Idiopathic nephrotic syndrome in children.

Background
In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While most children with nephrotic syndrome respond to corticosteroids, 80% experience a relapsing course. Corticosteroids have reduced the mortality rate to around 3%. However corticosteroids have well recognised potentially serious adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis and behavioural disturbances. This is an update of a review first published in 2000 and updated in 2003, 2005 and 2007.

Objectives
The aim of this review was to assess the benefits and harms of different corticosteroid regimens in children with steroid-sensitive nephrotic syndrome (SSNS). The benefits and harms of therapy were studied in two groups of children 1) children in their initial episode of SSNS, and 2) children who experience a relapsing course of SSNS.

Search methods
We searched the Cochrane Renal Group's Specialised Register to 26 February 2015 through contact with the Trials Search Co-ordinator using search terms relevant to this review.

Selection criteria
Randomised controlled trials (RCTs) performed in children (three months to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent.

Data collection and analysis
Two authors independently assessed risk of bias and extracted data. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).

Main results
Ten new studies were identified so a total of 34 studies (3033 total participants) were included in the 2015 review update. The risk of bias attributes were frequently poorly performed. Low risk of bias was reported in 18 studies for sequence generation, 16 studies for allocation concealment, seven for performance and detection bias, 15 for incomplete reporting and 16 for selective reporting. Three months or more of prednisone significantly reduced the risk of frequently relapsing nephrotic syndrome (FRNS) (6 studies, 582 children: RR 0.68, 95% CI 0.47 to 1.00) and of relapse by 12 to 24 months (8 studies, 741 children: RR 0.80, 95% CI 0.64 to 1.00) compared with two months. Five or six months of prednisone significantly reduced the risk of relapse (7 studies, 763 children: RR 0.62, 95% CI 0.45 to 0.85) but not FRNS (5 studies, 591 children: RR 0.78, 95% CI 0.50 to 1.22) compared with three months. However there was significant heterogeneity in the analyses. Subgroup analysis stratified by risk of bias for allocation concealment showed that the risk for FRNS did not differ significantly between two or three months of prednisone and three to six months among studies at low risk of bias but was significantly reduced in extended duration studies compared with two or three months in studies at high risk or unclear risk of bias. There were no significant differences in the risk of adverse effects between extended duration and two or three months of prednisone. Four studies found that in children with FRNS, daily prednisone during viral infections compared with alternate-day prednisone or no treatment significantly reduced the rate of relapse.

Authors' conclusions
In this 2015 update the addition of three well-designed studies has changed the conclusion of this review. Studies of long versus shorter duration of corticosteroids have heterogeneous treatment effects, with the older high risk of bias studies tending to over-estimate the effect of longer course therapy, compared with more recently published low risk of bias studies. Among studies at low risk of bias, there was no significant difference in the risk for FRNS between prednisone given for two or three months and longer durations or total dose of therapy indicating that there is no benefit of increasing the duration of prednisone beyond two or three months in the initial episode of SSNS.

The risk of relapse in children with FRNS is reduced by the administration of daily prednisone at onset of an upper respiratory tract or viral infection. Three additional studies have increased the evidence supporting this conclusion. This management strategy may be considered for children with FRNS. A paucity of data on prednisone use in relapsing nephrotic syndrome remains. In particular there are no data from RCTs evaluating the efficacy and safety of prolonged courses of low dose alternate-day prednisone although this management strategy is recommended in current guidelines.

Corticosteroid therapy for nephrotic syndrome in children

Nephrotic syndrome is defined by nephrotic-range proteinuria (≥40 mg/m2/hour or urine protein/creatinine ratio ≥200 mg/mL or 3+ protein on urine dipstick), hypoalbuminaemia (<25 g/L) and oedema. This review focuses on the classification, epidemiology, pathophysiology, management strategies and prognosis of idiopathic nephrotic syndrome of childhood, and includes a brief overview of the congenital forms.

Nephrotic syndrome in infants and children: pathophysiology and management

Nephrotic syndrome remains the most common manifestation of glomerular disease in childhood. Minimal change nephropathy is the most common cause of the syndrome in children. Despite its initial high response rate to corticosteroids and its favorable prognosis, relapses are common leading to increased morbidity and cost of treatment. This review seeks to appraise the common triggers of relapse and to highlight the evolving hypotheses about the pathogenesis of the syndrome. Literature search was conducted through PubMed, Google web search and Cochrane Database of Systematic reviews using relevant search terms. Acute respiratory infections and urinary tract infections are the most frequent infectious triggers of relapse. Targeted interventions like initiating corticosteroid or its dose-adjustment during episodes of acute respiratory infection and zinc supplementation are reportedly effective in reducing relapse rates. Hypotheses on pathogenesis of the syndrome have evolved from the concepts of ‘immune dysregulation’, ‘increased glomerular permeability’ to ‘podocytopathy’. Although development of drugs which can regulate the pathways for podocyte injury offers future hope for effective and targeted treatment, the relapse-specific interventions currently contribute to significant reduction in disease morbidity.

/pdf/steroid-sensitive-nephrotic-syndrome-in-children-triggers-of-3gzexdwc3o.pdf

Steroid-sensitive nephrotic syndrome in children: triggers of relapse and evolving hypotheses on pathogenesis.

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. Additionally, we highlight areas where no consensus regarding appropriate management has been reached. In this review, we detail the reasons why routine prophylactic antimicrobial and antithrombotic therapy are not warranted in INS and emphasise the conservative management of oedema. When pharmacological intervention is required for the treatment of oedema, we provide guidance to aid the clinician in determining the appropriate therapy. Additionally, we discuss obesity and growth, fracture risk, dyslipidaemia and thyroid dysfunction associated with INS. Where appropriate, we describe how recent developments in research have identified potential novel therapeutic targets.

/pdf/the-non-immunosuppressive-management-of-childhood-nephrotic-f2j43q4wg2.pdf

The non-immunosuppressive management of childhood nephrotic syndrome

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. The aim of PREDNOS 2 is to evaluate the effectiveness of a 6-day course of daily prednisolone therapy during an URTI in reducing the development of a subsequent relapse in a developed nation. The subjects will be 300 children with relapsing SSNS (≥2 relapses in preceding year), who will be randomised to receive either a 6-day course of daily prednisolone or no change to their current therapy (with the use of placebo to double blind) each time they develop an URTI over 12 months. A strict definition for URTI will be used. Subjects will be reviewed at 3, 6, 9 and 12 months to capture data regarding relapse history, ongoing therapy and adverse effect profile, including behavioural problems and quality of life. A formal health economic analysis will also be performed. The primary end point of the study will be the incidence of URTI-related relapse (3 days of Albustix +++) following the first infection during the 12-month follow-up period. DNA and RNA samples will be collected to identify a potential genetic cause for the disease. Subjects will be recruited from over 100 UK centres with the assistance of the Medicines for Children Research Network. PREDNOS 2 is funded by the National Institute for Health Research Health Technology Assessment Programme (11/129/261). We propose that PREDNOS 2 will be a pivotal study that will inform the future standard of care for children with SSNS. If it is possible to reduce the disease relapse rate effectively and safely, this will reduce the morbidity and cost associated with drug treatment, notwithstanding hospital admission and parental absence from employment. Current Controlled Trials (ISRCTN10900733)

/pdf/short-course-daily-prednisolone-therapy-during-an-upper-2l1ih3svuz.pdf

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.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Eric R Finlay

Author Tools

Chat about Author

Papers

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.