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Children with chronic kidney disease suffer from excessive cardiovascular mortality and early alterations of the cardiovascular system. Tissue doppler imaging is a validated echocardiographic tool to assess early systolic and diastolic cardiac dysfunction. We hypothesized that tissue Doppler velocities would reveal reduced cardiac function in children with chronic kidney disease compared to healthy children. A standardized echocardiographic exam was performed in 128 patients of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) Study aged 6-17 years with an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m 2 . Tissue Doppler measurements included early (E') and late (A') diastolic and systolic (S') velocity at the mitral and septal annulus of the left ventricle. Measured values were normalized to z-scores using published reference data. Predictors of E'/A', E/E', S' and left ventricular mass index (LVMI) were assessed by multiple linear regression analyses. Tissue Doppler E' was reduced and tissue Doppler A' increased, resulting in a reduced tissue Doppler E'/A' ratio (z-score -0.14, p < 0.0001) indicating reduced diastolic function compared to healthy children. Reduced tissue Doppler E'/A' Z-Scores were independently associated with lower eGFR (p = 0.002) and increased systolic blood pressure (p = 0.02). While E/E' Z-Scores were increased (Z-score 0.57, p < 0.0001), patients treated with pharmacological RAS blockade but not with other antihypertensive treatments had significantly lower E/E' and higher E'/A' Z-Scores. Systolic tissue Doppler velocities were significantly decreased (Z-score -0.24, p = 0.001) and inversely correlated with E/E' Z-Scores (r = -0.41, p < 0.0001). LVMI was not associated with systolic or diastolic tissue Doppler velocities. Concentric left ventricular hypertrophy showed a tendency to lower S' in multivariate analysis (p = 0.13) but no association to diastolic function. Concentric left ventricular geometry was significantly associated with lower midwall fractional shortening. In summary, systolic and diastolic function assessed by tissue Doppler is impaired. eGFR, systolic blood pressure and the type of antihypertensive medications are significant predictors of diastolic function in children with CKD. Left ventricular morphology is largely independent of tissue Doppler velocities. Tissue Doppler velocities provide sensitive information about early left ventricular dysfunction in this population.

The present article intends to provide an update of the article "Focus on prevention, diagnosis and treatment of hypertension in children and adolescents" published in 2013 (Spagnolo et al., Ital J Pediatr 39:20, 2013) in this journal. This revision is justified by the fact that during the last years there have been several new scientific contributions to the problem of hypertension in pediatric age and during adolescence. Nevertheless, for what regards some aspects of the previous article, the newly acquired information did not require substantial changes to what was already published, both from a cultural and from a clinical point of view. We felt, however, the necessity to rewrite and/or to extend other parts in the light of the most recent scientific publications. More specifically, we updated and extended the chapters on the diagnosis and management of hypertension in newborns and unweaned babies, on the use and interpretation of ambulatory blood pressure monitoring, and on the usefulness of and indications for physical activity. Furthermore, we added an entirely new section on the role that simple carbohydrates (fructose in particular) and uric acid may play in the pathogenesis of hypertension in pediatric age.

Background and Objectives: Newer parameters of cardiac mechanics provide additional insights on cardiac dysfunction in adult patients with CKD. The aim of this study was to identify prevalence of subclinical abnormalities in cardiac function through the analysis of novel indices of cardiac mechanics in a large population of children with CKD., Design, Setting, Participants, & Measurements: Between 2009 and 2011, the prospective observational Cardiovascular Comorbidity in Children with CKD Study enrolled patients with CKD ages 6-17 years old with eGFR=10-45 ml/min per 1.73 m(2) in 14 European countries. Cardiac morphology and function were assessed through echocardiography. The analysis presented encompasses global radial, longitudinal, and circumferential strains as well as time to peak analysis. Data were compared with 61 healthy children with comparable age and sex., Results: Data on 272 patients with CKD with complete echocardiographic assessment are reported (age =12.8±3.5 years old; 65% boys). Patients with CKD showed mildly higher office BP values and higher prevalence of left ventricular hypertrophy, but no differences were observed among groups in left ventricular ejection fraction. Strain analysis showed significantly lower global radial strain (29.6%±13.3% versus 35.5%±8.9%) and circumferential strain components (-21.8%±4.8% versus -28.2%±5.0%; both P<0.05) in patients with CKD without significant differences observed in longitudinal strain (-15.9%±3.4% versus -16.2%±3.7%). Lower values of global radial strain were associated with lower circumferential endocardial-to-epicardial gradient (r=0.51; P<0.01). This association remained significant after adjusting for BP, eGFR, and presence of left ventricular hypertrophy. Eventually, patients with CKD also showed higher delay in time to peak cardiac contraction (58±28 versus 37±18 milliseconds; P<0.05)., Conclusions: A significant proportion of children with CKD show impaired systolic mechanics. Impaired systolic function is characterized by lower radial strain, transmural circumferential gradient, and mild cardiac dyssynchrony. This study suggests that analysis of cardiac strain is feasible in a large multicenter study in children with CKD and provides additional information on cardiac pathophysiology of this high-risk population., (Copyright © 2015 by the American Society of Nephrology.)

