Daily low-dose prednisolone to prevent relapse of steroid-sensitive nephrotic syndrome in children with an upper respiratory tract infection: PREDNOS2 RCT.

Background: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5-7 days during an upper respiratory tract infection reduces the risk of relapse.

Objectives: To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none.

Steroid treatment for the first episode of childhood nephrotic syndrome: comparison of the 8 and 12 weeks regimen using an individual patient data meta-analysis.

Steroids are the cornerstone of the treatment of childhood nephrotic syndrome. The optimal duration for the first episode remains a matter of debate. The aim of this study is to determine whether the 8 weeks International Study of Kidney Disease in Children (ISKDC) regimen is equally effective as the 12 weeks steroid regimen from the German society of pediatric nephrology (Arbeitsgemeinschaft für Pädiatrische Nephrologie [APN]).

Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome.

Background: Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis.

Sixteen-week versus standard eight-week prednisolone therapy for childhood nephrotic syndrome: the PREDNOS RCT.

Background: The optimal corticosteroid regimen for treating the presenting episode of steroid-sensitive nephrotic syndrome (SSNS) remains uncertain. Most UK centres use an 8-week regimen, despite previous systematic reviews indicating that longer regimens reduce the risk of relapse and frequently relapsing nephrotic syndrome (FRNS).

Objectives: The primary objective was to determine whether or not an extended 16-week course of prednisolone increases the time to first relapse.

Glucocorticoid therapy regulates podocyte motility by inhibition of Rac1.

Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes excessively permeable leading to massive proteinuria. In childhood NS, immune system dysregulation has been implicated and increasing evidence points to the central role of podocytes in the pathogenesis. Children with NS are typically treated with an empiric course of glucocorticoid (Gc) therapy; a class of steroids that are activating ligands for the glucocorticoid receptor (GR) transcription factor.

Dyslipidemia after pediatric renal transplantation-The impact of immunosuppressive regimens.

Dyslipidemia contributes to cardiovascular morbidity and mortality in pediatric transplant recipients. Data on prevalence and risk factors in pediatric cohorts are, however, scarce. We therefore determined the prevalence of dyslipidemia in 386 pediatric renal transplant recipients enrolled in the CERTAIN registry.

Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management.

Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenotypic analysis.

Standardised Outcomes in Nephrology-Children and Adolescents (SONG-Kids): a protocol for establishing a core outcome set for children with chronic kidney disease.

Background: Children with chronic kidney disease (CKD), requiring dialysis or kidney transplantation, have a mortality rate of up to 30-fold higher than the general aged-matched population, and severely impaired quality of life. Symptoms such as fatigue and pain are prevalent and debilitating. Children with CKD are at risk of cognitive impairment, and poorer educational, vocational, and psychosocial outcomes compared with their well peers, which have consequences through to adulthood.

Recent developments in the detection and management of acute kidney injury.

Acute kidney injury (AKI) is a common condition in children admitted to hospital and existing serum and urine biomarkers are insensitive. There have been significant developments in stratifying the risk of AKI in children and also in the identification of new AKI biomarkers. Risk stratification coupled with a panel of AKI biomarkers will improve future detection of AKI, however, paediatric validation studies in mixed patient cohorts are required.

2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents.

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions.

Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir.

Background: Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection.

Methods: We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity.

Single-dose pharmacokinetics and safety of azilsartan medoxomil in children and adolescents with hypertension as compared to healthy adults.

Purpose: This open-label, multicenter, single-dose study characterized the pharmacokinetics and short-term safety of azilsartan medoxomil (AZL-M) in hypertensive pediatric subjects (12-16 years [cohort 1a; n = 9]; 6-11 years [cohort 2; n = 8]; 4-5 years [cohort 3; n = 3]).

Methods: Model-based simulations were performed to guide dosing, especially in 1-5-year olds, who were difficult to enroll. AZL-M was dosed according to body weight (20-60-mg tablet, cohorts 1a and 2; 0.

The non-immunosuppressive management of childhood nephrotic syndrome.

Idiopathic nephrotic syndrome (INS) is one of the most common renal diseases found in the paediatric population and is associated with significant complications, including infection and thrombosis. A high proportion of children enter sustained remission before adulthood, and therapy must therefore mitigate the childhood complications, while minimising the long-term risk to health. Here we address the main complications of INS and summarise the available evidence and guidance to aid the clinician in determining the appropriate treatment for children with INS under their care.

Towards a biomarker panel for the assessment of AKI in children receiving intensive care.

Background: Critically ill children and neonates are at high risk of developing acute kidney injury (AKI). AKI is associated with short- and long-term renal impairment and increased mortality. Current methods of diagnosing AKI rely on measurements of serum creatinine, which is a late and insensitive marker.

Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of kidney disease.

Background: Mutations in podocyte and basement membrane genes are associated with a growing spectrum of glomerular disease affecting adults and children. Investigation of familial cases has helped to build understanding of both normal physiology and disease.

Methods: We investigated a consanguineous family with a wide clinical phenotype of glomerular disease using clinical, histological, and new genetic studies.

Corticosteroid-free Kidney Transplantation Improves Growth: 2-Year Follow-up of the TWIST Randomized Controlled Trial.

Background: Corticosteroid withdrawal (CW) after pediatric kidney transplantation potentially improves growth while avoiding metabolic and other adverse events. We have recently reported the results of a 196 subject randomized controlled trial comparing early CW (tacrolimus, mycophenolate mofetil (MMF), daclizumab, and corticosteroids until day 4) with tacrolimus, MMF, and corticosteroid continuation (CC). At 6 months, CW subjects showed better growth with no adverse impact on acute rejection or graft survival (Am J Transplant 2010; 10: 828-836).

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS.

Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. Mutations in COL4A3 and COL4A4 are known to cause Alport syndrome (AS), thin basement membrane nephropathy, and to result in pathognomonic glomerular basement membrane (GBM) findings. Secondary FSGS is known to develop in classic AS at later stages of the disease.

A novel Interactive Health Communication Application (IHCA) for parents of children with long-term conditions: Development, implementation and feasibility assessment.

Background: Few evidence-based, on-line resources exist to support home-based care of childhood long-term conditions.

Methods: In a feasibility study, children with stages 3, 4, or 5 chronic kidney disease, parents and professionals collaboratively developed a novel Online Parent Information and Support (OPIS) application. Parents were randomized to an intervention arm with access to OPIS or a control arm without access.

A randomized, open-label, dose-response study of losartan in hypertensive children.

Background And Objectives: Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6-16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years.

Design, Setting, Participants, & Measurements: This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension.

Short course daily prednisolone therapy during an upper respiratory tract infection in children with relapsing steroid-sensitive nephrotic syndrome (PREDNOS 2): protocol for a randomised controlled trial.

Background: Relapses of childhood steroid-sensitive nephrotic syndrome (SSNS) are treated with a 4- to 8-week course of high-dose oral prednisolone, which may be associated with significant adverse effects. There is a clear association between upper respiratory tract infection (URTI) and relapse development. Previous studies in developing nations have suggested that introducing a 5- to 7-day course of daily prednisolone during an URTI may prevent a relapse developing and the need for a treatment course of high-dose prednisolone.

Bladder dysfunction and hypertension in children with Guillain-Barre syndrome.

Background: Guillain-Barre syndrome (GBS) causes acute motor, sensory and autonomic dysfunction. There is a relative paucity of published data regarding the autonomic features of GBS. The aims of this study were to describe the incidence, management and outcome of bladder dysfunction and hypertension in GBS and to ascertain whether these features relate to muscle weakness severity.