Role of glucocorticoid metabolism in childhood obesity-associated hypertension.

Objective: Childhood obesity is associated with alterations in hypothalamus-pituitary-adrenal axis activity. We tested the hypothesis that multiple alterations in the metabolism of glucocorticoids are required for the development of hypertension in children who become overweight.

Methods: Spot urine for targeted gas chromatography-mass spectrometry steroid metabolome analysis was collected from (1) overweight/hypertensive children (n = 38), (2) overweight/non-hypertensive children (n = 83), and (3) non-overweight/non-hypertensive children (n = 56).

Is There an Association Between Cortisol and Hypertension in Overweight or Obese Children?

Objective: The precise mechanisms behind the development of hypertension in overweight or obese children are not yet completely understood. Alterations in hypothalamic-pituitary-adrenal axis activity may play a role. We aimed to investigate the association between cortisol parameters and hypertension in overweight or obese children.

Population Pharmacokinetics of Prednisolone in Relation to Clinical Outcome in Children With Nephrotic Syndrome.

Background: The relapse frequency in children with nephrotic syndrome (NS) is highly variable despite standardized prednisolone treatment regimens. Existing evidence on the relationship between prednisolone pharmacokinetics (PK) and clinical response in children with NS is scarce and limited. The aim of this study was to develop a pediatric popPK model for prednisolone based on our previous model based on healthy adults using salivary measurements in children with NS and to correlate clinical outcome with between-subject variability in prednisolone exposure.

Is the prevalence of hypertension in overweight children overestimated?

Objectives: The aim of this study is to explore different methods for screening and diagnosing hypertension-which definitions and criteria to use-in children and in addition to determine the prevalence of hypertension in Dutch overweight children.

Design: A cross-sectional study performed in the Dutch Child Health Care setting.

Setting: Four Child Health Care centres in different cities in the Netherlands.

Screening, diagnosis and treatment of hypertension in obese children: an international policy comparison.

Hypertension in obese children may require a different diagnostic and treatment approach from that for children with secondary hypertension, yet there is neither consensus nor a clear guideline. The aim of this study was to assess how obese children with hypertension are currently diagnosed and treated by paediatric nephrologists, what obstacles exist and what can be improved. In the period May-November 2014, an online questionnaire was sent to all members of the European Society for Paediatric Nephrology (n = 2148).

Genetic and in vivo determinants of glucocorticoid sensitivity in relation to clinical outcome of childhood nephrotic syndrome.

Following initial glucocorticoid treatment, the clinical course in children with nephrotic syndrome is highly variable. Intrinsic sensitivity to glucocorticoids might be a determinant of this variability. Functional polymorphisms of the glucocorticoid receptor gene NR3C1 have been associated with either relatively impaired (GR-9β) or increased (BclI) glucocorticoid sensitivity.

Monitoring prednisolone and prednisone in saliva: a population pharmacokinetic approach in healthy volunteers.

Background: Prednisolone (PLN) is a widely used corticosteroid in a variety of immune-mediated diseases. Treatment regimes generally consist of empirically derived treatment doses, whereas therapeutic response among patients is highly variable. Drug monitoring of serum PLN levels might support a more rational approach to dose selection, yet is invasive and laborious.

[Guideline 'Overweight' for child health care].

The '5th National Growth Study' indicates that the percentage of overweight children in the Netherlands has risen from 9-12% in 1997 to 13-15% in 2009. Child Health Care is a unique setting for promotion of development, growth and behaviour of children, in which tailored prevention can be offered. Detection of overweight in children and intervention by Child Health Care takes place in a multidisciplinary setting linking general practitioners, paediatricians, dieticians, teachers, physiotherapists, pedagogues and psychologists.

Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome.

Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo (n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months.

High prevalence of hypertension in obese children in the Caribbean.

Background: The prevalence of obesity is increasing worldwide. Obesity in children and adults leads to diabetes mellitus type 2 and cardiovascular disease.

Aim: To determine the prevalence of high blood pressure in overweight and obese children in the Caribbean.

High cardiovascular risk in severely obese young children and adolescents.

Objective: To assess the prevalence of cardiovascular risk factors in severely obese children and adolescents.

Methods: A nationwide prospective surveillance study was carried out from July 2005 to July 2007 where paediatricians were asked to report all new cases of severe obesity in 2-18-year-old children to the Dutch Paediatric Surveillance Unit. Severe obesity is defined by gender and age-dependent cut-off points for body mass index based on Dutch National Growth Studies corresponding to the adult cut-off point of 35 kg/m(2).

Regulatory allospecific T cell clones abrogate chronic allograft rejection.

True alloantigen-specific tolerance is the ultimate goal of solid organ transplantation, eliminating the need for long-term immunosuppression. Recent evidence suggests that Th1-derived cytokines are associated with rejection and Th2-derived cytokines with long-term allograft survival, but the roles of these subsets in rejection and tolerance are incompletely understood. Here, we analyzed the functional and regulatory capacities of T cell clones derived from tolerant and rejecting rats (Wistar rat donors, Lewis rat recipients).

Nephrocalcinosis in preterm neonates.