The burden of hypertension has become increasingly prevalent in children. Hypertension that begins in childhood can carry on into adulthood, therefore early detection, accurate diagnosis and effective therapy of high blood pressure may improve long-term outcomes of children and adolescents. As far as pediatric hypertension is concerned, doubts still persist about the right instruments, modalities and standards of reference that should be used in routine practice. Due to the dynamic process of growth and development, many physiological parameters undergo intensive change with age. Therefore, in children, the definition of hypertension can not rely on a single blood pressure level but should be based on age- and height-specific percentiles. In this review, we introduce the nephrologist to the correct definition of high blood pressure in children. Moreover, we specifically address the main characteristics of different modalities for blood pressure measurement in children, focusing on practical aspects. The latest international guidelines and appropriate standards of reference for office, ambulatory and home blood pressure data collection are presented. As clinicians are being faced with a greater number of children with hypertension, they should be aware of these peculiarities.

The European Society of Hypertension has recently published its recommendations on prevention, diagnosis and treatment of high blood pressure in children and adolescents. Taking this contribution as a starting point the Study Group of Hypertension of the Italian Society of Pediatrics together with the Italian Society of Hypertension has conducted a reappraisal of the most recent literature on this subject. The present review does not claim to be an exhaustive description of hypertension in the pediatric population but intends to provide Pediatricians with practical and updated indications in order to guide them in this often unappreciated problem. This document pays particular attention to the primary hypertension which represents a growing problem in children and adolescents. Subjects at elevated risk of hypertension are those overweight, with low birth weight and presenting a family history of hypertension. However, also children who do not present these risk factors may have elevated blood pressure levels. In pediatric age diagnosis of hypertension or high normal blood pressure is made with repeated office blood pressure measurements that show values exceeding the reference values. Blood pressure should be monitored at least once a year with adequate methods and instrumentation and the observed values have to be interpreted according to the most updated nomograms that are adjusted for children's gender, age and height. Currently other available methods such as ambulatory blood pressure monitoring and home blood pressure measurement are not yet adequately validated for use as diagnostic instruments. To diagnose primary hypertension it is necessary to exclude secondary forms. The probability of facing a secondary form of hypertension is inversely proportional to the child's age and directly proportional to blood pressure levels. Medical history, clinical data and blood tests may guide the differential diagnosis of primary versus secondary forms. The prevention of high blood pressure is based on correct lifestyle and nutrition, starting from childhood age. The treatment of primary hypertension in children is almost exclusively dietary/behavioral and includes: a) reduction of overweight whenever present b) reduction of dietary sodium intake c) increase in physical activity. Pharmacological therapy will be needed rarely and only in specific cases.

Background and Objectives: Left ventricular hypertrophy (LVH) and abnormal systolic function are present in a high proportion of children with CKD. This study evaluated changes in left ventricular (LV) geometry and systolic function in children with mild to moderate CKD as an ancillary project of the Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of Chronic Renal Failure in Pediatric Patients trial., Design, Setting, Participants, & Measurements: Echocardiograms and ambulatory BP monitoring were performed at baseline and at 1- or 2-year follow-up in 84 patients with CKD and 24-hour mean BP above the 50th percentile and/or receiving fixed high-dose angiotensin converting enzyme inhibition and randomized to conventional or intensified BP control., Results: LVH prevalence decreased from 38% to 25% (P<0.05). Changes in LV mass index (LVMI) were restricted to patients with LVH at baseline (-7.9 g/m(2.7); P<0.02). Changes in LVMI were independent of randomization, reduction in BP, hemoglobin, and estimated GFR. A significant increase in midwall fractional shortening was observed in the total cohort (P<0.05), and was greater in the intensified group compared with the conventional BP control group (12%±1.9% versus 8%±1.5%; P=0.05). In multivariate analysis, improvement in myocardial function was associated with reduction in BP (r=-0.4; P<0.05), independently of LVMI reduction., Conclusions: In children with CKD, angiotensin converting enzyme inhibition with improved BP control, LVH regression, and improved systolic function was observed within 12 months. Lowering BP to the low-normal range led to a slightly more marked improvement in myocardial function but not in LVMI.

