A significant increase in the prevalence of end-stage renal disease (ESRD) has been reported over the last three decades, paralleling the increasing prevalence of obesity and insulin resistance, also in the pediatric population. Overweight, obesity and the metabolic syndrome, which frequently coexist, contribute substantially to cardiovascular disease and ESRD. A higher body mass index, the presence of type 2 diabetes, hypertension and, of particular importance, reduced insulin sensitivity (IS), have recently emerged as strong independent risk factors for chronic kidney disease and ESRD. Of particular concern, the long-term cardiovascular impact of obesity, although deferred to adult life, has its origins in childhood. Clustering of cardiovascular risk factors is seen in children and adolescents with the highest degree of reduced IS, suggesting that adult consequences of obesity on target organs, including the kidney, are more likely to develop in these young people. This review will discuss the association between obesity and the risk of kidney disease, focusing on the way in which obesity and its metabolic complications may lead to renal involvement and injury, with particular regard to childhood. It is beyond the scope of this article to examine kidney disease as a component of syndromes that result in obesity in childhood.

Increasing attention has been focused on the implications of obesity in adults on the development of kidney disease, but data on the obese pediatric population are lacking. The aim of this study was to investigate whether changes in various renal function indexes/markers, as expressed by the glomerular filtration rate [GFR, as estimated by the Schwartz formula (eGFR)], serum cystatin C (CysC) level, albumin excretion rate (AER), and modifications in nitric oxide (NO; an important modulator of renal function and morphology), urinary isoprostanes (markers of oxidative stress), and blood pressure (BP), can be detected in obese children and adolescents when compared to normal weight controls. Blood and urinary samples were collected to evaluate markers of renal function, serum and urinary NO, and urinary isoprostanes in 107 obese Caucasian subjects and 50 controls. Ambulatory BP monitoring (ABPM) was performed in all cases. Obesity was expressed by the body mass index standard deviation score (SDS-BMI), and insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR). CysC and eGFR did not significantly differ between the two groups; AER was increased in obese children. CysC and GFR were related to HOMA-IR, and AER was related to HOMA-IR and SDS-BMI. Obese subjects had reduced NO levels and increased urinary isoprostanes and BP measurements; all three parameters were related to SDS-BMI and insulin resistance. ABPM showed an increased incidence of hypertension and non-dipping in the obese group. Based on our comparison of obese and nonobese children, we conclude that renal involvement is not an early clinically evident manifestation of adiposity in childhood, since no overt changes in eGFR and only a mild albuminuria were detected. A longer exposure to obesity is probably needed before renal function impairment appears.

Anticardiolipin antibodies are found frequently in those suffering from migraine, but it is not clear if this association is real or coincidental. Moreover, there are no data on the prevalence of anticardiolipin antibodies in children. In this study, 40 patients were divided into two groups according to the type of migraine: group I included 22 cases (15 females and 7 males, mean age+/-SD 13.7+/-8.9 years) suffering from migraine with and without aura; group II consisted of 18 children (10 females and 8 males, age 14.7+/-6.9 years) having migraine with prolonged aura or migrainous infarction, also called complicated migraine. We studied two groups of children as controls: a group of 35 children (25 females and 10 males, mean age 13.9+/-7.1 years) with juvenile chronic arthritis (group III) and a group of 40 healthy sex- and age-matched children who did not suffer from migraine or any other neurological disease (group IV). No statistically significant differences in levels of anticardiolipin antibodies were found between group I and II and controls. Our data demonstrate that, in children with migraine, anticardiolipin antibodies are not more frequent than in healthy controls, and suggest that anticardiolipin antibodies are not implicated in the pathogenesis of migraine.

Valproic acid (VPA) is effective for the treatment of many types of epilepsy, but its use can be associated with an increase in body weight. We report a case of nonalcoholic fatty liver disease (NAFLD) arising in a child who developed obesity during VPA treatment. Laboratory data revealed hyperinsulinemia with insulin resistance. After the withdrawal of VPA therapy, our patient showed a significant weight loss, a decrease of body mass index, and normalization of metabolic and endocrine parameters; moreover, ultrasound measurements showed a complete normalization. The present case suggests that obesity, hyperinsulinemia, insulin resistance, and long-term treatment with VPA may be all associated with the development of NAFLD; this side effect is reversible after VPA withdrawal.

