Elsevier

The Lancet

Volume 362, Issue 9384, 23 August 2003, Pages 629-639
The Lancet

Seminar
Nephrotic syndrome in childhood

https://doi.org/10.1016/S0140-6736(03)14184-0Get rights and content

Summary

Childhood nephrotic syndromes are most commonly caused by one of two idiopathic diseases: minimal-change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS). A third distinct type, membranous nephropathy, is rare in children. Other causes of isolated nephrotic syndrome can be subdivided into two major categories: rare genetic disorders, and secondary diseases associated with drugs, infections, or neoplasia. The cause of idiopathic nephrotic syndrome remains unknown, but evidence suggests it may be a primary T-cell disorder that leads to glomerular podocyte dysfunction. Genetic studies in children with familial nephrotic syndrome have identified mutations in genes that encode important podocyte proteins. Patients with idiopathic nephrotic syndrome are initially treated with corticosteroids. Steroid-responsiveness is of greater prognostic use than renal histology. Several secondline drugs, including alkylating agents, ciclosporin, and levamisole, may be effective for complicated and steroid-unresponsive MCNS and FSGS patients. Nephrotic syndrome is associated with several medical complications, the most severe and potentially fatal being bacterial infections and thromboembolism. Idiopathic nephrotic syndrome is a chronic relapsing disease for most steroid-responsive patients, whereas most children with refractory FSGS ultimately develop end-stage renal disease. Research is being done to further elucidate the disorder's molecular pathogenesis, identify new prognostic indicators, and to develop better approaches to treatment.

Section snippets

Epidemiology and classification

Idiopathic nephrotic syndrome has a reported incidence of two to seven cases per 100 000 children and a prevalence of nearly 16 cases per 100 000. There are three distinct histological variants of primary idiopathic nephrotic syndrome: minimal-change nephrotic syndrome (MCNS), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (figure 1). MCNS and FSGS may represent opposite ends of one pathophysiological process or distinct disease entities. By contrast, membranous

Primary glomerular defect

The glomerular capillary wall consists of three structural elements that constitute the permselectivity barrier: endothelial cells separated by fenestrae, the glomerular basement membrane made up of a network of matrix proteins, and specialised epithelial cells (podocytes) connected to each other via an interdigitating network of slit diaphragms. Normally, proteins the size of albumin (69 kd) and larger are excluded from filtration, a restriction that depends substantially on the integrity of

Natural history and prognosis

The most important prognostic indicator in nephrotic syndrome is steroid responsiveness. Overall, 60–80% of steroid-responsive nephrotic children will relapse and about 60% of those will have five or more relapses. Age older than 4 years at presentation and remission within 7–9 days of the start of steroid treatment in the absence of microhaematuria are predictive of fewer relapses.137, 138, 139 In a natural-history study of 398 children, the proportion that became non-relapsers rose from 44%

Search Strategy

We searched the PubMed on-line database for all Englishlanguage papers on nephrotic syndrome published between 1996 and 2002. Our key search terms were “nephrotic syndrome”, limited to “all children”. We chose papers relevant to the paediatric population and pertaining to the topics of epidemiology, pathophysiology, diagnosis, and management as the basis of further review for this seminar.

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