Background and Objectives: Clinical and experimental data have shown that differences in nephron endowment result in differences in renal mass and predisposition to chronic renal failure, hypertension, and proteinuria. We hypothesized that a significant proportion of the variance in GFR, as estimated by serum creatinine, is attributable to differences in renal size in normal children., Design, Setting, Participants, & Measurements: A total of 1748 normal renal ultrasounds that were performed in children older than 6 months were reviewed. For each ultrasound, serum creatinine, serum blood urea nitrogen, and systolic and diastolic office BP were recorded. Renal size was evaluated as a function of renal length and thickness. All data were normalized for height, weight, age, and gender., Results: When expressed as SD scores, a significant correlation was found between kidney size and serum creatinine (P < 0.0001) and between kidney size and serum blood urea nitrogen (P < 0.002). When dividing kidney size data per quintiles, a difference of 0.51 SD score in serum creatinine was observed between the lowest and highest quintile. No significant correlation was found with office BP measurements., Conclusions: These data show that, even in the normal pediatric population, differences in renal function are significantly explained by differences in renal mass. Methodologic limitations of this study are likely to underestimate this relationship.

Background: Abnormal cardiovascular reactivity at rest and during physical exercise may be a risk factor for left ventricular hypertrophy (LVH) in pediatric renal transplanted (Tx) patients. Data on total peripheral vascular resistance (TPR) are not available., Methods: Eleven renal Tx patients treated with cyclosporine (7 females and 4 males; mean age 14.6 +/- 3.3 years; mean time since transplantation 43 +/- 35 months) were evaluated for 24-hour blood pressure (BP), TPR and echocardiographic left ventricular mass (LVM). TPR values of patients were compared with data of a group of 11 healthy controls matched for sex and age., Results: Twenty-four-hour ambulatory blood pressure monitoring showed that all but one patient had normal daytime BP values and six patients showed a reduced or inverse nocturnal dip. LVH was found in 72% of the patients. In comparison with healthy controls, patients showed significantly elevated TPR at rest and during exercise suggesting an increased vascular tone. The degree of LVH in these patients is severe and appears disproportionate to the BP values., Conclusion: The high incidence of LVH can reflect an augmented cardiovascular reactivity associated with a disturbed circadian pattern. The increase in TPR and the reduction of the nocturnal fall of BP also might contribute to the development of LVH in young renal Tx patients.

Background: Hypertension and left ventricular hypertrophy (LVH) are possible complications in pediatric patients after renal transplantation., Methods: We performed left ventricular echocardiography, 24-hour ambulatory blood pressure monitoring (24-hr ABPM), and treadmill tests in 28 pediatric renal transplant patients (mean age 16.1 +/- 3.7; time since transplantation 36 +/- 23 months). Left ventricular mass (LVM) was indexed for height 2.7., Results: LVH was found in 82% of the patients. Seven of these patients were normotensive by 24-hour ABPM, but five patients showed a hypertensive systolic BP response during the treadmill test. LVM/height 2.7 correlated significantly with the mean 24-hour systolic BP (P = 0.002) and with the maximal exercise systolic BP (P = 0.002)., Conclusion: LVH is frequent in pediatric renal transplant patients. More information is needed with respect to the risk for LVH, including data from 24-hour ABPM and treadmill testing.

In a 3-year prospective study, 49 Italian children with the hemolytic-uremic syndrome (HUS) were examined for evidence of infection with Vero cytotoxin-producing Escherichia coli (VTEC). Diagnosis of infection was established in 37 patients (75.5%) by the combined use of stool examination for VTEC and for free fecal neutralizable Vero cytotoxin and serum analysis for antibodies to the Vero toxins and the lipopolysaccharides (LPS) of three major VTEC serogroups (O157, O26, O111). Anti-LPS antibodies were detected in sera from 30 patients: 25 had antibody to O157 LPS, 4 to O26, and 1 to O111. In as many as 27 patients (55.1%), diagnosis of infection relied only on serologic findings, and the presence of antibody to LPS was the sole evidence of VTEC infection in 20 patients (40.8%). The use of LPS from different E. coli serogroups provided evidence that in Italy O157 strains are the most prevalent VTEC involved in HUS.

Verotoxin-producing Escherichia coli O157:H7 was isolated for the first time in Italy from a child with hemolytic-uremic syndrome and his asymptomatic sister. Both parents remained asymptomatic, and neither had evidence of this infection. The source of the infection was not identified, but the children had eaten ground beef during the 15 days prior to the onset of symptoms.