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Several techniques have been used to diagnose gastroesophageal reflux (GER) in children, but no single test is sufficiently accurate to completely investigate the problem. Gastroesophageal US has been described as a widely available, noninvasive and sensitive method. It provides morphological and functional information, but its role in the diagnosis of GER in children is still debated. In this paper we review diagnostic approaches to GER in children. We focus on current use of US in the management of children with suspected GER. Reports suggest that US allows exclusion of several non-GER causes of symptoms and that it provides morphological and functional data with high sensitivity and positive predictive value for the diagnosis of GER. Sonographic assessment of findings such as abdominal esophageal length, esophageal diameter, esophageal wall thickness and gastroesophageal angle provide important diagnostic indicators of reflux and related to the degree of GER. There is a need for standardization of the procedure and for defining diagnostic criteria.

OBJECTIVE -The aim of the present study was to evaluate serum and urinary nitric oxide (NO) concentrations in children and adolescents with diabetes compared with age-matched healthy control subjects to find out whether Doppler ultrasonography could be used to detect changes in renal resistive indexes (RIs) in children with diabetes and to assess whether there are correlations between these parameters and NO excretion.RESEARCH DESIGN AND METHODS -We studied 42 children with type 1 diabetes and 41 matched healthy control subjects, both divided into prepubertal or pubertal children. Serum and urinary nitrite and nitrate (NO 2 Ϫ ϩNO 3 Ϫ ) concentrations were evaluated as an index of NO production. Doppler ultrasonographic registration of intrarenal RI was performed.RESULTS -Compared with healthy control subjects, children with diabetes had significantly increased concentrations of serum (30.26 Ϯ 6.52 vs. 24.47 Ϯ 7.27 mmol/l, P ϭ 0.001) and urinary NO 2 Ϫ ϩNO 3 Ϫ (345.07 Ϯ 151.35 vs. 245.86 Ϯ 80.25 mmol/l, P ϭ 0.002); the same was true for Doppler RI values (0.64 Ϯ 0.03 vs. 0.60 Ϯ 0.04, P ϭ 0.035). This occurs in both prepubertal and the pubertal children. A significant positive correlation was found between serum and urinary NO 2 Ϫ ϩNO 3 Ϫ levels (P ϭ 0.002, r ϭ 0.374). Serum NO 2 Ϫ ϩNO 3 Ϫ concentrations also correlated positively with Doppler RI (P ϭ 0.032, r ϭ 0.262) and HbA 1c (A1C) (P ϭ 0.004, r ϭ 0.329); urinary NO 2 Ϫ ϩNO 3 Ϫ concentrations correlated positively with A1C (P ϭ 0.001, r ϭ 0.394). Doppler RI correlated positively with A1C (P ϭ 0.000, r ϭ 0.424).CONCLUSIONS -This study demonstrates that in children with diabetes, chronic hyperglycemia may act through a mechanism that involves increased NO production and/or action and contributes to generating intrarenal hemodynamic abnormalities, which are detectable by Doppler ultrasonography even in early diabetic nephropathy. Diabetes Care 29:2676 -2681, 2006C linically evident diabetes-related microvascular complications are extremely rare in childhood and adolescence. Nonetheless, early functional and structural abnormalities may be present a few years after the onset of the disease. Chronic hyperglycemia is central in the pathophysiology of microangiopathy and in the evolution of diabetes complications, such as diabetic nephropathy. It sets in motion a series of biochemical disturbances in critical tissue, including the kidney, leading to functional changes followed by irreversible structural changes, and finally to the features that we recognize as clinical disease (1-3). Hyperglycemia is associated with excessive free radical generation and oxidant stress and reduction in the antioxidant status. One of the many consequences of oxidant stress that has been linked to diabetes is altered nitric oxide (NO) production and action (4). NO, an endothelium-derived relaxing factor, has been identified as a pleiotropic intercellular messenger that regulates a variety of cellular functions (5). All isoforms of NO synthase have been isolated in the renal proximal tub...

Pediatric renal cystic diseases include a variety of hereditary or non-hereditary conditions. Numerous classifications exist and new data are continuously published. Ultrasound is the primary technique for evaluating kidneys in children: conventional and high-resolution US allows a detailed visualization of renal parenchyma and of number, size and location of the cysts, hence representing the most important diagnostic imaging technique for the first diagnosis and follow-up of these young patients. The purpose of this pictorial essay is to review the spectrum of renal cystic lesions in children from simple, complex or malignant single cysts to the several poly/multicystic kidney diseases.