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-H 2 O 2 ), 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-H 2 O 2 , 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-H 2 O 2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H 2 O 2 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 Abbreviations: ABPM, ambulatory blood pressure monitoring; eGFR, estimated glomerular filtration rate; HOMA-IR, homoeostasis model assessment of insulin resistance; hs-CRP, high-sensitivity C-reactive protein; MAP, mean arterial pressure; MPO, myeloperoxidase; NO, nitric oxide; NOS, NO synthase; P-Isop, plasma isoprostanes; P-NOx, plasma nitrates and nitrites; PWV, pulse wave velocity; ROS, reactive oxygen species; TAS, total antioxidant status; U-H 2 O 2 , urinary hydrogen peroxide; U-Isop, urinary isoprostanes; U-NOx, urinary nitrates and nitrites; WHtR, waist:height ratio.

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. t he role of the obesity epidemic in the risk of kidney disease has been recognized in adults, independently of diabetes, with the prevalence of end-stage renal disease raising tremendously in the past 3 decades in parallel with the increased prevalence of obesity (1,2). Obesity was also identified as a strong and potentially modifiable risk factor for the development and progression of kidney disease (3,4) and, in children, recent data confirmed a similar trend, with obesity contributing to renal injury and to an important increase of chronic kidney disease (5).Studies in the general pediatric population only recently started to arise and the results concerning glomerular filtration rate (eGFR) differences in obese and normal weight children are somehow contradictory; some studies reported higher eGFR in obese children reflecting a state of hyperfiltration (6), while others found either the opposite (7,8) or no differences (9,10).It is difficult to evaluate renal function in the general pediatric population and to which extent the kidney is involved in the metabolic cluster of conditions that emerge with the onset of obesity in early ages. On the one hand, since exogenous and more accurate, but invasive, methods are not justifiable to apply in healthy children, one has to rely on eGFR formulas or in the 24-h urine creatinine clearance (CrCl). However, formulas to estimate eGFR are known to have some limitations and 24-h urine samples might be difficult to reliably obtain in children (11). On the other hand, the degree of kidney involvement related to obesity might be subt...

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.

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.