The prevalence of nephrocalcinosis (NC) in preterm neonates in recent reports is 7-41%. The wide range in prevalence is a consequence of different study populations and ultrasound equipment and criteria, in addition to a moderate interobserver variation. NC in preterm neonates has a multifactorial aetiology, consisting of low gestational age and birth weight, often in combination with severe respiratory disease, and occurs as a result of an imbalance between stone-promoting and stone-inhibiting factors.

Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome.

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m(2) per day (n = 12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period.

Renal phenotype in Lowe Syndrome: a selective proximal tubular dysfunction.

Background And Objectives: Lowe syndrome is defined by congenital cataracts, mental retardation, and proximal tubulopathy and is due to mutations in OCRL. Recently, mutations in OCRL were found to underlie some patients with Dent disease, characterized by low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis. This phenotypic heterogeneity is poorly understood.

Absence of tolerance and toxicity to high-dose continuous intravenous furosemide in haemodynamically unstable infants after cardiac surgery.

Aim: To evaluate a high-dose continuous furosemide regimen in infants after cardiac surgery.

Methods: Fifteen haemodynamically unstable infants with volume overload admitted to a paediatric intensive care unit were treated with an aggressive furosemide regimen consisting of a loading bolus (1-2 mg kg(-1)) followed by a continuous infusion at 0.2 mg kg(-1) h(-1) which was adjusted according to a target urine output of 4 ml kg(-1) h(-1).

Is nephrocalcinosis in preterm neonates harmful for long-term blood pressure and renal function?

Objective: The aim of our study was to examine long-term effects of nephrocalcinosis in prematurely born children.

Patients And Methods: Preterm neonates (gestational age <32 weeks) with (n = 42) and without (n = 32) nephrocalcinosis were prospectively studied at a mean age of 7.5 (+/-1.

Evaluation of furosemide regimens in neonates treated with extracorporeal membrane oxygenation.

Introduction: Loop diuretics are the most frequently used diuretics in patients treated with extracorporeal membrane oxygenation (ECMO). In patients after cardiopulmonary bypass (CPB) surgery, the use of continuous furosemide infusion is increasingly documented. Because ECMO and CPB are 'comparable' procedures, continuous furosemide infusion is used in newborns on ECMO.

Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study.

In some children with bilateral Wilms' tumor, reduction of tumor burden cannot be accomplished without total nephrectomy. In Denys-Drash syndrome, nephrectomy is required for associated Wilms' tumor or after progression to end stage renal disease secondary to diffuse mesangial sclerosis because of risk of development of Wilms' tumor. Current recommendation is to wait at least 1-2 yr after completion of chemotherapy for Wilms' tumor before renal transplantation.

Selectin blockade plus therapy with low-dose sirolimus and cyclosporin a prevent brain death-induced renal allograft dysfunction.

Both antigen-dependent and -independent factors influence long-term organ allograft function and survival. Brain death (BD), a significant antigen-independent, donor-related injury upregulates a variety of inflammatory mediators in peripheral organs. One of the earliest responses to such an insult is the expression of selectins by endothelial cells of the transplanted tissues; these in turn trigger a cascade of nonspecific events, that enhance host alloresponses and which may be worsened by toxic effects of long-term immunosuppression.

Chronic rejection: insights from a novel immunosuppressive-free model of kidney transplantation.

The use of immunosuppressive drugs in models of chronic rejection may limit their usefulness for mechanistic studies. We have developed a new minor histocompatibility-mismatched rat kidney transplant model without the need for immunosuppression. Kidneys from LEW (RT1(l)) donors were transplanted to congenic WF.

Preterm neonates with nephrocalcinosis: natural course and renal function.

The aim of the study was to evaluate the natural course of nephrocalcinosis (NC) in preterm neonates and the effect of NC on blood pressure and renal glomerular and tubular function. In a prospective observational study of 201 preterm neonates (gestational age <32 weeks) NC was present at term in 83 patients (41%), who were subsequently examined at 6, 12, and 24 months, and until August 2000 annually (with a maximum of 4 years) if NC persisted. Examination consisted of blood pressure measurement, renal ultrasonography, and glomerular and tubular function tests.

Prospective study of renal insufficiency after bone marrow transplantation.

Since more and more children survive allogeneic bone marrow transplantation (BMT), knowledge of acute and late complications becomes increasingly important. Besides the major complications [(opportunistic) infections, veno-occlusive disease, graft versus host disease, and recurrence of primary disease], acute and chronic renal insufficiency are significant post-transplant complications that may contribute to transplant-related mortality. To elucidate risk factors for acute and chronic renal insufficiency post BMT, we performed a prospective study of all 66 children who received a BMT in a 2-year period at our institution; 21% had acute renal insufficiency post BMT.

Regulatory functions of alloreactive Th2 clones in human renal transplant recipients.

Background: Chronic allograft rejection is the major clinical problem in organ transplantation. There is evidence that indirect T cell recognition of donor-specific HLA peptides may play an important role in the immunopathogenesis of chronic allograft rejection. We have recently shown that HLA allopeptide-specific T cell clones generated from renal transplant recipients with chronic allograft nephropathy are of the Th1 phenotype, while those from stable patients are Th2.