 2017 Mar 23.

Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal.

Background: We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (HO) play a role in the putative association.

Methods: Cross-sectional evaluation of 305 children aged 8-9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and HO by a microplate fluorometric assay.

Results: U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary HO decreased with P-AGT.

Conclusions: A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin-angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary HO and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.
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http://dx.doi.org/10.1007/s00467-017-3639-yDOI Listing
August 2017

Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function.

Br J Nutr 2016 09 2;116(5):805-15. Epub 2016 Aug 2.

4Department of Pharmacology and Therapeutics, Faculty of Medicine,University of Porto,Rua Dr. Plácido da Costa, 91, Piso 3, 4200-450 Porto,Portugal.

Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.
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http://dx.doi.org/10.1017/S0007114516002804DOI Listing
September 2016

Determinants of carotid-femoral pulse wave velocity in prepubertal children.

Int J Cardiol 2016 Sep 14;218:37-42. Epub 2016 May 14.

EPIUnit - Institute of Public Health, University of Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine of University of Porto, Portugal.

Background: Pulse wave velocity (PWV) is a noninvasive technique to evaluate arterial stiffness, a dynamic property of the vessels, reflecting their structure and function. Childhood obesity is associated with several cardiovascular comorbidities and to the progression of atherosclerosis. We aimed to compare carotid-femoral PWV between normal weight and overweight/obese prepubertal children and to quantify its association with other cardiovascular risk factors.

Methods: Cross-sectional study of 315 children aged 8-9years. Anthropometrics, 24-h ambulatory blood pressure (BP) and carotid-femoral PWV were measured. Classification of obesity was according to World Health Organization (WHO) body mass index (BMI)-for-age reference values.

Results: Compared to normal weight children, overweight and obese children presented significantly higher levels of PWV (4.95 (P25-P75: 4.61-5.23), 5.00 (4.71-5.33), 5.10 (4.82-5.50) m/s, respectively; ptrend<0.001). Significant positive correlations were found between PWV and total cholesterol, LDL cholesterol, triglycerides, fasting insulin and insulin resistance levels (HOMA-IR) and with high-sensitivity C-reactive protein (hs-CRP). In a multivariate linear regression model adjusted for sex, age, height and 24-h systolic blood pressure z-score, the independent determinants of PWV were BMI, HOMA-IR and the absence of dipping.

Conclusions: The association between PWV and the loss of dipping and insulin resistance levels, independently of the BMI, reinforces the contribution of these comorbidities to vascular injury in early life.
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http://dx.doi.org/10.1016/j.ijcard.2016.05.060DOI Listing
September 2016

Normalization of glomerular filtration rate in obese children.

Pediatr Nephrol 2016 08 23;31(8):1321-8. Epub 2016 Mar 23.

Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto (ISPUP), Rua das Taipas nr. 135, 4050-600, Porto, Portugal.

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.
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http://dx.doi.org/10.1007/s00467-016-3367-8DOI Listing
August 2016

Accelerated growth during childhood is associated with increased arterial stiffness in prepubertal children.

Int J Cardiol 2016 Feb 23;204:83-5. Epub 2015 Nov 23.

EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine of University of Porto, Portugal.

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http://dx.doi.org/10.1016/j.ijcard.2015.11.149DOI Listing
February 2016

Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children.

Eur J Clin Invest 2016 Jan 1;46(1):50-9. Epub 2015 Dec 1.

EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal.

Introduction: Myeloperoxidase (MPO), an enzyme linking obesity and cardiovascular (CV) risk in adults, has rarely been studied in young children and no studies assessed its association with renal function. We sought to explore a possible association between serum MPO levels, obesity, CV risk factors and renal function in prepubertal children.

Materials/methods: Cross-sectional evaluation of 309 children aged 8-9 years (161 normal weight, 148 overweight/obese), members of the birth cohort Generation I (Portugal). Anthropometrics (body mass index (BMI), waist-to-height ratio (WHtR) and % body fat mass (%BFM) by bioelectrical impedance analysis), 24-h ambulatory blood pressure monitoring and pulse wave velocity (PWV) were measured. Insulin resistance was estimated by the HOMA index (considering serum fasting glucose and insulin determinations). Serum MPO levels were assessed by immunoenzymatic assay.

Results: MPO levels were positively associated with obesity indices (BMI z-score, WHtR and %BFM). Higher MPO levels were associated with higher 24-h and night-time mean arterial pressure, with nondipping and with higher values of insulin resistance. In normal weight children, the endothelial function, as evaluated indirectly by PWV, was an independent predictor of MPO levels. In overweight/obese children, estimated glomerular filtration rate increased significantly across tertiles of MPO (Ptrend = 0·031) and this association held after adjustment for age, sex, neutrophil and monocyte counts and CV risk factors.

