What is pediatric nephrotic syndrome?

Updated: Mar 04, 2020
  • Author: Jerome C Lane, MD; Chief Editor: Craig B Langman, MD  more...
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Answer

Pediatric nephrotic syndrome, also known as nephrosis, is defined by the presence of nephrotic-range proteinuria, edema, hyperlipidemia, and hypoalbuminemia. Nephrotic-range proteinuria in adults is characterized by protein excretion of 3.5 g or more per day. However, because of the great range of body sizes in children, the pediatric definition of nephrotic-range proteinuria is more cumbersome.

Nephrotic-range proteinuria in children is protein excretion of more than 40 mg/m2/hr. Because 24-hour urine collections are potentially unreliable and burdensome, especially in young children, many pediatric nephrologists instead rely on a single, first-morning urine sample to quantify protein excretion by the ratio of protein to creatinine. [2]

The use of a first-morning urine sample eliminates the contribution of potentially nonpathological orthostatic proteinuria, which might otherwise falsely elevate the protein level in a urine sample collected while a patient is active during the day. A urine protein/creatinine value of more than 2-3 mg/mg indicates nephrotic range proteinuria and correlates with results from 24-hour urine collection.

Nephrotic syndrome is a constellation of clinical findings that is the result of massive renal losses of protein. Thus, nephrotic syndrome is not a disease itself, but the manifestation of many different glomerular diseases. These diseases might be acute and transient, such as postinfectious glomerulonephritis, or chronic and progressive, such as focal segmental glomerulosclerosis (FSGS). Still other diseases might be relapsing and remitting, such as minimal change nephrotic syndrome (MCNS).

The glomerular diseases that cause nephrotic syndrome generally can be divided into primary and secondary etiologies. Primary nephrotic syndrome, also known as idiopathic nephrotic syndrome (INS), is associated with glomerular diseases intrinsic to the kidney and not related to systemic causes. The subcategories of INS are based on histological descriptions, but clinical-pathological correlations have been made.

A wide variety of glomerular lesions can be seen in INS. These lesions include MCNS, FSGS, membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulonephritis (C3GN), IgA nephropathy, and diffuse mesangial proliferation.

By definition, secondary nephrotic syndrome refers to an etiology extrinsic to the kidney. Among the many secondary causes of nephrotic syndrome are the following:

Genetic abnormalities may cause nephrotic syndrome (NS). Congenital NS (presenting before age 3 mo) and infantile NS (presenting at age 4-12 mo) have been associated with defects in the nephrin gene (NPHS1), phospholipase C epsilon 1 gene (PLCE1), and the Wilms tumor suppressor gene (WT1). Mutations in the podocin gene (NPHS2) are associated with a familial, autosomal-recessive form of FSGS. Mutations in the α-actinin-4 gene (ACTN4) and the gene TRPC6 are associated with autosomal-dominant forms of familial FSGS.

More than 39 genes have been associated with nephrotic syndrome, and approximately 30% of children with steroid-resistant nephrotic syndrome may be found to have a single-gene cause of their disease. [3] Additionally, other genetic syndromes have been associated with nephrotic syndrome, such as nail-patella syndrome, Pierson syndrome, and Schimke immuno-osseous dysplasia.

INS is divided into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndromes (SRNS) because a response to steroids has a high correlation with histologic subtype and prognosis. The landmark study of nephrotic syndrome in children, the International Study of Kidney Disease in Children (ISKDC), found that the vast majority of preadolescent children with INS had MCNS on kidney biopsy. [4, 5] Whereas 90% of children with MCNS responded to corticosteroid treatment with remission of their nephrotic syndrome, only 20% of children with FSGS responded to steroids.

This article focuses on primary (idiopathic) childhood nephrotic syndrome. The discussion of congenital and secondary nephrotic syndrome is beyond the scope of this article.


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