Conclusions: Our results reinforce the role of MPO as a risk marker in obesity and related CV morbidities in young children. MPO levels associate with the dipping pattern and PWV and, among overweight/obese children, an association exists between MPO and renal function.
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http://dx.doi.org/10.1111/eci.12564DOI Listing
January 2016

Urinary fibrogenic cytokines ET-1 and TGF-β1 are associated with urinary angiotensinogen levels in obese children.

Pediatr Nephrol 2016 Mar 19;31(3):455-64. Epub 2015 Oct 19.

Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.

Background: Fibrogenic cytokines are recognized as putative drivers of disease activity and histopathological deterioration in various kidney diseases. We compared urinary transforming growth factor β1 (U-TGF-β1) and endothelin 1 (U-ET-1) levels across body mass index classes and assessed their association with the level of urinary angiotensinogen (U-AGT), a biomarker of intrarenal renin-angiotensin-aldosterone system (RAAS).

Methods: The was a cross-sectional evaluation of 302 children aged 8-9 years. Ambulatory blood pressure (BP), insulin resistance (HOMA-IR), aldosterone level and renal function were evaluated. U-ET-1, U-TGF-β1 and U-AGT levels were determined by immunoenzymatic methods.

Results: Obese children presented with the lowest levels of U-ET-1 and U-TGF-β1, but the difference was only significant for U-ET-1. In obese children, the median levels of both U-ET-1 and U-TGF-β1 tended to increase across tertiles (T1-T3) of U-AGT (U-ET-1: T1, 19.9 (14.2-26.3); T2, 32.5 (23.3-141.6); T3, 24.8 (18.7-51.5) ng/g creatinine, p = 0.007; U-TGF-β1: T1, 2.2 (1.8-4.0); T2, 4.3 (2.7-11.7); T3, 4.9 (3.8-10.1) ng/g creatinine, p = 0.004]. In multivariate models, in the obese group, U-ET-1 was associated with HOMA-IR and aldosterone and U-AGT levels, and U-TGF-β1 was associated with U-AGT levels and 24 h-systolic BP.

Conclusions: Whereas the initial hypothesis of higher levels of urinary fibrogenic cytokines in obese children was not confirmed in our study, both TGF-β1 and U-ET-1 levels were associated with U-AGT level, which likely reflects an early interplay between tissue remodeling and RAAS in obesity-related kidney injury.
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http://dx.doi.org/10.1007/s00467-015-3232-1DOI Listing
March 2016

Gender and obesity modify the impact of salt intake on blood pressure in children.

Pediatr Nephrol 2016 Feb 29;31(2):279-88. Epub 2015 Sep 29.

Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Porto, Portugal.

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.
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http://dx.doi.org/10.1007/s00467-015-3210-7DOI Listing
February 2016

Decreased renal function in overweight and obese prepubertal children.

Pediatr Res 2015 Oct 7;78(4):436-44. Epub 2015 Jul 7.

EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal.

Background: Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl).

Methods: Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference.

Results: Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to -1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values.

Conclusion: Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity.
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http://dx.doi.org/10.1038/pr.2015.130DOI Listing
October 2015

Sex-Specific Mediating Role of Insulin Resistance and Inflammation in the Effect of Adiposity on Blood Pressure of Prepubertal Children.

PLoS One 2015 30;10(6):e0132097. Epub 2015 Jun 30.

EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal.

Objective: 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).

Materials And Methods: 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).

Results: 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.

Discussion: 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132097PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488421PMC
April 2016

Cystic fibrosis and beckwith-wiedemann syndrome: a case report.

J Clin Med Res 2015 Mar 29;7(3):186-8. Epub 2014 Dec 29.

Division of Pediatric Pneumology, Hospital Pediatrico Integrado, Centro Hospitalar Sao Joao, Porto, Portugal.

Cystic fibrosis (CF) is a hereditary disease of exocrine gland function that involves multiple systems but chiefly results in chronic respiratory infections, the major cause of death, pancreatic enzyme deficiency and severe malnutrition, mostly in untreated patients. The association between CF and other inherited diseases or congenital anomalies is rare. We describe for the first time the association of CF and Beckwith-Wiedemann syndrome (BWS). BWS is a genetic disorder commonly characterized by overgrowth. The most common features of BWS include macrosomia, macroglossia, abdominal wall defects, an increased risk for childhood tumors, kidney abnormalities, hypoglycemia in the newborn period and unusual ear creases or pits.
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http://dx.doi.org/10.14740/jocmr2003wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285066PMC
March 2015